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28 Jan, 2025 | 00:54h | UTC

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RCT: Sodium Zirconium Cyclosilicate Improves Spironolactone Uptitration in HFrEF but Raises Concern for Increased HF Events

28 Jan, 2025 | 10:00h | UTC

Background: Hyperkalemia remains a major barrier to optimal use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF). While MRAs significantly reduce morbidity and mortality, real-world data show that fears surrounding hyperkalemia often lead to MRA down-titration or discontinuation. Sodium zirconium cyclosilicate (SZC), a newer oral potassium binder, has shown promise in managing hyperkalemia. However, its impact on MRA optimization and clinical outcomes in HFrEF has not been fully established.

Objective: To determine whether SZC can enable optimal dosing of spironolactone (≥25 mg/day) by preventing hyperkalemia in patients with symptomatic HFrEF, and to assess potential effects on heart failure outcomes.

Methods: This prospective, double-blind, randomized-withdrawal trial (REALIZE-K) enrolled adult patients with left ventricular ejection fraction ≤40% (NYHA class II-IV), on guideline-directed medical therapy but not on a full-dose MRA due to either prevalent hyperkalemia (serum potassium [K⁺] 5.1-5.9 mEq/L) or high hyperkalemia risk. During an open-label run-in, spironolactone was up-titrated (target 50 mg/day), and participants with hyperkalemia received SZC. Only those who achieved normokalemia (3.5-5.0 mEq/L) on spironolactone ≥25 mg/day continued into a 6-month randomized-withdrawal phase (SZC vs placebo). The primary endpoint was maintenance of normokalemia while on ≥25 mg/day spironolactone without rescue therapy for hyperkalemia. Key secondary outcomes included the time to first hyperkalemia event, time to spironolactone dose reduction/discontinuation due to hyperkalemia, and changes in health-related quality of life (Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score).

Results: A total of 203 participants were randomized (SZC: n=102; placebo: n=101). SZC significantly increased the proportion of participants who maintained normokalemia on ≥25 mg/day spironolactone (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; p<0.001). Rates of hyperkalemia were also lower with SZC (HR: 0.51; 95% CI: 0.37-0.71; p<0.001), and fewer patients required spironolactone down-titration or discontinuation (HR: 0.37; 95% CI: 0.17-0.73; p=0.006). There was no difference in KCCQ-Clinical Summary Score between groups (p=0.72). Notably, more participants in the SZC arm had adjudicated heart failure events (10 vs 2 in placebo) over the 6-month period, although the trial was not powered to detect differences in clinical outcomes.

Conclusions: In patients with symptomatic HFrEF and prevalent or incident hyperkalemia, sodium zirconium cyclosilicate (SZC) successfully enabled higher spironolactone doses by maintaining potassium levels in the normal range. However, the increased rate of heart failure (HF) events in the SZC group raises concern, particularly given the study’s limited power for clinical outcomes and baseline imbalances favoring higher HF risk in the SZC group (older age, lower eGFR, higher NT-proBNP). Although these findings do not establish a definitive causal relationship, they underscore a possible risk of fluid retention and the importance of cautious use in higher-risk populations. Larger, event-driven trials are crucial to confirm whether SZC-related sodium exchange may exacerbate HF decompensation despite the benefits of more effective MRA therapy.

Implications for Practice: SZC offers clinicians a means to sustain or escalate spironolactone dosing in hyperkalemia-prone HFrEF patients who would otherwise face MRA discontinuation. Still, the unexpected signal of increased HF events highlights the need for vigilant patient selection, fluid status monitoring, and regular follow-up. Clinicians should balance the advantages of maintaining guideline-recommended MRA doses against potential costs, the patient’s baseline HF severity, and possible sodium retention. Individualized care, particularly in older patients or those with high NT-proBNP levels, remains critical until more robust outcome data are available.

Study Strengths and Limitations: Strengths include strict definitions of hyperkalemia, a rigorous protocol for titrating spironolactone and SZC, and high rates of concurrent guideline-directed therapies. Limitations encompass the modest sample size, short follow-up period, and imbalance in baseline risk factors favoring the placebo group. Also, the study was not powered for major clinical events, limiting interpretability of the heart failure outcome signals.

Future Research: Further large-scale, long-term investigations are needed to clarify whether the higher incidence of HF events seen with SZC reflects underlying population differences or a genuine treatment-related risk. Such studies should prioritize hard clinical endpoints (eg, HF hospitalization, cardiovascular mortality), capture real-world tolerability data, and incorporate cost-effectiveness analyses. Research into the mechanisms of sodium exchange in compromised HF patients may also help identify subgroups that stand to gain the most from potassium-binding strategies or, conversely, experience undue risk.

Reference: Kosiborod MN, Cherney DZI, Desai AS, et al. “Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure.” Journal of the American College of Cardiology. 2025; DOI: https://doi.org/10.1016/j.jacc.2024.11.014

 

SR: Lower BP Targets Reduce Stroke Risk and Cardiovascular Events in Older Adults

16 Jan, 2025 | 12:42h | UTC

Background: Hypertension is a prevalent condition in older adults and a major risk factor for cardiovascular morbidity and mortality. Despite widely accepted benefits of treating blood pressure (BP) above 160 mmHg in this population, the optimal BP target remains uncertain. Many guidelines recommend a systolic BP (SBP) goal of < 140 mmHg in all adults, including those aged ≥ 65 years. However, evidence suggests older, possibly frail individuals might experience different benefit–risk ratios with more relaxed BP targets. This Cochrane review updates the previous 2017 analysis to determine whether aiming for higher BP targets in older adults (e.g., < 150–160 mmHg systolic) confers comparable or better outcomes than standard or more aggressive targets (< 140 mmHg).

Objective: To assess the effects of a higher BP target (SBP < 150–160 mmHg or diastolic BP < 95–105 mmHg) versus a lower (conventional or more aggressive) BP target (< 140/90 mmHg or lower) on mortality, stroke, and serious cardiovascular events in hypertensive adults aged ≥ 65 years.

Methods:

  • Design and Searches: This is an updated Cochrane systematic review of randomized controlled trials (RCTs) comparing higher vs lower BP targets in older adults with hypertension. Databases searched through June 2024 included MEDLINE, Embase, CENTRAL, the Cochrane Hypertension Specialised Register, and ClinicalTrials.gov.
  • Inclusion Criteria: RCTs of ≥ 1 year’s duration enrolling participants aged ≥ 65 years with baseline systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. Trials had to compare a higher BP target range (SBP < 150–160/DBP < 95–105 mmHg) to a lower BP target (< 140/90 mmHg).
  • Outcomes: Primary outcomes were all-cause mortality, stroke, institutionalization, and serious cardiovascular adverse events (including myocardial infarction, heart failure, and renal failure). Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, total serious adverse events, and withdrawals due to adverse effects.

Results:

  • Included Studies: Four open-label RCTs (N = 16,732) from Japan and China, with mean ages around 70 years (range 65–77). Mean follow-up ranged from 2 to 4 years.
  • Mortality: Lower BP targets may result in little to no difference in all-cause mortality (RR 1.14, 95% CI 0.95–1.37; low-certainty).
  • Stroke Prevention: A lower BP target clearly reduced the risk of stroke (RR 1.33, 95% CI 1.06–1.67; high-certainty), with an absolute reduction of approximately 6 stroke events per 1000 individuals treated over ~3 years.
  • Serious Cardiovascular Events: A lower BP target likely reduced total serious cardiovascular adverse events (RR 1.25, 95% CI 1.09–1.45; moderate-certainty), equating to roughly 10 fewer cardiovascular events per 1000 people treated.
  • Adverse Effects: Lower BP targets likely did not increase withdrawals due to adverse effects (RR 0.99, 95% CI 0.74–1.33; moderate-certainty). Data on other adverse events (e.g., hypotension) were limited but showed small absolute differences.

Conclusions: Treating older adults’ systolic BP to < 140 mmHg (vs < 150–160 mmHg) reduces stroke and likely reduces overall serious cardiovascular events without clearly affecting all-cause mortality or increasing dropouts due to adverse effects. While these findings support standard BP targets (< 140 mmHg) for many older patients, the absolute reduction in events is modest. Caution may be warranted in individuals aged ≥ 80 years or those who are frail, as the included studies had fewer such participants.

Implications for Practice: For most older adults, targeting SBP < 140 mmHg can prevent a modest but meaningful number of cardiovascular events, particularly stroke. Clinicians should balance these benefits against patient-specific concerns, such as frailty, multiple comorbidities, and polypharmacy. Monitoring for hypotension, renal function changes, and other adverse effects remains important.

Study Strengths and Limitations:

  • Strengths: Inclusion of four RCTs with low attrition rates; assessment of major vascular endpoints relevant to older adults.
  • Limitations: All trials were open-label, increasing risk of bias in subjective outcomes. Adverse event reporting was incomplete, and very elderly or frail individuals were often underrepresented. Most data originated from Asian populations, limiting generalizability to other regions.

Future Research: Further RCTs in populations aged ≥ 80 years, those with significant frailty, or living in nursing homes are essential to clarify optimal BP targets. Studies should capture quality-of-life measures and long-term safety outcomes, especially regarding adverse drug–drug interactions in complex older patients.

Reference: Falk JM, Froentjes L, Kirkwood JE, Heran BS, Kolber MR, Allan GM, Korownyk CS, Garrison SR. Higher blood pressure targets for hypertension in older adults. Cochrane Database of Systematic Reviews. 2024; Issue 12. DOI: http://doi.org/10.1002/14651858.CD011575.pub3

 

RCT: Empagliflozin Lowers Urinary Supersaturation in Nondiabetic Adults With Calcium and Uric Acid Kidney Stones

15 Jan, 2025 | 12:03h | UTC

Background: Kidney stones represent a major health challenge worldwide, with calcium-based (calcium oxalate or phosphate) and uric acid (UA) stones accounting for most cases. Despite multiple preventive measures—including hydration, dietary modification, and, in certain cases, pharmacotherapy—recurrence rates remain high. Recent retrospective analyses suggest sodium-glucose cotransporter 2 (SGLT2) inhibitors may reduce stone episodes in patients with type 2 diabetes. These agents could theoretically lower stone risk by promoting urinary citrate excretion, altering urine pH, and enhancing UA clearance. However, prospective data are lacking in nondiabetic individuals. This phase 2, single-center, double-blind, placebo-controlled, crossover study (SWEETSTONE) explored whether empagliflozin (25 mg daily) modifies urinary relative supersaturation ratios (RSRs)—a validated surrogate of stone risk—in adults without diabetes who have a history of either calcium or UA stones.

Objective: To determine if empagliflozin significantly reduces RSRs for calcium oxalate (CaOx), calcium phosphate (CaP), and UA in nondiabetic adults with recurrent kidney stones and to assess short-term safety.

Methods: A total of 53 participants (28 calcium stone formers, 25 UA stone formers) were randomized to empagliflozin 25 mg once daily or placebo for two weeks, followed by a 2–6-week washout, then crossed over to the alternative treatment. Primary outcomes were changes in RSR CaOx, RSR CaP, and RSR UA. Secondary measures included 24-hour urine pH, citrate, calcium, and UA, as well as key blood parameters. Analyses were performed separately for calcium and UA stone groups using a generalized linear mixed effects model. The per protocol set was used for the main analysis, with additional intention-to-treat assessments for confirmation.

Results: In calcium stone formers, empagliflozin lowered RSR CaP by 36% (95% CI −48% to −21%; p<0.001) compared with placebo but did not significantly change RSR CaOx. Uric acid supersaturation rose modestly, yet nonsignificantly. Among UA stone formers, empagliflozin reduced RSR UA by 30% (95% CI −44% to −12%; p=0.002), with no significant effect on RSR CaOx or RSR CaP. Both groups showed substantial increases in 24-hour urine citrate (60% for calcium stones, 40% for UA stones) and marked reductions in plasma UA levels. Urine calcium rose in some calcium stone formers, but no severe adverse events were reported during the study.

Conclusions: Short-term treatment with empagliflozin produced meaningful decreases in key urinary supersaturation indices among nondiabetic adults with calcium or UA stones, while exhibiting an acceptable safety profile. These favorable laboratory changes offer mechanistic promise but do not establish definitive evidence that long-term stone recurrence is reduced.

Implications for Practice: Although the pronounced improvement in urinary lithogenic profiles is encouraging, it remains unclear whether these shifts will translate into sustained reductions in actual stone formation. Consequently, clinicians should be cautious about recommending off-label SGLT2 inhibition for stone prevention solely on the basis of these short-term biochemical improvements. Larger, longer-duration trials with clinical endpoints (i.e., stone recurrence) are warranted before SGLT2 inhibitors can be broadly endorsed for this indication. In addition, practical considerations—such as cost, insurance coverage, and potential off-target effects—must be weighed in individualized clinical decisions.

Study Strengths and Limitations: Strengths include the randomized crossover design and distinct analyses for calcium and UA stone phenotypes. Nevertheless, the sample size was modest, and the treatment duration too brief to capture definitive impacts on stone recurrence. The predominance of white male participants also limits generalizability to more diverse populations.

Future Research: Extended follow-up is crucial to determine the long-term clinical effectiveness of empagliflozin in preventing stone events. Future work should also explore potential mechanisms in larger cohorts, assess cost-effectiveness in real-world settings, and evaluate whether other SGLT2 inhibitors elicit comparable effects.

Reference: Anderegg MA, Schietzel S, Bargagli M, et al. Empagliflozin in nondiabetic individuals with calcium and uric acid kidney stones: a randomized phase 2 trial. Nature Medicine (2025). DOI: https://doi.org/10.1038/s41591-024-03330-x

 

Observational Study Emulation: Denosumab vs. Oral Bisphosphonates in Dialysis-Dependent Patients Shows Reduced Fractures but Possible Elevated Cardiovascular Risk

8 Jan, 2025 | 11:55h | UTC

Background: Patients receiving dialysis have a markedly increased risk of osteoporotic fractures, yet management options in this population remain challenging. Although oral bisphosphonates are the usual first-line treatment for osteoporosis, safety concerns exist for those with severe chronic kidney disease (CKD). Denosumab, which is not cleared via the kidney, offers a potential alternative, but limited data compare its fracture-prevention benefit and cardiovascular (CV) safety against bisphosphonates in dialysis-dependent patients.

Objective: To estimate the risk for major adverse cardiac events (MACE) and the effectiveness in preventing fractures when using denosumab compared with oral bisphosphonates among patients undergoing dialysis.

Methods: This study emulated a target trial using an observational Japanese administrative claims database (April 2014 to October 2022). Adults aged 50 years or older, receiving dialysis and newly prescribed denosumab (60 mg subcutaneously) or oral bisphosphonates (alendronate, risedronate, ibandronate, or minodronate) were included. Exclusions involved recent acute myocardial infarction, stroke, or heart failure. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline characteristics. The primary safety outcome was MACE (acute myocardial infarction, stroke, hospitalization for heart failure, or CV death), and the primary effectiveness outcome was all fractures. Three-year risks, risk differences, and risk ratios were estimated.

Results: Among 658 denosumab users and 374 oral bisphosphonate users (mean age, 74.5 years; 62.9% women) followed for up to 3 years, denosumab was associated with a higher weighted risk of MACE (3-year risk ratio, 1.36 [95% CI, 0.99 to 1.87]; risk difference, 8.2% [–0.2% to 16.7%]) compared with oral bisphosphonates. Although the point estimate suggests a notable increase, the 95% CI includes 1.0, indicating that statistical significance was not definitively achieved. Denosumab showed a significantly lower composite fracture risk (3-year risk ratio, 0.55 [0.28 to 0.93]; risk difference, –5.3% [–11.3% to –0.6%]). Individual fracture sites (e.g., hip, vertebral) had imprecise estimates but trended toward fewer nonvertebral fractures with denosumab. Mortality rates did not differ substantially between the groups.

Conclusions: In dialysis-dependent patients with osteoporosis, denosumab may reduce fracture risk while potentially elevating the likelihood of MACE. However, the higher MACE estimate did not surpass the conventional threshold for statistical significance, warranting cautious interpretation. Although these data suggest a clinically meaningful reduction in fractures, the findings regarding cardiovascular outcomes remain imprecise and require further confirmation.

Implications for Practice: Clinicians treating dialysis-dependent patients should weigh denosumab’s fracture-prevention advantage against its possible heightened CV risk. Oral bisphosphonates, though sometimes restricted in severe CKD, may confer lower risk of MACE. Careful monitoring of electrolyte levels, especially calcium, and CV status is essential when administering denosumab in end-stage kidney disease.

Study Strengths and Limitations: Strengths include a large, real-world cohort and the use of target trial emulation with robust propensity score weighting. Limitations involve potential residual confounding, reliance on claims-based definitions of outcomes, and absent lab data (e.g., serum calcium, glomerular filtration rate). Consequently, causality and generalizability should be interpreted with caution, especially outside Japan.

Future Research:
Prospective trials and additional observational studies using detailed clinical data (including renal function parameters and bone mineral density) are needed to clarify the relative net benefits of denosumab versus bisphosphonates in advanced CKD. Investigations into other safety outcomes, such as long-term renal function and hypocalcemia-related complications, would further inform clinical decision-making.

Reference: Masuda S, Fukasawa T, Matsuda S, Kawakami K. “Cardiovascular Safety and Fracture Prevention Effectiveness of Denosumab Versus Oral Bisphosphonates in Patients Receiving Dialysis: A Target Trial Emulation.” Annals of Internal Medicine. DOI:
https://doi.org/10.7326/ANNALS-24-03237

 

Meta-Analysis: Tailored Hydration Strategies Decrease CI-AKI and MACE in Coronary Angiography

6 Jan, 2025 | 13:00h | UTC

Background: Contrast-induced acute kidney injury (CI-AKI) poses a considerable burden on patients undergoing coronary angiography or percutaneous coronary intervention (PCI). Beyond the direct tubular toxicity of iodine contrast, several risk factors, including chronic kidney disease (CKD) and hemodynamic instability, further increase the likelihood of renal damage. Although guideline-based prevention strategies recommend peri-procedural intravenous hydration, the optimal volume and method remain unclear.

Objective: This meta-analysis aimed to determine whether patient-tailored intravenous fluid administration (using parameters other than body weight alone) can reduce the incidence of CI-AKI, as well as major adverse cardiovascular events (MACE), compared with conventional non-tailored hydration protocols in patients undergoing coronary angiography and/or PCI.

Methods: A systematic review of randomized controlled trials (RCTs) was performed, including 13 studies and 4,458 participants. Tailored hydration strategies encompassed left ventricular end-diastolic pressure (LVEDP)-guided infusion, diuresis-driven matched replacement (RenalGuard®), bioimpedance vector analysis, central venous pressure, or inferior vena cava ultrasound measurements. These were compared against standard non-tailored fluid protocols. The primary outcome was CI-AKI (variously defined but measured within 7 days), and secondary outcomes included MACE, all-cause mortality, and renal replacement therapy (RRT).

Results: Across 12 RCTs (n=3,669), tailored hydration significantly reduced CI-AKI rates (risk ratio 0.56, 95% CI [0.46–0.69], p<0.00001; I²=26%). Ten studies (n=3,377) revealed lower MACE incidence in the tailored hydration arm (RR=0.57, 95% CI [0.42–0.78], p=0.0005; I²=12%). A significant reduction in all-cause mortality (RR=0.57, 95% CI [0.35–0.94], p=0.03) and RRT requirement (RR=0.51, 95% CI [0.29–0.89], p=0.02) was also observed, with no significant increase in pulmonary edema. Subgroup analyses (e.g., CKD) supported the overall benefit of individualizing fluid regimens.

Conclusions: Tailored hydration strategies appear superior to standard approaches in lowering the risk of CI-AKI, MACE, mortality, and RRT after coronary angiography or PCI. Although LVEDP-guided protocols are simple to implement and effective, the RenalGuard® system may offer additional benefits in selected populations, albeit at higher cost and complexity.

Implications for Practice: Clinicians should consider personalized hydration based on physiological or hemodynamic parameters to optimize fluid volume, reduce renal injury, and potentially improve clinical outcomes. Nevertheless, practical challenges include access to specialized equipment and the need for close monitoring in some techniques.

Study Strengths and Limitations: This systematic review highlights consistent treatment effects across diverse RCTs and methods. However, potential biases due to lack of blinding, varying CI-AKI definitions, and limited head-to-head comparisons among tailored approaches constrain definitive conclusions. The small sample size of certain studies and underpowered subgroup analyses also limit the generalizability of findings.

Future Research: Further large-scale trials are warranted to compare various tailored protocols directly, focusing on cost-effectiveness, ease of implementation, and patient-centered endpoints. Ongoing investigations, such as the NEPTUNE trial, aim to clarify whether combining multiple parameters (like LVEDP and contrast volume/eGFR ratio) yields optimal renal protection.

Reference: Cossette F, Trifan A, Prévost-Marcotte G, et al. Tailored Hydration for the Prevention of Contrast-Induced Acute Kidney Injury After Coronary Angiogram or PCI: A Systematic Review and Meta-Analysis. American Heart Journal. Published online January 4, 2025. DOI: http://doi.org/10.1016/j.ahj.2025.01.002

RCT: Chlorthalidone Shows No Renal Advantage Over Hydrochlorothiazide Under Equivalent Dosing in Older Adults With Hypertension

3 Jan, 2025 | 09:00h | UTC

Background: Hypertension is a critical factor in chronic kidney disease (CKD) progression and cardiovascular risk. Thiazide-type diuretics, such as chlorthalidone and hydrochlorothiazide, are first-line antihypertensive treatments. However, whether one agent confers stronger renal protection remains contested, especially at doses considered pharmacologically comparable. Prior observational studies suggested potential discrepancies in kidney outcomes and hypokalemia incidence. This secondary analysis of the Diuretic Comparison Project (DCP) further clarifies the comparative effectiveness of chlorthalidone versus hydrochlorothiazide on renal endpoints.

Objective: To evaluate whether chlorthalidone (12.5–25 mg/day) prevents CKD progression more effectively than hydrochlorothiazide (25–50 mg/day) in adults ≥65 years with hypertension and no pre-specified exclusion by renal function.

Methods: The DCP is a pragmatic, open-label randomized clinical trial embedded in Veterans Affairs (VA) facilities across the United States. Between June 1, 2016, and December 31, 2023, patients already receiving hydrochlorothiazide (25 or 50 mg/day) for hypertension were randomized either to continue that medication or switch to chlorthalidone (12.5–25 mg/day), reflecting equivalent potency.
The prespecified primary kidney outcome was a composite of doubling of serum creatinine, a terminal estimated glomerular filtration rate (eGFR) <15 mL/min, or dialysis initiation. Secondary measures included ≥40% eGFR decline, incident CKD (new eGFR <60 mL/min), eGFR slope, and relevant adverse events. Laboratory data were obtained through usual clinical care rather than protocol-driven testing.

Results: Among 13,523 randomized participants, 12,265 had analyzable renal data (mean [SD] age, 71 [4] years; 96.8% male). The mean (SD) follow-up was 3.9 (1.3) years. Chlorthalidone did not demonstrate superiority over hydrochlorothiazide for the composite kidney endpoint (6.0% vs 6.4%; hazard ratio, 0.94; 95% CI, 0.81–1.08; P=.37). Additional analyses showed no differences in CKD incidence, ≥40% eGFR decline, or eGFR slope. Hypokalemia occurred more frequently in chlorthalidone users (overall ~2% higher rate of low potassium measurements), and hospitalizations for hypokalemia also trended higher.

Conclusions: Under dosing regimens designed to achieve equivalent antihypertensive potency, chlorthalidone provided no measurable renal benefit over hydrochlorothiazide but posed a modestly elevated risk of hypokalemia. These findings reinforce the clinical interchangeability of both agents for long-term blood pressure management in older adults, provided serum potassium is monitored.

Implications for Practice: Clinicians can confidently employ either chlorthalidone or hydrochlorothiazide in older patients with hypertension, including those with mild or moderate CKD, since renal deterioration rates did not differ significantly. Importantly, the trial used half the milligram amount of chlorthalidone (12.5–25 mg/day) to match the usual doses of hydrochlorothiazide (25–50 mg/day). Recognizing this equivalence helps guide therapy transitions and dosing decisions. Vigilant monitoring of electrolytes remains essential, particularly when prescribing chlorthalidone, given the slightly higher incidence of hypokalemia.

Study Strengths and Limitations: Strengths include the randomized design, broad participant inclusion, and pragmatic structure that mirrors real-world prescribing. Limitations involve potential underestimation or overestimation of renal events due to reliance on routine (rather than scheduled) lab tests. Also, nearly all participants had prior hydrochlorothiazide exposure, which may have influenced tolerance and adherence patterns.

Future Research: Further clinical trials focusing on more advanced CKD stages, distinct comorbidities, or combination regimens (e.g., with potassium-sparing agents) would expand our understanding of how thiazide-type diuretics influence long-term kidney outcomes. Extended follow-up or additional subgroup analyses could also shed light on the interplay of dose-response effects in highly vulnerable populations.

Reference: Ishani A, Hau C, Raju S, et al. “Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial.” JAMA Netw Open. 2024;7(12):e2449576. DOI: http://doi.org/10.1001/jamanetworkopen.2024.49576

 

Meta-Analysis: Moderately Rapid Sodium Correction Linked to Better Outcomes in Severe Hyponatremia

20 Nov, 2024 | 16:10h | UTC

Background: Severe hyponatremia is a critical condition that can lead to hyponatremic encephalopathy, necessitating prompt treatment to prevent neurological damage or death. Traditional guidelines recommend limiting sodium correction rates to prevent osmotic demyelination syndrome (ODS). However, emerging evidence suggests that slower correction rates may be associated with increased mortality.

Objective: To evaluate the association between sodium correction rates and mortality among hospitalized adults with severe hyponatremia.

Methods: This systematic review and meta-analysis included 16 cohort studies published between January 2013 and October 2023, involving 11,811 hospitalized adults with severe hyponatremia (serum sodium <120 mEq/L or <125 mEq/L with severe symptoms). Patients were categorized based on sodium correction rates: rapid (≥8-10 mEq/L per 24 hours), slow (<8 or 6-10 mEq/L per 24 hours), and very slow (<4-6 mEq/L per 24 hours). Primary outcomes were in-hospital and 30-day mortality; secondary outcomes included hospital length of stay (LOS) and incidence of ODS.

Results: Rapid correction was associated with significantly lower in-hospital mortality compared to slow correction (odds ratio [OR], 0.67; 95% CI, 0.55-0.82) and very slow correction (OR, 0.29; 95% CI, 0.11-0.79), corresponding to 32 and 221 fewer deaths per 1,000 patients, respectively. At 30 days, rapid correction was associated with 61 and 134 fewer deaths per 1,000 patients compared to slow and very slow correction, respectively. Rapid correction also resulted in shorter hospital LOS by 1.20 days (95% CI, 0.51-1.89) compared to slow correction and 3.09 days (95% CI, 1.21-4.94) compared to very slow correction. There was no statistically significant increase in ODS risk with rapid correction.

Conclusions: In hospitalized adults with severe hyponatremia, rapid sodium correction was associated with reduced mortality and shorter hospital stays without a significant increase in ODS risk.

Implications for Practice: These findings suggest that more aggressive sodium correction may benefit patients with severe hyponatremia, challenging current guidelines that recommend slower correction rates to prevent ODS. Clinicians should weigh the potential benefits of rapid correction against the traditionally emphasized risks, although caution is still warranted given the seriousness of ODS.

Study Strengths and Limitations: Strengths include a large sample size and inclusion of recent studies reflecting current practices. Limitations involve the observational nature of included studies, potential confounding factors, heterogeneity in correction rate definitions, and possible underreporting of ODS due to its rarity and diagnostic challenges.

Future Research: Randomized controlled trials are needed to establish causality and optimal correction rates, as well as to identify patient subgroups that may benefit most from rapid correction while minimizing ODS risk.

Reference: Ayus JC, Moritz ML, Fuentes NA, et al. Correction Rates and Clinical Outcomes in Hospitalized Adults With Severe Hyponatremia: A Systematic Review and Meta-Analysis. JAMA Internal Medicine. Published online November 18, 2024. DOI: http://doi.org/10.1001/jamainternmed.2024.5981

 

Review: Comparative Analysis of ESC and ESH Hypertension Guidelines

20 Nov, 2024 | 15:03h | UTC

Introduction: Hypertension remains a significant global health challenge with increasing prevalence and substantial morbidity and mortality rates. To address this, the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) have independently published updated guidelines on hypertension management. This review provides a pragmatic comparison of these guidelines, highlighting their major similarities and differences to assist clinicians in optimizing patient care.

Key Recommendations:

Shared Recommendations:

  1. Diagnosis Criteria: Both guidelines recommend diagnosing hypertension based on office systolic and diastolic blood pressures of ≥140/90 mmHg.
  2. Blood Pressure Targets: Both advocate aiming for an optimal blood pressure of <130/80 mmHg. The ESH emphasizes personalized targets for specific populations like the elderly, while the ESC adopts the ALARA (as low as reasonably achievable) principle.
  3. Out-of-Office Measurements: Emphasis is placed on home blood pressure monitoring and ambulatory measurements to confirm diagnoses and tailor treatments.
  4. Comprehensive Assessment: Both recommend thorough initial evaluations, including screening for orthostatic hypotension, comorbidities, and hypertension-mediated organ damage (HMOD).
  5. Early Treatment Initiation: Both suggest starting antihypertensive therapy promptly, preferably using a single-pill combination of two agents after lifestyle interventions.
  6. Treatment Goals and Follow-Up: Both aim for patients to reach blood pressure targets within three months, underscoring the importance of close monitoring.
  7. Adjunctive Therapies: The use of SGLT-2 inhibitors is recommended for patients with chronic kidney disease and/or heart failure. Renal denervation is considered for true resistant hypertension.

Differences:

  1. Blood Pressure Classification: The ESC introduces a new category of “elevated blood pressure,” altering patient classification but with minimal impact on practical management.
  2. Screening for Secondary Hypertension: The ESC strongly encourages screening for secondary hypertension, particularly primary aldosteronism; the ESH does not emphasize this as strongly.
  3. Age Stratification: Different age thresholds for the very elderly are used (ESH: ≥80 years; ESC: ≥85 years), with the ESH providing more detailed treatment personalization for this group.
  4. Treatment Targets Philosophy: The ESC supports the ALARA principle for blood pressure targets, aiming for the lowest achievable levels without adverse effects, while the ESH provides specific target ranges.
  5. Beta-Blocker Use: The ESH includes beta-blockers as first-line therapy options, whereas the ESC positions them as third-line agents.

Conclusion: Despite minor discrepancies, the ESC and ESH hypertension guidelines are largely concordant and based on the same evidence base. Both sets provide clear, pragmatic recommendations emphasizing early diagnosis, personalized treatment, and close follow-up. Clinicians can confidently use either guideline to inform practice, as both aim to improve patient outcomes by effectively managing hypertension in the primary care setting.

Reference: Virdis A, et al. Juxtaposing Hypertension Guidelines: Are They Different? A Pragmatic Look to ESC and ESH Guidelines on (Arterial) Hypertension. High Blood Pressure & Cardiovascular Prevention. 2024; DOI: https://doi.org/10.1007/s40292-024-00693-7

 

RCT: Intensive Systolic Blood Pressure Target Reduces Cardiovascular Events in Type 2 Diabetes

16 Nov, 2024 | 16:49h | UTC

Background: Patients with type 2 diabetes frequently have elevated systolic blood pressure, heightening their risk for cardiovascular disease. Optimal systolic blood-pressure targets in this population remain unclear due to inconclusive results from previous trials.

Objective: To determine whether intensive treatment targeting a systolic blood pressure of less than 120 mm Hg reduces major cardiovascular events compared to standard treatment targeting less than 140 mm Hg in patients with type 2 diabetes.

Methods: In this randomized controlled trial conducted at 145 sites in China, 12,821 patients aged 50 or older with type 2 diabetes, elevated systolic blood pressure, and increased cardiovascular risk were assigned to intensive treatment (target <120 mm Hg) or standard treatment (target <140 mm Hg). The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes.

Results: Over a median follow-up of 4.2 years, the intensive-treatment group achieved a mean systolic blood pressure of 121.6 mm Hg versus 133.2 mm Hg in the standard-treatment group at 1 year. Primary outcome events occurred in 393 patients in the intensive group (1.65 events per 100 person-years) versus 492 patients in the standard group (2.09 events per 100 person-years) (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). Serious adverse events were similar between groups, but symptomatic hypotension and hyperkalemia were more frequent in the intensive-treatment group.

Conclusions: Intensive systolic blood-pressure control to less than 120 mm Hg significantly reduced major cardiovascular events in patients with type 2 diabetes compared to standard treatment.

Implications for Practice: These findings support adopting more aggressive systolic blood-pressure targets in patients with type 2 diabetes to prevent cardiovascular events. Clinicians should balance the benefits with potential risks, monitoring for hypotension and hyperkalemia.

Study Strengths and Limitations: Strengths include a large sample size, multicenter design, and sufficient power to detect differences in cardiovascular outcomes. Limitations involve unblinded treatment assignment, which may introduce bias, and reliance on self-reported home blood-pressure measurements during the COVID-19 pandemic, potentially affecting data accuracy. The exclusive enrollment of Chinese patients may limit generalizability to other populations. The increased incidence of hypotension and hyperkalemia raises concerns about the safety of intensive blood-pressure lowering in broader practice.

Future Research: Further studies should assess the long-term safety and efficacy of intensive blood-pressure control in diverse populations and explore strategies to minimize adverse events. Investigations into personalized blood-pressure targets based on patient characteristics may enhance clinical outcomes.

Reference: Bi Y, Li M, Liu Y, et al. Intensive Blood-Pressure Control in Patients with Type 2 Diabetes. New England Journal of Medicine. Published November 16, 2024. DOI: http://doi.org/10.1056/NEJMoa2412006

 

Meta-analysis: Urea May be Effective for the Treatment of SIADH-Induced Hyponatremia

15 Nov, 2024 | 14:01h | UTC

Background: Hyponatremia, defined as a serum sodium level below 135 mEq/L, is the most common electrolyte disorder in clinical practice, associated with increased mortality and prolonged hospital stays. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a frequent cause of euvolemic hyponatremia, particularly among hospitalized patients. Traditional treatments like fluid restriction and hypertonic saline have limitations, and guidelines are inconsistent regarding their use. Urea, an osmotic diuretic, has been proposed as an alternative therapy but is underutilized due to concerns about efficacy, safety, and patient tolerability.

Objective: To evaluate the effectiveness and safety of urea in treating hyponatremia caused by SIADH.

Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Searches of MEDLINE, EMBASE, Cochrane CENTRAL, and Google Scholar up to November 2023 identified studies involving patients with SIADH-related hyponatremia treated with oral or nasogastric urea. Inclusion criteria encompassed clinical trials and observational studies reporting outcomes on serum sodium levels, symptom resolution, or adverse effects.

Results: Sixteen observational studies involving 518 patients (430 treated with urea) met inclusion criteria. Urea treatment significantly increased serum sodium levels (mean difference [MD], 9.21 mEq/L [95% CI, 7.36-11.06]; P < 0.01) despite high heterogeneity (I² = 89%). Subgroup analyses showed significant sodium increases at 24 hours and at 2, 3, 5, 7, 14 days, and 1 year post-treatment. Patients with severe hyponatremia (<120 mEq/L) experienced greater sodium increases (MD, 18.04 mEq/L [95% CI, 13.68-22.39]) compared to those with moderate (120-129 mEq/L) or mild (130-135 mEq/L) hyponatremia. Urea’s efficacy was comparable to fluid restriction (MD, 0.81 mEq/L [95% CI, –0.93 to 2.55]; P = 0.4) and vaptans (MD, –2.43 mEq/L [95% CI, –6.31 to 1.45]; P = 0.2), and superior to no treatment (MD, 7.99 mEq/L [95% CI, 6.25-9.72]; P < 0.01). Adverse events were minor; poor palatability was the most common complaint.

Conclusions: Urea is an effective and safe treatment for SIADH-induced hyponatremia, significantly increasing serum sodium levels, particularly in severe cases. It offers a viable alternative to fluid restriction and vaptans with minimal adverse effects.

Implications for Practice: Urea should be considered a valuable treatment option for SIADH-induced hyponatremia, especially in resource-limited settings or when other therapies are contraindicated or poorly tolerated. Its cost-effectiveness and ease of administration may improve patient outcomes and reduce healthcare costs.

Study Strengths and Limitations: Strengths include a comprehensive search strategy and inclusion of diverse studies across multiple settings. Limitations are the reliance on observational studies due to the absence of randomized controlled trials, significant heterogeneity among studies, and the potential for publication bias.

Future Research: Randomized controlled trials are necessary to confirm urea’s efficacy and safety, establish standardized dosing regimens, and develop strategies to enhance palatability and patient adherence.

Reference: Chander S, et al. Urea to Treat Hyponatremia Due to Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Systematic Review and Meta-Analysis. American Journal of Kidney Diseases. 2024. DOI: http://doi.org/10.1053/j.ajkd.2024.07.011

 

Meta-analysis: Hemodiafiltration Reduces Mortality in Kidney Failure Patients Compared to Hemodialysis

7 Nov, 2024 | 12:19h | UTC

Background: Kidney failure patients undergoing hemodialysis face high mortality rates, with approximately 50% dying within five years of initiating treatment. Hemodiafiltration, a convection-based therapy that removes a broader spectrum of uraemic toxins, has been proposed to improve survival outcomes. Previous studies have shown mixed results regarding its efficacy, and uncertainties remain about its effects on specific patient subgroups, dose-response relationships with convection volume, and cause-specific mortality.

Objective: To compare the effects of online hemodiafiltration versus standard hemodialysis on all-cause and cause-specific mortality in patients with kidney failure.

Methods: An individual patient data meta-analysis of five randomized controlled trials was conducted, encompassing 4,153 patients (2,083 on hemodiafiltration and 2,070 on hemodialysis). Databases including MEDLINE, Embase, and the Cochrane Central Register were searched up to July 17, 2024. The primary outcome was all-cause mortality. Subgroup analyses based on patient characteristics and dose–response analyses using convection volume were performed.

Results: Over a median follow-up of 30 months, all-cause mortality occurred in 477 patients (23.3%) receiving hemodiafiltration and 559 patients (27.0%) receiving hemodialysis. Hemodiafiltration significantly reduced all-cause mortality (hazard ratio [HR] 0.84, 95% CI 0.74–0.95) compared to hemodialysis. Cardiovascular mortality was also lower in the hemodiafiltration group (HR 0.78, 95% CI 0.64–0.96), particularly deaths due to cardiac causes (HR 0.67, 95% CI 0.50–0.89). No differential effects were observed across predefined patient subgroups. A dose-dependent relationship was found between higher convection volumes and reduced mortality risk.

Conclusions: Hemodiafiltration significantly reduces all-cause and cardiovascular mortality in patients with kidney failure compared to standard hemodialysis. The mortality benefit is dose-dependent, with higher convection volumes associated with greater risk reductions.

Implications for Practice: These findings support the adoption of online hemodiafiltration as a superior alternative to conventional hemodialysis. Clinicians should consider implementing high-dose hemodiafiltration to improve survival outcomes in patients with kidney failure.

Study Strengths and Limitations: Strengths include the large sample size and use of individual patient data, allowing for comprehensive subgroup and dose–response analyses. Limitations involve heterogeneity among the included studies and potential biases due to open-label designs. The lack of blinding may have influenced outcome reporting.

Future Research: Further studies are needed to evaluate the long-term benefits of hemodiafiltration on patient-reported outcomes, cost-effectiveness, and environmental impacts. Investigations into the optimal convection volumes and the mechanisms underlying the observed mortality reductions are also warranted.

Reference: Vernooij RWM, Hockham C, Strippoli G, Green S, Hegbrant J, Davenport A, et al. Hemodiafiltration versus hemodialysis for kidney failure: an individual patient data meta-analysis of randomised controlled trials. The Lancet. 2024 Oct 25;404(10464). DOI: http://doi.org/10.1016/S0140-6736(24)01859-2

 

RCT: Atrasentan Reduces Proteinuria in Patients with IgA Nephropathy

3 Nov, 2024 | 18:29h | UTC

Background: IgA nephropathy is the most common primary glomerular disease worldwide, leading to a substantial risk of kidney failure. Despite treatment with renin–angiotensin system (RAS) inhibitors, many patients experience persistent proteinuria and progressive kidney function decline. Endothelin-1, acting via the endothelin type A receptor, contributes to the disease’s pathophysiology. Atrasentan, a selective endothelin type A receptor antagonist, has shown potential in reducing proteinuria in prior studies.

Objective: To evaluate the efficacy and safety of atrasentan in reducing proteinuria among patients with IgA nephropathy.

Methods: In this phase 3, multinational, double-blind, randomized controlled trial, adults with biopsy-proven IgA nephropathy, urinary protein excretion of at least 1 g/day, and an estimated glomerular filtration rate (eGFR) of at least 30 ml/min/1.73 m² were enrolled. Patients on maximum tolerated doses of ACE inhibitors or ARBs were randomized 1:1 to receive atrasentan (0.75 mg/day) or placebo for 132 weeks. The primary outcome was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36, assessed in a prespecified interim analysis of the first 270 patients.

Results: Among these patients (135 per group), the geometric mean percentage reduction in the urinary protein-to-creatinine ratio at week 36 was significantly greater with atrasentan (−38.1%) compared to placebo (−3.1%), yielding a between-group difference of −36.1 percentage points (95% CI, −44.6 to −26.4; P<0.001). Adverse events were similar between groups. Fluid retention was reported in 11.2% of the atrasentan group and 8.2% of the placebo group but did not lead to discontinuation. No cases of cardiac failure or severe edema occurred.

Conclusions: Atrasentan significantly reduced proteinuria compared to placebo in patients with IgA nephropathy without significant safety concerns.

Implications for Practice: Atrasentan may serve as an effective additional therapy for patients with IgA nephropathy who remain at high risk of progression despite standard care, potentially influencing clinical decision-making toward more aggressive proteinuria reduction strategies.

Study Strengths and Limitations: Strengths include the randomized controlled design and a representative high-risk population. Limitations involve the interim analysis nature of the data and underrepresentation of Black patients, which may limit generalizability.

Future Research: Long-term effects on eGFR decline and the potential benefits of combining atrasentan with other therapies, such as SGLT2 inhibitors, warrant further investigation.

Reference: Heerspink HJL, Jardine M, Kohan DE, Lafayette RA, Levin A, Liew A, Zhang H, et al. Atrasentan in Patients with IgA Nephropathy. New England Journal of Medicine. Published October 25, 2024. DOI: http://doi.org/10.1056/NEJMoa2409415

 

Clinical Trial Follow-up: Empagliflozin Continues to Reduce Cardiorenal Risks Post-Discontinuation in CKD Patients

3 Nov, 2024 | 13:08h | UTC

Background: Chronic kidney disease (CKD) progression leads to end-stage kidney disease, adversely affecting quality of life, increasing cardiovascular morbidity and mortality, and imposing high economic costs. Previous trials, including the EMPA-KIDNEY trial, demonstrated that empagliflozin, a sodium–glucose cotransporter 2 (SGLT2) inhibitor, provides cardiorenal benefits in CKD patients at risk of progression. The persistence of these benefits after discontinuation of the drug remains uncertain.

Objective: To assess how the effects of empagliflozin on kidney disease progression and cardiovascular outcomes evolve after discontinuation in patients with CKD.

Methods: In this randomized, double-blind, placebo-controlled trial, 6,609 patients with CKD were assigned to receive empagliflozin 10 mg daily or placebo and followed for a median of 2 years during the active trial period. Eligible patients had an estimated glomerular filtration rate (eGFR) between 20 and less than 45 ml/min/1.73 m², or between 45 and less than 90 ml/min/1.73 m² with a urinary albumin-to-creatinine ratio of at least 200 mg/g. After the active trial, 4,891 surviving patients consented to a 2-year post-trial follow-up without the trial drug, during which local practitioners could prescribe open-label SGLT2 inhibitors. The primary composite outcome was kidney disease progression or cardiovascular death from the start of the active trial to the end of the post-trial period.

Results: During the combined active and post-trial periods, a primary outcome event occurred in 26.2% of patients in the empagliflozin group and 30.3% in the placebo group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.72–0.87). During the post-trial period alone, the HR was 0.87 (95% CI, 0.76–0.99), indicating continued benefit after drug discontinuation. The risk of kidney disease progression was 23.5% in the empagliflozin group versus 27.1% in the placebo group (HR, 0.79; 95% CI, 0.72–0.87). Cardiovascular death occurred in 3.8% and 4.9% of patients, respectively (HR, 0.75; 95% CI, 0.59–0.95). No significant effect was observed on death from noncardiovascular causes (5.3% in both groups).

Conclusions: In patients with CKD at risk for progression, empagliflozin continued to confer cardiorenal benefits for up to 12 months after discontinuation. These findings suggest that short-term treatment with empagliflozin has lasting effects on kidney and cardiovascular outcomes.

Implications for Practice: Empagliflozin should be considered for a broad range of CKD patients to slow disease progression and reduce cardiovascular risk, with benefits extending beyond active treatment. Clinicians should initiate empagliflozin therapy in eligible CKD patients to maximize long-term cardiorenal protection.

Study Strengths and Limitations: Strengths include the large sample size, broad eligibility criteria, and high follow-up rates. Limitations involve the exclusion of certain regions during post-trial follow-up and reliance on local eGFR measurements during this period.

Future Research: Further studies are needed to understand the mechanisms behind the sustained benefits of empagliflozin after discontinuation and to explore the long-term effects of extended treatment durations.

Reference: The EMPA-KIDNEY Collaborative Group. Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease. New England Journal of Medicine. Published October 25, 2024. DOI: http://doi.org/10.1056/NEJMoa2409183

 

Post-trial Follow-up: Empagliflozin Shows Sustained Benefits Post-Discontinuation in Chronic Kidney Disease

25 Oct, 2024 | 20:29h | UTC

Background: Chronic kidney disease (CKD) progression leads to end-stage kidney disease, affecting quality of life and increasing cardiovascular morbidity and mortality. Empagliflozin, an SGLT2 inhibitor, has shown renal and cardiovascular benefits during active treatment. The persistence of these effects post-discontinuation is uncertain.

Objective: To evaluate how the cardiorenal benefits of empagliflozin evolve after stopping the medication, by assessing the composite outcome of kidney disease progression or cardiovascular death during both the active trial and a subsequent post-trial follow-up.

Methods: In the EMPA-KIDNEY trial, 6609 patients with CKD were randomized to receive empagliflozin 10 mg daily or placebo and were followed for a median of 2 years during the active trial. Eligible patients had an eGFR of 20–45 ml/min/1.73 m² or an eGFR of 45–90 ml/min/1.73 m² with a urinary albumin-to-creatinine ratio ≥200 mg/g. After the active trial, 4891 surviving patients (74%) consented to a 2-year post-trial follow-up without the trial medication, although open-label SGLT2 inhibitors could be prescribed by local practitioners. The primary outcome was a composite of kidney disease progression or cardiovascular death assessed from the start of the active trial to the end of the post-trial period.

Results: During the combined active and post-trial periods, a primary outcome event occurred in 26.2% of patients in the empagliflozin group and 30.3% in the placebo group (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.72–0.87). During the post-trial period alone, the HR was 0.87 (95% CI, 0.76–0.99), indicating sustained benefits after discontinuation. The risk of kidney disease progression was 23.5% with empagliflozin versus 27.1% with placebo. Cardiovascular death occurred in 3.8% of the empagliflozin group and 4.9% of the placebo group (HR, 0.75; 95% CI, 0.59–0.95). There was no significant difference in noncardiovascular mortality.

Conclusions: Empagliflozin continued to confer cardiorenal benefits for up to 12 months after discontinuation in patients with CKD at risk for progression. The sustained reduction in kidney disease progression and cardiovascular death suggests long-term advantages of empagliflozin beyond active treatment, supporting its role in CKD management.

Implications for Practice: These findings support the early initiation and continued use of empagliflozin in patients with CKD to maximize long-term cardiorenal benefits. Clinicians should consider empagliflozin as part of standard care for a broad range of CKD patients, regardless of diabetes status, to slow disease progression and reduce cardiovascular risk.

Study Strengths and Limitations: While the study’s large, diverse CKD population and extended follow-up enhance its generalizability, reliance on local creatinine measurements and lack of hospitalization data during post-trial follow-up are limitations.

Future Research: Further studies should explore the mechanisms underlying the sustained benefits of empagliflozin after discontinuation and assess long-term effects on hospitalization and quality of life in CKD patients.

Reference: The EMPA-KIDNEY Collaborative Group. Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease. New England Journal of Medicine 2024; DOI: http://doi.org/10.1056/NEJMoa2409183

 

Systematic Review: Intensive Blood Pressure Targets Do Not Reduce Mortality or Cardiovascular Events in Hypertensive Patients with Chronic Kidney Disease

20 Oct, 2024 | 17:50h | UTC

Background: Chronic kidney disease (CKD) is a significant independent risk factor for cardiovascular disease and mortality, affecting approximately 10% of the global population. Hypertension is prevalent in CKD patients, ranging from 22% to 80% depending on disease stage. While lowering blood pressure is essential in managing CKD, the optimal blood pressure targets remain uncertain, particularly whether lower-than-standard targets provide additional benefits.

Objective: To compare the effects of standard versus lower-than-standard blood pressure targets on mortality and morbidity outcomes in hypertensive patients with CKD.

Methods: A systematic review and meta-analysis of six randomized controlled trials (RCTs) involving 7348 participants were conducted. Studies included adults with hypertension and CKD randomized to lower blood pressure targets (≤130/80 mmHg) versus standard targets (≤140–160/90–100 mmHg) with at least 12 months of follow-up. Primary outcomes were total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease (ESRD). Data were analyzed using GRADE methodology to assess the certainty of evidence.

Results: Over a mean follow-up of 3.6 years, lower blood pressure targets likely resulted in little to no difference in total mortality (risk ratio [RR] 0.90; 95% confidence interval [CI], 0.76 to 1.06; moderate-certainty evidence), total serious adverse events (RR 1.01; 95% CI, 0.94 to 1.08; moderate-certainty), and total cardiovascular events (RR 1.00; 95% CI, 0.87 to 1.15; moderate-certainty) compared to standard targets. Lower targets may result in little to no difference in cardiovascular mortality (RR 0.90; 95% CI, 0.70 to 1.16; low-certainty) and progression to ESRD (RR 0.94; 95% CI, 0.80 to 1.11; low-certainty). Participants in the lower target groups achieved greater reductions in systolic and diastolic blood pressure but required more antihypertensive medications.

Conclusions: Intensive blood pressure targets probably do not reduce total mortality, serious adverse events, or cardiovascular events compared to standard targets in hypertensive patients with CKD, and may have little to no effect on cardiovascular mortality or progression to ESRD.

Implications for Practice: Clinicians should consider that lowering blood pressure below standard targets in hypertensive CKD patients may not provide additional benefit in reducing mortality or cardiovascular events. The increased medication burden and potential for adverse effects with intensive targets should be weighed against the lack of demonstrated benefit.

Study Strengths and Limitations: Strengths include the use of individual participant data from six RCTs and a comprehensive analysis using GRADE methodology. Limitations involve the open-label design of the included studies, potential risk of bias, heterogeneity in blood pressure targets and CKD definitions, and limited adverse event reporting.

Future Research: Further high-quality RCTs are needed to determine optimal blood pressure targets in hypertensive CKD patients, including those with varying levels of proteinuria and using out-of-office blood pressure monitoring. Ongoing studies may provide additional evidence in the near future.

Reference: Erviti J, Saiz LC, Leache L, et al. Blood pressure targets for hypertension in people with chronic renal disease. Cochrane Database Syst Rev. 2024; Issue 10. Art. No.: CD008564. DOI: http://doi.org/10.1002/14651858.CD008564.pub3

 

Observational Study: Kidney Transplantation from Donors with HIV Safe for Recipients with HIV

20 Oct, 2024 | 17:30h | UTC

Background: Kidney transplantation improves survival for persons with HIV and end-stage renal disease but is limited by organ shortages. Transplantation from donors with HIV to recipients with HIV is emerging under the HIV Organ Policy Equity (HOPE) Act but is currently approved only for research. The Department of Health and Human Services is considering expanding this practice to clinical care, but data are limited to small case series without control groups.

Objective: To assess whether kidney transplantation from donors with HIV is noninferior to transplantation from donors without HIV regarding safety outcomes in recipients with HIV.

Methods: In an observational, noninferiority study at 26 U.S. centers, 408 transplantation candidates with HIV were enrolled. Of these, 198 received a kidney transplant: 99 from deceased donors with HIV and 99 from deceased donors without HIV. The primary outcome was a composite safety event (death, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (upper bound of 95% CI for hazard ratio ≤3.00). Secondary outcomes included overall survival, survival without graft loss, rejection rates, infections, cancer, and HIV superinfection.

Results: The adjusted hazard ratio for the composite primary outcome was 1.00 (95% CI, 0.73 to 1.38), demonstrating noninferiority. Overall survival at 1 year was 94% for recipients of kidneys from donors with HIV and 95% for those from donors without HIV; at 3 years, survival was 85% and 87%, respectively. Survival without graft loss at 1 year was 93% vs. 90%; at 3 years, 84% vs. 81%. Rejection rates were similar at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer did not differ significantly between groups. HIV breakthrough infection occurred more frequently among recipients of kidneys from donors with HIV (incidence rate ratio 3.14; 95% CI, 1.02 to 9.63), primarily due to nonadherence to antiretroviral therapy; viral suppression was regained in all cases. One potential HIV superinfection occurred without clinical consequences.

Conclusions: Kidney transplantation from donors with HIV to recipients with HIV was noninferior to transplantation from donors without HIV regarding safety outcomes, supporting the expansion of this practice from research to clinical care.

Implications for Practice: Expanding kidney transplantation involving donors and recipients with HIV to clinical practice could increase organ availability and reduce disparities in transplantation access for persons with HIV. Clinicians should monitor for HIV breakthrough infections and encourage adherence to antiretroviral therapy.

Study Strengths and Limitations: Strengths include a multicenter design and direct comparison groups. Limitations involve the observational design, inability to randomize due to allocation constraints, and heterogeneity in immunosuppression protocols.

Future Research: Further studies are needed to confirm these findings, evaluate long-term outcomes, and assess potential risks such as HIV superinfection.

Reference: Durand CM, et al. (2024) for the HOPE in Action Investigators. Safety of Kidney Transplantation from Donors with HIV. New England Journal of Medicine. DOI: http://doi.org/10.1056/NEJMoa2403733

 

RCT: Nonstandard Arm Positions Overestimate Blood Pressure Readings in Adults

12 Oct, 2024 | 22:55h | UTC

Background: Accurate blood pressure (BP) measurement is crucial for the diagnosis and management of hypertension, a leading cause of cardiovascular disease and mortality worldwide. Guidelines recommend measuring BP with the arm supported on a desk at heart level. However, in clinical practice, nonstandard arm positions—such as resting the arm on the lap or having it unsupported at the side—are commonly used, potentially leading to inaccurate readings.

Objective: To determine the effect of commonly used nonstandard arm positions on BP measurements compared to the standard, recommended position.

Methods: In a crossover randomized clinical trial from August 2022 to June 2023, 133 adults aged 18 to 80 years were recruited. Participants were randomly assigned to receive sets of triplicate BP measurements with the arm in three positions: (1) supported on a desk with the midcuff at heart level (desk 1; reference), (2) hand supported on the lap (lap), and (3) arm unsupported at the side (side). To account for intrinsic BP variability, all participants underwent a fourth set of BP measurements with the arm supported on a desk (desk 2). The primary outcomes were the difference in differences in mean systolic BP (SBP) and diastolic BP (DBP) between the reference BP (desk 1) and the two nonstandard arm positions (lap and side).

Results: Among 133 participants (mean age 57 years; 53% female), 36% had SBP ≥130 mm Hg, and 41% had a body mass index ≥30 kg/m². Compared to the reference position, the lap and side positions resulted in significantly higher BP readings. The difference in differences for the lap position was an increase in SBP of 3.9 mm Hg (95% CI, 2.5-5.2) and DBP of 4.0 mm Hg (95% CI, 3.1-5.0). For the side position, the increases were SBP 6.5 mm Hg (95% CI, 5.1-7.9) and DBP 4.4 mm Hg (95% CI, 3.4-5.4). These patterns were consistent across subgroups.

Conclusions: Commonly used nonstandard arm positions during BP measurements, such as resting the arm on the lap or having it unsupported at the side, significantly overestimate BP readings compared to the standard recommended position. This overestimation may lead to misdiagnosis and overestimation of hypertension.

Implications for Practice: Clinicians should adhere to guideline-recommended arm positioning during BP measurements to ensure accurate readings. Proper arm support with the midcuff at heart level is necessary to avoid overestimation of BP, which can result in unnecessary follow-up and overtreatment due to hypertension overdiagnosis.

Study Strengths and Limitations: Strengths include the randomized crossover design ideal for studying BP differences, a larger sample size than previous studies, and focus on arm positions commonly used in clinical practice with an automated BP device. Limitations include unequal randomization due to the randomization function used, small sample sizes in some subgroups, and uncertain generalizability to other settings or devices.

Future Research: Further studies are needed to investigate strategies to improve adherence to guideline-recommended arm positions in clinical practice, assess the impact of educational interventions on BP measurement accuracy, and explore the effects of arm position on BP readings using different devices or in diverse populations.

Reference: Liu H., et al. (2024). Arm Position and Blood Pressure Readings: The ARMS Crossover Randomized Clinical Trial. JAMA Internal Medicine. DOI: http://doi.org/10.1001/jamainternmed.2024.5213

 

Guideline Summary: Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Adults with Chronic Kidney Disease

4 Oct, 2024 | 11:14h | UTC

Introduction

A recent clinical practice guideline published in The BMJ titled “Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease” provides evidence-based recommendations on the use of SGLT-2 inhibitors in adults with chronic kidney disease (CKD), regardless of diabetes status. The guideline aims to assist clinicians in making informed decisions to improve patient outcomes in CKD management.

Key Recommendations and Patient Care Implications

  1. Risk Stratification
    • Assessment: Patients with CKD should be stratified based on their risk of disease progression and complications using estimated glomerular filtration rate (eGFR) and albuminuria levels, following the Kidney Disease Improving Global Outcomes (KDIGO) classification.
    • Clinical Implication: Proper risk stratification guides the intensity of treatment and monitoring.
  2. Use of SGLT-2 Inhibitors
    • Low to Moderate Risk Patients: For adults at low or moderate risk, the guideline suggests administering SGLT-2 inhibitors (weak recommendation in favor).
      • Patient Care Impact: Clinicians should discuss potential benefits and risks with patients, considering individual preferences.
    • High to Very High Risk Patients: For adults at high or very high risk, a strong recommendation is made to administer SGLT-2 inhibitors.
      • Patient Care Impact: Clinicians should prioritize initiating SGLT-2 inhibitors in these patients to reduce risks of mortality and progression to kidney failure.
  3. Benefits of SGLT-2 Inhibitors
    • Outcomes: Reduction in all-cause mortality, cardiovascular mortality, hospitalization for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke.
    • Clinical Implication: SGLT-2 inhibitors provide significant protective effects on cardiovascular and kidney health in CKD patients.
  4. Potential Harms and Monitoring
    • Adverse Effects: Minimal increase in risks of acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolemia.
    • Patient Counseling: Patients should be informed about possible side effects and advised on when to seek medical attention.
    • Monitoring: Routine laboratory monitoring is not generally necessary, except in high-risk individuals.
  5. Practical Considerations for Prescribing
    • Initiation: Start SGLT-2 inhibitors in patients with eGFR ≥20 mL/min/1.73 m².
    • Continuation: Medications can be continued even if eGFR falls below 20 mL/min/1.73 m² until dialysis is initiated.
    • Dosage: Initiate at the highest possible dose without the need for titration.
    • Drug Selection: Canagliflozin, dapagliflozin, and empagliflozin are suitable options.
    • Concurrent Medications: Review and adjust diuretics to prevent volume depletion.
  6. Patient Education and Self-Management
    • Sick Day Rules: Advise patients to temporarily discontinue SGLT-2 inhibitors during acute illnesses causing dehydration.
    • Lifestyle Modifications: Encourage adherence to medication and healthy lifestyle changes to enhance treatment efficacy.
  7. Applicability and Exceptions
    • Applicable Populations: Recommendations apply broadly to adults with CKD, with or without type 2 diabetes.
    • Exceptions: Caution or alternative approaches may be necessary for patients:
      • Receiving kidney replacement therapy.
      • With kidney transplants, polycystic kidney disease, rare kidney diseases.
      • With eGFR <20 mL/min/1.73 m² not on replacement therapy.

Conclusion

The guideline underscores the importance of incorporating SGLT-2 inhibitors into the management plan for adults with CKD to improve survival and reduce cardiovascular and kidney-related complications. Clinicians should evaluate each patient’s risk profile and engage in shared decision-making to optimize treatment outcomes.

Reference: Agarwal A, Zeng X, Li S, et al. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease: a clinical practice guideline. BMJ. DOI: https://doi.org/10.1136/bmj-2024-080257

 

Summary of “Dialysis for Chronic Kidney Failure: A Review”

3 Oct, 2024 | 22:46h | UTC

In their comprehensive review published in JAMA on October 2, 2024, Dr. Jennifer E. Flythe and Dr. Suzanne Watnick discuss current evidence regarding the pathophysiology, diagnosis, and management of dialysis-dependent chronic kidney failure. The article emphasizes clinical considerations that directly impact patient care, particularly in the initiation and management of dialysis therapy.

Key Aspects Influencing Patient Care

  1. Initiation of Dialysis
    • No Specific eGFR Threshold: There is no recommended estimated glomerular filtration rate (eGFR) for starting dialysis. Decisions should be individualized, focusing on persistent uremic symptoms (e.g., nausea, fatigue), volume overload (e.g., dyspnea, peripheral edema), worsening eGFR, metabolic acidosis, and hyperkalemia.
    • Shared Decision-Making: The timing of dialysis initiation should involve a collaborative approach between clinicians and patients, considering symptoms, laboratory trends, and patient preferences.
    • No Mortality Benefit from Early Initiation: A randomized clinical trial found no mortality advantage in starting dialysis at higher eGFR levels (10–14 mL/min/1.73 m²) compared to lower levels (5–7 mL/min/1.73 m²).
  2. Dialysis Modalities
    • Hemodialysis vs. Peritoneal Dialysis: Observational data indicate no significant difference in 5-year mortality rates between the two modalities.
    • Modality Selection Factors: Decisions should consider patient lifestyle, comorbid conditions, availability of home support, and resource accessibility.
  3. Common Complications
    • Cardiovascular Risks: Cardiovascular complications, such as arrhythmias and cardiac arrest, are leading causes of death among dialysis patients.
    • Infections:
      • Hemodialysis: Catheter-related bloodstream infections occur at rates of 1.1 to 5.5 episodes per 1000 catheter-days.
      • Peritoneal Dialysis: Peritonitis occurs at a rate of 0.26 episodes per patient-year.
    • Systemic Complications: Anemia, hyperphosphatemia, hypocalcemia, and hypertension are prevalent and often require pharmacologic intervention.
    • Dialysis-Related Issues: Hypotension during dialysis, muscle cramps, itching, and vascular access malfunction can hinder effective treatment.
  4. Management Strategies
    • Anemia: Initiate intravenous iron and/or erythropoietin-stimulating agents when hemoglobin is below 10 g/dL, aiming to maintain levels between 10 and 11.5 g/dL.
    • Mineral and Bone Disorders: Use dietary phosphorus restrictions and phosphorus binders; monitor and manage parathyroid hormone levels to mitigate fracture risk.
    • Hypertension: Implement dietary salt restriction, adjust ultrafiltration, and prescribe antihypertensive medications, recognizing there’s no specific BP target in dialysis patients.
  5. Practical Considerations for Clinicians
    • Medication Management: Avoid nephrotoxic agents like NSAIDs and iodinated contrast media in patients with residual kidney function. Adjust dosages for medications excreted renally.
    • Symptom Control: Address common symptoms such as pruritus with appropriate therapies such as oral antihistamines and moisturizers. Difelikefalin is a new agent that can also be used.
    • Patient Education: Counsel on dietary restrictions (salt, fluid, potassium) and ensure vaccinations are up to date, including hepatitis B, pneumococcal, COVID-19, and RSV vaccines.

Conclusion

For the over 540,000 patients in the U.S. receiving maintenance dialysis, individualized care plans that involve shared decision-making are crucial. Understanding when to initiate dialysis, selecting the appropriate modality, managing complications, and addressing patient-specific needs can significantly influence outcomes and quality of life.

Reference: Flythe JE, Watnick S. Dialysis for Chronic Kidney Failure: A Review. JAMA. Published online October 2, 2024. doi:10.1001/jama.2024.16338

 

RCT: Renal Denervation Reduces Blood Pressure in Chinese Patients With Uncontrolled Hypertension

7 Sep, 2024 | 14:57h | UTC

Study Design and Population: This was a prospective, multicenter, randomized, sham-controlled trial investigating the efficacy and safety of catheter-based radiofrequency renal denervation (RDN) in Chinese patients with uncontrolled hypertension despite standardized triple antihypertensive therapy. A total of 217 patients (mean age 45.3 years, 21% female) were randomized 1:1 to receive RDN or a sham procedure.

Main Findings: At 6 months, patients who underwent RDN showed a significantly greater reduction in 24-hour ambulatory systolic blood pressure (−13.0 mm Hg) compared to the sham group (−3.0 mm Hg), with a baseline-adjusted difference of −9.4 mm Hg (P<0.001). Significant reductions were also observed in 24-hour diastolic BP and office systolic and diastolic BP. One access site complication occurred in the RDN group but resolved without further issues.

Implications for Practice: This trial demonstrates that RDN is an effective and safe option for reducing blood pressure in patients with uncontrolled hypertension, offering a potential adjunct to antihypertensive therapy in this population. Further research may solidify its role in managing resistant hypertension.

Reference: Jiang X et al. (2024). Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Chinese Patients With Uncontrolled Hypertension: The Randomized, Sham-Controlled, Multi-Center Iberis-HTN Trial. Circulation.  https://doi.org/10.1161/CIRCULATIONAHA.124.069215

Link: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.069215

 

RCT: No Difference in Postoperative Complications Between Continuation and Discontinuation of Renin-Angiotensin System Inhibitors Before Major Surgery – JAMA

31 Aug, 2024 | 19:12h | UTC

Study Design and Population: This multicenter randomized clinical trial included 2,222 patients who had been treated with renin-angiotensin system inhibitors (RASIs) for at least 3 months and were scheduled for major noncardiac surgery at 40 hospitals in France between January 2018 and April 2023. The participants were randomly assigned to either continue RASIs until the day of surgery or to discontinue them 48 hours before surgery.

Main Findings: The trial found no significant difference in the primary outcome—a composite of all-cause mortality and major postoperative complications within 28 days—between the continuation and discontinuation groups (22% in both groups, RR 1.02, 95% CI 0.87-1.19). However, the continuation group experienced a higher incidence of intraoperative hypotension (54% vs. 41%, RR 1.31, 95% CI 1.19-1.44).

Implications for Practice: Continuation of RASIs before major noncardiac surgery does not increase the risk of postoperative mortality or major complications, but it does elevate the risk of intraoperative hypotension. Clinicians should weigh these risks when deciding whether to continue or discontinue RASIs before surgery.

Reference: Legrand M, Falcone J, Cholley B, et al. (2024). Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery: The Stop-or-Not Randomized Clinical Trial. JAMA. https://doi.org/10.1001/jama.2024.17123

 

Meta-Analysis: Renal Denervation Modestly Reduces Blood Pressure in Uncontrolled Hypertension – J Am Heart Assoc

17 Aug, 2024 | 16:14h | UTC

Study Design and Population: This updated meta-analysis evaluated 15 randomized clinical trials, encompassing 2,581 patients, to assess the efficacy and safety of catheter-based renal denervation (RDN) in patients with uncontrolled hypertension. The trials included both patients on antihypertensive medications (ON-Med) and those off medications (OFF-Med), with comparisons made between RDN and sham or standard therapy.

Main Findings: RDN led to a modest but statistically significant reduction in blood pressure across both ON-Med and OFF-Med groups. In the OFF-Med group, 24-hour ambulatory systolic BP was reduced by 3.7 mm Hg (95% CI, -5.41 to -2.00). In the ON-Med group, the reduction was 2.23 mm Hg (95% CI, -3.56 to -0.90). Sham-controlled trials reinforced these findings, showing consistent BP reductions, thus validating the effect of RDN. However, the degree of BP reduction is modest and may be clinically limited.

Implications for Practice: While RDN appears to have a favorable safety profile and provides consistent BP reductions, the modest nature of these reductions suggests that its clinical utility may be more limited. Further research is needed to identify which patient populations might benefit the most from RDN and to optimize procedural techniques for greater efficacy.

Reference: Mufarrih et al. (2024). Randomized Trials of Renal Denervation for Uncontrolled Hypertension: An Updated Meta-Analysis. Journal of the American Heart Association, 13(e034910). DOI: 10.1161/JAHA.124.034910.

 

RCT: Dietary Acid Reduction with Fruits and Vegetables Slows CKD Progression and Lowers CVD Risk in Hypertensive Patients – Am J Med

17 Aug, 2024 | 15:49h | UTC

Study Design and Population: This five-year randomized control trial included 153 hypertensive patients with macroalbuminuria and normal kidney function. Participants were randomly assigned to one of three groups: a diet rich in base-producing fruits and vegetables, oral sodium bicarbonate (NaHCO3), or Usual Care. The primary objective was to assess the effects of dietary acid reduction on chronic kidney disease (CKD) progression and cardiovascular disease (CVD) risk.

Main Findings: The study found that both fruits and vegetables and NaHCO3 slowed CKD progression compared to Usual Care, with significantly higher estimated glomerular filtration rates in the intervention groups. However, only the fruits and vegetables group showed significant reductions in systolic blood pressure, LDL cholesterol, and body mass index, leading to greater improvements in CVD risk indices.

Implications for Practice: The results support using fruits and vegetables as a foundational treatment for hypertension to reduce CKD progression and lower CVD risk, potentially with reduced reliance on pharmacological interventions.

Reference: Goraya, N., Madias, N. E., Simoni, J., Kahlon, M., Aksan, N., & Wesson, D. E. (2024). Kidney and Cardiovascular Protection Using Dietary Acid Reduction in Primary Hypertension: A Five-Year, Interventional, Randomized, Control Trial. The American Journal of Medicine, 000(000), 1-14. DOI: https://doi.org/10.1016/j.amjmed.2024.06.006.

 

RCT: Intravenous Amino Acids Reduce AKI Incidence in Cardiac Surgery Patients – N Engl J Med

3 Aug, 2024 | 19:12h | UTC

Study Design and Population: In this multinational, double-blind, randomized clinical trial, 3511 adult patients scheduled for cardiac surgery with cardiopulmonary bypass were recruited from 22 centers across three countries. Patients were randomly assigned to receive an intravenous infusion of either a balanced mixture of amino acids (2 g/kg/day) or a placebo (Ringer’s solution) for up to three days.

Main Findings: The primary outcome, occurrence of acute kidney injury (AKI), was significantly lower in the amino acid group (26.9%) compared to the placebo group (31.7%) with a relative risk of 0.85 (95% CI, 0.77 to 0.94; P=0.002). The incidence of severe AKI (stage 3) was also reduced in the amino acid group (1.6% vs. 3.0%; relative risk, 0.56; 95% CI, 0.35 to 0.87). There were no substantial differences between the groups regarding secondary outcomes such as the use and duration of kidney-replacement therapy or all-cause 30-day mortality.

Implications for Practice: The infusion of amino acids in adult patients undergoing cardiac surgery appears to reduce the incidence of AKI, indicating a potential protective renal effect. However, this intervention did not significantly impact other secondary outcomes, including mortality and the use of kidney-replacement therapy. These findings suggest that amino acids could be considered as a strategy to mitigate AKI risk in this patient population, although further research is needed to explore long-term benefits and other clinical outcomes.

Reference: Landoni G, Monaco F, Ti LK, Baiardo Redaelli M, Bradic N, Comis M, Kotani Y, for the PROTECTION Study Group. (2024). A randomized trial of intravenous amino acids for kidney protection. New England Journal of Medicine, 390(24), 1765-1774. DOI: 10.1056/NEJMoa2403769.

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