Clinical and Experimental Nephrology最新文献

{"title":"HDAC9-mediated deacetylation of CALML6 promotes excessive proliferation of glomerular mesangial cells in IgA nephropathy.","authors":"Xingxing Zhuang, Fei Xiao, Feihu Chen, Shoudong Ni","doi":"10.1007/s10157-024-02620-5","DOIUrl":"https://doi.org/10.1007/s10157-024-02620-5","url":null,"abstract":"<p><strong>Purpose: </strong>This study seeks to investigate the fundamental molecular processes through which histone deacetylase 9 (HDAC9) governs the proliferation of glomerular mesangial cells in the context of immunoglobulin A nephropathy (IgAN) and to identify novel targets for clinical research on IgAN.</p><p><strong>Methods: </strong>Data from high-throughput RNA sequencing for IgAN were procured from the Gene Expression Omnibus database to assess the expression profiles and clinical diagnostic significance of histone deacetylase family proteins (HDACs). Blood samples from 20 IgAN patients were employed in RT-qPCR analysis, and the spearman linear regression method was utilized to analyze the clinical correlation. The proliferation of glomerular mesangial cells (GMCs) under the influence of HDAC9 was examined using the 5-ethynyl-2'-deoxyuridine (EdU) assay. Proteins interacting with HDAC9 were predicted utilizing the STRING database. Immunoprecipitation and protein immunoblotting employing anti-acetylated lysine antibodies were conducted to determine the acetylation status of calmodulin-like protein 6 (CALML6).</p><p><strong>Results: </strong>Analysis of the GSE141295 dataset revealed a significant upregulation of HDAC9 expression in IgAN and the results of RT-qPCR demonstrated a substantial increase in HDAC9 expression in IgAN patients. Receiver operating characteristic (ROC) analysis indicated that the area under the curve (AUC) value for HDAC9 were 0.845 and Spearman correlation analysis showed that HDAC9 expression was positively correlated with blood levels of blood urea nitrogen (BUN) and serum creatinine (Crea). The EdU cell proliferation assay indicated that HDAC9 facilitated the excessive proliferation of GMCs. The STRING database and recovery experiments identified CALML6 as a downstream effector of HDAC9 in controlling abnormal GMC multiplication. Co-immunoprecipitation assays demonstrated that HDAC9 modulates CALML6 expression through acetylation modification.</p><p><strong>Conclusion: </strong>HDAC9 is markedly upregulated in IgAN, and it mediates the excessive proliferation of GMCs by regulating the deacetylation of CALML6.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glomerular diameter is associated with a reduction in urinary protein by treatment with dapagliflozin in patients with chronic kidney disease.","authors":"Arata Osanami, Hiroaki Komatsu, Yufu Gocho, Keitaro Nishizawa, Marenao Tanaka, Yuichi Nakamura, Masato Furuhashi","doi":"10.1007/s10157-025-02625-8","DOIUrl":"https://doi.org/10.1007/s10157-025-02625-8","url":null,"abstract":"<p><strong>Background: </strong>Several clinical trials showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors have protective effects against chronic kidney disease (CKD) in both patients with and those without type 2 diabetes mellitus. Since one of the renoprotective mechanisms of SGLT2 inhibitors is thought to be amelioration of glomerular hyperfiltration, we hypothesized that an enlarged glomerular diameter, which suggests increased single-nephron glomerular filtration rate, is associated with a reduction in urinary protein after treatment with an SGLT2 inhibitor.</p><p><strong>Methods: </strong>This study was a retrospective multicentered study including 28 adult patients with CKD who underwent kidney biopsy and were then treated with dapagliflozin, an SGLT2 inhibitor. The association of glomerular diameter with changes in urinary protein 4-8 weeks after the initiation of treatment with dapagliflozin was investigated.</p><p><strong>Results: </strong>Maximum glomerular diameter was significantly and positively correlated with change in urinary protein-to-creatinine ratio (UPCR) (R² = 0.44; P < 0.001). Maximum glomerular diameter was significantly larger in patients who achieved ≥ 30% reduction in UPCR after the initiation of treatment with dapagliflozin than in patients who achieved < 30% reduction in UPCR (219.4 ± 23.9 vs. 188.0 ± 29.0; P = 0.005). After adjustment of age, sex and estimated glomerular filtration rate, maximum glomerular diameter was independently associated with change in UPCR (β = 0.645, P < 0.001). Furthermore, maximum glomerular diameter was independently associated with ≥ 30% reduction in UPCR (odds ratio: 1.07, 95% confidential interval: 1.01-1.14).</p><p><strong>Conclusion: </strong>Glomerular diameter is independently associated with an early change in UPCR after the initiation of treatment with dapagliflozin in patients with CKD.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of different timings of protein supplementation on variable outcomes in hemodialysis patients: a randomized clinical trial.","authors":"Mohamed Mamdouh Elsayed, Amr Mohamed Elkazaz","doi":"10.1007/s10157-025-02626-7","DOIUrl":"https://doi.org/10.1007/s10157-025-02626-7","url":null,"abstract":"<p><strong>Background: </strong>Oral nutritional supplements (ONS) are commonly prescribed to provide protein and energy to hemodialysis (HD) patients. There is a debate about the appropriate timing to administer ONS. We aimed to study the effect of different timings of ONS on variable outcomes in HD patients.</p><p><strong>Methods: </strong>This research is a prospective, randomized, multicentric clinical trial (RCT) that included 120 patients on regular HD. Patients were allocated to receive ONS (25 gm protein powder/HD session) for 8 weeks either predialytic (1 h before the start of the session), intradialytic (2 h after the start of the session), or interdialytic (on non-dialysis days). Laboratory parameters, blood pressure (BP), dialysis adequacy, and nutritional parameters were assessed during the study.</p><p><strong>Results: </strong>At study end, BP at the end of HD dropped significantly in the intradialytic group compared to the other groups (p < 0.001). Serum albumin improved significantly in the predialytic (p < 0.001) and intradialytic (p = 0.039) groups. The mean subjective global assessment score increased significantly in the interdialytic group (p = 0.040). The Kt/V and urea reduction ratio decreased significantly only in the intradialytic group (p value < 0.001 and 0.001). Serum sodium, potassium, phosphorus, cholesterol, triglycerides, and adverse events did not significantly differ between the different groups.</p><p><strong>Conclusions: </strong>Predialytic ONS supplementation is a favorable option due to improved serum albumin with minimal effects on hemodynamics and dialysis adequacy compared to intradialytic and interdialytic supplementation.</p><p><strong>Clinical trials registration: </strong>ClinicalTrials.gov NCT05953636. First registration date: 1/07/2023.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study.","authors":"Shisheng Han, Guangliang Xie, Yi Wang","doi":"10.1007/s10157-024-02623-2","DOIUrl":"https://doi.org/10.1007/s10157-024-02623-2","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.</p><p><strong>Methods: </strong>The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies. Weighted generalized multivariate linear regression was employed to estimate the association between estradiol and eGFR and ACR, and a restricted cubic spline analysis was utilized to investigate potential nonlinear relationships.</p><p><strong>Results: </strong>A total of 8932 participants were included. Serum estradiol concentration was positively associated with eGFR after adjusting for potential covariates (β, 0.76; 95% CI 0.24 to 1.27) and with ACR (β, 5.99; 95% CI 1.62 to 10.36). A nonlinear positive association was found between estradiol and eGFR, while an inverse \"V\"-shaped relationship was seen with ACR. Sensitivity analyses confirmed the stability of the relationship between estradiol and eGFR but indicated a less robust association with ACR. Stratified analysis showed that the association between estradiol and eGFR was particularly significant in populations with CKD and hypertension. All forward MR analyses demonstrated a positive causal relationship between estradiol and eGFR, but no causality was found between estradiol and ACR. No reverse causal association was observed.</p><p><strong>Conclusions: </strong>Serum estradiol concentration was causally associated with eGFR. Further longitudinal research is needed to validate these findings.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of renal fibrosis using scanning acoustic microscopy.","authors":"Takane Ito, Hideki Kumagai, Takahiro Kanai, Jun Aoyagi, Yuko Ono, Katsutoshi Miura, Kazuto Kobayashi, Toshihiro Tajima, Hitoshi Osaka","doi":"10.1007/s10157-024-02621-4","DOIUrl":"https://doi.org/10.1007/s10157-024-02621-4","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis is strongly correlated with renal functional outcomes. Therefore, this is a significant finding in determining renal prognosis. There are various reports on the imaging evaluation of renal fibrosis, but these are not well established. Scanning acoustic microscopy (SAM) uses ultra-high-frequency ultrasound to visualize tissues in just over a minute. SAM can simultaneously measure acoustic data such as speed of sound (SOS). SOS indicates the elasticity (stiffness) of a material. In this study, we aimed to compare and evaluate SAM acoustic intensity images and SOS data with light microscopy images of renal lesions, especially renal fibrosis.</p><p><strong>Methods: </strong>Renal specimens containing fibrosis were selected. The acoustic intensity images were compared to PAS-stained images. SOS data of the tubulointerstitium were compared with Masson's trichrome (MT)-stained images. The blue intensity of MT staining, which indicates fibrosis, was numerically valued using image-processing software. Furthermore, the correlations between it and the SOS values were evaluated.</p><p><strong>Results: </strong>The acoustic intensity images suggested tubular atrophy and interstitial expansion in the same areas as in the PAS staining. SOS values of interstitial expansion with fibrosis were higher than normal area, interstitial expansion without fibrosis. A weak positive correlation was observed between the SOS values and the blue intensity of MT staining.</p><p><strong>Conclusions: </strong>SOS data can be used to evaluate renal fibrosis. The combination of SOS data and MT-stained images enables a more detailed evaluation of renal fibrosis. This study can contribute to the evaluation of renal fibrosis and has potential clinical applications in the future.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of kidney function prediction: traditional statistical methods vs. deep learning techniques.","authors":"Mizuki Ohashi, Yuya Ishikawa, Satoshi Arai, Tomoharu Nagao, Kaori Kitaoka, Hajime Nagasu, Yuichiro Yano, Naoki Kashihara","doi":"10.1007/s10157-024-02616-1","DOIUrl":"https://doi.org/10.1007/s10157-024-02616-1","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic kidney disease is a major risk factor for mortality in triglyceride deposit cardiomyovasculopathy patients.","authors":"Yasuyuki Nagasawa, Satomi Okamura, Yuki Nishimura, Tomomi Yamada, Hideyuki Miyauchi, Yusuke Nakano, Tetsuya Amano, Yuko Kawaguchi, Shinichiro Fujimoto, Ken-Ichi Hirano","doi":"10.1007/s10157-024-02618-z","DOIUrl":"https://doi.org/10.1007/s10157-024-02618-z","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Fc-gamma receptor IIIA polymorphism on late-onset neutropenia and clinical outcomes in kidney transplant recipients following rituximab induction therapy.","authors":"Yuki Tashiro, Yoji Hyodo, Satoshi Kitamura, Takuya Fujimoto, Takahito Endo, Shun Nishioka, Naoki Yokoyama, Takuto Hara, Koji Chiba, Hideaki Miyake","doi":"10.1007/s10157-024-02610-7","DOIUrl":"https://doi.org/10.1007/s10157-024-02610-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luminal flow in the connecting tubule induces afferent arteriole vasodilation.","authors":"Hong Wang, Pablo A Ortiz, Cesar A Romero","doi":"10.1007/s10157-024-02615-2","DOIUrl":"10.1007/s10157-024-02615-2","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Change in kidney volume growth rate and renal outcomes of tolvaptan treatment in autosomal dominant polycystic kidney disease: post-hoc analysis of TEMPO 3:4 trial.","authors":"Eiji Higashihara, Miyuki Matsukawa, Huan Jiang","doi":"10.1007/s10157-024-02589-1","DOIUrl":"https://doi.org/10.1007/s10157-024-02589-1","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}