Reduction In eGFR Research Articles

Kidney hyperfiltration and mitochondrial changes are associated with eGFR decline in young people with type 1 diabetes.

To examine the relationship between kidney hyperfiltration during adolescence and subsequent changes in estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR) in a young cohort of participants with type 1 diabetes. Additionally, to explore urinary mitochondrial DNA:nuclear DNA ratio (mtDNA:nDNA) as a marker of metabolic stress and its association with early changes in kidney function. Eighty adolescents were studied at baseline [mean (SD) age 14.2 (1.5) years; mean diabetes duration 6.7 (3.0) years] and followed up 9.2 (1.3) years later. Blood pressure, HbA1c, lipids, eGFR, UACR and heart rate variability were assessed at each visit. Urinary mtDNA:nDNA was measured by quantitative PCR (qPCR). Overall, 4.2% of participants had diabetic kidney disease (DKD) at follow-up. Hyperfiltration at baseline (>135 mL/min/1.73m2) was seen in 31% of adolescents and was associated with a decline in eGFR at follow-up when adjusted for sex, diabetes duration and HbA1c [hyperfiltration -1.46 (3.07) mL/min/1.73 m2/year vs non-hyperfiltration -0.51 (2.48) mL/min/1.73m2/year, P=0.02]. Participants with hyperfiltration also had higher odds of undergoing rapid eGFR decline (>3 mL/min/1.73m2/year) compared to those without hyperfiltration [OR 14.11, 95% CI (2.30-86.60), P=0.004]. Baseline urinary mtDNA:nDNA was significantly associated with both greater annual rate of eGFR decline and rapid eGFR decline in univariable but not multivariable modelling. Hyperfiltration during adolescence is significantly associated with greater reduction in eGFR and higher risk of rapid eGFR decline after ∼9 years, following transition into young adulthood in type 1 diabetes. Urinary mtDNA:nDNA measured during adolescence may be a novel predictor of early changes in kidney function.

Predictive biomarkers for severity of respiratory syndrome: the role of eGFR and hematological parameters in ICU patients

Introduction: Studying respiratory syndromes like COVID-19 is crucial for understanding viral-induced inflammatory responses and their impact on organ function. Insights from these studies are essential for managing current and future pandemics and improving patient outcomes in respiratory health crises. This study investigates the behavior of the estimated glomerular filtration rate (eGFR) and its correlation with hematological parameters in ICU patients with COVID-19. Objective: To assess eGFR behavior and its correlation with hematological parameters in respiratory syndromes ICU patients. Materials and Methods: 217 patient records were analyzed, with 144 discharged and 73 deaths. Patients were divided into discharge and death groups and laboratory parameters such as glomerular filtration rate and blood count were.evaluated at admission and outcome. Results and Discussion: There was a significant reduction in eGFR among patients in the death group at both admission and outcome. Significant correlations were observed between eGFR and hemoglobin (Hb), total neutrophils (N), and platelets (PLT) at the outcome. These findings suggest that the reduction in eGFR is a predictor of poor prognosis in COVID-19 ICU patients. Additionally, the significant correlations between eGFR and hematological parameters highlight their role in the inflammatory process and clinical deterioration. Conclusion: The reduction of eGFR is a significant predictor of poor prognosis in ICU patients with COVID-19. Significant correlations between eGFR and hematological parameters underscore their importance in the inflammatory process and disease progression. Studying respiratory syndromes like COVID-19 is crucial for understanding viral-induced inflammatory responses and improving critical care strategies for future respiratory health crises.

Chronic kidney disease in patients with psoriatic arthritis: a cohort study

ObjectivesChronic kidney disease (CKD) is a comorbidity in psoriatic arthritis (PsA). We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes and identify...

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<.0001) and at week 2 to 44.18±6.51 ml/min/1.73m2 (-2.08±1.2; P<.001). At week 4 mean eGFR decreased to 42.73±6.86 ml/min/1.73m2 (-1.45±1.1; P<.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<.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<.05). The incidences of severe hyperkalemia (HK) (K+≥6.0mmol/L) were in three patients < 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<.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<.01). By multivariate analysis older age, diabetes, low diastolic BP (<60 mm Hg), eGFR≤40 ml/min/1.73m2 at baseline were associated with decreased RF (0.378, P<.01; 0.632, P<.001; 0.771, P<.0001; 0.397, P<.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<.0001; 0.542, P<.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.

To analyse the correlation between UAER and eGFR and the risk factors for reducing eGFR in patients with type 2 diabetes

ObjectiveTo analyse the correlation between urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR) and the risk factors for reducing eGFR in patients with type 2 diabetes mellitus (T2DM).MethodsA total of 431 T2DM patients admitted between January 2019 and March 2020 were selected and divided into two groups according to eGFR level. Comparing the differences between baseline data and clinical indicators, multivariate logistic regression was used to analyse the risk factors of eGFR reduction and to analyse the association between UAER and eGFR.ResultsIn total, 167 patients were included in the study group and 264 patients were included in the conventional group. The study group participants were older, had longer diabetes duration, and had higher fatty liver, peripheral vascular disease (PVD), hypertension prevalence, and mean body mass index (P < 0.05). The levels of various indicators were lower than those of the conventional group (P < 0. 05). Additionally, PVD, nocturnal systolic blood pressure, fatty liver, and beta-2-microglobulin (β 2-MG) were independent risk factors for eGFR decline, with high density lipoprotein (HDL) and fasting C-peptide (CP) as protective factors. There was no obvious correlation between UAER and eGFR.ConclusionPeripheral vascular disease, systolic blood pressure, fatty liver, and beta-2-microglobulin are risk factors for decreased eGFR levels in patients with T2DM, which should be applied for control DKD. HDL and fasting CP have important effects on maintaining eGFR, and blood pressure and fasting CP can be used as new targets for subsequent diabetic kidney disease treatment.

Unveiling the interaction and combined effects of multiple metals/metalloids exposure to TNF-α and kidney function in adults using bayesian kernel machine regression and quantile-based G-computation

BackgroundExposure to multiple metals may cause adverse effects, particularly in the kidneys. However, studies on the combined and interaction effects of metal mixtures on human health remain limited. ObjectiveThe study aims to evaluate the interaction between metals and assess the combined effects of exposure to metal mixtures on tumor necrosis factor-alpha (TNF-α) levels and kidney function MethodsParticular emphasis has been placed on the impact of various metals, including arsenic (As), cadmium (Cd), lead (Pb), as well as essential trace elements, such as cobalt (Co), copper (Cu), selenium (Se), and zinc (Zn), on human health and their potential collective influence on both TNF-α and kidney function. This cross-sectional study analyzed the data of 421 adults who underwent a health examination. Generalized linear model (GLM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation (qgcomp) were used to evaluate the association and joint effects between the metals and TNF-α, as well as kidney function. ResultsIncreased concentrations of As (β = 0.11, 95 % CI = 0.05, 0.17) and Pb (β = 0.30, 95 % CI = 0.23, 0.37) in the blood were associated with elevated levels of TNF-α, while elevated Cu (β = −0.42, 95 % CI = −0.77, −0.07) levels were linked to a significant reduction in TNF-α. The overall effect of metals mixture showed a significant association with a decline in eGFR and an increase TNF-α in the BKMR model. Qgcomp analysis of the metals mixture (β = −0.06, 95 % CI = −0.07, −0.05) indicated that As, Pb, and Zn were the primary contributors to the reduction in eGFR, while As and Pb were the major contributors in metals mixture (β = 0.12, 95 % CI = 0.08, 0.15) to the elevation of TNF-α levels. ConclusionExposure to multiple metals could have joint association with the TNF-α levels and kidney function. Furthermore, TNF-α could act as a mediator between metal mixtures and eGFR.

Association between serum uric acid variability and mild eGFR decline in Chinese adults: a retrospective cohort study

BackgroundThe present retrospective cohort study focused on evaluating the effects of fluctuations in serum uric acid (SUA) on a mildly reduced glomerular filtration rate (eGFR) in a population with a normal eGFR in Urumqi, China.MethodsA total of 2,154 normal individuals with a normal eGFR were recruited from 2018 to 2021. This study included questionnaire surveys, physical measurements, and blood sampling. We deemed the mildly reduced eGFR to be 60–90 ml·min–1·(1.73 m2)–1. The relationship between changes in SUA levels and the eGFR was assessed.Results(1) During the 3-year follow-up period, 433 individuals (20.10%) presented mildly reduced eGFR. (2) After stratification by the degree to which uric acid changed into five groups, the group showing the greatest change in uric acid concentration had significantly lower eGFR values than the other four groups. As the uric acid concentration (ΔSUA) increased, the degree of mild eGFR reduction (ΔeGFR) also increased (P < 0.05). When classified into five groups by the degree of eGFR change (ΔeGFR), analysis of variance revealed no statistically significant differences between baseline SUA and follow-up SUA (P > 0.05). Pearson correlation analysis showed a negative correlation between ΔSUA and ΔeGFR (r = -0.211, P < 0.01). (3) Multifactorial logistic regression, in which the endpoint event was an eGFR decreasing to 60 to 90 ml·min–1·(1.73 m2)–1, revealed that the ΔSUA was a risk factor that independently predicted a reduced eGFR (OR = 1.347, P < 0.001).ConclusionIn people with a normal eGFR in Urumqi, a high SUA level is associated with a mild reduction in the eGFR.

Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

Background: Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown. Methods: A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months. Results: 183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching -11 (95% CI: -18 to -8) mL/min/1.73m2 . Conclusions: Rituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab further associated with long-term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.

Dynamic prediction of kidney allograft and patient survival using post-transplant estimated glomerular filtration rate trajectory.

Allograft loss is the most feared outcome of kidney transplant recipients. We aimed to develop a dynamic Bayesian model using estimated glomerular filtration rate (eGFR) trajectories to predict long-term allograft and patient survivals. We used data from the Australian and New Zealand Dialysis and Transplant registry and included all adult kidney transplant recipients (1980-2017) in Australia (derivation cohort) and New Zealand (NZ, validation cohort). Using a joint model, the temporal changes of eGFR trajectories were used to predict patient and allograft survivals. The cohort composed of 14 915 kidney transplant recipients [12 777 (86%) from Australia and 2138 (14%) from NZ] who were followed for a median of 8.9 years. In the derivation cohort, eGFR trajectory was inversely associated with allograft loss [every 10ml/min/1.73 m2 reduction in eGFR, adjusted hazard ratio [HR, 95% credible intervals (95%CI) 1.31 (1.23-1.39)] and death [1.12 (1.10-1.14)]. Similar estimates were observed in the validation cohort. The respective dynamic area under curve (AUC) (95%CI) estimates for predicting allograft loss at 5-years post-transplantation were 0.83 (0.75-0.91) and 0.81 (0.68-0.93) for the derivation and validation cohorts. This straightforward model, using a single metric of eGFR trajectory, shows good model performance, and effectively distinguish transplant recipients who are at risk of death and allograft loss from those who are not. This simple bedside tool may facilitate early identification of individuals at risk of allograft loss and death.

In-hospital initiation of sodium-glucose co-transporter-2 inhibitors in patients with acute heart failure.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors provide cardiovascular and kidney benefits to patients with heart failure (HF) and/or chronic kidney disease (CKD), regardless of diabetes status and left ventricular ejection fraction (LVEF). Despite robust data demonstrating the efficacy of SGLT-2 inhibitors in both ambulatory and hospital settings, real-world evidence suggests slow and varied adoption of SGLT2 inhibitors among patients hospitalized for HF. Barriers to implementation of SGLT2i may include clinicians' concerns regarding potential adverse events such as diabetic ketoacidosis (DKA), volume depletion, and symptomatic hypoglycemia; or concerns regarding physiologically expected reductions in eGFR. Guidelines lack specific, practical safety data and definitive recommendations regarding in-hospital initiation and continuation of SGLT2i in patients hospitalized with HF. In this review, we discuss the safety of in-hospital SGLT2 inhibitor initiation based on recent trials and highlight the clinical implications of their early use in patients hospitalized for HF.

A comparative study of postadrenalectomy hyperuricemia and renal impairment in patients with unilateral primary aldosteronism: does histopathology subtype matter?

BackgroundPrimary aldosteronism (PA), which is present in 5–18% of hypertensive patients, is a leading cause of secondary hypertension. Adrenalectomy is often recommended for patients with unilateral primary aldosteronism (uPA), yielding good long-term outcomes. PA patients without hyperuricemia and chronic renal failure before adrenalectomy were enrolled in this cohort study. Serum uric acid (SUA) and renal filtration were measured one year post-adrenalectomy. Their relationships with pathologic features, histopathological subtype (classical or nonclassical (HISTALDO consensus)), and vessel stiffness were explored. The aim of this cohort study is to evaluate the correlation between post-adrenalectomy serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) with the pathologic features delineated by the HISTALDO consensus. Additionally, the study seeks to assess the impact of these biochemical markers on peripheral vessel stiffness and brachial-ankle pulse wave velocity (baPWV) at a one-year follow-up visit.MethodsThis prospective cohort study included patients (N = 100) diagnosed with uPA who underwent adrenalectomy from Jan 1, 2007 to Dec 31, 2022.ResultsAt follow-up, elevated SUA, hyperuricemia, and a > 25% eGFR decrease were significantly more common in the classical than the nonclassical group. The incidence of postoperative hyperuricemia, herein referred to as post-adrenalectomy hyperuricemia (PAHU), was 29% (29/100) overall, 34.8% (23/66) in the classical group and 17.6% (6/34) in the nonclassical group. The incidence of eGFR reduction > 25% was 33% (33/100), 43.9% (29/66), and 11.8% (4/34), respectively. baPWV decreased more in the classical group than the nonclassical group.ConclusionFor PA patients with PAHU and/or renal impairment, we suggest monitoring SUA, pH, urine uric acid, and urine crystals and performing a KUB study and peripheral vascular and renal sonography (on which pure uric acid stones in the KUB are radiolucent) to determine whether drug intervention is required for cases of asymptomatic PAHU, especially patients in male gender, classical histopathology, or renal impairment.

Efficacy and Safety of Nefecon in Patients with Immunoglobulin A Nephropathy from Mainland China: 2-Year NefIgArd Trial Results.

Immunoglobulin A nephropathy (IgAN), an immune-mediated kidney disease, is particularly prevalent among individuals of East Asian ancestry. Nefecon is a novel, oral, targeted-release budesonide formulation designed to inhibit galactose-deficient-IgA1 formation underlying IgAN pathophysiology. We present findings in patients with IgAN from mainland China participating in the 2-year, multicenter, randomized, double-blind, phase 3 NefIgArd trial of Nefecon. Patients (aged ≥18 years) with primary IgAN (estimated glomerular filtration rate [eGFR] 35-90 ml/min per 1.73 m2, persistent proteinuria [urine protein-creatinine ratio ≥0.8 g/g or proteinuria ≥1 g/24 h] despite optimized renin-angiotensin system blockade) received Nefecon or placebo over 9 months, followed by a 15-month follow-up phase on supportive care alone. The primary efficacy end point was time-weighted average of eGFR over 2 years. Sixty-two patients from mainland China were included in this prespecified analysis. The primary efficacy end point was 9.6 ml/min per 1.73 m2 (95% confidence interval [CI], 2.0 to 19.8) in favor of Nefecon versus placebo. This was consistent with (and numerically greater than) that of the global study population. Time to confirmed 30% eGFR reduction or kidney failure from baseline was substantially delayed with Nefecon (patients with an event: 9%) versus placebo (30%; hazard ratio, 0.21; 95% CI, 0.04 to 0.73]). No deaths were reported in the China cohort. In the Nefecon group, treatment-emergent serious adverse events were reported by one patient during treatment and two patients during follow-up (versus no patients and seven patients, respectively, in the placebo group). No severe infections requiring hospitalization were reported. Nefecon treatment for 9 months showed greater preservation of eGFR over 2 years compared with placebo. The efficacy outcomes were consistent with global study results, with a numerically greater treatment benefit observed in patients from China. Nefecon was well tolerated, with no unexpected safety signals.

8675 Dosing of Radioactive Iodine for Papillary Thyroid Cancer in Advanced Chronic Kidney Disease

Abstract Disclosure: C. Cheatham: None. D. Beckman: None. INTRO Radioactive Iodine (RAI) ablation is an important treatment for patients diagnosed with papillary thyroid carcinoma. Most studies completed on RAI in renal dysfunction were focused on End Stage Renal Disease (ESRD) patients on dialysis to establish protocols on timing of dialysis to allow desired clinical response to RAI without increased risks and minimizing exposure of dialysis staff to radiation dose. The ideal RAI dosing and monitoring of patients with advanced chronic kidney disease (CKD) stage 4 or 5 not requiring dialysis has not been systematically reviewed. CASE 26 year-old female with CKD stage 4/5 secondary to chronic hydronephrosis from vesicoureteral reflux with baseline eGFR 15-20 mL/min/1.73 m2 was diagnosed with papillary thyroid cancer. She underwent total thyroidectomy with central and left lateral neck dissection, resulting in pathologic stage I, pT2 N1b M0 disease, high risk for recurrence according to the 2015 American Thyroid Association guidelines due to 17 positive lymph nodes from left level II-IV and VI, multiple with extranodal extension, as well as 1 vessel angioinvasion. She was referred for adjuvant RAI ablation after withdrawal from thyroid hormone. Decision was made to proceed with a 50% dose reduction and close monitoring of radioactivity clearance as an inpatient given decrease of eGFR to 10-12 mL/min/1.73 m2. She was cleared for discharge 4 days after RAI dose of 74.8mCi when activity level dropped to &amp;lt;2mR/hr. Post-ablation whole body scan showed activity in the thyroid bed and parasternal notch without evidence of metastatic disease. Post-treatment non-stimulated thyroglobulin 6 weeks later was 0.4 ng/mL down from 269.7 ng/mL. DISCUSSION Given RAI is predominately renally cleared, decreased renal function affects clearance rates and associated exposure to radiation. Risks with decreased RAI clearance include bone marrow toxicity and prolonged isolation requirements. In a 2017 retrospective review, patients with eGFR &amp;lt;30 mL/min/1.73 m2 had delayed clearance leading to a mean proportional reduction of exposure rate at 48 hours of -67.2% compared to -94.3% in healthy controls. While protocols exist for patients on hemodialysis, no such protocols have been established for patients with advanced CKD not requiring dialysis. For this patient, after multidisciplinary discussion with nuclear medicine, health physics, and nephrology in setting of further eGFR reduction during hormone withdrawal, decision was made to reduce the intended dose by 50% with inpatient monitoring and backup to dialyze if no significant decrease in radiation activity level was seen or if she were to progress to anuric or oliguric renal failure. This case highlights the need for established protocols and long-term studies to evaluate risk and treatment response in relation to dosing of RAI in this population, but a 50% dose reduction appears to be effective without adverse event. Presentation: 6/2/2024

Finerenone and Kidney Outcomes in Patients with Heart Failure: The FINEARTS-HF Trial.

Finerenone has kidney protective effects in patients with chronic kidney disease (CKD) with type 2 diabetes, but effects on kidney outcomes in patients with heart failure (HF) with and without diabetes and/or CKD are not known. Examine the effects of finerenone on kidney outcomes in FINEARTS-HF, a randomized trial of finerenone vs. placebo among patients with HF with mildly reduced or preserved ejection fraction. We explored the effects of finerenone on the secondary outcome of a sustained ≥50% eGFR decline or kidney failure (sustained eGFR decline <15 mL/min/1.73 m2; initiation of maintenance dialysis; renal transplant). In this prespecified analysis, we also report effects of finerenone on: 1) sustained ≥57% eGFR decline or kidney failure; 2) eGFR slope; 3) changes in urine albumin/creatinine ratio (UACR). Among 6,001 participants, mean baseline eGFR was 62 ±20mL/min/1.73m2; 48% had eGFR <60mL/min/1.73m2. Overall, 5,797 had baseline UACR data (median 18 [7,67]mg/g). Over 2.6 years median follow-up, the incidence of the composite kidney outcome (≥50% eGFR decline or kidney failure) was numerically, but non-significantly, higher for finerenone vs. placebo (75 vs. 55 events; HR 1.33; 95%CI 0.94, 1.89). Similar results were observed for the composite of ≥57% eGFR decline or kidney failure (41 vs. 31 events; HR 1.28; 95%CI 0.80, 2.05), though the overall event frequency was relatively low. During the first 3 months, finerenone led to an acute decline in eGFR of -2.9 mL/min/1.73m2 (95%CI -3.4, -2.4) but did not alter chronic (from 3 months) eGFR slope (+0.2 mL/min/1.73m2/year; 95%CI -0.1, +0.4), vs. placebo. The difference in total slope was -0.7 (95%CI -0.9 to -0.4) mL/min/1.73 m2/year. Finerenone reduced UACR by 30% (95%CI 25%, 34%) over 6 months vs. placebo, an effect that persisted throughout follow-up. Finerenone reduced the risk of new-onset of micro- and macroalbuminuria by 24% (HR 0.76; 95%CI 0.68, 0.83) and 38% (HR 0.62; 95%CI 0.53, 0.73), respectively. In FINEARTS-HF, a population at low risk of adverse kidney outcomes, finerenone did not significantly modify the kidney composite outcomes. Finerenone led to a greater reduction in initial eGFR, but did not result in a significant difference in chronic eGFR slope, vs. placebo. Finerenone led to early and sustained reductions in albuminuria and reduced the risk of new-onset micro- and macroalbuminuria.

Incident Hypertension in Young Adults with a Modest eGFR Reduction

Incident Hypertension in Young Adults with a Modest eGFR Reduction

How histopathological diagnosis interacts with kidney ultrasound parameters and glomerular filtration rate.

The evaluation of estimated GFR (eGFR) is a pivotal staging step in patients with chronic kidney disease (CKD), and renal ultrasound plays an important role in diagnosis, prognosis and progression of CKD. The interaction between histopathological diagnosis and ultrasound parameters in eGFR determination has not been fully investigated yet. The study examined the results of native kidney biopsies performed in 48 Italian centers between 2012 and 2020. The primary goal was if and how the histopathological diagnosis influences the relationship between ultrasound parameters and eGFR. After exclusion of children, patients with acute kidney injury and patients without measure of kidney length or parenchymal thickness, 2795 patients have been selected for analysis. The median values were 52years for patient age, 11cm for bipolar kidney diameter, 16mm for parenchymal thickness, 2.5g/day for proteinuria and 70ml/min/1.73 m2 for eGFR. The bipolar kidney diameter and the parenchymal thickness were directly related with eGFR values (R square 0.064). Diabetes and proteinuria were associated with a consistent reduction of eGFR, improving the adjusted R square up to 0.100. Addition of histopathological diagnosis in the model increased the adjusted R square to 0.216. There is a significant interaction between histopathological diagnosis and longitudinal kidney diameter (P 0.006). Renal bipolar length and parenchymal thickness are directly related with eGFR. The magnitude of proteinuria and histopathological kidney diagnosis are associated with eGFR. The relationship between kidney length and the level of eGFR depends on the nature of the kidney disease.

Prognosis of IgA nephropathy patient with proteinuria remission by supportive therapy: cohort from screening failed Chinese patients in TESTING study

Background During the run-in phase of the TESTING study, approximately half of patients with IgA nephropathy (IgAN) were excluded due to proteinuria below 1 g/24 h after intensive supportive therapy. The long-term prognosis of these patients needs further investigation. Methods 112 screening failed patients in the TESTING study from 10 centers in China were enrolled in this retrospective study. The prognosis of 88 patients, who were excluded because of proteinuria below 1 g/24 h, was analyzed by Landmark Kaplan-Meier analysis. The composite kidney endpoint was defined by a ≥ 50% reduction in eGFR, ESKD (eGFR <15 mL/min per 1.73 m2), chronic dialysis for at least 6 months, or renal transplantation. Results In total, 88 patients were excluded due to proteinuria less than 1 g/24 h. During the follow-up, 73/88 (83.0%) patients received renin-angiotensin system blocker. 72/88 (81.8%) had stable proteinuria remission and did not receive immunosuppressive therapy (IST), and 16/88 (18.2%) received IST because of a relapse of proteinuria. Landmark Kaplan–Meier analysis revealed that, the kidney survival from dialysis or composite kidney outcome of these excluded patients with IST was similar to those without IST during the early stages of follow-up (dialysis, before 60 months, p = 0.778; composite kidney outcome, before 48 months, p = 0.862); whereas the risk for dialysis of patients receiving IST was significantly higher than those without IST after 60 months (OR = 11.3, p = 0.03). Similarly, the risk for the composite kidney outcome of patients receiving IST was also significantly higher than those without IST after 48 months (OR = 5.92, p = 0.029). Conclusions IgAN patients who maintained a persistent remission of proteinuria after intensive supportive therapy had a much better long-term kidney outcome than those who experienced a relapse of proteinuria and needed IST.

Abstract 07: Ambulatory Blood Pressure Variability, Progression of Kidney Disease, and Cardiovascular Outcomes in the Chronic Renal Insufficiency Cohort

Background: Visit-to-visit blood pressure variability is strongly associated with adverse kidney and cardiovascular outcomes in a wide range of patient populations. Patients with chronic kidney disease (CKD) have abnormal circadian blood pressure patterns which may affect 24-hour ambulatory blood pressure variability (ABPV). Methods: We used ambulatory blood pressure monitoring (ABPM) data from participants in the Chronic Renal Insufficiency Cohort (CRIC). Blood pressures were obtained every 30 minutes during day and night. We assessed 24-hour, daytime and nighttime systolic ABPV using average real time variability (ARV); the sum of the absolute differences between consecutive BP readings divided by the total number of readings minus one. Cox proportional hazards models were used to evaluate the association of ARV with the development of 50% reduction in eGFR or end stage kidney disease or adverse cardiovascular (CV) events (myocardial infarction, stroke, peripheral artery disease, new atrial fibrillation, and heart failure). Results: There were 1502 CRIC participants included in the analysis of whom 44% were female and mean age was 63 years (standard deviation 10). Anthropometric and clinical factors associated with higher tertile of ARV included older age, higher BMI, higher urine protein to creatinine ratio, lower estimated glomerular filtration rate, diabetes, hypertension, dyslipidemia and atherosclerotic heart disease. In unadjusted Cox proportional hazard models, 24-hour systolic ARV was associated with both adverse kidney (Hazard Ratio [HR] 1.16 95% confidence interval [CI] 1.06-1.27) and CV events (HR 1.35 95%CI 1.22-1.50). However, in adjusted models that included clinical and sociodemographic factors, there were no statistically significant associations of 24-hour systolic ARV with either adverse kidney (HR 1.02, 95%CI 0.91-1.14) or CV events (HR 0.93, 95%CI 0.84 -1.04). Similarly, daytime and nighttime ARV were not statistically significantly associated with kidney and CV events in adjusted analyses. Conclusions: In a large cohort of patients with CKD, ABPV was not associated with adverse kidney and CV outcomes in adjusted models. Thus, in the context of the many cardiometabolic risk factors present in patients with CKD, ABPV is not an independent mechanism of adverse clinical outcomes in this high-risk population.

Renoprotective Effects of Daprodustat in Patients with Chronic Kidney Disease and Renal Anemia.

Many large-scale studies revealed that exogenous erythropoietin, erythropoiesis-stimulating agents, have no renoprotective effects. We reported the renoprotective effects of endogenous erythropoietin production on renal function in ischemic reperfusion injury (IRI) of the kidney using the prolyl hydroxylase domain (PHD) inhibitor, Roxadustat. The purpose of this study was to investigate the effects of daprodustat on the progression of chronic renal failure. We retrospectively investigated the effects of daprodustat on the progression of chronic renal failure and renal anemia in patients with stages 3a-5 chronic kidney diseases (estimated glomerular filtration rate, eGFR < 60 mL/min/1.73 m2). The results show that daprodustat largely slowed the reduction in eGFR. The recovery of renal function was observed in some patients. Daprodustat is useful not only for renal anemia but also for the preservation of renal function. The renoprotective effect of daprodustat was small in patients with serum creatinine larger than 3-4 mg/dL because of low residual renal function. The appearance of renal anemia would be a sign of the time to start using daprodustat.

705: A hierarchical Bayesian model to predict eGFR reduction following Kidney SBRT

705: A hierarchical Bayesian model to predict eGFR reduction following Kidney SBRT