Abstract Introduction: Four-level graded organ response criteria provide a more refined alternative to traditional binary classification in systemic light chain (AL) amyloidosis. However, the prognostic value of graded renal responses for kidney outcomes requires further validation. Methods: We retrospectively analyzed 475 patients with renal AL amyloidosis who achieved at least a hematologic partial response. Renal responses were categorized as renal complete response (RenCR), renal very good partial response (RenVGPR), renal partial response (RenPR), and renal no response (RenNR) based on reductions in 24-hour proteinuria, in the absence of a ≥25% worsening of serum creatinine. The composite kidney outcome served as the primary renal endpoint. Results: Among the 475 enrolled patients, RenCR, RenVGPR, RenPR, and RenNR accounted for 17.7%, 46.1%, 15.1%, and 21.1%, respectively. Deeper renal responses were associated with better overall survival (OS) and a lower risk of the composite kidney outcome. The 5-year OS rates were 98.8% (RenCR), 93.5% (RenVGPR), 68.5% (RenPR), and 46.8% (RenNR) (P < 0.001). The median time to composite kidney outcome was not reached, 158 months, 63 months, and 36 months, respectively (P < 0.001). Landmark analyses, time-varying covariate Cox regression, competing risk regression, and subgroup analyses further supported the independent prognostic value of graded renal responses. Time-dependent receiver operating characteristic (ROC) curve analyses demonstrated that graded renal response criteria performed better than two-level classifications for predicting the composite kidney outcome. Conclusions: Graded renal response criteria provided superior discrimination in predicting the composite kidney outcome, with deeper responses associated with better survival.
Introduction:Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are crucial in managing proteinuria in chronic kidney disease (CKD), yet individual responses vary. Whether urinary glucose excretion, a direct pharmacodynamic marker of SGLT2is, could predict proteinuria reduction efficacy remains unclear and has not been specifically investigated. Methods:We enrolled 277 CKD patients treated with empagliflozin (10 mg/day) between July 2024 and September 2025 at a single center, stratifying them into low (<46.4 mmol/L, n = 69) and high (≥46.4 mmol/L, n = 208) urinary glucose groups by 24-h urinary glucose levels after 3 months of treatment. We evaluated changes in proteinuria levels following 3 and 6 months of medication across the different urinary glucose groups. Changes in laboratory values over time were analyzed using paired Wilcoxon signed-rank tests. Results:Proteinuria was significantly reduced at both 3 (-0.42 g/24 h [95% confidence interval [CI]: -0.55 to -0.32]) and 6 months (-0.46 g/24 h [95% CI: -0.61 to -0.33]) after treatment initiation. After adjusting for covariates, urinary glucose excretion predicted proteinuria reduction from 3 to 6 months (β = 2.47, 95% CI: 0.49-4.45, p = 0.015), with higher urinary glucose correlating with greater proteinuria decline. The high urinary glucose group had significant proteinuria reduction from baseline at 3 and 6 months (p < 0.001), unlike the low group. Following propensity score adjustment for age, sex, body mass index, baseline estimated glomerular filtration rate (eGFR), and renin-angiotensin-aldosterone system inhibitors use, the high urinary glucose group had a significantly higher relative risk of ≥30% proteinuria reduction (risk ratio = 2.82, 95% CI: 1.20-6.65, p = 0.017), particularly in patients with baseline proteinuria ≥1 g/24 h. Urinary glucose concentration was weakly positively correlated with 6-month eGFR change (r = 0.17, p = 0.011). Conclusions:Urinary glucose concentration can serve as a predictor of SGLT2i-mediated proteinuria reduction, providing a practical clinical reference for personalized CKD management.
Chronic hyperkalemia in patients with chronic kidney disease (CKD) often limits the use of vital renin-angiotensin-aldosterone system inhibitors (RAASi). This prospective cohort study compared the efficacy and safety of patiromer (n=40) versus sodium polystyrene sulfonate (SPS) (n=40) for chronic hyperkalemia management in 80 adult CKD patients. Over a six-month follow-up, both agents effectively reduced serum potassium from similar baseline levels (patiromer: 5.73 ± 0.59 mmol/L; SPS: 5.62 ± 0.50 mmol/L) with no significant difference in efficacy (p>0.05). However, key differences in the clinical impact on RAASi therapy emerged, alongside numerical but statistically non-significant differences in tolerability. Patients receiving patiromer had a significantly lower rate of RAASi therapy discontinuation compared to the SPS group (5.2% vs. 36.3%; p=0.033), enabling continuation of guideline-directed medical therapy. A trend towards poorer compliance was noted in the SPS group (22.5% vs. 7.5%; p=0.060). An exploratory analysis revealed that patiromer initiation significantly increased tacrolimus levels in post-kidney transplant recipients (p=0.003), necessitating dose adjustments. While both agents showed comparable potassium-lowering efficacy, patiromer's numerical advantages in tolerability and significant benefit in maintaining RAASi therapy position it as a valuable therapeutic option in this high-risk population.
Introduction:It has been recognized that periodic acid-Schiff (PAS) staining of amyloid deposits is typically weak or negative in the majority of AL amyloidosis. However, a subset of patients exhibits PAS-positive deposits, and their clinicopathological significance remains unclear. Methods:We retrospectively analyzed 269 patients with renal biopsy-proven AL amyloidosis from our institution; 72 were classified as PAS positive and 197 as PAS negative. Baseline demographics, clinical data, renal pathology features, treatment strategies, and prognostic information were collected. Multivariable linear regression and Cox proportional hazards models were used to determine the impact of PAS-positive amyloid deposition on renal function and patients' outcomes. Results:Compared with the PAS-negative group, PAS-positive patients had higher serum creatinine (94.40 vs. 79 μmol/L, p = 0.005) and increased renal insufficiency ratio (31.94% vs. 14.72%, p = 0.002). Histopathology showed more severe glomerular and interstitial amyloid deposition (p = 0.037, p = 0.049, respectively). In multivariable linear regression, PAS-positive deposits (β = 0.158, p = 0.005) were independently associated with higher serum creatinine. PAS-positive patients showed significantly worse renal survival (HR: 3.05, 95% CI: 1.40-6.65, p = 0.005), independent of age, treatment regimens, renal stage, and pathological cores. Meanwhile, PAS-positive staining was an adverse prognostic factor (HR: 2.34, 95% CI: 1.24-4.43, p = 0.009) for overall survival after adjusting for AL type, age, treatment, organ involvement, interstitial fibrosis and tubular atrophy, and total amyloid burden. Conclusion:PAS-positive amyloid deposits are associated with more severe renal injury and poorer prognosis in AL amyloidosis.
Introduction:Kidney disease is a major global health burden with limited regenerative treatment options. Induced pluripotent stem cells (iPSCs) offer patient-specific pluripotency and the potential to generate renal cells and organoids, making them a promising approach for kidney repair. Methods:A systematic literature search was conducted in PubMed, ScienceDirect, Web of Science, and Cochrane Library for peer-reviewed studies investigating the therapeutic application of iPSCs in kidney disease up to February 2026. Risk of bias was assessed using the SYRCLE tool. Random effects meta-analyses were performed, and subgroup and meta-regression analyses were conducted to explore potential sources of heterogeneity. Result:In this search, 23 preclinical studies encompassing 372 animals met the inclusion criteria, and no eligible human trials were identified. iPSC-based therapy was associated with reduced mortality (OR = 0.17; 95% CI: 0.05-0.52; p = 0.002) and improvements in blood urea nitrogen, serum creatinine, and histological injury scores. Subgroup and meta-regression analyses suggested that therapeutic response was influenced by biological factors, including cell type, disease model, delivery route, and treatment conditions. Notably, stronger effects were observed in acute kidney injury models and with direct iPSC-based interventions. However, substantial heterogeneity was observed across most renal outcomes (I 2 > 90%), indicating considerable variability among studies. Conclusion:iPSC-based therapy demonstrates beneficial effects in experimental kidney disease, particularly in acute models. However, the high degree of heterogeneity, potential risk of bias, and limited safety data constrain the reliability and generalizability of these findings. Further optimization of therapeutic strategies and rigorous long-term safety evaluations are required to support clinical translation.
