Dapagliflozin treatment in patients with chronic kidney disease associated with autosomal dominant polycystic kidney disease.

Introduction: The DAPA-CKD study showed a protective effect of dapagliflozin on kidney function in chronic kidney disease (CKD) patients with and without diabetes mellitus. Although dapagliflozin is expected to be effective also in CKD patients with autosomal dominant polycystic kidney disease (ADPKD), its efficacy and safety in this population remain unknown because ADPKD was an exclusion criterion in the DAPA-CKD study. Therefore, we evaluated the effects of dapagliflozin in CKD patients with ADPKD. Methods: We performed a retrospective observational study of seven patients with ADPKD treated with dapagliflozin at Toranomon Hospital, Tokyo, Japan. We analyzed changes in estimated glomerular filtration rate (eGFR) slope and annual height-corrected total kidney volume before and after starting dapagliflozin treatment. Results: The median observation period after starting dapagliflozin was 20 months. Four patients received concomitant tolvaptan. The eGFR slope before and after initiation of dapagliflozin could be calculated in six patients and improved in all of them except the one who did not receive a renin-angiotensin system (RAS) inhibitor. Annual height-corrected total kidney volume increased in all patients. Concurrent tolvaptan treatment had no effect. Conclusion: In CKD patients with ADPKD, dapagliflozin may increase kidney volume but may have a protective effect on kidney function when used concomitantly with RAS inhibitors.

Outcomes of Early Versus Delayed Anemia Treatment in Nondialysis-Dependent CKD.

Introduction: The association of hemoglobin level at treatment initiation with renal and cardiovascular outcomes in patients with anemia in nondialysis-dependent (NDD) chronic kidney disease (CKD) is unclear. Methods: This retrospective cohort study utilized 2 Japanese databases (Medical Data Vision Co. Ltd., Tokyo, Japan [MDV]; and Real World Data Co. Ltd, Kyoto, Japan [RWD]). Patients initiated on long-acting erythropoiesis-stimulating agent (ESA) treatment were divided into early (hemoglobin levels ≥9.0 g/dl) and delayed (<9.0 g/dl) treatment groups. The primary outcome was a renal composite (renal replacement therapy, ≥50% estimated glomerular filtration rate [eGFR] reduction, eGFR <6.0 ml/min per 1.73 m2, and all-cause mortality), and secondary outcomes were a cardiovascular composite (hospitalization by ischemic heart disease, including myocardial infarction, hospitalization by stroke and heart failure, and cardiovascular death) and components of the composite outcomes. Results: After propensity score matching, 1472 (MDV) and 1264 (RWD) patients were evaluated. Delayed treatment was not associated with a risk of the renal composite outcome (MDV: hazard ratio [HR]: 1.15, 95% confidence interval [CI]: 0.99-1.33; RWD: HR: 1.08, 95% CI: 0.92-1.28). However, delayed treatment was associated with higher risks of the cardiovascular composite outcome (MDV: HR: 1.47, 95% CI: 1.16-1.84; RWD: HR: 1.34, 95% CI: 1.09-1.64), heart failure (MDV: HR: 1.50, 95% CI: 1.13-2.00; RWD: HR: 1.53, 95% CI: 1.20-1.96) and all-cause mortality (MDV: HR: 1.83, 95% CI: 1.32-2.54; RWD: HR: 1.64, 95% CI: 1.21-2.22). Conclusion: Although the risk of renal events was not increased following delayed treatment of anemia in patients with NDD-CKD, the risks of cardiovascular events and all-cause mortality were increased, suggesting the importance of early intervention before hemoglobin falls below 9.0 g/dl.

Gross Hematuria after the COVID-19 mRNA Vaccination: Nationwide Multicenter Prospective Cohort Study in Japan.

BACKGROUND: In the past three years, cases of gross hematuria (GH) after the vaccination for coronavirus disease 2019 (COVID-19) in IgA nephropathy (IgAN) patients have been frequently reported worldwide. However, the post-event renal prognosis of these patients, their clinical backgrounds, and underlying mechanisms remain unknown. Therefore, we conducted a nationwide multicenter prospective cohort study in Japan. METHODS: We analyzed laboratory findings at the time of the first presentation to the hospital, and 3 and 6 months after in patients with GH after the vaccination, and histopathological findings in their kidney biopsy specimens. Moreover, changes in pathological biomarkers of IgAN such as galactose-deficient IgA1 (Gd-IgA1) and its immune complexes (ICs) were also evaluated. RESULTS: During the study period, 127 newly presenting with GH after the vaccination were enrolled, with a clear female bias (73.2%). GH was observed after the second or subsequent vaccinations in most patients (92.9%). Of the 37 patients undergoing kidney biopsy prior to the vaccination, 36 patients had been diagnosed with IgAN/IgA vasculitis (IgAV). In remaining 90 patients, 69 of the 70 who newly underwent kidney biopsy were diagnosed with IgAN (N=67)/IgAV (N=2). Their histopathology did not show a high incidence of acute lesions such as endocapillary hypercellularity and crescentic lesions. Most cases showed a temporary increase in proteinuria, but no sustained worsening in renal function. Among the biomarkers measured, serum Gd-IgA1 and ICs were comparable throughout the observation period, however, only urinary Gd-IgA1 was increased at the time of GH. CONCLUSIONS: We found that GH after the vaccination is more likely to occur in IgAN/IgAV patients, with a female bias, but without progressive exacerbation of renal function. Although further investigation is needed regarding causal relationship between vaccination and GH, this study provides many insights into the molecular mechanisms of GH.

Aberrant proximal tubule DNA methylation underlies phenotypic changes related to kidney dysfunction in patients with diabetes.

Epigenetic mechanisms are considered to contribute to diabetic nephropathy by maintaining memory of poor glycemic control during the early stages of diabetes. However, DNA methylation changes in the human kidney are poorly characterized, because of the lack of cell type-specific analysis. We examined DNA methylation in proximal tubules purified from diabetic nephropathy patients and identified differentially methylated CpG sites, given the critical role of proximal tubules in the kidney injury. Hypermethylation was observed at CpG sites annotated to genes responsible for proximal tubule functions, including gluconeogenesis, nicotinamide adenine dinucleotide synthesis, transporters of glucose, water, phosphate, and drugs, in diabetic kidneys, while genes involved in oxidative stress and the cytoskeleton exhibited demethylation. Methylation levels of CpG sites annotated to ACTN1, BCAR1, MYH9, UBE4B, AFMID, TRAF2, TXNIP, FOXO3, and HNF4A were correlated with the estimated glomerular filtration rate, while methylation of the CpG site in RUNX1 was associated with interstitial fibrosis and tubular atrophy. Hypermethylation of G6PC and HNF4A was accompanied by decreased expression in diabetic kidneys. Proximal tubule-specific hypomethylation of metabolic genes related to HNF4A observed in control kidneys was compromised in diabetic kidneys, suggesting a role for aberrant DNA methylation in the dedifferentiation process. Multiple genes with aberrant DNA methylation in diabetes overlapped genes with altered expressions in maladaptive proximal tubule cells, including transcription factors PPARA and RREB1. In conclusion, DNA methylation derangement in the proximal tubules of patients with diabetes may drive phenotypic changes, characterized by inflammatory and fibrotic features, along with impaired function in metabolism and transport.

Genetic Analysis of Severe Polycystic Liver Disease in Japan.

BACKGROUND: Polycystic liver disease (PLD) is present in most patients with autosomal dominant polycystic kidney disease (ADPKD). PLD can alternatively be found with few, if any, kidney cysts as a diagnosis of isolated polycystic liver disease (ADPLD). Several genes are identified as causative for this spectrum of phenotypes, however, the relative incidence of genetic etiologies amongst patients with severe PLD is unknown. METHODS: Patients with ADPKD or ADPLD having severe PLD defined as height-adjusted total liver volume (hTLV) over 1,800mL/m were recruited. Subsequent clinical care was followed. Genetic analysis was performed using whole exome sequencing. RESULT: We enrolled and sequenced 49 patients (38 females, 11 males). Pathogenic or suspected pathogenic variants in polycystic disease genes were found in 44 out of 49 patients (90%). The disease gene was PKD1 in 20/44 (45%), PKD2 in 15/44 (34%), PRKCSH in 5/44 (11%), GANAB in 2/44 (5%), SEC63 in 1/44 (2%), and ALG8 in 1/44 (2%). The median hTLV was no different between genetically-defined ADPKD and ADPLD groups (4431 (range 1817-9148) versus 3437 (range 1860-8211) mL, p=0.77), whereas height-adjusted kidney volume (hTKV) was larger as expected in ADPKD than ADPLD (607 (range 190-2842) versus 179 (range 138-234) mL/m, p<0.01). Of the clinically-defined ADPKD cases, 20/38 (53%) were PKD1, 15/38 (39%) were PKD2, and 3 (8%) remain genetically unsolved. Among patients with a pathogenic PKD1 or PKD2 variant, we found three cases with a liver-dominant ADPKD (severe PLD with hTKV <250mL/m). CONCLUSION: ADPLD-related genes represent 20% of severe PLD patients in our cohort. Of those enrolled with ADPKD, we observed a higher frequency of PKD2 carriers than in any previously reported ADPKD cohorts. While there was no significant difference in the hTLV between PKD1 versus PKD2 patients in this cohort, our data suggests that enrollment on the basis of severe PLD may enrich for PKD2 patients.

Protocol for the nationwide registry of patients with polycystic kidney disease: japanese national registry of PKD (JRP).

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are major genetic polycystic kidney diseases that can progress to end-stage kidney disease (ESKD). Longitudinal data on the clinical characteristics associated with clinical outcomes in polycystic kidney disease (PKD), including the development of ESKD and cardiovascular disease (CVD) are lacking in Japan. To address this unmet need the authors are establishing a novel, web-based, Nationwide Cohort Registry Study-the Japanese Registry of PKD (JRP). METHODS: The JRP is a prospective cohort study for ADPKD (aim to recruit n = 1000 patients), and both a retrospective and prospective study for ARPKD (aim to recruit n = 100). In the prospective registry, patients will be followed-up for 10 years every 6 months and 12 months for patients with ADPKD and ARPKD, respectively. Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on April 1, 2024, with recruitment ending on March 31, 2029. (jRCT 1030230618). RESULTS: Data to be collected include: baseline data, demographics, diagnostic and genetic information, radiological and laboratory findings, and therapeutic interventions. During follow-up, clinical events such as development of ESKD, hospitalization, occurrence of extra kidney complications including CVD events, and death will be recorded, as well as patient-reported health-related quality of life for patients with ADPKD. CONCLUSIONS: The JRP is the first nationwide registry study for patients with ADPKD and ARPKD in Japan, providing researchers with opportunities to advance knowledge and treatments for ADPKD and ARPKD, and to inform disease management and future clinical practice.

Exercise instruction during haemodialysis treatment after changes to the insurance regime: a nationwide questionnaire survey in Japan.

In April 2022, an additional medical fee for exercise instruction during haemodialysis treatment was approved for insurance claims in Japan. We conducted a questionnaire survey to investigate the current situation regarding exercise therapy during haemodialysis treatment after this change. Questionnaires were mailed to 4257 haemodialysis facilities, almost all the haemodialysis facilities in Japan, on January 31, 2023. In total, 1657 facilities responded, of which 550 (33%) provided exercise instruction during haemodialysis treatment, and 65% of these claimed the new fee. Of the 550 facilities that had claimed the fee at the time of survey, 245 (55%) started exercise instruction in April 2022 or later. Exercise instruction focused on resistance training (81%) and aerobic exercise (62%) for 20-30 min (66%) three times a week (80%). The instructors included physicians in 45% of facilities, nurses in 74%, and physical therapists in 36%. Efficacy was evaluated in 76% of the facilities providing instruction, mainly by assessing change in muscle strength (49%). Overall, 39% of facilities had experienced some adverse events, but none were life-threatening. In conclusion, after the change in the insurance regime, exercise instruction during haemodialysis treatment has become more popular, and more patients on haemodialysis are undergoing exercise therapy.

Renal outcome of living kidney donors aged more than 70 years.

BACKGROUND: The number of marginal living kidney donors has increased. Medically complex donors who have hypertension, older age, or low estimated glomerular filtration rate (eGFR) have been more likely to be used. METHODS: We conducted a retrospective cohort study of living kidney donors at a single center. We analyzed 309 living donors and divided them into three groups: group with older donors (aged ≥70 years) (n = 41), middle-aged (aged 46-69 years) (n = 239), and young donors (aged <46 years) (N = 29). Donor factors associated with chronic kidney disease (CKD) stage 3b or worse within 5 years post-donation were investigated. RESULTS: Of the 309 live donors, 86 (27.8%) developed CKD stage3b or worse within 5 years post-donation. The incidence of CKD stage3b or worse within 5 years post-donation was significantly higher in older donor (p < 0.01). Cox regression models revealed that older donor ages and lower eGFR were significantly related to the development of CKD stage3b or worse, independent of comorbidities such as obesity and hypertension [hazard ratio (95% CI); 4.59 (1.02-20.6), p = 047, 0.95 (0.94-0.96), p ≤ 0.01, respectively]. However, recovery of eGFR 4-5 years after donation was noted in the middle-aged and older donor groups, whereas the level of eGFR remained unchanged in the young group. CONCLUSIONS: Older donors tend to develop CKD stage3b within 5 years post-donation but with the potential of recovery. Healthy older people (aged ≥70 years) could be candidates for living donors under careful monitoring of kidney function after donation.

Factors associated with early-onset intracranial aneurysms in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Recently, the importance of attribute-based medicine has been emphasized. The effects of early-onset intracranial aneurysms on patients can be significant and long-lasting. Herein, we compared the factors associated with intracranial aneurysms in patients with autosomal dominant polycystic kidney disease (ADPKD) according to age categories (≥ 50 years, < 50 years). METHODS: We included 519 ADPKD patients, with a median age of 44 years, estimated glomerular filtration rate of 54.5 mL/min/1.73 m2, and total follow-up duration of 3104 patient-years. Logistic regression analyses were performed to determine factors associated with intracranial aneurysms. RESULTS: Regarding the presence of intracranial aneurysm, significant interactions were identified between the age category (age ≥ 50 years), female sex (P = 0.0027 for the interaction) and hypertension (P = 0.0074 for the interaction). Female sex and hypertension were associated with intracranial aneurysm risk factors only in patients aged ≥ 50 years. The presence of intracranial aneurysm was significantly associated with chronic kidney disease (CKD) stages 4-5 (odds ratio [OR] = 3.87, P = 0.0007) and family history of intracranial aneurysm or subarachnoid hemorrhage (OR = 2.30, P = 0.0217) in patients aged < 50 years. For patients aged ≥ 50 years, in addition to the abovementioned factors [OR = 2.38, P = 0.0355 for CKD stages 4-5; OR = 3.49, P = 0.0094 for family history of intracranial aneurysm or subarachnoid hemorrhage], female sex (OR = 4.51, P = 0.0005), and hypertension (OR = 5.89, P = 0.0012) were also associated with intracranial aneurysm. CONCLUSION: Kidney dysfunction and family history of intracranial aneurysm or subarachnoid hemorrhage are risk factors for early-onset intracranial aneurysm. Patients aged < 50 years with a family history of intracranial aneurysm or subarachnoid hemorrhage or with CKD stages 4-5 may be at an increased risk of early-onset intracranial aneurysm.

Trajectory of GFR Decline and Fluctuation in Albuminuria Leading to End-Stage Kidney Disease in Patients With Biopsy-Confirmed Diabetic Kidney Disease.

Introduction: Data on longitudinal trajectory of kidney function decline and fluctuation in albuminuria leading to end-stage kidney disease (ESKD) is sparse in patients with type 2 diabetes. Methods: Using data from an observational study of patients with type 2 diabetes and biopsy-confirmed diabetic kidney disease (DKD), generalized additive mixed models (GAMMs) were performed to quantify patterns of longitudinal trajectory of estimated glomerular filtration rate (eGFR) decline to ESKD associated with repeated measures of urine albumin-to-creatinine ratio (ACR). Results: Over a median follow-up period of 3.3 years, 155 of 319 patients progressed to ESKD. Among these patients, 91.6% exhibited a curvilinear pattern in their eGFR trajectory. The median coefficient of variation for ACR, representing the variability in ACR measurements, was 48.9 (interquartile range: 36.9, 68.2). The median compound annual growth rate (CAGR) for ACR, reflecting the variation in ACR progression over time, was 43.6% (interquartile range: 0.0, 102.5); and 84.5% of patients developed nephrotic-range albuminuria, with a majority remaining nephrotic and subsequently progressing to ESKD. There was a positive association between the instantaneous speed of eGFR decline and ACR. Conclusion: The observed curvilinear pattern in eGFR trajectory, high variability in ACR progression over time, and positive correlation between the speed of eGFR decline and ACR highlight the complex dynamics of disease progression and emphasize close monitoring of ACR fluctuation over time in patients with DKD.

PLA2R-positive membranous nephropathy in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory disease that affects multiple organs, including the pancreas, lacrimal glands, salivary glands, periaortic/retroperitoneum, and kidney. Interstitial nephritis is a typical renal disorder associated with IgG4-RD, but membranous nephropathy is also seen in some cases. CASE PRESENTATION: Herein we report on the case of a 77-year-old male patient with nephrotic syndrome and IgG4-related lung disease. His serum phospholipase A2 receptor (PLA2R) antibody was positive. His renal biopsy specimen was also positive for PLA2R. The renal biopsy specimen showed membranous nephropathy with equal IgG3 and IgG4 immunofluorescence staining and no interstitial nephritis, suggesting IgG4-RD manifesting as membranous nephropathy. CONCLUSIONS: Nephrotic syndrome caused by membranous nephropathy is sometimes associated with IgG4-RD. In such cases, even if serum PLA2R antibody is positive, it should be considered that the membranous nephropathy may be secondary to IgG4-RD.

Minimum-incision transsubclavian transcatheter aortic valve replacement with balloon-expandable valve for dialysis patients.

BACKGROUND: Dialysis patients undergoing transcatheter aortic valve replacement (TAVR) face increased risk and have poorer outcomes than non-dialysis patients. Moreover, TAVR in dialysis patients using an alternative approach is considered extremely risky and little is known about the outcomes. We routinely perform minimum-incision transsubclavian TAVR (MITS-TAVR), which is contraindicated for transfemoral (TF) TAVR. This study aimed to evaluate the outcomes of MITS-TAVR compared with those of TF-TAVR in dialysis patients. METHODS: This single-center, observational study included 79 consecutive dialysis patients who underwent MITS-TAVR (MITS group, n = 22) or TF-TAVR (TF group, n = 57) under regional anesthesia. RESULTS: The rates of peripheral artery disease (MITS vs. TF, 72.7 % vs. 26.3 %; p < 0.01), shaggy aortas (MITS vs. TF, 63.6 % vs. 5.26 %; p < 0.01), and tortuous aortas (MITS vs. TF, 13.6 % vs. 1.75 %; p = 0.031) were significantly higher in the MITS group. The 30-day mortality was 2.53 % and comparable between the two groups (MITS vs. TF, 4.54 % vs. 1.75 %; p = 0.479). In the MITS group, 14 patients had ipsilateral dialysis fistulas, and three patients had patent in situ ipsilateral internal thoracic artery grafts; however, no vascular complications were observed. Kaplan-Meier survival curves for the two groups showed no significant difference in the survival rate (at 2 years; MITS vs. TF, 77.3 % vs. 68.8 %; p = 0.840) and freedom from cardiovascular mortality (at 2 years; MITS vs. TF, 90.9 % vs. 96.5 %; p = 0.898). The multivariable Cox proportional hazard model also indicated that survival in the MITS group was not significantly different from that in the TF group (hazard ratio 1.48; 95 % confidence interval, 0.77-2.85, p = 0.244). The patency rate of ipsilateral dialysis fistula was 100 % during follow-up. CONCLUSION: The outcome of MITS-TAVR was comparable to that of TF-TAVR in dialysis patients, despite the higher risk of patient characteristics.

Autopsy of a 45-year-old Man with Liver Failure Due to Polycystic Liver Disease.

A 37-year-old man with autosomal polycystic kidney disease (ADPKD) was admitted to our hospital with a liver volume of 8,000 cm3. Hepatic arterial embolization was performed using a microcoil but was ineffective. Eight years later, the hepatomegaly progressed to liver failure and death. At autopsy, the liver weighed 21.5 kg, and the entire liver had been replaced by cysts; in the few remaining areas of liver parenchyma, microscopic, small cysts of various sizes and fibrosis were evident, with only a few normal hepatocytes observed. Hepatic arterial branches developed; however, the portal vein could not be observed.

Health-related Quality of Life in 10 years Long-term Survivors of Chronic Kidney Disease: A From-J Study.

OBJECTIVE: The Chronic Kidney Disease (CKD) practice facilitation program in the Frontier of Renal Outcome Modifications in Japan study reduced cardiovascular disease (CVD) events in patients with CKD. 10-year long-term survivors with CKD lived with serious complications, including end-stage kidney disease and CVD. This study aimed to measure health-related quality of life in 10-year long-term CKD survivors and examine the predictors and determinants of clinical indices for measured quality of life (QOL) scores. METHODS: The EQ-5D-5L, a generic preference-based instrument, was administered to 1,473 CKD survivors enrolled in the Frontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in JapanFrontier of Renal Outcome Modifications in Japan study. The 10th-year data collection was performed by either primary care physicians or participants who filled out questionnaires from October 2018 to March 31, 2019. RESULTS: The response rate was 38.2% (423/1,473). The mean QOL score was 0.893 (95% confidence interval (CI), 0.880-0.906), and the median QOL score was 1.000 (interquartile range (IQR), 0.826-1.000). The mean QOL score in participants with renal replacement therapy was 0.824 (95% CI, 0.767-0.881), and the median was 0.828 (IQR, 0.755-1.000). The mean QOL score in participants with CVD was 0.877 (95% CI, 0.811-0.943), and the median was 1.000 (IQR, 0.723-1.000). The mean QOL score in participants with 50% decline in estimated glomerular filtration was 0.893 (95% CI, 0.860-0.926), and the median was 0.889 (IQR, 0.825-1.000). The decrease in QOL scores with baseline CKD stages was significant according to the Jonckheere-Terpstra test for trend (P = .002). Baseline age, systolic blood pressure, and history of hyperuricemia were significant predictors of 10th-year QOL scores. CONCLUSION: We suggest that CKD complications negatively affect the QOL scores in 10-year long-term survivors with CKD. CKD guideline-based practices, prevention of end-stage kidney disease/CVD and management of hypertension, diabetes and hyperuricemia, might contribute to future health-related quality of life in patients with CKD.

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography and computed tomography for differentiating polymyalgia rheumatica and rheumatoid arthritis: Using classification and regression tree analysis.

OBJECTIVES: Determining which sites were important to differentiate polymyalgia rheumatica (PMR) from rheumatoid arthritis (RA) using 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET-CT) is challenging. METHODS: Patients with PMR or RA who were undergoing PET-CT were recruited at two mutual-aid hospitals in Japan between 2009 and 2018. Classification and regression tree (CART) analyses were performed to identify FDG uptake patterns that differentiated PMR from RA. RESULTS: We enrolled 35 patients with PMR and 46 patients with RA. Univariate CART analysis showed that FDG uptake in the shoulder joints, spinous processes of the lumbar vertebrae, pubic symphysis, sternoclavicular joints, ischial tuberosities, greater trochanters, and hip joints differentiated PMR from RA. Multivariate CART analysis revealed that FDG uptake by at least one of the ischial tuberosities had the highest diagnostic value for distinguishing PMR from RA (sensitivity, 77.1%; specificity, 82.6%). We performed the same CART analysis to patients who had not undergone treatment (PMR, n = 28; RA, n = 9). Similar results were obtained, and sensitivity and specificity were increased (sensitivity, 89.3%; specificity, 88.8%). CONCLUSIONS: In PET-CT, FDG uptake by at least one of the ischial tuberosities best discriminates between PMR and RA.

Immediate drop of urine osmolality upon tolvaptan initiation predicts impact on renal prognosis in patients with ADPKD.

BACKGROUND AND HYPOTHESIS: Tolvaptan, a vasopressin V2 receptor antagonist, is used for treating autosomal dominant polycystic kidney disease (ADPKD). We focused on changes in urinary osmolality (U-Osm) after tolvaptan initiation to determine whether they were associated with the therapeutic response to tolvaptan. METHODS: This was a single-centre, prospective, observational cohort study. Seventy-two patients with ADPKD who received tolvaptan were recruited. We analysed the relationship between changes in U-Osm and annual estimated glomerular filtration rate (eGFR) in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The mean value of U-Osm immediately before tolvaptan initiation was 351.8 ± 142.2 mosm/kg H2O, which decreased to 97.6 ± 23.8 mosm/kg H2O in the evening. The decrease in U-Osm was maintained in the outpatient clinic 1 month later. However, the values of U-Osm showed higher variability (160.2 ± 83.8 mosm/kg H2O) than did those in the first evening of tolvaptan administration. Multivariate analysis revealed that the baseline eGFR, baseline urinary protein, and U-Osm change in the evening of the day of admission (initial U-Osm drop) were significantly correlated with the subsequent annual change in eGFR. CONCLUSIONS: U-Osm can be measured easily and rapidly, and U-Osm change within a short time after tolvaptan initiation may be a useful index for the renal prognosis in actual clinical practice.