A Case of Castleman's Disease during the Long-Term Course of Membranous Nephropathy.

Concomitant with nephrotic syndrome and multicentric castleman's disease (MCD) has only been described in a limited number of small studies and case reports. Among those, none confirmed the renal pathology prior to the onset of MCD, and none of the cases had a history of nephrotic syndrome. A 76 year-old Japanese man visited a nephrologist because of incident nephrotic syndrome. He had previously experienced three episodes of nephrotic syndrome, the last one 13 years ago, and had been diagnosed with membranous nephropathy by renal biopsy. Apart from these previous episodes, he also suffered from systemic lymphadenopathy, anemia, elevated C-reactive protein, polyclonal hypergammopathy, and elevated interleukin (IL)-6. An inguinal lymph node biopsy revealed CD138-positive plasma cells in the interfollicular region. Based on these findings, MCD was diagnosed. Renal biopsy indicated primary membranous nephropathy with spike lesions and bubbling in the basement membranes and deposition of immunoglobulin (Ig) G, IgA, IgM, and phospholipase A2 receptor along the glomerular basement membrane. Corticosteroid monotherapy successfully reduced the edema, proteinuria, and IL-6, but hypoalbuminemia was not sufficiently improved due to castleman's disease and remission of the nephrotic syndrome was not achieved. Later, tocilizumab was administered for remission induction in another facility. To the best of our knowledge, this represents the first report of Castleman's disease with previously diagnosed membranous nephropathy. This case does not provide a causal mechanism for the pathophysiology, but it may be worth suggesting possible involvement of MCD as a trigger for recurrence of membranous nephropathy.

Long-term effectiveness of a primary care practice facilitation program for chronic kidney disease management: an extended follow-up of a cluster-randomized FROM-J study.

BACKGROUND: Practice facilitation program by multidisciplinary care for primary care physicians (PCPs) is expected to improve chronic kidney disease (CKD) outcomes, but there is no clear evidence of its long-term effectiveness. We have previously performed a cluster-randomized controlled trial for 3.5 years (the Frontier of Renal Outcome Modifications in Japan (FROM-J) study) with two arms-group A without the program and group B with the program. We aimed to assess the long-term effectiveness of the practice facilitation program on CKD outcomes via an extended 10-year follow-up of the FROM-J study. METHODS: We enrolled patients who were in the FROM-J study. The primary composite endpoint comprised cardiovascular disease (CVD), renal replacement therapy initiation and a 50% decrease in the estimated glomerular filtration rate (eGFR). The secondary endpoints were survival rate, eGFR decline rate and collaboration rate between PCPs and nephrologists. RESULTS: The occurrence of the primary composite endpoint tended to be lower in group B (group A: 27.1% versus group B: 22.1%, P = 0.051). Furthermore, CVD incidence was remarkably lower in group B (group A: 10.5% versus group B: 6.4%, P = 0.001). Although both mortality and the rate of eGFR decline were identical between both groups, the eGFR decline rate was significantly better in group B than in group A only in patients with stage G3a at enrollment (group A: 2.35 ± 3.87 mL/min/1.73 m2/year versus group B: 1.68 ± 2.98 mL/min/1.73 m2/year, P = 0.02). The collaboration rate was higher in group B. CONCLUSIONS: The CKD practice facilitation program for PCPs reliably decreases CVD events and may reduce the progression of cases to end-stage kidney disease.

Concomitant Nephrotic Syndrome and Cryoglobulinemia in a Case of Malignant Mesothelioma.

Malignant pleural mesothelioma is rarely associated with nephrotic syndrome. Cryoglobulinemia is found in various pathological statuses, such as hepatitis C virus infection but rarely in malignant neoplasms. We recently encountered a patient with malignant mesothelioma coincident with nephrotic syndrome and cryoglobulinemia in the course of chemotherapy. A 60-year-old man employed as a building painter was diagnosed with malignant mesothelioma by lung biopsy two years earlier and was started on chemotherapy. Nivolumab seemed effective in controlling mesothelioma, but skin immune-related adverse events occurred during the course of treatment. After discontinuation of nivolumab and administration of gemcitabine as an alternative therapy, the patient was referred to a nephrologist because of the subsequent development of edema, renal injury, and proteinuria. Following the investigation, he was diagnosed with nephrotic syndrome and cryoglobulinemia with C4-dominant cold activation. However, a percutaneous renal biopsy could not be performed due to persistent severe cough induced by pleural involvement. The patient died a little over three years after the pathological diagnosis of pleural mesothelioma. Our case had three key features nephrotic syndrome was possibly associated with malignant mesothelioma; cryoglobulinemia occurred in malignant mesothelioma; and concomitant nephrotic syndrome and cryoglobulinemia occurred after chemotherapy. Unfortunately, our rare case lacks a basis in renal pathology or evidence of links between the pathogenesis of malignant mesothelioma, cryoglobulinemia, and nephrotic syndrome. This case does not provide a causal mechanism, but may be worth adding to the case list as one of the rare renal involvement in a patient with malignant mesothelioma.

Ten Cases of Biopsy-Proven Acute Tubulointerstitial Nephritis: Report from a Single Center in a Rural Area from 2008 to 2021.

Acute tubulointerstitial nephritis (ATIN) can be caused by any number of factors, and it accounts for several percent of renal biopsy cases. In Japan, case reports exist, but there are few single-center series of ATIN cases. Case 1. A teenage male patient developed fever and cough on day X-61 and was found to have normal renal function and positive C-reactive protein (CRP) by his primary care physician. On day X-20, he presented with cough and nasal discharge in addition to low-grade fever, and his doctor noted renal dysfunction with serum creatinine of 2.12 mg/dL, negative urine occult blood, and positive urine glucose. Renal biopsy results showed diffuse interstitial nephritis with scarce glomerular involvement. There was no concurrent uveitis. Renal function normalized after 4 months of treatment with moderate-dose prednisolone. Cases 2-10. Of the 422 cases for which renal biopsies were performed at our institution from 2008 to 2021, acute tubulointerstitial nephritis was confirmed clinically and pathologically in 9 cases in addition to case 1, accounting for 2.4% of all biopsy cases. In the analysis of the 10 patients, the median age was 40 years old, eGFR at diagnosis was 19.4 (3.2-49.1) mL/min/1.73 m2, and 2 of them underwent hemodialysis, but both were weaned from dialysis, and the eGFR after treatment was 53.6 (20.8-110.0) mL/min/1.73 m2; all patients showed improvement (P < 0.001). Treatment consisted of steroids in 8 patients and no steroids in 2 patients, the latter being treated by discontinuation of the suspect drugs and treatment of infection; 7 of the 10 patients were examined for ocular uveitis, and uveitis was diagnosed in 5 patients. The causes and clinical course of ATIN are diverse, but it is treated according to individual judgment in addition to standard treatment, and it generally has a good renal prognosis.

POEMS Syndrome with Biclonal Gammopathy and Renal Involvement.

Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin changes (POEMS) syndrome manifests as elevated levels of vascular endothelial growth factor (VEGF) and monoclonal gammopathy. We treated a case of POEMS syndrome showing monoclonality in both IgA-λ and IgG-κ. Serial renal biopsies before treatment and after normalization of the VEGF levels suggested that glomerular microangiopathy had developed due to VEGF, while biclonal gammopathy was not eliminated. The renal pathology, proteinuria, and renal function all clearly improved. Although severe polyneuropathy limited activities of daily living and enforced a bedridden state, the patient dramatically regained his motor function, achieving crutch walking after induction of remission. This case is highly notable due to the presence of biclonality and repeated biopsies.

Levels of Soluble NKG2D Ligands and Cancer History in Patients Starting Hemodialysis.

Background: Immune dysfunction in hemodialysis patients is partially due to NK cell impairment. Ligands for NK activating receptors such as NKG2D expressed on cancer cells are involved in NK cell dysfunction and can lead to cancer development. Methods: A cohort with 370 patients who started hemodialysis (HD) was investigated. Serum levels of soluble NKG2D ligands were measured. Cancer history was defined as any cancer diagnosis at induction and hospitalization and death due to cancer during 2-year follow-up. Results: Sixty-two patients with and 308 patients without a cancer history showed mostly comparable biochemical parameters and uremic status at HD induction. Soluble MICB, ULBP-1, and ULBP-2 were detected in sera from most patients starting HD rather than MICA, the most representative NKG2D ligand. Measured NKG2D ligands, except for ULBP-1, were strongly correlated with each other. Correlations between NKG2D ligands and renal function were significant but modest in patients starting HD. Cancer history did not have any impact on levels of soluble NKG2D ligands. Discussion: Even though this investigation lacked a control cohort and serial measurement of parameters, expression patterns of NKG2D ligands were comprehensively described, and the significance of cancer in patients starting HD was elucidated for the first time. Elevated levels of soluble NKG2D ligands occurred potentially due to complex mechanisms of oxidative stress, with insufficient metabolism and excretion in a uremic milieu, but they might mask the significance of elevations in serum levels of soluble NKG2DLs in patients with a cancer history.

Ratio of serum creatinine to cystatin C is related to leg strength in predialysis CKD patients.

BACKGROUND AND OBJECTIVES: Chronic kidney disease (CKD) patients have lower levels of physical function. Especially, leg strength is important for daily living and preventing falls. However, physical function screenings are difficult to perform at clinical sites. To find clinically useful method to evaluate physical function in predialysis CKD patients, we tried to evaluate the relationship between the ratio of serum creatinine to serum cystatin C (Cre/CysC), and knee extensor muscle strength/body weight (KEMS) which reflects their leg strength. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We recruited 147 outpatients with CKD (87 men; mean age, 61.6 ± 9.8 years; mean eGFRcreat, 40.7 ± 12.9 mL/min/1.73m2) in this cross-sectional study. KEMS was assessed using a wire strain gauge dynamometer. Skeletal muscle mass and body fat mass were assessed by bioelectrical impedance analysis. RESULTS: The mean value of Cre/CysC was 1.01 ± 0.18. The mean value of KEMS was 1.60 ± 0.47 Nm/kg. In multivariate linear regression analysis, skeletal muscle mass (p < 0.01), body fat mass (p < 0.01), hemoglobin (p = 0.01), and Cre/CysC (p < 0.01) was independently related to KEMS. The correlation between Cre/CysC and KEMS is stronger in high quantile of Cre/CysC. CONCLUSIONS: In predialysis CKD patients, KEMS showed lower as CKD stage advanced. Cre/CysC is significantly related to KEMS independently. Cre/CysC may be an alternative marker for leg strength in CKD patients and even more valuable to utilize in cases with high Cre/CysC.

Physical functioning in patients with chronic kidney disease stage G3b-5 in Japan: The reach-J CKD cohort study.

AIM: Chronic kidney disease (CKD) is an important public health problem. Recently, CKD has been found to be associated with poor physical functioning in community-dwelling elderly individuals. However, the physical functioning of non-dialysis (ND) patients with advanced CKD treated by nephrologists is unknown. METHODS: Patients with ND-CKD stage G3b-5 who participated in a nationwide Reach-J CKD cohort study were included in this study. Physical functioning and physical activity were assessed by the Katz Index, Lawton-Body instrumental activities of daily living (IADL) scale, and Rapid Assessment of Physical Activity questionnaire of the international CKD Outcomes and Practice Patterns Study (CKDopps) questionnaires. Dichotomies between good and poor physical functioning and physical activity scores were explored. RESULTS: Among 1628 patients, 84.3% had good physical functioning. Poor physical functioning was more common with older age (p < .001), higher CKD stage (p < .05), and comorbid conditions such as diabetes (p < .001), cardiovascular disease (p < .05), cerebrovascular disease (p < .001), and cancer (non-skin) (p < .05). Forty percent of the patients were inactive. Physical inactivity was more common with older age (p < .001) and higher CKD stage (p < .001). CONCLUSION: A minority, but sizeable proportion of patients with advanced CKD treated by nephrologists in Japan have some disability in ADLs/IADLs. Nephrologists need to routinely assess the physical functioning and physical activity of patients with advanced CKD to provide individualized guidance and comprehensive support to these patients for their daily life.

Estimating the prevalence of definitive chronic kidney disease in the Japanese general population.

BACKGROUND: Most data on chronic kidney disease (CKD) prevalence has been based on single measurements of renal function and proteinuria. The aim was to determine the prevalence of CKD diagnosed by chronic proteinuria and/or reduced eGFR in a recent year in Japan. METHODS: In the main study, using a population-based cohort in Japan, the overall prevalence of CKD, defined as persistent positive proteinuria and/or eGFR < 60 ml/min/1.73 m2, was determined. Of 2,849,557 persons, 763,104 had data for eGFR and proteinuria in both 2014 and 2015. For estimating number of CKD cases in Japanese adults, a regional cohort data with age ranging 22-87 years (N = 22,037) was further applied to the analysis. RESULTS: Definitive CKD was present in 2.3-23.0% of men and 1.7-17.1% of women age from 40 to 74 years in the main cohort. The estimated prevalence of reduced eGFR and/or proteinuria in the baseline year alone was 15.7% in men and 13.6% in women; the prevalence of definitive CKD was 10.9% in men and 9.2% in women. The number of CKD cases based on a single-year test in Japanese adults over 20 years of age increased from 13.3 million to 14.8 million between 2005 and 2015. CONCLUSIONS: Recent changes in prevalence of CKD seem to be mainly caused by an increase in Japan's elderly population. Although past reports may lead to overdiagnosis of CKD by a single-year test, the estimated number of definitive CKD was 10.2 million in 2015.

Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis.

Natural killer (NK) cells are known to play an important role in defense against infection and tumors. Although there is no clear consensus, most studies have shown that the number and cytotoxicity of NK cells decreases in end-stage kidney disease (ESKD) patients undergoing hemodialysis. Uremic patients chronically suffer from oxidative stress, which could be responsible for downregulation of the activating receptors on NK cells and modulation of ligand expression for activating receptors. Theoretically, the reduced number of NK cells and decreased function might increase susceptibility to viral infections and cancer development in patients with ESKD. There is emerging evidence that NK cell numbers may be an outcome predictor in renal transplantation; however, the clinical significance of NK cell dysfunction in dialysis patients requires clarification. In this review, I describe NK cell number, cytotoxic activity, and activating mechanisms in the context of uremia and oxidative stress, which is anticipated to assist in elucidating the mechanisms underlying immunodeficiency in dialysis patients.

Recovery from severe metabolic alkalosis with acute kidney injury due to gastric cancer: a case report.

Objective: Most cases of severe metabolic alkalosis have many causes that may result in renal failure and death. Therefore, these should be treated promptly for successful recovery. Patient: A 61-year-old man was hospitalized due to an acute kidney injury (creatinine level of 4.36 mg/dL) after a 3-month history of anorexia and recurrent vomiting. He had been treated for tuberculosis in the past. Results: Blood gas analysis revealed severe metabolic alkalosis with pH=7.66, HCO3=94 mmol/L, and pCO2=82.0 mmHg. Routine biochemical examination revealed severe hypokalemia (K 2.9 mEq/L) that was associated with prolonged QTc interval (0.52 seconds) on the electrocardiogram. Gastrofiberscopic examination also revealed severe stenosis and ulcerated scarring of the gastric pylorus and severe esophagitis. Intravenous hydration and correction of hypokalemia improved renal function and resolved metabolic alkalosis. An investigation that was repeated after 6 days revealed a creatinine level of 1.58 mg/dL, pH=7.47, HCO3=23.4 mmol/L, K=3.6 mEq/L, and QTc of 0.45 seconds. The patient underwent gastrectomy and adenocarcinoma was observed. Conclusion: We described a resolved case of severe metabolic alkalosis and acute kidney injury in a rural medical setting following conservative management.

Literature review of allograft adenovirus nephritis and a case presenting as mass lesions in a transplanted kidney without symptoms of urinary tract infection or acute kidney injury.

Adenovirus (AdV) infection is a common complication in bone marrow/hematopoietic stem cell transplant and solid organ transplant recipients. AdV infection usually presents as hemorrhagic cystitis, but sometimes it can progress to acute kidney injury showing AdV nephritis (AdVN). We present the case of a 52-year-old Japanese female who had received a living kidney transplantation (KT) from her husband. At 21 months post-KT, the patient presented with a fever, but no renal dysfunction and no abnormal urine findings. A contrast-enhanced computed tomography (CT) scan revealed a few mass lesions with hypoperfusion in the transplanted kidney. An enhanced CT-guided biopsy targeting one of these lesions revealed a necrotizing tubulointerstitial nephritis suggesting AdVN. The polymerase chain reaction tests for ADV were negative in a urine sample but positive in the sera and the frozen kidney biopsy samples. AdVN can manifest as an unusual pattern of acute lobar nephritis/acute focal bacterial nephritis-like localization without symptoms of acute kidney injury or urinary tract infection. Enhanced CT can provide clues for clinical diagnosis.

Anti-PM/Scl Antibody-positive Systemic Sclerosis Complicated by Multiple Organ Involvement.

A 40-year-old Japanese woman developed malignant-phase hypertension complicated by thrombotic microangiopathy, progressing to end-stage renal disease. Five years later, she was diagnosed with pulmonary arterial hypertension and interstitial pneumonia. Despite a lack of overt skin sclerosis, nucleolar staining in our indirect immunofluorescence analysis and nailfold capillaroscopy facilitated the diagnosis of anti-PM/Scl antibody-positive systemic sclerosis. We observed the persistent presence of anti-PM/Scl antibodies throughout the clinical course, suggesting that her kidney disease was scleroderma renal crisis. Anti-PM/Scl antibodies can be associated with multiple organ diseases. Careful attention to a patient's antinuclear antibody pattern and dermatological findings may help clarify the etiology of undiagnosed diseases.

Co-inhibitory Receptor Signaling in T-Cell-Mediated Autoimmune Glomerulonephritis.

Autoimmune glomerulonephritis occurs as a consequence of autoantibodies and T-cell effector functions that target autoantigens. Co-signaling through cell surface receptors profoundly influences the optimal activation of T cells. The scope of this review is signaling mechanisms and the functional roles of representative T-cell co-inhibitory receptors in the regulation of autoimmune glomerulonephritis, along with current therapeutic challenges mainly on preclinical trials. Co-inhibitory receptors utilize both shared and unique signaling pathway, suggesting specialized functions that provide the rationale behind therapies for autoimmune glomerulonephritis by targeting these inhibitory receptors. These receptors largely suppress Th1 immunity, modify Th17 and Th2 immune response, and enhance Treg function. Anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immunoglobulin (Ig), which is able to block both activating CD28 and inhibitory CTLA4 signaling, has been shown in preclinical and clinical investigations to have effects on glomerular disease. Other inhibitory receptors for treating glomerulonephritis have not been clinically tested, and efficacy of manipulating these pathways requires further preclinical investigation. While immune checkpoint inhibition using anti-CTLA4 antibodies and anti-programmed cell death 1 (PD-1)/PD-L1 antibodies has been approved for the treatment of several cancers, blockade of CTLA4 and PD-1/PD-L1 is associated with adverse effects that resemble autoimmune disorders, including systemic vasculitis. A renal autoimmune vasculitis model features an initial Th17 dominancy followed later by a Th1-dominant outcome and Treg cells that attenuate autoreactive T-cell function. Toward the development of effective therapies for T-cell-mediated autoimmune glomerulonephritis, it would be preferable to pay attention to the impact of the inhibitory pathways in immunological renal disease settings.

Cause-specific mortality in the general population with transient dipstick-proteinuria.

Recently, changes in urinary albumin and in GFR have been recognized as risk factors for the development of end-stage kidney disease and mortality. Though most clinical epidemiology studies of chronic kidney disease (CKD) used renal function and proteinuria at baseline alone, definitive diagnosis of CKD with multiple measurements intensifies the differences in the risk for mortality between the CKD and non-CKD populations. We hypothesized that a transient diagnosis of proteinuria and reduced renal function each indicate a significantly higher mortality compared to definitive non-CKD as the negative control and lower mortality compared with definitive CKD as the positive control. The present longitudinal study evaluated a general-population cohort of 338,094 persons who received annual health checkups, with a median 4.3-year study period. There were 2,481 deaths, including 510 CVD deaths (20.6%) and 1,328 cancer deaths (53.5%), and mortality risk was evaluated for transient proteinuria and for transiently reduced renal function. The hazard ratios (HRs) for all-cause mortality and cancer mortality were not significant, but that for cardiovascular mortality was significantly higher for transient proteinuria (HR, 1.94 [95% confidence interval, 1.27-2.96] in men and 2.78 [1.50-5.16] in women). On the other hand, transiently reduced renal function was not significant for either cardiovascular mortality risk or cancer mortality risk. We surmise that this is the first study of the mortality risk of transient dipstick proteinuria in a large general-population cohort with cause-specific death registration. Transiently positive proteinuria appears to be a significant risk specifically for cardiovascular mortality compared with definitely negative for proteinuria.

A nationwide prospective cohort study of patients with advanced chronic kidney disease in Japan: The Reach-J CKD cohort study.

BACKGROUND: Epidemiology and outcomes of Japanese patients with advanced chronic kidney disease (CKD)-an estimated glomerular filtration rate (eGFR) < 45 ml/min/1.73 m2-has remained largely unexamined. METHODS: We conducted a nationwide survey to determine the distribution of Japanese CKD patients, and are conducting a cohort study of these patients. A questionnaire eliciting details about facilities and their CKD practices was sent to all clinics/hospitals with nephrologists. Based on the survey results, we recruited 2400 advanced CKD patients receiving nephrologist care from at least 30 representative facilities throughout Japan, selected randomly with stratification by region and facility size. Through patient questionnaires and nephrologist-practice surveys aligned with the international CKD Outcomes and Practice Patterns Study (CKDopps), we shall annually or semi-annually collect patient, physician and clinic data prospectively, detailing CKD practices for 5 years, with a primary outcome of death or renal replacement therapy initiation, and secondary outcomes being decline of eGFR by 30% or 50%, CKD progression to CKD G5, or a cardiovascular event. RESULTS: Of 790 eligible, responding facilities, 330 (41.8%) treat ≥80 advanced CKD patients in the average 3-month period. Regional distribution of these facilities is similar to that of persons in the general population. Hence, the 30 facilities selected for data collection appear to be geographically representative in Japan. CONCLUSIONS: Our study will enhance understanding of various CKD practices and biological data associated with CKD progression, and allow international comparisons using the CKDopps platform. This will provide evidences to improve the health and quality of life for patients with advanced CKD.

Involvement of pentraxin-3 in anti-neutrophil cytoplasmic antibody production induced by aluminum salt adjuvant.

OBJECTIVES: Pentraxin 3 (PTX3) is a multifunctional soluble factor. PTX3 can be involved in the regulation of vasculitis and is expressed in the cytoplasm of neutrophils. As anti-neutrophil cytoplasmic antibody (ANCA) is recognised as a cause of vasculitis, we aimed to discover the role of PTX3 in ANCA production in vivo. METHODS: To this end, we used aluminum salt (alum), which induces neutrophil extracellular traps, as an adjuvant for producing anti-myeloperoxidase-ANCA (MPO-ANCA). Specifically, we intraperitoneally injected alum and recombinant MPO (rMPO) into MPO-deficient mice and then measured the concentration of anti-MPO IgG in their blood. To show the involvement of extracellular PTX3 in this model, we assessed PTX3 protein content and host double-stranded DNA levels in the mice's peritoneal fluid after alum injection. In addition, we simultaneously administered recombinant PTX3, rMPO and alum to MPO-deficient mice to assess the function of PTX3 in producing anti-MPO IgG in vivo. RESULTS: Anti-MPO IgG was produced by the alum + rMPO immunisation model in MPO-deficient but not wildtype mice. Injection of alum induced extracellular PTX3 as well as double-stranded DNA and dead cells in MPO-deficient mice. Simultaneous injection of recombinant PTX3 with rMPO and alum attenuated the production of anti-MPO IgG in MPO-deficient mice. CONCLUSIONS: Our current findings provide evidence that PTX3 attenuates the production of murine MPO-ANCA.

Two autosomal dominant polycystic kidney (ADPKD) cases with advanced renal dysfunction, effectively treated with tolvaptan.

We report here two cases of autosomal dominant polycystic kidney disease (ADPKD) with renal dysfunction that were treated with tolvaptan. Case 1 was a 47-year-old man with a glomerular filtration rate (GFR) of 17.0 ml/min/1.73 m2 who received tolvaptan treatment (30 mg/day). After treatment, kidney pain was alleviated, and the estimated GFR (eGFR) decline improved from -9.84 ml/min/1.73 m2 per year to -4.08 ml/min/1.73 m2 per year, respectively. The rate of increase in total kidney volume was reduced from 18 % per year before treatment to 4 % per year following tolvaptan administration. Case 2 was a 44-year-old man with a GFR of 22.6 ml/min/1.73 m2, and the eGFR decline improved from -5.76 ml/min/1.73 m2 per year before treatment to -3.12 ml/min/1.73 m2 per year following tolvaptan treatment (30 mg/day). The rate of increase in total kidney volume was also decreased from 10 % per year before treatment to -7 % per year following tolvaptan administration. These results suggested that tolvaptan may be effective in impeding kidney function aggravation and kidney volume increase in ADPKD patients with advanced renal dysfunction.