Clinical and Experimental Nephrology最新文献

Background: Chronic kidney disease (CKD) represents a significant public health challenge, with rates consistently on the rise. Enhancing kidney function prediction could contribute to the early detection, prevention, and management of CKD in clinical practice. We aimed to investigate whether deep learning techniques, especially those suitable for processing missing values, can improve the accuracy of predicting future renal function compared to traditional statistical method, using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry.

Methods: From the J-CKD-DB-Ex, a prospective longitudinal study within the J-CKD-DB, we selected individuals who had at least two eGFR measurements recorded between 12 and 20 months apart (n = 22,929 CKD patients). We used the multiple linear regression model as a conventional statistical method, and the Feed Forward Neural Network (FFNN) and Gated Recurrent Unit (GRU)-D (decay) models as deep learning techniques. We compared the prediction accuracies of each model for future eGFR based on the existing data using the root mean square error (RMSE).

Results: The RMSE values were 7.5 for multiple regression analysis, 7.9 for FFNN model, and 7.6 mL/min/1.73 m² for GRU-D model. In the subgroup analysis according to CKD stages, lower RMSE values were observed in higher stages for all models.

Conclusion: Our result demonstrate the predictive accuracy of future eGFR based on the existing dataset in the J-CKD-DB-Ex. The accuracy was not improved by applying deep learning techniques compared to conventional statistical methods.

Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare cardiovascular disorder caused by defective intracellular lipolysis of triglyceride, resulting in heart failure and diffuse narrowing atherosclerosis. Recently, the registry of TGCV patients in Japan revealed that the 3-year overall survival rate was 80.1% and the 5-year overall survival rate was 71.8%. In this study, the effect on mortality of chronic kidney disease (CKD), diabetes malleus (DM), hypertension (HT), and dyslipidemia (DL) was analyzed using this retrospective registry of TGCV patients. The 3-year survival rate was 71.3% in the CKD group and 91.7% in the non-CKD group, and the 5-year survival rate was 61.8% in CKD group and 84.4% in the non-CKD group. The Kaplan-Meier analysis revealed that CKD is a risk factor for mortality in TGCV patients (p = 0.006). Although TGCV patients with CKD were older than those without CKD, Cox proportional hazard model analyses including age indicated that CKD has a significant association of the prognosis of TGCV patients (hazard ratio 2.33 [1.12-4.86], p = 0.024). DM, HT, and DL did not increase mortality in TGCV patients, although these risk factors were established in the general population. TGCV might cause cardiac disorders and kidney disease at the same time, because podocyte foot process disorder in the glomeruli might be caused by TGCV itself, while CKD should be a risk factor for mortality in TGCV patients as is true in the general population. In conclusion, CKD is a major risk factor for mortality in TGCV patients and thus should be paid attention to in these patients.

Background: This study aimed to investigate the association between the Fc-gamma receptor IIIA (FCGR3A) 158 polymorphism and clinical outcomes in kidney transplantation (KTx) patients. Specifically, we focused on late-onset neutropenia (LON) in ABO-incompatible (ABOi) or HLA-incompatible (HLAi) KTx recipients who underwent rituximab (RTx) desensitization therapy.

Methods: FCGR3A 158F/V polymorphisms were identified in 85 ABOi or HLAi KTx recipients who underwent RTx desensitization at our institution between April 2008 and October 2021. We analyzed these polymorphism groups in relation to their preoperative background and incidence of LON, infection, and rejection. In addition, we examined the risk factors for LON development.

Results: The following FCGR3A 158F/V polymorphisms were identified: FF genotype (n = 45); FV genotype (n = 36), and VV genotype (n = 4). LON occurred in 25 out of 85 recipients within 1 year after KTx, significantly more frequently in patients with the FCGR3A FV + VV genotype (17/40) than in those with the FF genotype (8/45) (p = 0.01). A multivariate analysis identified the V-allele as an independent risk factor for LON (OR, 4.03; 95% CI, 1.38-11.73, p = 0.01). However, there were no significant differences in the incidence rates of post-transplant infection and rejection between the FF and FV + VV genotypes.

Conclusion: Recipients with the FCGR3A 158 V-allele were identified as having a higher risk of developing LON following KTx with RTx desensitization therapy. However, the presence of this V-allele did not affect the safety or efficacy of RTx desensitization before KTx.

Background: Renal autoregulatory mechanisms modulate renal blood flow. Connecting tubule glomerular feedback (CNTGF) is a vasodilator mechanism in the connecting tubule (CNT), triggered paracrinally when high sodium levels are detected via the epithelial sodium channel (ENaC). The primary activation factor of CNTGF-whether NaCl concentration, independent luminal flow, or the combined total sodium delivery-is still unclear. We hypothesized that increasing luminal flow in the CNT induces CNTGF via O2^- generation and ENaC activation.

Methods: Rabbit afferent arterioles (Af-Arts) with adjacent CNTs were microperfused ex-vivo with variable flow rates and sodium concentrations ranging from < 1 to 80 mM and from 5 to 40 nL/min flow rates.

Results: Perfusion of the CNT with 5 mM NaCl and increasing flow rates from 5 to 10, 20, and 40 nL/min caused a flow-rate-dependent dilation of the Af-Art (P < 0.001). Adding the ENaC blocker benzamil inhibited flow-induced Af-Art dilation, indicating a CNTGF response. In contrast, perfusion of the CNT with < 1 mM NaCl did not result in flow-induced CNTGF vasodilation (P > 0.05). Multiple linear regression modeling (R² = 0.51; P < 0.001) demonstrated that tubular flow (β = 0.163 ± 0.04; P < 0.001) and sodium concentration (β = 0.14 ± 0.03; P < 0.001) are independent variables that induce afferent arteriole vasodilation. Tempol reduced flow-induced CNTGF, and L-NAME did not influence this effect.

Conclusion: Increased luminal flow in the CNT induces CNTGF activation via ENaC, partially due to flow-stimulated O2- production and independent of nitric oxide synthase (NOS) activity.

Background: Despite of long-lasting tolvaptan treatment, individual renal outcomes are unclear in autosomal dominant polycystic kidney disease (ADPKD). This post-hoc analysis of the TEMPO 3:4 trial aimed to evaluate the predictability of estimated height-adjusted total kidney volume growth rate (eHTKV-α) on renal outcomes.

Methods: In TEMPO 3:4, 1445 patients with ADPKD were randomised to tolvaptan or placebo for 3 years. The present analysis included patients with total kidney volume (TKV) data available at baseline and month 12 (tolvaptan, n = 812; placebo, n = 453); tolvaptan-assigned patients were grouped into quartiles based on percent change in eHTKV-α from baseline at 1 year. Clinical parameters were compared between quartiles, and regression analyses evaluated the predictive value of 1-year percent change in eHTKV-α and other factors on annual changes in TKV and estimated GFR (eGFR) over 3 years.

Results: Trend tests identified significant differences between quartiles for several baseline parameters. Multivariate regression models confirmed that 1-year percent change in eHTKV-α was a significant predictor of annual changes in both TKV and eGFR over 3 years. Other significant predictors of annual changes in TKV and eGFR over 3 years were sex, age and body mass index, and first-year change in eGFR, race and baseline eGFR, respectively. Predicting factors using urine osmolality and plasma copeptin levels were not significant by backward stepwise selection analysis.

Conclusions: 1-year percent change in eHTKV-α is useful biomarker to identify treatment good responders and may be utilized for early estimate of trial outcomes of new drugs in ADPKD.

Background: There is limited evidence on clinical outcomes and treatment pattern in Japanese patients with severe chronic kidney disease (CKD), hospitalized for coronavirus disease-2019 (COVID-19). We aimed to describe patient characteristics, treatment pattern, and clinical outcomes in Japanese patients with severe CKD, hospitalized for COVID-19 who received remdesivir (RDV).

Methods: We used the anonymized claims database from Medical Data Vision Co., Ltd., Japan. The analysis included patients aged ≥ 18 years with severe CKD, hospitalized for moderate to severe COVID-19, and administered ≥ 1 dose of RDV between October 2021 and September 2023. All-cause inpatient mortality, disease progression, and recovery up to 56 days from hospitalization were evaluated.

Results: Data of 847 patients were analyzed (mean age 73.0 ± 14.1 years). Median (Q1-Q3) time to RDV initiation was 1.0 day (1.0-2.0) from hospitalization and treatment duration was 5.0 days (3.0-5.0). At RDV initiation, 44.27% patients required non-invasive positive pressure ventilation/high or low flow oxygen; 4.25% required invasive mechanical ventilation/extracorporeal membrane oxygenation/intensive care unit hospitalization. Proportion of patients with all-cause mortality was 11.45% (stage 4, 14.89%; stage 5, 10.47%) by 28 days and 12.28% (stage 4, 16.49%; stage 5, 11.08%) by 56 days. At 28 days, 12.28% had disease progression and 72.14% recovered.

Conclusion: Most patients with severe CKD received RDV immediately after hospitalization. The majority of patients recovered by 28 days. The study provided insights into RDV treatment in inpatient settings, which could contribute to the discussion on standard of care in this population in Japan.