eGFR Slope Research Articles

Arterial Stiffness and Subsequent Incidence of CKD and Kidney Function Decline in a Large Longitudinal Community Cohort: The Atherosclerosis in Communities (ARIC) Study.

Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive. Longitudinal cohort study. Using data from the Atherosclerosis Risk in Communities (ARIC) Study, the primary analysis included 3,161 participants without prevalent CKD at visit 5; a secondary analysis studied 4,341 participants with any estimated glomerular filtration rate (eGFR) record across visits 5 to 7. Carotid-femoral pulse wave velocity (cfPWV), heart-femoral PWV (hfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-carotid PWV (hcPWV), and femoral-ankle PWV (faPWV). Primary analysis - incident CKD, defined as an eGFR <60 ml/min/1.73m2 accompanied by >25% decline eGFR or CKD hospitalization. Secondary analysis - eGFR slope. Primary analysis - Cox regression models to calculate hazard ratio (HR). Secondary analysis - multilevel mixed effects models to estimate the eGFR slope across visits. Median follow-up was 6.6 years. 460 participants developed incident CKD (incidence rate 22.0/1,000 person-years). The highest quartiles (Q4) of cfPWV, hfPWV, and haPWV were associated with an increased risk of incident CKD compared to the lowest quartile (Q1) (HRs, 1.53 [95% CI, 1.15 to 2.04] and 1.49 [95% CI, 1.12 to 1.99], and 1.56 [95% CI, 1.16 to 2.08], respectively). The results were consistent in subgroups. In the secondary analysis, the Q4s of cfPWV, hfPWV, haPWV, baPWV, and hcPWV were significantly associated with a faster eGFR decline compared to Q1 (e.g., for cfPWV, -0.44 mL/min/1.73 m2/year [95% CI, -0.56 to -0.33] in Q4 versus -0.37 [95% CI, -0.48 to -0.26] in Q1). All p-value <0.05. faPWV was not associated with incident CKD or eGFR slope. Residual confounding. Greater arterial stiffness, especially higher cfPWV, hfPWV, and haPWV, was prospectively associated with a higher risk of incident CKD and faster decline in eGFR among community-dwelling older adults, supporting a pathophysiological contribution of arterial stiffness to the development of CKD.

Clinically Meaningful eGFR Slope as a Surrogate Endpoint Differs across CKD Stages and Slope Evaluation Periods: the CKD-JAC Study

Abstract Background The slope of estimated glomerular filtration rate (eGFR) is a promising surrogate endpoint in patients with chronic kidney disease (CKD). However, current evidence is mainly derived from Western populations with CKD stages 1–3. In addition, stage-by-stage analysis has never been formally performed. Methods We analyzed data from the Chronic Kidney Disease Japan Cohort Study, which included a large proportion of patients with CKD stages 4 and 5. We estimated eGFR slopes over three evaluation periods (0.5, 1, and 2 years) using mixed effects models and examined their associations with kidney failure with replacement therapy (KFRT) across CKD stages. Results Of 2713 patients with an available 1-year eGFR slope, 985 subsequently initiated kidney replacement therapy. Overall, a slower eGFR decline was strongly associated with a lower risk of subsequent KFRT. The association was pronounced with higher baseline CKD stages and attenuated with shorter evaluation periods. The estimated deceleration in eGFR decline over 1 year associated with a 20% lower risk of subsequent KFRT was 1.91 (1.60–2.37), 1.12 (1.00–1.28), and 1.06 (0.81–1.60) mL/min/1.73 m2 per year in patients with CKD stages 3, 4, and 5, respectively. Conclusion Our results support the potential of eGFR slope as a surrogate across different stages of CKD in Asians and suggest that a shorter evaluation period than 2 years may be feasible for patients with late-stage CKD. Our findings provide valuable insights for the future design of clinical trials in CKD patients, especially those with more advanced CKD.

Integrated Use of Autosomal Dominant Polycystic Kidney Disease Prediction Tools for Risk Prognostication.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Specific treatment is indicated upon observed or predicted rapid progression. For the latter, risk stratification tools have been developed independently based on either total kidney volume or genotyping as well as clinical variables. This study aimed to improve risk prediction by combining both imaging and clinical-genetic scores. We conducted a retrospective multi-center cohort study of 468 patients diagnosed with ADPKD. Clinical, imaging, and genetic data were analyzed for risk prediction. We defined rapid disease progression as an estimated glomerular filtration rate (eGFR) slope ≥3 ml/min/1.73m2/year over two years, Mayo imaging classification (MIC) 1D-1E, or a Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score of ≥7 points. Using MIC, PROPKD, and Rare Exome Variant Ensemble Learner (REVEL) scores, several combined models were designed to develop a new classification with improved risk stratification. Primary endpoints were the development of advanced chronic kidney disease (aCKD) stages G4-G5, longitudinal changes in eGFR, and clinical variables such as hypertension or urological events. Statistically, logistic regression, survival, Receiver Operating Characteristic (ROC) analyses, linear mixed models, and Cox proportional hazards models were used. PKD1-genotype (p <0.001), MIC class 1E (p <0.001), early-onset hypertension (p <0.001) and early-onset urological events (p =0.003) correlated best with rapid progression in multivariable analysis. While the MIC showed satisfactory specificity (77%), the PROPKD was more sensitive (59%). Among individuals with an intermediate risk in one of the scores, integration of the other score (combined scoring) allowed for more accurate stratification. The combined use of both risk scores was associated with higher ability to identify rapid progressors and resulted in a better stratification, notably among intermediate risk patients.

Factors associated with awareness of chronic kidney disease, and impact of awareness on renal prognosis.

Chronic kidney disease (CKD) awareness could help prevent disease progression through modifiable risk factors. However, few patients with CKD are aware of their disease. We aimed to investigate the factors associated with CKD awareness and impact of CKD awareness on renal prognosis. We investigated the proportion of participants with CKD who answered 'aware of CKD' in the questionnaire among those undergoing health check-ups from 2013 to 2022. Participants included working-age employees and their dependents covered by health insurance associations for large and medium-sized companies. The outcome was defined as the change from 'unaware' to 'aware' of CKD; multivariable logistic regression analysis assessed the association of urine tests or nutritional guidance with CKD awareness. A control group was randomly selected from the unaware group and matched for age, sex, estimated glomerular filtration rate (eGFR), urinary protein categories, and follow-up period. Changes in eGFR slopes before and after awareness were compared using linear mixed-effects models. Of the 13,489 participants, 2.8% were aware of CKD at baseline; of the 1,614 with CKD-related disease codes, only 19.6% were aware. The odds ratios of urine tests or nutritional guidance in relation to awareness occurrence were 1.98 (1.29-3.05) and 3.01 (1.38-6.53), respectively. The difference in the eGFR slope improvement from before to after CKD awareness was + 0.92mL/min/1.73m2 per year (0.18-1.67; P = 0.015) in the aware group. Our findings suggest that urine tests and nutritional guidance may promote CKD awareness, which may help slow its progression.

EGFR slope modelling predicts long-term clinical benefit with nefecon in a real-world IgAN population

Abstract Background Nefecon is an oral, targeted-release formulation of budesonide approved to reduce kidney function loss in patients with immunoglobulin A nephropathy (IgAN). In the phase 3 NefIgArd trial, 9 months of nefecon treatment preserved estimated glomerular filtration rate (eGFR) and reduced urine protein–creatinine ratio versus placebo, for 15 months post-treatment. A modelling analysis was conducted to predict nefecon's long-term benefits on clinical outcomes. Methods A published linear regression model was used to extrapolate nefecon's effect on eGFR slope in NefIgArd to predict its effect on the clinical outcome of kidney failure, eGFR &amp;lt;15 mL/min/1.73 m2, or sustained doubling of serum creatinine. This model was applied to registry data from patients with IgAN at Leicester General Hospital (LGH), whose records were matched to individual NefIgArd patients based on their urine protein–creatinine ratio and eGFR values. Results 1684 LGH-NeflgArd ‘matched-pairs’ were obtained. Nefecon was predicted to delay the time to clinical outcome by 12.8 years (95% confidence interval 4.8–27.9), with median time to outcome of 9.6 years for patients receiving supportive care only versus 22.4 years for nefecon-treated patients. The NeflgArd 2-year eGFR slope yielded a log hazard ratio for the clinical outcome of 0.38 (95% confidence interval 0.21–0.63), a 62% risk reduction versus placebo. 52% of patients receiving supportive care only were modelled to have a clinical outcome within 10 years versus 24% of nefecon-treated patients. Conclusion This modelling analysis indicates that the eGFR benefit seen with nefecon predicts a substantial delay in progression to kidney failure.

Kidney outcomes associated with SGLT2 inhibitors compared to other glucose-lowering drugs: a real-world study from China.

This study aimed to investigate the association between the utilization of Sodium-dependent glucose cotransporters inhibitors (SGLT2i) in real-world settings and kidney outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) in mainland China. In a retrospective analysis of electronic medical records from West China Hospital of Sichuan University, patients with T2D and CKD were included. Patients were divided into two groups, those initiating treatment with SGLT2i and those receiving other glucose-lowering drugs (oGLDs). The primary focus lies in examining the impact of SGLT2i on the decline slope of eGFR and major kidney events in these patients. We enrolled 944 patients diagnosed with both T2D and CKD. Out of these, 605 patients were prescribed SGLT2i, while the remaining 339 patients received oGLDs. The median follow-up duration were 16.8 months and 20.6 months, respectively. Throughout the follow-up period, we observed a significant decrease in the rate of eGFR decline in patients using SGLT2i (4.94mL/min/1.73m2 per year reduction compared to oGLDs, 95% CI: 4.73-5.15). A total of 101 kidney composite endpoint events occurred, with 31 events in the SGLT2i group and 70 events in the oGLDs group. The use of SGLT2i was associated with a 65% decrease in the risk of kidney composite endpoint events (hazard ratio 0.35, 95% CI 0.19-0.63). In clinical practice, SGLT2i have shown favorable effects on kidney prognosis in patients with T2D and CKD in mainland China. These effects remain consistent across patients with varying risks of CKD progression. ChiCTR2300068497.

Urine complement-related proteins in IgA nephropathy and IgA vasculitis nephritis, possible biomarkers of disease activity

Abstract Introduction The activation of the complement system plays an important role in the pathogenesis of IgA nephropathy (IgAN). Our primary aim was to evaluate a range of complement-related proteins, including pentraxin-3 (PTX-3), in blood and urine at diagnosis and their association with disease activity in the kidney biopsy, eGFR, albuminuria, and outcome. Our secondary aim was to compare the same biomarkers between patients with IgAN and IgA vasculitis with renal involvement (IgAVN). Methods In a longitudinal Swedish cohort of 96 patients with IgAN (n = 65) or IgAVN (n = 31), with a median follow-up time of 10.8 years, we analysed mainly lectin-pathway-related proteins and PTX-3 in plasma and urine (u) samples stored at the time of kidney biopsy. Outcome was defined by the GFR slope or by the combined outcome of 50% loss of eGFR or ESKD. Results Patients with detectable vs undetectable u-PTX-3 and u-Mannose-binding lectin (MBL) more frequently had mesangial hypercellularity, endocapillary proliferation, and crescents in their kidney biopsy. U-C4c levels were higher in patients with advanced tubulointerstitial fibrosis, and u-C4c was also an independent predictor of a more severe eGFR slope. There were no differences in the levels of biomarkers between patients with IgAN and IgAVN. Conclusion U-PTX-3 and u-MBL might be biomarkers of an active proliferative stage of the disease, while higher u-C4c levels indicate more chronic lesions in both IgAN and IgAVN. These results must, however, be confirmed in larger and multiethnic cohorts.

Favorable changes in the eGFR slope after dapagliflozin treatment and its association with the initial dip.

Renoprotective effects of sodium glucose transporter 2 (SGLT2) inhibitors, including dapagliflozin, were observed in randomized controlled trials (RCTs). The suspected underlying mechanism is a correction of hyperfiltration, observed as an "initial dip". Whether SGLT2 inhibitors can attenuate the rate of decline in the estimated glomerular filtration rate (eGFR) in clinical settings, even when considering the pre-treatment decline rate, is unknown. Although several RCTs identified an association between the initial dip and long-term renal prognoses, a conclusion has not been reached. We collected the eGFR data of patients for whom dapagliflozin was initiated in our hospital and then calculated their eGFR slopes before and after the start of the treatment. We investigated the changes in the eGFR slopes (ΔeGFR slope) and the association between the ΔeGFR slope and the initial dip. Risks for rapid eGFR decliners (eGFR slope < -3mL/min/1.73m2/year) were also examined. The eGFR slope was significantly milder after dapagliflozin treatment (p < 0.01). A deeper initial dip was associated with a milder rate of eGFR decline (adjusted beta: -0.29, p < 0.001). Dapagliflozin treatment reduced the proportion of rapid eGFR decliners from 52.9 to 14.7%, and a smaller initial dip was identified as a significant risk for post-treatment rapid eGFR decline (adjusted odds ratio: 1.73, p < 0.05). Compared to before the administration of dapagliflozin, the rate of eGFR decline was significantly milder after its administration. The initial dip was significantly associated with long-term renoprotective effects and may be a useful predictor of treatment response.

Association of trimethylamine N-oxide and metabolites with kidney function decline in patients with chronic kidney disease

BackgroundTrimethylamine N-oxide (TMAO) is a gut microbial metabolite derived from dietary L-carnitine and choline. High plasma TMAO levels are associated with cardiovascular disease and overall mortality, but little is known about the associations of TMAO and related metabolites with the risk of kidney function decline among patients with chronic kidney disease (CKD). MethodsWe prospectively followed 152 nondialysis patients with CKD stages 3–5 and measured plasma TMAO and related metabolites (trimethylamine [TMA], choline, carnitine, and γ-butyrobetaine) via liquid chromatography‒mass spectrometry. An estimated glomerular filtration rate (eGFR) slope >3 ml/min/per 1.73 m2 per year was defined as a rapid decline. We performed logistic regression to determine the probability of rapid or slow eGFR decline, with each metabolite as the main predictor. The gut microbiota was profiled via whole metagenomic sequencing. ResultsThe participants had a median age of 66 years, 41.4% were women, 39.5% had diabetes, and the median eGFR was 23 mL/min/1.73 m2. A rapid decrease in the eGFR occurred in 65 patients (42.8%) over a median follow-up of 3.3 years. After adjustment for baseline eGFR, proteinuria, and clinical factors, plasma TMAO levels were independently associated with increased odds of rapid eGFR decline (odds ratio, 2.42; 95% CI, 1.36–4.32), whereas plasma TMA, choline, carnitine, and γ-butyrobetaine levels were not. Patients who exhibited rapid eGFR decline had a distinct gut microbial composition characterized by increased α-diversity and an abundance of TMA-producing bacteria, including those of the genera Desulfovibrio and Collinsella tanakaei, as well as increased expression of the TMA-producing enzymes bbuA and cutC. ConclusionOur findings suggest the relevance of plasma TMAO in the progression of kidney disease among patients with CKD.

MSR21 Comparing Methods for eGFR Slope Estimates Among Adult CKD Patients in a UK Electronic Health Record System: Challenges and Opportunities

MSR21 Comparing Methods for eGFR Slope Estimates Among Adult CKD Patients in a UK Electronic Health Record System: Challenges and Opportunities

EGFR slope as predictor of mortality in heart failure patients.

Heart failure (HF) leads to an imbalance between heart and kidney function, resulting in poor outcomes. However, the prognostic significance of the estimated glomerular filtration rate (eGFR) trajectory in HF patients remains unclear. We analysed electronic health records (EHRs) of real-world HF patients, assessing eGFR trajectories and their impact on mortality. Retrospective clinical data of HF patients were processed using natural language processing. Chronic kidney disease (CKD) was evaluated, and eGFR trajectories were analysed using linear mixed-effects models. Cox proportional hazard models were used to evaluate the relationship between baseline variables and mortality, while joint modelling combined eGFR trends and mortality. The dataset comprised 1986 patients, with a mean age of 74.8years (SD±11.7) and 58% male. At the time of HF diagnosis, 58% of patients were diagnosed with CKD, and 39% presented with heart failure with preserved ejection fraction (HFpEF). The median follow-up duration was 3.16years, during which 399 patients (20%) died. Patients with CKD were significantly older and exhibited a higher prevalence of myocardial infarction (P=0.048), coronary revascularization (P=0.004), stroke (P<0.001), atrial fibrillation (P<0.001) and type 2 diabetes (P<0.001). Mortality rates at 1 and 2years were nearly twice as high in CKD patients compared with those without (P<0.001). Notably, CKD was significantly less prevalent among survivors (55% vs. 71%, P<0.001). Key predictors of mortality included older age, beta-blocker use, prior stroke, lower serum haemoglobin levels, and elevated potassium and NT-proBNP levels. Each 10mL/min/1.73m2 decrease in eGFR was associated with a 1.22 (95% CI: 1.10-1.35, P<0.001) increase in mortality hazard. Additionally, a 1-year decline of 10mL/min/1.73m2 in eGFR resulted in a mortality hazard of 1.97 (95% CI: 1.45-2.69, P<0.001). CKD is prevalent in a real-world HF population and is an independent predictor of mortality. The current eGFR value and the eGFR slope from the previous year have the potential to be used for assessing individual mortality risk in the clinical follow-up of HF patients.

Long-term outcomes of IgA nephropathy in China.

The long-term prognosis of IgA nephropathy (IgAN) and the optimal target for proteinuria treatment remain controversial. This study, utilizing a large prospective cohort from China, aims to assess the long-term outcomes of IgAN and to explore the definition of proteinuria remission. We enrolled 2 141 patients with biopsy-proven IgAN, all with at least 12 months of follow-up, from a prospective IgAN cohort at Peking University First Hospital. We utilized Kaplan-Meier analysis, Cox regression, and an eGFR slope calculated via a linear mixed model to investigate kidney outcomes. The median (Q1, Q3) baseline proteinuria was 1.26 (0.65, 2.40) g/d, and the estimated GFR was 80 (52, 103) mL/min/1.73m2. After a mean follow-up of 5.8 (±4.4) years, 509 (24%) patients progressed to end-stage kidney disease (ESKD). The median kidney survival time was 12.4 years, the annual event rate of ESKD was 41.1 per 1000 person-years, and the 15-year kidney survival rate was 40%. Time-averaged proteinuria level was strongly associated with kidney failure (adjusted HR: 1.76, 95%CI: 1.65 to 1.88). Restriction cubic spline analysis indicated that the risk of ESKD increases rapidly when time-average proteinuria exceeded 0.5g/d. There was no significant difference in long-term kidney survival between patients with proteinuria<0.3g/d and those with 0.3-0.5g/d, with both groups demonstrating a better prognosis. The long-term outcomes for patients with IgAN under current treatment strategies remain poor, with most progressing to ESKD within 15 years. Patients with time-averaged proteinuria≥0.5g/d experience worse kidney outcomes, challenging the previous view that proteinuria<1.0g/d was associated with a low risk of kidney failure.

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

Prior nonrandomized studies have suggested nephroprotective effects of arteriovenous fistula (AVF) formation, but these are plausibly susceptible to immortal time and selection biases. We studied patients attending nephrology clinics in the West of Scotland during 2010-22 with an estimated glomerular filtration rate (eGFR) ≤15mL/min/1.73 m2 and no prior AVF. Using target trial emulation and a sequential trial design, we simulated a hypothetical trial that would randomize 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 6months 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. A total of 1364 unique patients (mean age 51.1years, 55.7% male) contributed 3125 person-trials, with 561 in the AVF and 2564 in the no AVF group. Mean eGFR was 12.6mL/min/1.73 m2 and the median number of eGFR measurements per person-trial was 7 (interquartile range 4-12). Slope of eGFR decline did not differ significantly between the AVF and no AVF groups (between-group difference -0.67mL/min/1.73 m2/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. In this study of patients with advanced chronic kidney disease, there was no evidence of a nephroprotective effect of AVF formation.

Post-hoc analysis of the CARES trial suggests delayed progression of chronic kidney disease in patients with gout during urate-lowering therapy

Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc analysis on patients who received ULT with either febuxostat or allopurinol for more than six months in the CARES trial. The estimated glomerular filtration rate (eGFR) slope (annual rate of change in eGFR) was calculated using the CKD- EPI creatinine equation and linear mixed modeling. Among the 5,002 patients with gout, 3,264 (65.3%) demonstrated an increased eGFR while receiving ULT over a median follow-up of 2.5 years. Increased average sUA levels were significantly associated with declines in eGFR slope (per 1 mg/dL increase, (adjusted beta of -0.1912). Propensity score matched analysis demonstrated a significant association between low average sUA levels below 6 mg/dL during ULT and a reduced risk of eGFR decline (adjusted odds ratio: 0.66, 95% confidence interval 0.57–0.77). Despite the well-documented natural decline of eGFR over time in the general population, more than half of the patients enrolled in the CARES trial did not experience declines in eGFR while receiving ULT. Thus, our study shows maintaining low sUA levels with ULT was significantly associated with a decreased risk of CKD progression in patients with gout.

Lupus nephritis: redefining the treatment goals

The course of proliferative lupus nephritis (LN) is characterized by flares of activity alternating with periods of quiescence, against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serological and histological tools to evaluate disease activity and how they may be applied to redefine the treatment goals in LN. Traditionally, treatment response is judged by the degree of proteinuria reduction and improvement of kidney function, but this fails to differentiate ongoing inflammatory disease from chronic damage. Despite intensive research, no novel biomarker has proved useful for clinical practice, and we continue to rely on anti-double-stranded DNA antibody levels (anti-dsDNA) to assess serological activity. Repeat kidney biopsies sometimes reveal persistent inflammation despite apparent clinical remission, giving credibility to the conviction that histological remission should be a treatment goal and protocol biopsies part of the decision-making process. However, the discrepancies between clinical and histological responses to therapy can be explained by persistent systemic autoimmunity with low-grade immune complex deposition or, alternatively, by delayed clearance of intrarenal inflammation once immunological remission has been achieved. Since persistent immune dysregulation is the motor of disease activity in LN, it should be the principal focus of therapy and monitoring. We propose to replace the traditional induction-remission maintenance protocol by a more dynamic and individualized approach, and aim for 3 treatment goals, concomitantly rather than sequentially: 1) Clinical remission, by attenuating renal inflammation, using microscopic hematuria, proteinuria, eGFR and complement levels as biomarkers; 2) Immunological remission, by decreasing immune complex generation, using anti-dsDNA as biomarker; 3) Preservation of kidney function, by curtailing chronic kidney damage, using eGFR slope as biomarker.

Obesity and renal impairment in patients with heart failure and reduced ejection fraction: another obesity paradox?

Abstract Background Obesity is associated with poor cardiovascular outcomes in patients with HF and reduced ejection fraction (HFrEF). However, whether obesity is associated with worse kidney outcomes in HFrEF has not been evaluated. Purpose To estimate the association between obesity and change in estimated glomerular filtration rate (eGFR) over time in patients with HFrEF. Methods In this post hoc analysis of the PARADIGM-HF trial, body mass index (BMI) and eGFR was collected in 8,389 patients. Change in eGFR over time was assessed according to baseline BMI (normal weight: BMI &amp;lt;25.0, overweight: BMI 25-29.9, and obesity: BMI ≥30). Results The number of patients in each BMI category was: 2,421 (BMI &amp;lt;25.0), 3,249 (BMI 25-29.9), and 2,719 (BMI ≥30), respectively. Patients with obesity were younger but had worse health status (worse NYHA class and KCCQ scores) and had more comorbidities including diabetes mellitus and hypertension. At baseline, eGFR was lower in patients who were overweight (BMI 25-29.9) and obese (BMI ≥30), compared to those with normal weight. Urine albumin-creatinine ratio (UACR) and kidney injury molecule-1 (KIM-1) were also higher in patients with obesity. However, the rate of change in eGFR per year (eGFR "slope") in the overall cohort did not differ according to BMI: change in eGFR per year was -1.8 [-2.1, -1.6] mL/min/1.73m2 for the normal weight category, -1.6 [-1.8, -1.3] mL/min/1.73m2 for those who were overweight, and -1.5 [-1.8, -1.3] mL/min/1.73m2 for those with obesity; P=0.21) (Figure 1). Among those without diabetes at baseline, those who were obese had a significantly less steep eGFR slope compared to patients in the other BMI categories. In those with diabetes at baseline, the eGFR slope was steeper than in patients without diabetes but was similar across all three BMI categories (Figure 2). Conclusions Although baseline kidney function was more impaired in HFrEF patients with obesity, high BMI was not associated with a more rapid subsequent rate of decline in eGFR. Figure 1. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF Figure 2. eGFR slope over time according to BMI at baseline in patients with HFrEF in PARADIGM-HF with and without diabetes at baselineFigure 1Figure 2-A and 2-B

Prediction of subsequent CKD according to eGFR decline slope varies by the presence of hypertension

Abstract Background We reported that a declining slope in eGFR evaluated from 3-year observation could predict subsequent CKD among the relatively healthy population, even adjusted for baseline eGFR. However, its certainty may vary depending on the presence of comorbidities such as diabetes and hypertension, which are also recognized as the risk factors of CKD. Methods Annual health check-up data from a Japanese company spanning from 2009 to 2022 was used. The analyses included participants having 4 times continuous eGFR measurements for 3 years, undergoing health checkups at least once during a follow-up period, with negative for urinary protein (UP), and non-diabetic. Individual ‘eGFR slopes’ were calculated by the regression line with 4 times eGFR measurements. Participants with slopes of &amp;lt; -5 per year were categorized as the “decreased” group and -5 or more were categorized as the “stable” group. The cases of positive UP or less than 45mL/min/1.73m2 in eGFR during a follow-up period were defined as CKD. Cox regression analyses adjusted for sex, age, and eGFR at baseline were performed to calculate the hazard ratios and 95% CIs for CKD in the decreased group (reference; stable), stratified by hypertension. Results Out of 5598 study participants(men 36%, mean age 48.2±10.1years, mean follow-up period 4.3 years), 260 CKD cases (4.6%) were observed. CKD cases accounted for 4.5% (235/5218) in the stable group and 6.6% (25/380) in the decreased group. Multivariate-adjusted hazard ratios [95%CIs] of CKD by eGFR decline was 1.50[0.99-2.27]. The eGFR decline increased the risk of CKD only in participants with hypertension (2.09[1.09-4.04]), but not in those without hypertension (1.25[0.73-2.13]). After excluding individuals with eGFR slopes exceeding 10 per year to consider for hyperfiltration of eGFR, the results were consistent. Conclusions The eGFR decline over a 3-year observation may predict subsequent CKD only in individuals with hypertension. Key messages • With a relatively short-term evaluation period of three years, eGFR decline can predict subsequent CKD only in hypertensive individuals. • In middle-aged hypertensive patients, it would be important for the prevention of CKD to pay attention not only to low eGFR but also to the progression of eGFR decline.

Long-Term Results from an Open-Label Extension Study of Atacicept for the Treatment of IgA Nephropathy.

Key Points Participants who completed a 36-week double-blind study of atacicept were eligible for a 60-week, open-label extension study.Atacicept 96-week treatment resulted in sustained reductions in galactose-deficient IgA1, hematuria, and urine protein-creatinine ratio.The slope of the eGFR was similar to that observed in the general population without kidney disease. Background B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in the pathogenesis of IgA nephropathy. Atacicept is a novel fully humanized fusion protein, self-administered at home by subcutaneous injection, that binds and inhibits BAFF and APRIL. By inhibiting BAFF and APRIL, atacicept targets the underlying B-cell–mediated pathogenesis driving disease progression. This study evaluated the long-term efficacy and safety of atacicept in patients with IgA nephropathy over 96 weeks. Methods Participants with IgA nephropathy who received atacicept (25, 75, or 150 mg) or placebo in a 36-week phase 2b, randomized, blinded trial were enrolled in an open-label extension study and received atacicept 150 mg for an additional 60 weeks. Key efficacy outcomes were changes in galactose-deficient IgA1 (Gd-IgA1), percentage of participants with hematuria, urine protein-creatinine ratio (UPCR), and eGFR over 96 weeks. Long-term safety data were also evaluated. Results There were 113 participants (67 [59%] male; 46 [41%] female) who ranged in age from 18 to 67 years who received ≥1 atacicept dose. Over 96 weeks, safety data demonstrated that atacicept was generally well tolerated. There were also sustained reductions (mean±SEM) in Gd-IgA1 (−66%±2%), percentage of participants with hematuria (−75%; 95% confidence intervals, −87 to −59; in participants with baseline hematuria), and UPCR (−52%±5%). The mean annualized slope of eGFR was −0.6±0.5 ml/min per 1.73 m2 through 96 weeks. Conclusions Atacicept was also well tolerated over the duration of the study. Atacicept treatment reduced Gd-IgA1, hematuria, and UPCR with stabilization of eGFR through 96 weeks. Clinical Trial registry name and registration number: Atacicept in Subjects with IgA Nephropathy (ORIGIN 3), NCT04716231.

Normothermic Ex Vivo Perfusion Before Transplantation of the Kidney (NEXT-Kidney): A Single-center, Nonrandomized Feasibility Study.

There is conflicting evidence regarding the efficacy of normothermic machine perfusion (NMP) in suboptimal deceased donor kidneys. We aimed to assess the feasibility and short-term efficacy of brief preimplantation NMP in circulatory death (DCD) kidneys. In this nonrandomized, single-center, prospective clinical trial, DCD kidneys underwent 1 to 3 h of NMP before implantation, aiming to achieve short ischemic times off NMP. The primary outcomes included feasibility and safety. Secondary outcomes included efficacy outcomes (delayed graft function and estimated glomerular filtration rate (eGFR) at 1, 6, and 12 mo), which were compared with the contralateral kidney that did not receive NMP. Eighteen DCD kidneys underwent NMP between 2020 and 2022, with at least 1 h completed in 16 (88.9%) of these kidneys (median 1 h); one kidney was removed after 5 min because of cannula failure and another at 54 min because of a sudden drop in blood flows. There was no episode of graft loss on the machine or postoperative vascular thromboses. All 18 kidneys were transplanted, with no cases of PNF or graft loss at 12 mo. Seventeen of the contralateral CS kidneys were transplanted. Compared with the contralateral kidneys, a lower incidence of delayed graft function (23.5% versus 64.7%; P = 0.046) was observed. There were no differences in the eGFR slopes between the two groups over time (P = 0.254). NMP is safe, feasible and efficacious in the Australian setting, with this relatively small cohort demonstrating good early outcomes compared to CS alone in our study of DCD kidneys.

Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium.

Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups (P < 0.0001). The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.