American Journal of Nephrology最新文献

Introduction: Black and African American (AA) people are over-represented in the kidney failure population; therefore, the safety and efficacy of difelikefalin in Black/AA patients was evaluated.

Methods: This was a post hoc, pooled exploratory subgroup analysis of the Phase 3 KALM-1 and -2 studies. Patients undergoing hemodialysis (HD) who had moderate-to-severe chronic kidney disease-associated pruritus (CKD-aP) at enrollment were stratified into self-reported Black/AA or White subgroups. Patients were randomized (1:1) to receive intravenous (IV) difelikefalin 0.5 µg/kg or placebo for 12 weeks. Difelikefalin efficacy was assessed with validated patient-reported outcome questionnaires: 24-h Worst Itch Numerical Rating Scale (WI-NRS), 5-D itch, and Skindex‑10.

Results: There were 249 (29.3%) patients from the KALM studies that self-identified as Black/AA (n = 135 difelikefalin; n = 114 placebo). Clinically meaningful (≥3-point) reduction in WI-NRS score was achieved by 47.9% of Black/AA patients with difelikefalin versus 24.6% with placebo (p < 0.001). More Black/AA patients achieved a ≥5-point 5-D itch total improvement (54.9% vs. 35.7%; p = 0.013) and a ≥15-point Skindex-10 score improvement with difelikefalin versus placebo (49.0% vs. 28.9%; p = 0.006) compared with White patients. Incidence of treatment-emergent adverse events (TEAEs) was higher for Black/AA patients (difelikefalin: 78.5%; placebo: 70.8%) versus White patients (difelikefalin: 64.8%; placebo: 61.8%).

Conclusion: In this post hoc analysis, difelikefalin was efficacious in the Black/AA population and had an acceptable safety profile.

Introduction: In 2016, the Oxford Classification of IgA nephropathy (IgAN) updated its scoring system for the glomerular crescents. Despite this, the clinical significance of crescentic lesions in the updated Oxford classification is still unexplored through prospective cohort studies.

Methods: 134 patients diagnosed with IgAN accompanied with C2 lesions at Peking University First Hospital were consecutively enrolled and prospectively followed up for analysis. Multivariate Cox regression in combination with LASSO regression was used to analyze risk factors associated with end-stage kidney disease (ESKD).

Results: During biopsy, the mean estimated glomerular filtration rate (eGFR) was 39.3 mL/min/1.73 m2, and the mean proteinuria was 4.4 g/day. The proportion of kidney failure at 1 year, 2 years, and 3 years were 24%, 34%, and 47%, respectively. The results of LASSO in combination with Cox regression showed that mean arterial pressure (hazard ratio [HR] = 1.035, 95% confidence interval [95% CI] 1.013-1.056, p = 0.001), eGFR at biopsy (HR = 0.968, 95% CI [0.948-0.990], p < 0.004) and T2 lesions (HR = 2.490, 95% CI [1.179-5.259], p = 0.017) were independent risk factor associated with ESKD in patients with C2 lesions. Furthermore, based on univariate analyses, we found that patients with kidney function declined more than 50% within 3 months prior to biopsy or pathological findings indicated a proportion of crescents exceeding 50% were both associated with a poor kidney prognosis. Lastly, when the proportion of the crescent was less than 50%, patients receiving combined steroid and immunosuppressant treatment did not exhibit a better renal prognosis than those receiving steroid only.

Conclusion: Patients diagnosed with IgAN and concurrent C2 lesions exhibited a poor clinical prognosis, necessitating more effective treatment strategies.

Introduction: Rituximab has been proven effective and safe in pediatric patients with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). We aimed to analyze the efficacy and safety of rituximab in adult FR/SDNS patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS).

Methods: A retrospective cohort study at three nephrology centers in China included adult FR/SDNS patients with biopsy-proven MCD or FSGS. Primary outcomes were relapse frequency and first relapse-free survival time. Adverse events were well recorded, and logistic regression analyses were used to investigate the risk factors of relapse.

Results: Eighty-one patients (age, 25.0 years; interquartile range, 20.0-40.5; 67% males; 82.7% MCD) received an average rituximab dose of 1,393.8 ± 618.7 mg/2 years during the 2-year follow-up period. The relapse frequency, calculated as the ratio of relapse times to follow-up years, significantly decreased after rituximab treatment (0.04 [0.00, 0.08] vs. 1.71 [1.00, 2.45], p < 0.001). The first relapse-free survival time was 16.7 ± 8.0 months. Fifty-seven patients (70.4%) achieved cessation of corticosteroids and immunosuppressants within 3 months after the first rituximab infusion. Adverse events were mostly mild, and no severe treatment-related adverse events were observed. Low serum albumin level before rituximab and high CD56+CD16+ natural killer cell count after rituximab were independent risk factors of relapse within 2 years after rituximab treatment.

Conclusion: Rituximab was proven an effective and safe treatment option for adult FR/SDNS patients with MCD or FSGS in maintaining disease remission and minimizing corticosteroid exposure.

Introduction: The aim of the study was to investigate associations between diabetic retinopathy (DR) and chronic kidney disease (CKD) in patients with type 2 diabetes (TD2).

Methods: The participants of the cross-sectional, community-based Tongren Health Care Study underwent a detailed medical and ophthalmological examination. We defined TD2 by a fasting plasma glucose concentration of ≥7.0 mmol/L or a medical history. CKD was classified as either reduced estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 mm2 or presence of albuminuria. DR was assessed using color fundus photographs.

Results: Out of 62,217 participants of the Tongren Health Care Study, 5,103 (8.2%) patients had TD2. The prevalence of DR was 12.8% (95% CI, 11.8%, 13.7%), CKD was 13.3% (95% CI, 12.4%, 14.3%), and the subtypes of CKD including reduced eGFR and albuminuria was 4.6% (95% CI, 4.2%, 5.1%) and 10.1% (95% CI, 9.3%, 10.9%), respectively. DR was detectable in 21.0% of the patients with CKD, while CKD was present in 20.9% of the DR patients. Higher DR prevalence was associated with higher prevalence of albuminuria and reduced eGFR (both p < 0.05). Factors independently associated with the presence of CKD instead of DR were older age (p < 0.001, OR = 1.05), a higher body mass index (p < 0.001, OR = 1.14), a higher serum concentration of triglycerides (p < 0.001, OR = 1.26), and a lower blood glucose (p < 0.001, OR = 0.93). Having hypertension was additionally associated with the presence of reduced eGFR as compared with DR (p = 0.005, OR = 4.47).

Conclusions: TD2 patients of older age and with higher body mass index, hypertension, and dyslipidemia had a higher probability of being affected by CKD rather than DR, while those with a higher blood glucose level were more prone to DR than CKD.

Introduction: There is a great clinical need for novel markers to predict kidney function decline in patients with type 2 diabetes. We explored the potential of posttranslationally modified fetuin-A fragments in urine (uPTM-FetA) as such a marker.

Methods: We included patients with type 2 diabetes from two independent, nonoverlapping prospective cohort studies. A cut-off for uPTM-FetA, measured via ELISA method, was determined using the Youden index in the primary cohort of patients with type 2 diabetes from Taiwan. Kidney endpoint was defined as an estimated glomerular filtration rate (eGFR) decline ≥30% from baseline, reaching of an eGFR <15 mL/min/1.73 m2, or a need of renal replacement therapy. Prospective associations were assessed in Cox regression models. All analyses were replicated in a cohort of patients with type 2 diabetes from the Netherlands.

Results: In total, 294 patients with type 2 diabetes (age 61 ± 10 years, 55% male, eGFR 88 ± 16 mL/min/1.73 m2) were included in the primary cohort. During a follow-up of median 4.6 years, 42 participants (14%) experienced the kidney endpoint. Using the defined cut-off, a high uPTM-FetA was associated with a higher risk of renal function decline (Plog-rank < 0.0001). This association was similar in subgroups depending on albuminuria. This association remained, independent of age, sex, baseline eGFR, albuminuria, HbA1c, and other potential confounders (HR: 9.94; 95% CI: 2.96-33.40; p < 0.001 in the final model). Analyses in the validation cohort (376 patients with type 2 diabetes, age 64 ± 11 years, 66% male, eGFR 76 ± 24 mL/min/1.73 m2) using the same cut-off yielded similar results.

Conclusion: uPTM-FetA was independently associated with kidney function decline in patients with type 2 diabetes validated in a 2-cohort study. The significant additive predictive power of this biomarker from conventional risk factors suggests its clinical use for renal function progression in patients with type 2 diabetes.

Introduction: Aldosterone synthase (AS) inhibition may overcome increased aldosterone production in response to renin-angiotensin system inhibition. BI 690517 is an AS inhibitor under investigation for chronic kidney disease (CKD).

Methods: This multinational, phase II, double-blind study (NCT05182840) investigated the efficacy and safety of daily oral BI 690517, with or without empagliflozin 10 mg, in participants with CKD. The primary endpoint was change from baseline in urine albumin:creatinine ratio (UACR) at week 14. Between February 18, 2022, and December 30, 2022, 714 adults already treated by angiotensin-converting enzyme inhibitor (30.5%) or angiotensin receptor blocker (69.8%) were randomized (1:1) to an 8-week run-in to assign background empagliflozin (n = 356) or placebo (n = 358). Participants in each group were then randomized (1:1:1:1) to a 14-week treatment period with BI 690517 (3 mg, 10 mg, or 20 mg) or placebo. Of the 714 participants who entered run-in, 586 were randomized to the treatment period. They were predominantly men (66.6%) of white race (58.4%) with a mean (standard deviation [SD]) age of 63.8 (11.3) years. Type 2 diabetes was present in 414 participants (70.6%). The baseline mean (SD) estimated glomerular filtration rate was 51.9 (17.7) mL/min/1.73 m2, and median (interquartile range) UACR was 426.3 mg/g (205.3-888.5).

Conclusion: This study will inform dose selection for further clinical development and determine whether BI 690517, with or without background empagliflozin, has a favorable safety profile and potential for additive kidney protection in participants with CKD already treated with a renin-angiotensin system inhibitor.

Renal anemia is treated with erythropoiesis-stimulating agents (ESAs), even though epoetin alfa and darbepoetin increase the risk of cardiovascular death and thromboembolic events, including stroke. Hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) inhibitors have been developed as an alternative to ESAs, producing comparable increases in hemoglobin. However, in advanced chronic kidney disease, HIF-PHD inhibitors can increase the risk of cardiovascular death, heart failure, and thrombotic events to a greater extent than that with ESAs, indicating that there is a compelling need for safer alternatives. Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of major cardiovascular events, and they increase hemoglobin, an effect that is related to an increase in erythropoietin and an expansion in red blood cell mass. SGLT2 inhibitors increase hemoglobin by ≈0.6-0.7 g/dL, resulting in the alleviation of anemia in many patients. The magnitude of this effect is comparable to that seen with low-to-medium doses of HIF-PHD inhibitors, and it is apparent even in advanced chronic kidney disease. Interestingly, HIF-PHD inhibitors act by interfering with the prolyl hydroxylases that degrade both HIF-1α and HIF-2α, thus enhancing both isoforms. However, HIF-2α is the physiological stimulus to the production of erythropoietin, and upregulation of HIF-1α may be an unnecessary ancillary property of HIF-PHD inhibitors, which may have adverse cardiac and vascular consequences. In contrast, SGLT2 inhibitors act to selectively increase HIF-2α, while downregulating HIF-1α, a distinctive profile that may contribute to their cardiorenal benefits. Intriguingly, for both HIF-PHD and SGLT2 inhibitors, the liver is likely to be an important site of increased erythropoietin production, recapitulating the fetal phenotype. These observations suggest that the use of SGLT2 inhibitors should be seriously evaluated as a therapeutic approach to treat renal anemia, yielding less cardiovascular risk than other therapeutic options.

Introduction: Acute kidney injury (AKI) requiring treatment with renal replacement therapy (RRT) is a common complication after admission to an intensive care unit (ICU) and is associated with significant morbidity and mortality. However, the prevalence of RRT use and the associated outcomes in critically patients across the globe are not well described. Therefore, we describe the epidemiology and outcomes of patients receiving RRT for AKI in ICUs across several large health system jurisdictions.

Methods: Retrospective cohort analysis using nationally representative and comparable databases from seven health jurisdictions in Australia, Brazil, Canada, Denmark, New Zealand, Scotland, and the USA between 2006 and 2023, depending on data availability of each dataset. Patients with a history of end-stage kidney disease receiving chronic RRT and patients with a history of renal transplant were excluded.

Results: A total of 4,104,480 patients in the ICU cohort and 3,520,516 patients in the mechanical ventilation cohort were included. Overall, 156,403 (3.8%) patients in the ICU cohort and 240,824 (6.8%) patients in the mechanical ventilation cohort were treated with RRT for AKI. In the ICU cohort, the proportion of patients treated with RRT was lowest in Australia and Brazil (3.3%) and highest in Scotland (9.2%). The in-hospital mortality for critically ill patients treated with RRT was almost fourfold higher (57.1%) than those not receiving RRT (16.8%). The mortality of patients treated with RRT varied across the health jurisdictions from 37 to 65%.

Conclusion: The outcomes of patients who receive RRT in ICUs throughout the world vary widely. Our research suggests that differences in access to and provision of this therapy are contributing factors.

Background: Both atrial fibrillation and venous thromboembolism (VTE) are highly prevalent among patients with chronic kidney disease (CKD). Until recently, warfarin was the most commonly prescribed oral anticoagulant. Direct oral anticoagulants (DOACs) have important advantages and have been shown to be noninferior to warfarin with respect to stroke prevention or recurrent VTE in the general population, with lower bleeding rates. This review article will provide available evidence on the use of DOACs in patients with CKD.

Summary: In post hoc analyses of major randomized studies with DOACs for stroke prevention in atrial fibrillation, in the subgroup of participants with moderate CKD, defined as a creatinine clearance (CrCl) of 30-50 mL/min, dabigatran 150 mg and apixaban were associated with lower rates of stroke and systemic embolism, whereas apixaban and edoxaban were associated with lower bleeding and mortality rates, compared with warfarin. In retrospective observational studies in patients with advanced CKD (defined as a CrCl <30 mL/min) and atrial fibrillation, DOACs had similar efficacy with warfarin with numerically lower bleeding rates. All agents warrant dose adjustment in moderate-to-severe CKD. In patients on maintenance dialysis, the VALKYRIE trial, which was designed initially to study the effect of vitamin K on vascular calcification progression, established superiority for rivaroxaban compared with a vitamin K antagonist (VKA) in the extension phase. Two other clinical trials using apixaban (AXADIA and RENAL-AF) in this population were inconclusive due to recruitment challenges and low event rates. In post hoc analyses of randomized studies with DOACs in patients with VTE, in the subgroup of participants with moderate CKD at baseline, edoxaban was associated with lower rates of recurrent VTE, whereas rivaroxaban and dabigatran were associated with lower and higher bleeding rates, respectively, as compared to warfarin.

Key messages: DOACs have revolutionized the management of atrial fibrillation and VTE, and they should be preferred over warfarin in patients with moderate-to-severe CKD with appropriate dose adjustment. Therapeutic drug monitoring with a valid technique may be considered to guide clinical management in individualized cases. Current evidence questions the need for oral anticoagulation in patients on maintenance dialysis with atrial fibrillation as both DOACs and VKAs are associated with high rates of major bleeding.