Mean eGFR Research Articles

Communicating treatment options to older patients with advanced kidney disease: a conversation analysis study

BackgroundChoosing to have dialysis or conservative kidney management is often challenging for older people with advanced kidney disease. While we know that clinical communication has a major impact on patients’ treatment decision-making, little is known about how this occurs in practice. The OSCAR study (Optimising Staff-Patient Communication in Advanced Renal disease) aimed to identify how clinicians present kidney failure treatment options in consultations with older patients and the implications of this for patient engagement.MethodsAn observational, multi-method study design was adopted. Outpatient consultations at four UK renal units were video-recorded, and patients completed a post-consultation measure of shared decision-making (SDM-Q-9). Units were sampled according to variable rates of conservative management. Eligible patients were ≥ 65 years old with an eGFR of ≤ 20 mls/min/1.73m2 within the last 6 months. Video-recordings were screened to identify instances where clinicians presented both dialysis and conservative management. These instances were transcribed in fine-grained detail and recurrent practices identified using conversation-analytic methods, an empirical, observational approach to studying language and social interaction.Results110 outpatient consultations were recorded (105 video, 5 audio only), involving 38 clinicians (doctors and nurses) and 94 patients: mean age 77 (65–97); 61 males/33 females; mean eGFR 15 (range 4–23). There were 21 instances where clinicians presented both dialysis and conservative management. Two main practices were identified: (1) Conservative management and dialysis both presented as the main treatment options; (2) Conservative management presented as a subordinate option to dialysis. The first practice was less commonly used (6 vs. 15 cases), but associated with more opportunities in the conversation for patients to ask questions and share their perspective, through which they tended to evaluate conservative management as an option that was potentially personally relevant. This practice was also associated with significantly higher post-consultation ratings of shared decision-making among patients (SDM-Q-9 median total score 24 vs. 37, p = 0.041).ConclusionsPresenting conservative management and dialysis as on an equal footing enables patient to take a more active role in decision-making. Findings should inform clinical communication skills training and education.Clinical trial numberNo trial number as this is not a clinical trial.

Association of Fibroblast Growth Factor 23 and Cardiac Mechanics in the Cardiovascular Health Study.

Elevated levels of fibroblast growth factor 23 (FGF23) are associated with left ventricular hypertrophy and heart failure (HF) in individuals with and without kidney disease. Prior studies investigated the association of FGF23 and structural cardiac changes using conventional echocardiography, which is limited in its ability to detect early cardiac dysfunction. We investigated the relationship between FGF23 levels and cardiac dynamics using two-dimensional speckle tracking echocardiography (2D-STE), a novel imaging modality. This was a cross-sectional analysis of data from the Cardiovascular Health Study, an ongoing prospective, population-based cohort study. The study population included 506 participants from CHS with available c-terminal (cFGF23) and intact FGF23 (iFGF23) measurements from 1996-1997 and 2D-STE images from 1994-1995. Forty two percent of the study population had CKD, defined as an eGFR < 60 ml/min/1.73m2, and the mean eGFR was 63 ml/min/1.73m2. The primary exposures were cFGF23 and iFGF23. The primary outcomes were six 2D-STE parameters performed at the 1994-1995 study visit. Linear regression models were used to examine the independent associations of FGF23 with six cardiac 2D-STE indices adjusting for demographics, cardiovascular risk factors, markers of kidney disease severity, and inflammation. cFGF23 levels were moderately correlated with iFGF23 levels in the CHS population. In fully adjusted models, cFGF23 was associated with left atrial dysfunction, but no other cardiac imaging parameter (β estimate -2.47; 95% Confidence Interval -4.68, -0.25; Table 2). iFGF23 was not associated with any of the six 2D-STE indices. Limitations include small sample size and noncurrent FGF23 measurements and 2D-STE imaging. In a limited sample of individuals enrolled in the CHS with c- and i-FGF23 measurements, we did not find consistent associations between FGF23 levels and 2D-STE parameters. Further investigations in a larger population with concurrent 2D-STE are needed to better understand the associations of FGF23 with early changes in cardiac mechanics.

Impact of arteriovenous fistula formation on trajectory of kidney function decline: a target trial emulation

Abstract Background Prior nonrandomised studies have suggested nephroprotective effects of arteriovenous fistula (AVF) formation, but these are plausibly susceptible to immortal time and selection biases. Methods We studied patients attending nephrology clinics in the West of Scotland during 2010-2022 with an eGFR ≤15mL/min/1.73m2 and no prior AVF. Using target trial emulation and a sequential trial design, we simulated a hypothetical trial that would randomise patients to either undergo AVF formation immediately or not to undergo AVF formation. The primary outcome was the difference in eGFR slope for the first six months of follow-up, estimated using a mixed-effects model. The secondary outcomes were 5-year absolute risks of dialysis and death, estimated using the Aalen-Johansen and Kaplan-Meier estimators respectively. Results 1,364 unique patients (mean age 51.1, 55.7% male) contributed 3,125 person-trials, with 561 in the AVF and 2,564 in the no AVF group. Mean eGFR was 12.6mL/min/1.73m2 and the median number of eGFR measurements per person-trial was 7 (IQR 4 – 12). Slope of eGFR decline did not differ significantly between the AVF and no AVF groups (between group difference -0.67mL/min/1.73m2/year, 95%CI -1.43, 0.10). The 5-year absolute risk of dialysis was 87% (95%CI 84, 91) in the AVF group and 75% (95%CI 73, 77) in the no AVF group and the 5-year survival probability was 77% (95%CI 70, 83) in the AVF group and 67% (95%CI 64, 69) in the no AVF group. Conclusions In this study of patients with advanced CKD, there was no evidence of a nephroprotective effect of AVF formation.

EGFR Evalutation among the Hypothyroid Patients Attending at a Tertiary Center of Chattogram

Background: Hypothyroidism is a prevalent endocrine illness that affects people all over the world. The modulation of renal hemodynamics and basal metabolic rate is disrupted in hypothyroidism. The kidney is generally involved in thyroid hormone metabolism, breakdown and excretion. Chronic renal hypoperfusion affects the hypothalamic pituitary-thyroid axis, resulting in low circulating thyroid hormone levels, changed peripheral hormone metabolism, decreased tissue thyroid hormone content and altered thyroid iodine storage. Recent research has linked an increased risk of hypothyroidism to a decreased estimated Glomerular Filtration Rate (eGFR). The purpose of the study is to determine the association between eGFR with hypothyroidism in a tertiary care hospital of Chattogram. Materials and methods: A cross-sectional study was done during July 2022 to June 2023 including 100 diagnosed hypothyroidism cases attending in Chittagong Medical College Hospital. Serum Thyroid Stimulating Hormone (TSH) serum free thyroxine (FT4) serum creatinine, and blood urea were measured. The estimated glomerular filtration rate (eGFR) were determined. The result were analysed using SPSS version 25. Results: The mean age was 42.76±10.18 years with 93% female. Most of the patients (92%) were in a subclinical hypothyroid state and 8% were in an overt hypothyroid state. The mean ±SD serum creatinine levels and urea levels were 0.8±0.2mg/dl and 25.4±6.5 mg/dl, respectively. The mean eGFR was 75.36±7.54 ml/min/1.73 m2. There was a significant decrease in mean eGFR in the &lt; 60 ml/min/1.73m2 group among the study population. There was a significant association between decreased eGFR and hypothyroidism. Serum TSH had significantly shown a negative correlation with eGFR. Serum TSH level had a significant positive correlation with serum creatinine (r=0.56, p&lt;0.05) and serum urea (r=0.25, p&lt;0.05). There was a significant eGFR difference between subclinical hypothyroidism and overt hypothyroidism. Conclusion: It can be concluded from this study that the hypothyroidism was significantly correlated with decreased eGFR. IAHS Medical Journal Vol 7(1), June 2024; 86-90

Abstract 4113961: Contemporary Guideline Directed Medical Therapy in Heart Failure in Clinical Practice - Results from the EMPACE Study

Background: Guideline directed medical therapy (GDMT) for heart failure (HF) evolves, incorporating newer therapies such as SGLT2i within recommendations for HFmrEF and HFpEF. Understanding the contemporary profile of real-world HF patients, in combination with real-world utilization of GDMT, is important for informing GDMT implementation and quality improvement strategies. The EMPACE study aims to improve our comprehension of HF GDMT utilization in real-world settings during post-2020 . Objectives: To describe baseline demographic and clinical characteristics, including baseline treatments, of patients with HF hospitalization (HHF). Methods: This non-interventional, retrospective cohort study used patient data standardized to the OMOP Common Data Model from the Optum Market Clarity, an integrated EHR and Claims database in the U.S. The study period spanned from Jun-2020 to Oct-2023. Adult patients with a primary diagnosis of HF during hospitalization were stratified by HF phenotypes (HFrEF, HFmrEF, HFpEF) based on left ventricular ejection fraction (EF). Results: A total of 30,762 patients with HHF were included (74% HFrEF, 4% HFmrEF, and 22% HFpEF). The mean age was 70.1 years, 60% were male, mean BMI was 30.6 kg/m 2 , and mean eGFR was 58.7 mL/min/1.73m 2 . Of them, 72% had a history of HF and 43% has been previously hospitalized for HF in the past 1 year. The prevalence of baseline comorbidities was as follows: hypertension (90%), coronary artery disease (54%), chronic kidney disease (38%), atrial fibrillation (40%), peripheral artery disease (9%), stroke history (9%), and end-stage renal disease (1%). Medication prior to HF hospitalization are described in the figure 1. Overall, prior comorbidities and HF medication use in the last 365 days prior to HHF were similar between all HHF patients and the HFrEF, HFmrEF, and HFpEF phenotypes, except for the lower use of MRA and ARNI in HFmrEF, and HFpEF patients. Conclusion: This study showed a high comorbidity burden and a low utilization of many GDMT prior to hospitalization, especially for novel GDMT (ARNI and SGLT2i) and in HFmrEF and HFpEF. Despite many medications having a varying strength of guideline recommendation depending on EF, absolute differences in rates of GDMT utilization were relatively small across the EF phenotypes. Across the spectrum of EF, further efforts are needed to improve use of GDMT and reduce the missed opportunities for GDMT implementation that are occurring prior to HHF.

Abstract 4122694: The ICAM1 p.K56M Variant and Risk of Heart Failure Among Individuals with Chronic Kidney Disease

Background: Intercellular adhesion molecule-1 (ICAM-1) is a cell-surface protein that facilitates inflammation through leukocyte adhesion. Approximately 35% of African American individuals carry at least one copy of an ICAM1 missense variant (rs5491; p.K56M), which has been associated with increased risk of heart failure with preserved ejection fraction (HFpEF). Individuals with chronic kidney disease (CKD) are at high risk for HF, but whether the risk of HFpEF conferred by rs5491 extends to individuals with prevalent CKD is unknown. Hypothesis: We hypothesized that in a CKD population, rs5491 is specifically associated with HFpEF, but not HF with reduced ejection fraction (HFrEF). Methods: In the Chronic Renal Insufficiency Cohort (CRIC), participants were enrolled based upon an estimated glomerular filtration rate (eGFR) of 20 to 70 mL/min/1.73m 2 . We estimated associations of rs5491 with incident HF and HF subtypes among African American individuals who were free from HF at baseline in CRIC. Models were adjusted for age, sex, systolic blood pressure, eGFR, body mass index, smoking, diabetes, C-reactive protein, the first 10 principal components of ancestry, and study site. Results: Among 1267 African American participants without HF at baseline (mean age 57±11 years, 51% female, mean eGFR 45±15 mL/min/1.73m 2 ), 464 (37%) had at least one copy of rs5491. During a median follow-up of 10.3 years (IQR: 4.7 – 15.0 years), there were 309 incident overall HF hospitalizations (160 HFpEF, 111 HFrEF, and 38 HF with unknown EF). Each additional rs5491 allele was significantly associated with incident HFpEF (HR 1.35 [95% CI: 1.03-1.76], P=0.029; Figure). The rs5491 variant was not associated with incident overall HF (HR 1.14, 95% CI: 0.93-1.39, P = 0.20) or incident HFrEF (HR 0.76, 95% CI: 0.53-1.10, P=0.15). Conclusion: The ICAM1 p.K56M variant specifically confers increased risk of incident HFpEF among individuals with CKD.

Comparison of eGFR Levels in Patients Before and After Intravitreal Bevacizumab (Anti-VEGF) Injection

Background: Estimated glomerular filtration rate (eGFR) is a vital indicator of kidney function, particularly in patients receiving treatments that may impact renal health, such as intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections like bevacizumab. Bevacizumab, commonly used to treat retinal diseases like diabetic retinopathy, has raised concerns about its potential systemic effects, including its impact on kidney function due to the role of VEGF in maintaining glomerular integrity. This study investigates the effect of bevacizumab injections on renal function in patients with diabetic kidney disease (DKD) and those without. Objective: To assess changes in eGFR before and after intravitreal bevacizumab injections in patients with and without diabetic kidney disease, evaluating whether these injections significantly affect renal function. Methodology: This quasi-experimental study was conducted in the Department of Ophthalmology, Bangabandhu Sheikh Mujib Medical University (BSMMU), from April 2019 to August 2021. Forty patients with diabetic retinopathy were selected, divided equally into DKD and non-DKD groups. Serum creatinine and eGFR were measured within 30 days before the injection and one month after the third dose of intravitreal bevacizumab. eGFR was calculated using the CKD-EPI equation, and statistical analysis was performed using SPSS. Results: The mean pre-injection eGFR was 69.35±25.91 ml/min/1.73m² in the DKD group and 96.7±30.59 ml/min/1.73m² in the non-DKD group. Post-injection, the mean eGFR was 73.3±33.87 ml/min/1.73m² in DKD patients and 93.6±29.7 ml/min/1.73m² in non-DKD patients. The mean differences in eGFR were not statistically significant between pre- and post-injection measurements in either group (p&gt;0.05). Conclusion: Intravitreal bevacizumab injections did not cause significant changes in eGFR in both DKD and non-DKD patients, suggesting that the treatment is unlikely to have a detrimental impact on renal function in the short term. Further studies are needed to assess the long-term effects of repeated injections.

Angiotensin Receptor Neprilysin Inhibition and Cardiovascular Outcomes Across the Kidney Function Spectrum: The PARAGON-HF Trial.

Lower estimated glomerular filtration rate (eGFR) may be one of the major reasons for hesitation or failure to initiate potentially beneficial therapies in patients with heart failure (HF). This study sought to assess if the effects of sacubitril/valsartan (vs valsartan) on cardiovascular outcomes differ according to baseline kidney function in patients with HF with preserved ejection fraction. The PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction) trial was global clinical trial of 4,796 patients with chronic HF and left ventricular ejection fraction (LVEF)≥45% randomly assigned to sacubitril/valsartan or valsartan. We examined the effect of treatment on cardiovascular outcomes using Cox regression models, stratified by region, and assessed for differential treatment effects according to the baseline eGFR and ejection fraction. At randomization, mean eGFR was 67 ± 19mL/min/1.73m2; 1,955 (41%) participants had an eGFR<60mL/min/1.73m2. Compared with valsartan, sacubitril/valsartan reduced the primary cardiovascular outcome (cardiovascular death and total HF hospitalizations) to a greater extent among those with lower baseline eGFR (Pinteraction=0.07 for continuous eGFR), and was most pronounced for those with eGFR≤45mL/min/1.73m2 (RR:0.69; 95%CI: 0.51-0.94). The influence of eGFR on the treatment effect for cardiovascular death was nonlinear, with the most pronounced treatment effect for those with baseline eGFR<45mL/min/1.73m2 (HR: 0.65; 95%CI: 0.43-0.97). In further subgroup analyses according to LVEF and eGFR, the treatment effect for the primary outcome was most pronounced among those with LVEF≤57% and eGFR≤45mL/min/1.73m2 (HR: 0.66; 95%CI: 0.45-0.97). In the PARAGON-HF trial, the benefits of sacubitril/valsartan to reduce the frequency of HF hospitalizations and cardiovascular death were most apparent in patients with lower baseline eGFR and lower ejection fraction. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in HeartFailure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Randomized trial of dietary acid reduction and acid-base status of patients with CKD and normal eGFR

IntroductionModern acid-producing diets in patients with stage G3-G5 chronic kidney disease (CKD) can cause severe acid accumulation with metabolic acidosis and less severe accumulation causing eubicarbonatemic acidosis in stages G2-G3, each with kidney injury. The impact of these diets on acid accumulation in those with CKD but normal eGFR (G1) is unclear. MethodsWe assessed whether acid accumulation occurs in patients with CKD and normal eGFR, and if added base-producing fruits and vegetables (F&V) or oral NaHCO3 (HCO3-) reduces acid accumulation and/or lowers kidney injury. We randomized 153 macroalbuminuric, non-diabetic, G1 (mean eGFR = 101 ml/min/1.73 m2) participants with hypertension-associated CKD to receive F&Vs in amounts to reduce dietary acid intake 50% (F&V, n=51), oral NaHCO3 to match alkali intake of F&V (HCO3-, n=51), or usual care (UC, n=51) for five years. We assessed acid accumulation by comparing observed to expected increase in plasma total CO2 in response to retained bicarbonate (dose minus urine bicarbonate excretion) two hours after an oral NaHCO3 bolus. ResultsBaseline acid accumulation, eGFR, urine excretion of albumin, N-acetyl-β-D-glucosamine, and angiotensinogen were not different among groups. Five-year acid accumulation [mean(SD)] was lower in F&V [-1.2 (11.0) mmoles] and HCO3- [-1.7 (10.8) mmoles] than UC [5.2 (10.3) mmoles, p<0.003)], consistent with lower acid accumulation in F&V and HCO3-. Five-year urine excretion of albumin, N-acetyl-β-D-glucosamine, and angiotensinogen were lower in F&V and HCO3- than UC, consistent with less kidney injury. ConclusionsDietary acid reduction reduces acid accumulation and kidney injury in patients with CKD and normal eGFR.

Impaired Incretin Homeostasis in Nondiabetic Moderate-to-Severe CKD.

Key Points Total incretin levels and incretin response during oral glucose tolerance testing were significantly higher among patients with moderate-to-severe nondiabetic patients with CKD compared with healthy people.Unlike in healthy individuals, increased incretin response was not correlated with insulin response and coincided with persistently greater glucagon levels to oral glucose tolerance testing in CKD.Disruption in the incretin system and glucagon dynamics may contribute to metabolic complications in moderate-to-severe CKD. Background Incretins are regulators of insulin secretion and glucose homeostasis metabolized by dipeptidyl peptidase-4 (DPP-4). CKD may modify incretin release, metabolism, or response. Methods We performed 2-hour oral glucose tolerance testing in 59 people with nondiabetic CKD (eGFR &lt;60 ml/min per 1.73 m2) and 39 matched controls. We measured total area under the curve and incremental area under the curve (iAUC) of plasma total glucagon-like peptide-1 (GLP-1) and total glucose-dependent insulinotropic polypeptide (GIP). Fasting DPP-4 levels and activity were measured. Linear regression was used to adjust for demographic, body composition, and lifestyle factors. Results Mean (SD) eGFR was 38±13 and 89±17 ml/min per 1.73 m2 in patients with CKD and controls, respectively. GLP-1 total area under the curve and GIP iAUC were higher in patients with CKD than controls with a mean of 1531±1452 versus 1364±1484 pM×min and 62,370±33,453 versus 42,365±25,061 pg×min/ml, respectively. After adjustment, CKD was associated with 15,271 pM×min/ml greater GIP iAUC (95% confidence intervals [CIs], 387 to 30,154) compared with controls. Adjustment for covariates attenuated associations of CKD with higher GLP-1 iAUC (adjusted difference, 122; 95% CI, −619 to 864). Plasma glucagon levels were higher at 30 minutes (mean difference, 1.6; 95% CI, 0.3 to 2.8 mg/dl) and 120 minutes (mean difference, 0.84; 95% CI, 0.2 to 1.5 mg/dl) in patients with CKD compared with controls. There were no differences in insulin levels or plasma DPP-4 activity or levels between groups. Conclusions Overall, incretin response to oral glucose is preserved or augmented in moderate-to-severe CKD, without apparent differences in circulating DPP-4 concentration or activity. However, neither insulin secretion nor glucagon suppression is enhanced.

Safety and efficacy of initiation SGLT in heart failure with a reduced left ventricular ejection fraction and chronic kidney disease on top of standard therapy with ARNI or ACE-i

Abstract Quadruple therapy remains underused in cases of heart failure with a reduced ejection fraction (HFrEF). Among eligible patients most of them take ACE-i/ARB and B-blockers, less MRAs and ARNI. There are many questions of adding new foundational drugs, especially in the case of coexisting of HFrEF and chronic kidney disease (CKD). The aim was to compare the safety and effectiveness of initiation SGLT in patients (P) with HFrEF and CKD on standard therapy with ARNI or ACE-I. Methods we identified 54 symptomatic P with HFrEF (EF≤40%) and CKD 3 (eGFR between 30 and 60 ml/min) on standard therapy (ACE-I or ARNI, B-blockers, MRAs). All P were divided into 2 groups: group 1- 26 P on ARNI, B-blockers, MRAs; group 2- 28 P on ACE-I, B-blockers, MRAs. All P started on dapagliflozin (D) with a dose of 10 mg daily. The potassium (K), creatinine levels, eGFR, clinic BP were estimated at baseline and at weeks 1, 2, 4, 6, 8, 12. At baseline and at weeks 4, 12 NT-proBNP, urine albumin-to-creatinine ratio (UCAR) were estimated and P underwent 24-hour BP measurements. Results At week 1 after initiation of D a mean eGFR deсreased not significant in both group. At week 2 in group 1 mean eGFR decreased by 1,9±1.1 ml/min/1.73m2, P&amp;lt;.05 and group 2-2,5±1.9 ml/min/1.73m2, P&amp;lt;.05. At week 4 in both groups mean eGFR deсreased significantly, but in group 2 the decline of eGFR was more pronounced (-2,4±2.6 ml/min/1.73m2 vs.-3,3±2.5 ml/min/1.73m2, P=.04), with not significant decreasing to 6, 8, 12 weeks. At week 1mean K changed not significantly after start of therapy in both groups. At week 4 in group 1mean K deсreased significantly from 4.97±0.6 to 4.63±0.57 mEq/l (P&amp;lt;.05), in group 2 K deсreased not significant. At week 4 in group 1 was a greater reduction NT-proBNP than in group 2 (-234±42 vs. -143±32 ng/L, P&amp;lt;.05). At week 12 in both groups a significant decrease NT-proBNP were observed, but in group 1 more pronounced (-865±89 ng/L and -573±78 ng/L, (P&amp;lt;.01; P&amp;lt;.05 respectively). UCAR was also reduced significantly in both groups, but in group 1 more pronounced (P&amp;lt;.01; P&amp;lt;.05 respectively). In group 1, there were more cases of symptomatic hypotension (10 vs. 8, P&amp;lt;.05) and greater decrease mean BP than in group 2 (P&amp;lt;.05), but it didn’t result in a withdrew. In return, maen doses diuretics were carefully decreased in both groups. At baseline in patients with HFrEF was an inverse correlation between GFR and NT-proBNP level (r=−0.328, P&amp;lt;.05). By linear regression analysis the eGFR was associated with NT-proBNP change (P&amp;lt;.05). Conclusion In patients with HFrEF and CKD, adding SGLT to standard therapy with ARNI, B-blockers, MRAs were paralleled by marked improvements in the neurohumoral profile by significantly reduced NT-proBNP compared with ACE-I, B-blockers, MRAs. SGLT initiation caused an early drop in eGFR, but in group ARNI the decline of eGFR was less pronounced with greater reduction in the albuminuria and was accompanied by decreased potassium level.

Blood pressure and renal function changes in patients with severe chronic kidney disease undergoing radiofrequency renal denervation: 12 months outcomes from the Global SYMPLICITY Registry DEFINE

Abstract Background Radiofrequency renal denervation (RF RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension (HTN). The impact of renal function on safety and efficacy of RDN is unknown. Purpose To assess BP and renal function in patients with HTN following RDN. Methods All patients treated with RF RDN (n=3332) from the observational Global SYMPLICITY Registry Denervation Findings in Real World (GSR DEFINE) were included. Patients were categorized into CKD stages by the corresponding estimated glomerular filtration rate (eGFR; mL/min/1.73m2): &amp;lt;45 (CKD stage 3b and higher; n=339), 45-59 (CKD stage 3a; n=467), ≥60 (CKD stage 2 and lower; n=2334). BP (office, 24h ambulatory BP), eGFR changes from baseline through 12 months were compared between groups. Comparisons between groups were made after adjusting for baseline BP and change in number of antihypertensive drug classes from baseline. Results At baseline, office systolic SBP (OSBP) in eGFR groups &amp;lt;45, 45-59, and ≥60 ml/min/1.73 m2 was: 164±25, 163±26 and 165±25 mmHg, respectively (p=0.083). 24-h ambulatory systolic BP (ASBP) was: 156±19, 153±20 and 154±19 mmHg, respectively (p=0.082). Mean eGFR was: 32.5±11.2, 53.6±4.4, and 86.8±18.6 ml/min/1.73 m2, respectively. A total of 1.1% of patients were on dialysis. Patients in eGFR group &amp;lt;45 ml/min/1.73 m2 were significantly older, had higher rates of ischemic heart disease, heart failure, diabetes, on more antihypertensive drug classes compared to higher eGFR groups. Patients were on 5.0±1.3, 4.6±1.3, and 4.5±1.4 antihypertensive drugs in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (p&amp;lt;0.001). At 12 months, all had significant OSBP drop from baseline within the different eGFR groups (p&amp;lt;0.001). OSBP changed by -10.8±27.8, -10.5±25.9 and -14.7±26.6 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 groups, respectively (adjusted p=0.095; Figure 1A). Similarly at 12 months, all patients had significant ASBP reductions from baseline across the eGFR groups (p&amp;lt;0.01). ASBP changed by -5.2±18.0, -6.9±18.8, and -8.5±18.8 mmHg in eGFR &amp;lt;45, 45-59 and ≥60 ml/min/1.73 m2 subgroups, respectively (adjusted p=0.16). At 12 months, eGFR did not significantly change from baseline in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups (Figure 1B): 0.1±14.6 (p=0.92) and -0.6±12.8 ml/min/1.73 m2 (p=0.45), respectively. Estimated GFR changed from baseline by -5.6±15.5 ml/min/1.73 m2 in eGFR ≥60 ml/min/1.73 m2 group (p&amp;lt;0.001). Between group differences in eGFR changes were statistically significant (adjusted p&amp;lt;0.001), but by a numerically small difference. The no. of antihypertensive drug classes changed by -0.2±1.3, -0.1±1.0 and -0.1±1.0 in eGFR &amp;lt;45 and 45-59 ml/min/1.73 m2 groups, respectively. Conclusion Patients with uncontrolled HTN with different CKD severity including those with eGFR &amp;lt;45 ml/min/1.73 m2 had significant SBP reductions from baseline through 12 months, whilst renal function was preserved.Figure 1

Natriuretic peptides, kidney function and clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: pooled data from the I-PRESERVE, TOPCAT, PARAGON and DELIVER trials

Abstract Background The prognostic utility of N-terminal pro-B-type (NT-proBNP) in patients with heart failure and chronic kidney disease (CKD) is incompletely understood since elevations in NT-proBNP could be related either to decreased clearance by the kidney or to increased severity of structural heart disease. Purpose We sought to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. Methods We conducted a pooled analysis of individual participants with NT-proBNP and estimated glomerular filtration rate (eGFR) measured at baseline in the I-PRESERVE, TOPCAT (Americas region), PARAGON and DELIVER trials. We evaluated the relationship between NT-proBNP and kidney function using piecewise linear regression. Using multivariable Cox and Poisson regression models, we assessed the association of NT-proBNP with clinical outcomes across different levels of eGFR (≥60, 45-&amp;lt;60 and &amp;lt;45 mL/min/1.73m2). The primary outcome was hospitalisation for heart failure or cardiovascular death. Results Among 14,831 participants (mean age 72.1 years, 50.3% female, mean eGFR 63.3 mL/min/1.73m2 and median NT-proBNP 840 pg/mL) followed for a median 33.5 months, there were 3,092 primary outcomes, 2,184 heart failure hospitalisations, 1,465 cardiovascular and 1,049 non-cardiovascular deaths. Participants in lower eGFR categories were more likely to be older, female, and have atrial fibrillation and diabetes (all p&amp;lt;0.001). NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73m2 lower eGFR in patients with baseline eGFR ≥60, 45-60, and &amp;lt;45 mL/min/1.73m2, respectively (P for non-linearity &amp;lt;0.001). For any given NT-proBNP concentration, participants with eGFR &amp;lt;45 mL/min/1.73m2 were at highest risk (Figure 1). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR 1.37, 95% CI 1.34-1.41), consistent across different eGFR categories (P-interaction=0.42). Association between NT-proBNP and other clinical outcomes were also consistent across different levels of kidney function (all P-interaction&amp;gt;0.3; Figure 1). Equivalent risk for the primary outcome was apparent at NT-proBNP levels approximately 2.5- to 3.5-fold lower in patients eGFR &amp;lt;45 mL/min/1.73m2, compared to those with eGFR ≥60 mL/min/1.73m2. (Figure 2). Conclusion NTproBNP is a potent predictor of risk in patients with heart failure with mildly reduced or preserved ejection fraction across the spectrum of kidney function. However, in patients with reduced kidney function, lower NT-proBNP levels confer absolute risk of cardiovascular outcomes similar to substantially higher NT-proBNP levels in patients with normal kidney function. Accordingly, interpretation of NTproBNP levels should vary according to kidney function, particularly in those with eGFR &amp;lt;45 mL/min/1.73m2.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with or without chronic kidney disease undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR &amp;lt; 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

Heart failure and renal outcomes in patient treated with GLP1 agonists

Abstract Introduction Glucagon-like peptide-1 receptor (GLP1) agonists are emerging as a primordial treatment for diabetes and to reduce cardiovascular burden, both of them factors that play an important role in the developing of renal chronic disease and heart failure, and vice versa. The debut of renal chronic disease and the manifestation of acute renal injury/failure can lead to the discontinuation of treatment, which in patients suffering from heart failure who tend to be polymedicated could end up in lessening their survival. Methods A metanalysis of randomized clinical trials (RCT) comparing GLP1 agonists with placebo was performed. The endpoint of the study was to analyze all-cause mortality, hospitalization or urgent medical visit for heart failure, a kidney outcome composite, which is slightly heterogenic depending on the RCT, and the manifestation of acute renal injury/failure as an adverse effect or that lead to the discontinuation of treatment. The meta-analysis was performed using the inverse variance method, using the fixed effects model when there was no heterogeneity and the random effects model when heterogeneity is significant. Results A sum of 9 randomized controlled trial were included where a GLP1 agonists such as albiglutide, dulaglutide, exenatide, liraglutide, lixinatide or semaglutide compared with placebo. 77684 patients were incorporated, while 39497 were treated with a GLP1 agonists. The mean age was of 63.7 years (SD ± 1.97 years), 60080 (77.3%) suffered from diabetes, 60552 (77.9%) from cardiovascular disease and 14367 from chronic heart failure (18.4%). The mean eGFR was 77.3 mL/min (SD ± 3.3 mL/min). As showed in the forest plots, treatment with GLP1 agonists reduced all-cause mortality by 12% (RR: 0.88, 95% CI 0.83-0.92; p&amp;lt;0.001), hospitalization or urgent medical visit for heart failure by 10% (RR: 0.90, 95% CI 0.83-0.98; p&amp;lt;0.001), the kidney composite outcome by 22% (RR: 0.78, 95% CI 0.70-0.87; p&amp;lt;0.001), while it showed no statistical reduction in acute renal injury/failure (RR: 0.89, 95% CI 0.79-1.01; p=0.069). Conclusion Treatment with a GLP1 agonists reduced the incidence of all-cause mortality by 12%. In addition, hospitalization or urgent medical visit for heart failure was decreased by 10%. In terms of renal asessment, the composite of kidney function was reduced by 22%, while the manifestation of acute renal injury/failure, though no statistical signification was accomplished, showed some evidence of beneficial effect but more RCTs are needed to prove it. Hence, GLP1 analogues appear as a possible new pillar of treatment for heart failure and renal disease in determined patients.

Bidirectional relationship between kidney disease progression and cardiovascular events in type 2 diabetes: new Insights from the CANVAS Program and CREDENCE trial

Abstract Background The extent to which chronic kidney disease (CKD) progression increases cardiovascular risk, and whether different types of cardiovascular events affect risk of CKD progression, is incompletely understood. Purpose We sought to explore risk of cardiovascular events before and after CKD progression, and CKD progression before and after different cardiovascular events in patients with type 2 diabetes. Methods We conducted a pooled individual participant data analysis of the CANVAS Program and CREDENCE trial. Using Poisson regression, we assessed the incidence of major adverse cardiovascular events ([MACE] stroke, myocardial infarction, or cardiovascular death) and hospitalised heart failure (HHF) or cardiovascular death before and after CKD progression (defined as 40% decline in estimated glomerular filtration rate [eGFR] or kidney failure), and CKD progression before and after nonfatal cardiovascular events, with no adjustment for confounding related to subgroups defined by post-randomization variables. We estimated the cumulative incidence of all-cause mortality after different nonfatal cardiovascular and kidney outcomes, including different thresholds of CKD progression (kidney failure, 40% or 50% decline in eGFR or doubling of serum creatine) using Cox regression models. Results Among 14,464 participants (mean age 63.7 years, 35.3% female, mean eGFR 55mL/min/1.73m2 and median urinary albumin:creatinine ratio 34mg/g) over a median follow-up of 2.5 years, 1,482, 1,076 and 1,020 experienced MACE, HHF or cardiovascular death, and CKD progression, respectively. After (vs. before) CKD progression, there was an approximate 3-fold increase in incidence of MACE (30.2 vs. 93.8 per 1000-patient-years) and 4-fold increase in HHF or cardiovascular death (21.0 vs. 79.3 per 1000-patient-years). Conversely, the incidence of CKD progression was approximately 1.5-fold higher after (vs. before) nonfatal myocardial infarction or stroke (21.7 vs. 34.1 per 1000-patient-years) and 5-fold higher after HHF (21.2 vs. 108.2 per 1000-patient-years). These patterns were consistent in both treatment arms, with unadjusted incidence rates for clinical events appearing numerically lower in canagliflozin compared to placebo-treated participants (Figure 1). Of all non-fatal cardio-kidney outcomes, HHF and doubling of serum creatine or kidney failure conferred the highest risk of death (Figure 2). Conclusion Atherosclerotic and heart failure risk increases substantially after CKD progression. CKD progression was accelerated after cardiovascular events, particularly HHF. Treatment with canagliflozin was associated with lower event rates before and after a serious cardio-kidney outcome, suggesting continued use of canagliflozin may be beneficial even after cardiovascular events and CKD progression.Figure 1.Figure 2.

Differences in non-flow limiting non-culprit plaque characteristics after myocardial infarction in patients with versus without chronic kidney disease

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk for recurrent cardiovascular events after myocardial infarction compared to patients with preserved renal function. This disparity may be related to differences in plaque morphology. Purpose To compare non-flow limiting non-culprit (NC) plaque characteristics as assessed by optical coherence tomography in patients with versus without chronic kidney disease presenting with myocardial infarction. Methods 438 patients presenting with myocardial infarction with additional non-flow limiting (defined as a fractional flow reserve &amp;gt;0.80) NC lesions were included in the prospective observational PECTUS-obs study after treatment of the infarct related artery. An independent core laboratory performed all quantitative and qualitative OCT analyses. For the present subgroup analysis, patients were grouped according to the presence or absence of CKD, which was defined as an estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73 m². Baseline characteristics were compared between groups on a patient-level and OCT characteristics were compared on a lesion-level while accounting for within-patient clustering. Results Out of 420 patients with at least one analyzable OCT, baseline renal function was known in 416. Among them, there were 55 patients with and 361 patients without CKD (mean eGFR 47.4 ± 9.2 vs 84.7 ± 15.0 ml/min/1.73 m², p&amp;lt;0.001). Patients with CKD were older (mean age 73 ± 9 vs 62 ± 10 years, p&amp;lt;0.001), more frequently were female (29.1% vs 17.2%, p=0.035) and predominantly presented with a non-ST-segment elevation myocardial infarction (72.2% vs 44.9%, p&amp;lt;0.001). Comorbid disease was more prevalent among patients with CKD, including a higher prevalence of hypertension (p=0.010), hypercholesterolemia (p=0.020), diabetes (p&amp;lt;0.001), history of myocardial infarction (p&amp;lt;0.001), carotid artery disease (p=0.019) and peripheral artery disease (p=0.002). Coronary lesions in patients with CKD on average had a larger maximal calcium arc (188 ± 114 vs 137 ± 87º, p=0.003) and length (11.9 ± 10.3 vs 8.4 ± 7.4 mm, p=0.021). Lipid plaques were less prevalent among lesions in patients with CKD (63.6% vs 78.0%, p=0.016) and less frequently had a lipid arc ≥90º (60.6% vs 76.1%, p=0.018). Although the mean minimal fibrous cap thickness was lower in patients with CKD (p=0.025), no difference was observed in the prevalence of thin-cap fibroatheromas (p=0.984) or high-risk plaques according to the PECTUS-obs criteria (p=0.665). Conclusion Non-flow limiting NC lesions in patients with CKD differ from those in patients without CKD in a cohort of patients presenting with myocardial infarction. Overall, plaques in patients with CKD show more extensive calcification, whereas lesions in patients without CKD more often consist of lipid plaques, but the prevalence of high-risk plaques was comparable.

The safety of in-hospital initiation of SGLT2 inhibitor with MRA therapy in patients hospitalized for heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

Abstract Deferring in-hospital initiation of guideline-recommended medications in HFrEF has a few chances they will be initiated ambulatory, especially in the case of coexisting HFrEF and chronic kidney disease (CKD). The aim was to investigate the safety of in-hospital initiation of SGLT2i with MRA therapy for patients hospitalized for HFrEF and CKD 3. Methods 88 patients with HFrEF (on top of standard therapy ACE-I/ARB, B-blockers) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K), creatinine (C), uric acid (UA) levels were estimated at baseline and week 12. After biochemical evaluation, patients started on spironolactone (SP) treatment with a median dose of 20 mg daily (titrated) and dapagliflozin (D) with a dose of 10 mg daily (D+SP). Blood pressure (BP), K, and renal function (RF) were checked at weeks 1 (in-hospital), 2, 4, 6, 8, 12 (ambulatory), and more frequently as necessary. Results After the start of therapy D+SP mean eGFR decreased significantly at week 1 from 51.14±9.18 to 46.26±7.91 ml/min/1.73m2 (P&amp;lt;.0001) and at week 2 to 44.18±6.51 ml/min/1.73m2 (-2.08±1.2; P&amp;lt;.001). At week 4 mean eGFR decreased to 42.73±6.86 ml/min/1.73m2 (-1.45±1.1; P&amp;lt;.05). So, a significant decrease in eGFR was observed only during the first month with no significant decrease at 6 and 12 weeks after the start of therapy. Six patients (8%) experienced a significant decline in RF resulting in temporary withdrawal of SP. At week 2 mean K level increased significantly from 4.56±0.63 to 5.07±0.57 mmol/L (P&amp;lt;.001). At weeks 4, 6, 8 K levels remain stable. At week 12 mean K level decreased significantly compared with week 2 (to 4.92±0.57 mmol/L, P&amp;lt;.05). The incidences of severe hyperkalemia (HK) (K+≥6.0mmol/L) were in three patients &amp;lt; 2 %, and moderate HK (K 5.5–5.9 mmol/L) occurred in ten patients (11 %). Patients who experienced inpatient hyperkalemia had a significantly lower eGFR than patients without episodes of HK (38.70 vs. 55.21 mL/min/1.73 m2; P&amp;lt;.0001). Episodes of HK were predicted by baseline K≥5.0 mmol/L and eGFR≤40 ml/min/1.73m2. Additionally, there was a significant improvement in blood UA (-1,53±0.49 mg/dL, P&amp;lt;.01). By multivariate analysis older age, diabetes, low diastolic BP (&amp;lt;60 mm Hg), eGFR≤40 ml/min/1.73m2 at baseline were associated with decreased RF (0.378, P&amp;lt;.01; 0.632, P&amp;lt;.001; 0.771, P&amp;lt;.0001; 0.397, P&amp;lt;.01; respectively), whereas episodes of HK were predicted by baseline K≥5.0 mmol/L and eGFR≤40 ml/min/1.73m2 (0.785, P&amp;lt;.0001; 0.542, P&amp;lt;.001; respectively). Conclusion Initiation of SGLT2i with MRA in patients hospitalized for HFrEF and CKD 3 was mainly safe although it caused an early drop in eGFR. Importantly, a fall in eGFR was observed during the first month. Concern about the reduction in eGFR should be in older diabetic patients with eGFR≤40 and low diastolic blood pressure. Although hyperkalemia was common, the occurrence of it was predicted by baseline potassium level and eGFR.

ASSOCIATION OF SERUM ADENOSINE DEAMINASE LEVELS WITH ACUTE KIDNEY INJURY IN DIABETIC PATIENTS

Diabetes mellitus is a significant global health issue, and complications such as acute kidney injury (AKI) are prevalent in patients with type 2 diabetes. Serum adenosine deaminase (ADA) has been suggested as a potential biomarker for various metabolic conditions, including inflammation and kidney injury, but its association with diabetic kidney health remains understudied. Objective: To assess the association of serum adenosine deaminase (ADA) levels with acute kidney injury (AKI) in patients with type 2 diabetes. Methods: This observational comparative study was conducted at DHQ Teaching Hospital KDA, Kohat, from February 7, 2023, to August 7, 2023, following ethical approval. A total of 120 participants were enrolled, including 60 patients with type 2 diabetes and 60 non-diabetic controls. Laboratory investigations for both groups included serum ADA (U/L), HbA1c (%), and estimated glomerular filtration rate (eGFR) (mL/min/1.73 m²). Statistical comparisons between groups were made using appropriate tests, and correlations between serum ADA and other parameters were assessed. Results: The mean age of diabetic patients was 55.40 ± 8.29 years, and that of controls was 54.58 ± 21.64 years. The mean serum ADA level in diabetic patients was significantly higher at 43 ± 4.29 U/L compared to 16.32 ± 1.20 U/L in controls (p = 0.0001). Diabetic patients had a mean HbA1c of 8.30 ± 0.59%, significantly higher than that of controls (5.28 ± 0.59%) (p = 0.0001). The mean eGFR in diabetic patients was 82.61 ± 17.22 mL/min/1.73 m², lower than in controls (105.97 ± 12.07 mL/min/1.73 m²) (p = 0.0001). In diabetic patients, serum ADA levels were positively correlated with HbA1c (indicating poorer glycemic control) and negatively correlated with eGFR (suggesting declining kidney function). Conclusion: Elevated serum adenosine deaminase levels in type 2 diabetic patients are significantly associated with poor glycemic control and decreased kidney function. These findings indicate that serum ADA could serve as a potential biomarker for monitoring glycemic status and kidney health in diabetic patients at risk for acute kidney injury.

The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

Key Points Patients with IgA nephropathy and significant proteinuria are at high risk of progressive kidney function loss and kidney failure.We report the results of a clinical trial assessing the selective endothelin receptor antagonist SC0062 for the treatment of IgA nephropathy.SC0062 led to clinically meaningful improvements in proteinuria and did not increase risk of peripheral edema at higher doses. Background Endothelin receptor type A activation contributes to kidney injury in patients with IgA nephropathy. SC0062 is a novel selective endothelin receptor type A antagonist. We report the results of a phase 2 dose-finding trial to characterize the efficacy and safety of SC0062 in patients with IgA nephropathy. Methods We conducted a randomized, placebo-controlled, double-blind, clinical trial in adults with biopsy-proven IgA nephropathy and eGFR ≥30 ml/min per 1.73 m2 with urinary protein-creatinine ratio (UPCR) ≥0.75 g/g or proteinuria ≥1 g/24 hour despite using maximum tolerated doses of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Patients were randomized 1:1:1:1 to 24-week treatment with SC0062 5, 10, and 20 mg or matching placebo once daily. The primary efficacy outcome was percent change from baseline in UPCR in 24-hour urine samples after 12 weeks of treatment. Secondary end points included changes in eGFR. Safety outcomes including treatment emerging adverse events and serious adverse events were recorded. Results Overall, 131 patients (mean age 42 years [SD, 11]; mean eGFR 72 ml/min per 1.73 m2 [SD 24] and median 24-hour UPCR 1.2 g/g [25th–75th percentile, 0.9–1.5 g/g]) were randomized to placebo (n=34) or SC0062 5 mg (n=33), 10 mg (n=32), or 20 mg (n=32). All SC0062 doses reduced UPCR versus placebo throughout treatment. At week 12, placebo-corrected geometric mean changes (95% confidence interval) from baseline in UPCR with SC0062 5, 10, and 20 mg were−27.6% (−43.0 to −8.2), −20.5% (−37.4 to 1.0), and −38.1% (−51.4 to −21.0), respectively, and at week 24 they were−22.4% (−42.2 to 4.3), −30.9% (−48.6 to −7.0), and −51.6% (−64.2 to −34.6), respectively. No differences in eGFR were observed among treatment groups. The proportion of participants with treatment emerging adverse events or serious adverse events was balanced among treatment groups. Peripheral edema was reported by 2 (6%), 1 (3%), 1 (3%) participants in the 5, 10, and 20 mg SC0062-treated groups, respectively, compared with 5 (15%) in the placebo group. Conclusions In patients with IgA nephropathy, SC0062 reduced proteinuria and did not increase risk of peripheral edema. Clinical Trial registry name and registration number: A Study to Evaluate the Efficacy and Safety of SC0062 in the Treatment of CKD, NCT05687890.