American Journal of Nephrology最新文献

Background: The GFR-Ex study assessed the feasibility of a 12-month exercise training program to attenuate the rate of decline in isotope-measured (mGFR) and estimated (eGFR) Glomerular Filtration Rate.

Methods: In a multicentre feasibility study, people with stage 3-4 chronic kidney disease (CKD) with declining function were randomized to 12 months exercise training (home-based aerobic and resistance program) or control (usual care). Feasibility was assessed by recruitment and retention rates, intervention adherence, and harms. Differences in mGFR between groups at 12 months and between mGFR and eGFR were calculated. Qualitative interviews were used to explore participant experiences.

Results: 2,260 patients were screened; 74 participants were randomized (mean age (SD): 56(14) years; eGFR: 34(13)ml/min/1.73m2; 62% male; 61% white); and 34 completed the study (11 exercise; 23 control). The screening eligibility rate was 11%; consent rate was 48%; 12-month retention rate was 43%; and the median [IQR] exercise sessions completed was 69 [63, 72]%. No exercise-related harms were recorded. The mean mGFR at 12 months was 36.1 (exercise) vs. 33.8 (control); eGFR minus mGFR was -1.6 (95% Cl:-2.6, -0.6) ml/min/1.73m2. Qualitative interviews identified the importance of peer and professional support for patient engagement and a high level of patient commitment being required for the research procedures.

Conclusion: In people with progressive CKD, a 12-month exercise training program was safe and feasible. Exercise tended to attenuate GFR decline, and eGFR agreed well with mGFR. Progression to a definitive trial is warranted, provided modifications are made, including providing patient support and selection of eGFR as the primary outcome.

Introduction: Initiation of dialysis encompasses new cardiovascular challenges on patients with end-stage kidney disease (ESKD). The prognostic value of assessment of left ventricular (LV) myocardial function in peritoneal dialysis (PD) patients is still unclear. This study used global LV myocardial work (MW) indices to investigate the change of LV myocardial function undergoing PD within 1 year.

Methods: A total of 179 patients with ESKD were enrolled in this prospective study. Among them, 48 patients were diagnosed with diabetic kidney disease (DKD) and 131 patients were non-diabetic kidney disease (NDKD). We evaluated LV myocardial function of patients with ESKD by two-dimensional speckle-tracking echocardiography (2D-STE) with strains and MW indices. Echocardiography and clinical data were evaluated at baseline and 1 year after PD.

Results: Compared with NDKD group, patients with DKD had lower global longitudinal strain (GLS) (14.43±3.52 vs. 16.78±4.78 p=0.002), global work index (GWI) (1546.29±496.06 vs. 1750.51±416.97 p=0.006), and global constructive work (GCW) (1955.33±483.86 vs. 2129.65±459.04 p=0.028). After PD therapy, the NDKD group showed significant reduction of GWI (1616.78±360.18 vs. 1750.51±416.97 p＜0.001), GCW (1980.45±385.82 vs. 2129.65±459.04 p=0.006), and global wasted work (GWW) (158.00(102.00, 219.00) vs. 185.00(141.00, 250.00) p＜0.001) and increase of global work efficiency (GWE) (92.00(89.00, 94.00) vs. 91.00 (88.00, 93.00) p=0.008). Compared with NDKD group, the DKD group had less decrease of GWW (-14.00(-69.75, 85.00) vs. -36.00(-97.00, 21.00) p=0.020) and less increase of GWE (-1.00 (-4.00, 2.00) vs. 1.00(-2.00, 4.00) p=0.006) after PD therapy. After multivariable adjustment, Δresidual GFR (β=-0.165; p=0.034) and ΔDBP (β=-0.168; p=0.028) was the significant independent determinants of ΔGWE. ΔDBP was the only significant independent determinants of ΔGWW (β=0.343; p<0.001).

Conclusion: After one year of PD treatment, patients with NDKD showed improved LV myocardial function. However, the benefit for DKD patients was relatively limited, reflected in a smaller increase in GWE and a smaller reduction in GWW.

Introduction: The efficacy and safety of finerenone in patients with idiopathic membranous nephropathy (IMN) remains unclear, especially given the need for additional supportive therapeutic options.

Methods: This prospective-retrospective, multicentre, observational real-world study evaluated the efficacy and safety of finerenone in IMN patients with proteinuria ≥1 g/24h. The primary outcome was the percentage change in proteinuria from baseline to six months with finerenone treatment. Secondary outcomes included the stratified reduction in proteinuria, and changes in estimated glomerular filtration rate (eGFR), serum albumin (ALB), and total cholesterol (TCHO). Safety assessment focused on serum potassium. Data were primarily analysed using linear mixed-effects models.

Results: Among 112 IMN patients treated with finerenone, 79 were ultimately analyzed. All of them received tolerated doses of ACEIs or ARBs, and 53.2% (42/79) were treated with immunosuppressive therapy. The median baseline proteinuria was 3212.5 mg/24h (IQR 1977.0 - 7113.6). After six months of finerenone treatment, the geometric mean reduction in proteinuria was -58.5% (95% CI: - 67.7 to - 46.6; P < 0.001). The reduction was significantly greater in patients receiving immunosuppressive therapy than supportive treatment (- 67.1% vs. - 45.3%, P = 0.023). eGFR showed an initial decline but subsequently stabilized (-1.3 mL/min/1.73m², P = 0.226). Significant improvements were observed in ALB (4.6 g/L, P < 0.001) and TCHO (-0.8 mmol/L, P = 0.003). Although hyperkalaemia (>5 mmol/L) occurring in 5.1% of participants (4/79), no cases exceeded 5.5 mmol/L.

Conclusion: In combination with ACEIs or ARBs, finerenone appeared to reduce proteinuria in IMN patients with or without immunosuppressive therapy. Serum potassium did not exceed 5.5 mmol/L in any cases.

Introduction: The impact of the new potassium binder sodium zirconium cyclosilicate (SZC) on the real-world management of acute hyperkalemia remains unknown. The aim of this study was to evaluate changes in treatment strategies and clinical outcomes for acute hyperkalemia following the approval of SZC in Japan.

Methods: We conducted a retrospective cohort study using the RWD database, a nationwide electronic medical record and claims database in Japan, including adult patients who were hospitalized with hyperkalemia (serum potassium ≥5.5 mmol/L) between April 2015 and December 2024. Using an interrupted time series analysis, we evaluated changes in outcomes following SZC approval in April 2020. The post-approval period was stratified to distinguish the effects of the coronavirus disease 2019 (COVID-19) pandemic. The primary outcome was the monthly proportion of patients receiving renal replacement therapy (RRT). Secondary outcomes included in-hospital mortality, intensive care unit (ICU) admission, and maintenance hemodialysis initiation.

Results: Overall, 38,540 hospitalizations were included. While no significant immediate change in RRT use occurred upon SZC approval, a significant decreasing trend was subsequently observed (slope change, -0.7% per month; 95% confidence interval (CI), -1.2 to -0.1%). This downward trend in RRT use was highly pronounced after the COVID-19 pandemic ended. A significant decreasing trend in ICU admissions was observed in the post-pandemic period (slope change, -4.2% per month; 95% CI, -6.6 to -1.7%). Trends of in-hospital mortality and maintenance hemodialysis initiation did not significantly change.

Conclusions: Following SZC approval, a decreasing trend in the use of RRT for acute hyperkalemia was observed, along with a post-pandemic decrease in ICU admissions. These trends were not accompanied by an observable increase in in-hospital mortality or initiation of maintenance hemodialysis.

Introduction Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to slow progressive loss of kidney function in both diabetic and non-diabetic proteinuric kidney diseases. Despite the benefits of SGLT2i in patients with chronic kidney disease (CKD), the potential benefits of SGLT2i in autosomal dominant polycystic kidney disease (ADPKD) have not been assessed. Methods This is a randomized, placebo-controlled trial with empagliflozin (Jardiance®) with 1-year duration and 2 participating centers including the University of Colorado Anschutz Medical Campus and the University of Maryland Medical Center. Fifty non-diabetic ADPKD patients aged 18-55 years, and estimated glomerular filtration rate of 30-90 ml/min/1.73m2 are randomized in 1:1 ratio to receive 10 mg/day empagliflozin or matching placebo. After 1 month the dose is increased to 25 mg/day empagliflozin/placebo in all patients tolerating the lower dose. Results (Outcomes) The primary outcomes are safety and tolerability of empagliflozin, the latter determined by the percentage of patients tolerating the 25 mg dose of study drug/placebo at the end of the 12-month period. Safety is assessed by the frequency of all adverse events (AE) and of specific AEs including acute kidney injury compared to placebo. Secondary outcomes include changes in total kidney volume, kidney function, aortic stiffness, copeptin level, urinary KIM-1, and PKD-specific Health Related Quality of Life questionnaire. Conclusions The outcomes of this pilot trial will provide important data regarding the safety and tolerability of empagliflozin in patients with ADPKD. Preliminary insight into the potential kidney and vascular benefits of SGLT2i will aid the design of future large scale efficacy studies.

Introduction: Phospholipase A2 receptor (PLA2R) is the major autoantigen in membranous nephropathy (MN); however, the trajectories of anti-PLA2R antibodies and their prognostic implications remain unclear.

Methods: In this retrospective cohort study, we analyzed 1,528 patients with PLA2R-associated MN (2011-2022), each with at least three serial measurements of anti-PLA2R antibody levels. Group-based trajectory modeling was applied to identify distinct longitudinal patterns of antibody change. Associations between antibody trajectories and clinical outcomes were assessed using multivariable Cox proportional hazards and logistic regression models, complemented by Kaplan-Meier analysis.

Results: Four distinct serum anti-PLA2R antibody trajectories were identified: rising (5.3%), low-stable (74.8%), declining (14.9%), and high-stable (5.0%). The low-stable group had the lowest rates of renal function decline (15.3%), clinical non-remission (18.8%), and relapse (31.6%). Compared to this group, the risks of renal function decline were significantly higher in the rising (adjusted hazard ratio [aHR] = 3.69; 95% confidence interval [CI]: 2.57-5.30), declining (aHR = 1.66; 95% CI: 1.24-2.21), and high-stable (aHR = 4.18; 95% CI: 2.91-6.00) groups. Similarly, the rates of clinical remission were significantly lower (aHR = 0.38 for rising; aHR = 0.61 for declining; aHR = 0.28 for high-stable), while the odds of relapse were higher (adjusted odds ratio 3.13, 2.35, and 3.17, respectively) in these three groups. These associations remained consistent across sex and age subgroups.

Conclusion: Serum anti-PLA2R antibody trajectories represent a robust prognosis biomarker in MN, useful for risk stratification and clinical decision-making. Patients with high-stable or rising antibody trajectories require heightened clinical attention due to significantly increased risks of renal function decline, clinical non-remission, and relapse.

Background and hypothesis: Acute kidney injury (AKI) is common complication in the critically ill. Standard functional biomarkers are limited at predicting persistent severe AKI (PS-AKI) and long-term outcomes. This study evaluated the diagnostic and prognostic performance of a panel of urinary biomarkers (novel and standard) for predicting PS-AKI and major adverse kidney events (MAKE).

Methods: This was an exploratory post-hoc analysis of the prospective Dublin Acute Biomarker Group Evaluation (DAMAGE) multicentred prospective observational cohort study. ICU AKI (KDIGO Stage 1-3) patients were included. Sixteen urinary biomarkers were measured on the day of AKI diagnosis. The primary endpoint was PS-AKI (Stage 2/3 AKI ≥48 hours). Discrimination was assessed using AUC and logistic regression models, and reclassification metrics (IDI, cfNRI). Secondary endpoints included MAKE90 and MAKE365. Tertile trends for CCL14 also evaluated.

Results: Among 186 patients with AKI, 80 (43.0%) developed PS-AKI. Albumin (uAlb; AUC 0.82; 95% CI: 0.76-0.88), albumin/creatinine ratio (uAlb/Cr; AUC 0.79; 95% CI: 0.72-0.85), urine output (AUC 0.81; 95% CI: 0.74-0.87), and serum creatinine (AUC 0.77; 95% CI: 0.70-0.84) demonstrated the highest discrimination. In logistic regression analysis adjusted for a clinical model, IL-18 showed the strongest association with PS-AKI (aOR 3.09; 95% CI: 1.92-5.30), while uAlb, uAlb/Cr, cystatin C, CCL14, and MCP-1 were also significantly associated. CCL14 and uAlb tertiles showed a significant stepwise increase in PS-AKI. uAlb was the strongest discriminator for MAKE90 (AUC 0.70; 95% CI: 0.57-0.83). PiGST was negatively associated with MAKE365 (aOR 0.44; 95% CI 0.21-0.81).

Conclusion: Urine output, uAlb, and uAlb/Cr outperformed several novel biomarkers and demonstrated strong discrimination for PS-AKI. CCL14 showed moderate discrimination and was associated with early adverse outcomes. These findings support integrating standard and novel biomarkers to personalise AKI management.

Introduction: While the triglyceride-glucose (TyG) index, a validated surrogate for insulin resistance, has demonstrated prognostic value in IgA nephropathy (IgAN) progression, its specific relationship with tubular atrophy/interstitial fibrosis (TA/IF) remains undetermined. Given the established association between insulin resistance and hypertension in IgAN, we aimed to investigate the association of the TyG index and systolic blood pressure (SBP) with TA/IF and to develop a predictive model for early TA/IF detection.

Methods: This cross-sectional study included 691 patients with primary IgAN. Exposures examined included the TyG index and SBP at the time of kidney biopsy, the former being the logarithmized product of fasting triglyceride and glucose concentrations. We tested association between TyG index and TA/IF, defined as Oxford T1-2 scores, using logistic regression models. Mediation analysis was performed to assess the potential mediating role of SBP in this relationship. A novel model was established based on the identified variables to predict risk of TA/IF. The performance of this model was evaluated for discrimination (receiver operating characteristic curves), calibration (calibration curve), and clinical utility (decision-curve analysis).

Results: Patients in the highest tertile of TyG index had 3.09-fold higher risk for TA/IF compared with those in the lowest tertile. The TyG index was independently and positively associated with the risk of TA/IF (odds ratio [OR]:3.830, 95% confidence interval [CI] 2.578-5.691; p < 0.001). SBP was found to mediate the association between TyG index and TA/IF, with a proportion mediated of 20.7% observed in the highest TyG index tertile (OR [indirect association]: 1.319, 95% CI: 1.118-1.558). The developed predictive nomogram model incorporated SBP, estimated glomerular filtration rate, TyG index, high-density lipoprotein cholesterol, and proteinuria; it demonstrated good predictive performance with strong discrimination (area under the curve: 0.864; bootstrap corrected: 0.859) and calibration (calibration curves). Decision-curve analysis confirmed the model's clinical utility showing a positive net benefit over a wide range of threshold probabilities.

Conclusion: In patients with IgAN, the TyG index was independently associated with the risk of TA/IF and SBP partially mediating this relationship. The developed nomogram, consisting of TyG index, SBP, and other conventional risk factors, provides a practical tool for risk stratification of TA/IF and guidance on IgAN management.