Association of hyperphosphatemia with renal prognosis in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Serum phosphate (P) levels are generally lower in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney disorders, potentially masking the clinical significance of hyperphosphatemia. This study aimed to determine if serum P levels can predict renal outcomes in ADPKD patients. METHODS: We included 235 patients with ADPKD who were not taking drugs to treat hyperphosphatemia. Survival analysis was performed for the renal outcome of a 50% reduction in estimated glomerular filtration rate or initiation of renal replacement therapy. RESULTS: Multivariable Cox regression analyses revealed that serum P (1 mg/dL increase, HR = 2.03, P < 0.0001) was a significant risk factor for kidney disease progression. Similarly, hyperphosphatemia (P > 3.5 mg/dL, HR = 2.05; P > 4.0 mg/dL, HR = 1.90; P > 4.5 mg/dL, HR = 2.78; P > 5.0 mg/dL, HR = 27.22) was significantly associated with renal prognosis. Kaplan-Meier analysis showed significantly lower kidney survival rates in patients with P > 3.5 mg/dL than in those without hyperphosphatemia (log-rank test, P < 0.0001), and similar Kaplan-Meier analysis results were found for P > 4.0 mg/dL, P > 4.5 mg/dL, and P > 5.0 mg/dL. The 2 year kidney survival rate for ADPKD patients with P > 3.5 mg/dL was 66.7% overall and 41.4% in those with stage 4-5 CKD. For patients with P > 4.0 mg/dL, the survival rate dropped to 46.8% overall and 28.2% in those with stage 4-5 CKD, indicating a very poor prognosis. CONCLUSION: Hyperphosphatemia was associated with renal prognosis in patients with ADPKD. In these patients, attention should be paid to even mild serum P elevation of > 3.5 or > 4.0 mg/dL.

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.

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.

Public support for patients with intractable diseases in Japan: impact on clinical indicators from nationwide registries in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Clinical practice guidelines recommend antihypertensive and tolvaptan therapies for patients with autosomal dominant polycystic kidney disease (ADPKD) in Japan. However, tolvaptan therapy may pose an economic burden. The Japanese Ministry of Health, Labour and Welfare supports patients with intractable diseases. This study aimed to confirm the impact of the intractable disease system in Japan on the clinical treatment of ADPKD. METHODS: We analyzed the data of 3768 patients with ADPKD having a medical subsidy certificate from the Japanese Ministry of Health, Labour and Welfare in 2015-2016. The following quality indicators were use: the adherence rate to the 2014 clinical practice guideline for polycystic kidney disease (prescription rates of antihypertensive agents and tolvaptan in this cohort) and the number of Japanese patients with ADPKD nationwide started on renal replacement therapy in 2014 and 2020. RESULTS: Compared with new applications from 2015 to 2016, the prescription rates of antihypertensives and tolvaptan for the indicated patients at the 2017 renewal application increased by 2.0% (odds ratio = 1.41, p = 0.008) and 47.4% (odds ratio = 10.1, p > 0.001), respectively. These quality indicators improved with antihypertensive treatment, especially in patients with chronic kidney disease stages 1-2 (odds ratio = 1.79, p = 0.013) and in those aged < 50 years (odds ratio = 1.70, p = 0.003). The number of patients with ADPKD who were started on renal replacement therapy in Japan decreased from 999 in 2014 to 884 in 2020 in the nationwide database (odds ratio = 0.83, p < 0.001). CONCLUSIONS: The Japanese public intractable disease support system contributes to improvement of ADPKD treatment.

Initial decline in eGFR to predict tolvaptan response in autosomal-dominant polycystic kidney disease.

BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. METHODS: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The initial eGFR change was - 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. CONCLUSIONS: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.

Safety and efficacy of Tolvaptan in real-world patients with autosomal dominant polycystic kidney disease- interim results of SLOW-PKD surveillance.

BACKGROUND: Tolvaptan is a vasopressin type 2 receptor antagonist and has been used to treat autosomal dominant polycystic kidney disease (ADPKD) since 2014. There has been limited real-world data on the safety and efficacy of tolvaptan. METHODS: This post-marketing surveillance was conducted to evaluate the long-term safety and the efficacy of tolvaptan in Japanese patients with ADPKD in real-world clinical settings. The baseline characteristics of 1630 patients treated with tolvaptan are reported. Safety analysis comprises evaluation of adverse drug reactions (ADRs). The efficacy evaluation includes percent change in total kidney volume (TKV) and change in estimated glomerular filtration rate (eGFR) before and after tolvaptan treatment. RESULTS: Mean age was 49.7 ± 11.2 years and 843 (51.7%) patients were male. Baseline TKV was 2158 ± 1346 mL and eGFR was 44.4 ± 21.7 mL/min/1.73 m2. The majority of CKD patients were stage G3b (27.0%) and G4 (30.1%). Frequently reported ADRs were hepatic function abnormal (8.3%), thirst (8.2%), and hyperuricaemia (6.9%). The frequency of ALT elevation (> 30 and > 90 IU/L) was slightly high (32.9 and 8.3%) to previous studies. After tolvaptan treatment, the annual rate of percentage change in TKV reduced from 11.68%/year to 2.73%/year (P < 0.0001). Similar results were also obtained for the effect on change in eGFR from - 3.31 to - 2.28 mL/min/1.73 m2/year after initiation of tolvaptan treatment (P = 0.0403). CONCLUSION: There were no major problems with safety of tolvaptan treatment and comparable efficacy for TKV and eGFR was observed in relation to the previous pivotal two randomized control trials in this post-marketing surveillance.

Factors predicting decline in renal function and kidney volume growth in autosomal dominant polycystic kidney disease: a prospective cohort study (Japanese Polycystic Kidney Disease registry: J-PKD).

BACKGROUND: Factors affecting decline in renal function and cyst growth in patients with autosomal polycystic kidney disease (ADPKD) are not fully described, particularly in Japan. METHODS: This was the first multi-facility, prospective, observational cohort study conducted in ADPKD patients at 14 centers in Japan. Patients in the J-PKD registry were assessed from December 2009 to June 2012 (follow-up until June 2017). Patients' data including estimated glomerular filtration rate (eGFR) and total kidney volume (TKV) were assessed initially and a maximum of five times annually. Contributing factors to eGFR decline and TKV growth were identified using multiple linear regression analysis. RESULTS: Of the 340 patients in the J-PKD registry, data analysis was performed for 192 patients in whom serial changes for both eGFR and TKV were obtained. eGFR slope, eGFR change, and TKV change values were as follows: - 2.7 (- 4.2 to - 1.5) (ml/min/1.73 m2/year), - 5.0 (- 9.6 to - 2.3) (%/year), and 4.78 (0.86-8.22) (%/year), respectively. Lower high-density lipoprotein (HDL) cholesterol was an independent predictor of eGFR decline, using both eGFR slope and change (P = 0.04, P = 0.02, respectively), whereas lower hemoglobin and higher uric acid were significantly associated with greater eGFR change only (P = 0.02, P = 0.002, respectively). Younger age and higher fasting blood sugar were independent predictors of greater TKV change (P = 0.01, P = 0.02, respectively). CONCLUSIONS: This real-world study in Japan identified risk factors for renal function decline in ADPKD patients. These included lower HDL cholesterol, lower hemoglobin and higher uric acid for eGFR decline, and youth and higher blood sugar levels for TKV growth.

Impact of visceral fat area in patients with chronic kidney disease.

Longitudinal studies evaluating the association between visceral fat area (VFA) and kidney function decline in patients with chronic kidney disease (CKD) are limited, and little is known about VFA interactions contributing to the kidney prognosis (e.g. interactions between VFA ≥ 100 cm2 and age, sex, and CKD category). In this study, we stratified patients with CKD according to VFA category, as well as age, sex, CKD category, hyperglycemia, and diabetes mellitus, and determined the ability of obesity-related indicators (body mass index, waist circumference, subcutaneous fat area, visceral-to-subcutaneous fat ratio) to predict the renal prognosis. Kidney outcomes (≥ 50% estimated glomerular filtration rate decline or end-stage kidney disease) were examined in 200 patients with CKD (median follow-up, 12.3 years). On multivariable Cox analysis, an increase in VFA (10-cm2 increase) was significantly associated with kidney outcomes in the entire cohort, and VFA was significantly associated with kidney disease progression even in the VFA < 100 cm2 sub-cohort. Interestingly, the hazard ratio (HR) was higher for VFA (10-cm2 increase) than for the VFA ≥ 100 cm2 sub-cohort (HR 1.33 vs. 1.07). Overall, VFA was found to be the most versatile obesity-related indicator associated with kidney disease progression. VFA was associated with the primary outcome in the sub-cohorts of CKD stages 1-2, hyperglycemia, and diabetes mellitus. A high VFA was a significant kidney prognostic factor in the entire CKD cohort, with greater significance in patients with VFA < 100 cm2 than in patients with VFA ≥ 100 cm2. Our results may provide new insights into strategies for treating CKD.

Association between anemia and renal prognosis in autosomal dominant polycystic kidney disease: a retrospective study.

BACKGROUND: Though anemia is a sign of poor renal prognosis in chronic kidney disease (CKD), hemoglobin (Hb) levels are typically higher in autosomal dominant polycystic kidney disease (ADPKD) than in other kidney diseases, and anemia has not been examined as a potential prognosticator. Thus, we investigated anemia as a factor for renal prognosis in ADPKD. METHODS: In total, 115 non-dialysis patients, 48 men and 67 women, with ADPKD were evaluated. The renal outcome of a 50% reduction in the estimated glomerular filtration rate or renal replacement therapy was examined using the Cox regression analysis and Kaplan-Meier analysis. RESULTS: Patients were followed for a median of 5.5 years and 50 patients had reached the end point. The mean age of the patients at the first visit was 45.9 ± 13.3 years. The overall mean Hb was 12.90 ± 1.85 g/dL, and the mean Hb in men and women was 13.82 ± 1.72 g/dL and 12.25 ± 1.65 g/dL, respectively. Hb levels and uric protein content were statistically significant factors for poor renal prognosis, while hypertension and genetic mutations failed to reach significance. Furthermore, statistical significance was found in men with Hb < 12 g/dL and in women with Hb < 11 g/dL. Anemia had significant association with kidney disease progression in patients with ADPKD. CONCLUSIONS: We found that anemia might be a factor for poor renal prognosis in ADPKD. Furthermore, a sex difference was found, wherein men with Hb < 12 g/dL and women with Hb < 11 g/dL were at risk of renal disease progression.

The relationship between liver cyst volume and QOL in Japanese ADPKD patients.

BACKGROUND: Although it is widely accepted that the autosomal dominant polycystic kidney disease (ADPKD) patients with large liver cysts have a significant decrement in quality of life (QOL), there is insufficient evidence that clearly demonstrates the relationship between the size of the liver cysts and QOL. Therefore, we started this prospective longitudinal study to investigate the impact of liver cysts on QOL. METHODS: We grouped the 111 included ADPKD patients into 4 groups (control group A; < 25%, group B; 25-49%, group C; 50-75%, group D; > 75%) according to liver cysts-parenchyma ratio (CPR). QOL was measured by FANLTC + FACT-Hep scores. We compared QOL scores and several clinical parameters amongst these groups for 3 years. RESULTS: The number of patients in group A, B, C, and D was 31, 14, 14, and 23, respectively. Although there were no significant differences in AST (p = 0.107), ALT (p = 0.925), and serum albumin (p = 0.212) between the four groups, platelet count was significantly decreased along with the extension of cyst volume (p = 0.030). Overall, the mean FANLTC and FACT-Hep scores were 71.8 ± 12.5, and 32.4 ± 5.8, respectively. FANLTC (p = 0.017) and FACT-Hep scores (p = 0.003) were significantly decreased with increasing cyst volume. From the data collected at the time of registration, multivariate linear regression analysis demonstrated that the CPR had a significant influence on FANLTC and FACT-Hep scores. CONCLUSION: In this cross-sectional and prospective longitudinal study, we demonstrate the relationship between liver cyst volume and QOL in ADPKD patients. We hope to establish the long-term influence on QOL in this ongoing prospective longitudinal study.

A Body Mass Index-Based Cross-Classification Approach for the Assessment of Prognostic Factors in Chronic Kidney Disease Progression.

BACKGROUND/AIMS: Cross-classification analyses are rarely reported. We investigated the prognostic factors for chronic kidney disease (CKD) progression using a body mass index (BMI)-based cross-classification approach. METHODS: Patients' renal outcome (≥50% decline in the estimated glomerular filtration rate or end-stage renal disease) in each subcohort was examined. RESULTS: The number of prognostic factors identified in the multivariate Cox analysis was smaller in the "BMI ≥25, female" and CKD stage 3 subcohorts than in other subcohorts. Prognostic factors identified in the "BMI ≥25, CKD stage 3" subcohort only comprised albuminuria and male sex, and those in the "BMI ≥25, female" subcohort only comprised albuminuria, hyperphosphatemia, and anemia. Albuminuria, kidney impairment, male sex, hyperphosphatemia, anemia, and increased pulse pressure × heart rate product (PP × HR; pulsatile stress) were stable renal prognostic factors in almost all subcohorts. On the other hand, the prognostic value of increased BMI, younger age, hypoalbuminemia, increased intact parathyroid hormone, and decreased estimated 24-h urinary potassium excretion (e24hUK) differed according to subcohort. BMI was positively associated with CKD progression in the "BMI ≥25, age ≥65 years" and "BMI ≥25, CKD stages 4-5" subcohorts, whereas it was negatively associated with CKD progression in the "BMI <25, diabetes mellitus" subcohort. PP × HR was independently associated with CKD progression in the "BMI <25, CKD stage 3" subcohort, which had relatively few identified renal prognostic factors. Decreased e24hUK was a renal prognostic factor for CKD progression in the "BMI <25, CKD stages 4-5" subcohort, while no significant factors were observed in the "BMI ≥25, CKD stages 4-5" subcohort. CONCLUSION: A BMI-based cross-classification approach, which provides more comprehensive findings than that in previous approaches, is expected to be an effective method for evaluating renal prognostic factors in patients with CKD who are affected by multiple risk factors.

Low HDL cholesterol as a predictor of chronic kidney disease progression: a cross-classification approach and matched cohort analysis.

Emerging epidemiological evidence indicates that low serum high-density lipoprotein cholesterol (HDL-C) levels are associated with the risk of progression of chronic kidney disease (CKD). However, the differences in the influence of serum HDL-C levels on CKD progression in different subcohorts have rarely been examined in detail in previous studies. The aim of this study was to investigate the significance of low serum HDL-C levels as a predictor of disease progression in CKD patients according to sub-analyses using a cross-classified subcohort. We reviewed data obtained from 120 CKD patients. Prognostic factors for renal outcome were identified by the multivariate Cox proportional hazards method. Kaplan-Meier analysis was performed to assess disease progression, which was defined as a > 30% decline in the glomerular filtration rate (GFR), or end-stage renal disease. The mean age of the included participants was 58.3 ± 13.6 years. The subjects were divided into two groups (low HDL-C vs. high HDL-C). The median follow-up period was 112.8 months. The kidney survival rate in the low HDL-C group was significantly lower than that in the high HDL-C group (P < 0.0001). However, the age-stratified analysis showed no difference between the two groups in the cohort of patients ≥ 70 years old. Multivariate Cox regression analyses showed a significant association between low HDL-C [hazard ratio (HR) 4.80, P = 0.009] and a ≥ 30% eGFR decline or ESRD. This association was more evident in the cohort of patients < 70 years old (HR 4.96, P = 0.0165), especially the female subcohort (HR 13.86, P = 0.0033). Multivariate analysis showed a significant correlation between visceral fat area and serum HDL-C levels among both male (P = 0.0017) and female (P = 0.0449) patients. In a propensity score-matched cohort (patients < 70 years old), the kidney survival rate of CKD patients was significantly lower in the low HDL-C group than in the high HDL-C group (P = 0.0364). A low serum HDL-C level is a significant predictor of CKD progression, especially in female patients with CKD under 70 years of age. This finding is of importance to clinicians when determining the expected prognosis of CKD in patients.

Mutation analyses by next-generation sequencing and multiplex ligation-dependent probe amplification in Japanese autosomal dominant polycystic kidney disease patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), one of the most common hereditary kidney diseases, causes gradual growth of cysts in the kidneys, leading to renal failure. Owing to the advanced technology of next-generation sequencing (NGS), genetic analyses of the causative genes PKD1 and PKD2 have been improved. METHODS: We performed genetic analyses of 111 Japanese ADPKD patients using hybridization-based NGS and long-range (LR)-PCR-based NGS. Additionally, genetic analyses in exon 1 of PKD1 using Sanger sequencing because of an extremely low coverage of NGS and those using multiplex ligation-dependent probe amplification (MLPA) were performed. RESULTS: The detection rate using NGS for 111 patients was 86.5%. One mutation in exon 1 of PKD1 and five deletions detected by MLPA were identified. When combined, the total detection rate was 91.9%. CONCLUSION: Although NGS is useful, we propose the addition of Sanger sequencing for exon 1 of PKD1 and MLPA as indispensable for identifying mutations not detected by NGS.

Elevation of the serum liver enzyme levels during tolvaptan treatment in patients with autosomal dominant polycystic kidney disease (ADPKD).

BACKGROUND: In 2014, tolvaptan, a vasopressin receptor antagonist, was approved for the treatment of autosomal dominant polycystic kidney disease (ADPKD) in Japan. Clinical trials of tolvaptan revealed frequent occurrence of the liver function abnormality. According to the package insert in Japan, liver function tests should be performed once a month in patients receiving tolvaptan. Furthermore, immediate discontinuation of tolvaptan is recommended in the appearance of liver function abnormalities. METHODS: Seven patients of ADPKD who was discontinued tolvaptan because of elevation of the serum liver enzyme levels were described in detail and analyzed. RESULTS: None of them fulfilled the criteria for applicability of Hy's law, which predicts a high risk of severe, potentially fatal, drug-induced liver injury (DILI). In our patients, the rate of increase of total kidney volume (TKV) significantly decreased during tolvaptan administration, but increased after discontinuation; in Cases 1-5, mean annual growth rate of TKV during administration was - 10.15%/year, and during discontinuation was + 23.72%/year. After the serum liver enzyme levels returned to normal range, tolvaptan was resumed in six patients with informed consent. Except one patient, tolvaptan has been continued without increase of the serum liver enzyme levels. CONCLUSION: In patients with mild elevation of the serum liver enzyme, as is less than three times the upper limit of normal (ULN), resumption of tolvaptan may be considered after the serum liver enzyme levels return to normal range.

Defective renal autoregulation in the chronic bile duct ligation model of liver failure.

BACKGROUND: Cirrhosis of the liver is often associated with an impairment of renal function that is usually not associated with consistent structural abnormalities of the renal parenchyma, but is thought to be the functional consequence of arterial underfilling and reduced arterial blood pressure. METHOD: We have used the cirrhosis model of chronic bile duct ligation (BDL) to assess the response of renal blood flow to a change of blood pressure. We have measured renal haemodynamics in BDL rats. RESULT: Three weeks after BDL, rats showed elevated levels of total bilirubin, AST, and ALT as well as reduced arterial blood pressure. Creatinine clearance was significantly reduced, and plasma creatinine and urea nitrogen were elevated. Renal blood flow at baseline blood pressure was significantly lower in the BDL group than in the sham group. Clamp-induced reductions of renal perfusion pressure caused significantly greater changes of renal blood flow in BDL than control rats. The autoregulatory index over a comparable blood pressure range averaged 0.28 ± 0.35 in control rats and 1.26 ± 0.6 in BDL rats (p = 0.0004) indicating impairment of renal autoregulation in liver cirrhosis. CONCLUSION: Tubuloglomerular feedback (TGF) responses were significantly attenuated in BDL rats, especially in the subnormal flow range. Impairment of renal blood flow autoregulation, to some extent mediated by reduced TGF-mediated vasodilatation, may contribute to the renal vascular constrictor state in liver cirrhosis by preventing the full dilatory response to the blood pressure reduction.

Successful treatment with steroid and cyclosporine A in a patient with immunoglobulin A-proliferative glomerulonephritis with monoclonal immunoglobulin deposits.

We report a case of glomerulonephritis with monoclonal immunoglobulin (Ig) A deposits as a form of monoclonal gammopathy of renal significance (MGRS) caused by monoclonal immunoglobulins without blood disorders in a 41-year-old woman. She developed lower leg oedema and was hospitalized because of nephrotic syndrome. Serum and urine were negative for M protein, and the free light chain κ/λ ratio was within the normal range. Renal histopathological findings included mesangial proliferation, endocapillary cell proliferation, and a double-contour appearance of the capillary walls. Immunofluorescent staining indicated IgA and C3 deposits on the mesangium and capillary walls. Only λ chain and IgA1 deposits were noted. Fine granular sub-endothelial deposits with no specific structure were observed under electron microscopy. The patient was diagnosed with IgA-proliferative glomerulonephritis with monoclonal immunoglobulin deposits (IgA-PGNMID). The patient had decreased urine protein and sediment erythrocytes after she underwent two rounds of steroid pulse therapy and oral steroid therapy, but proteinuria and haematuria still remained. Four months later, the patient was administered 50 mg/day cyclosporine (CsA), and proteinuria and haematuria dramatically decreased. Only a few case reports have been published on IgA-PGNMID. This case is rare in that the patient achieved successful treatment using a combination of steroids and CsA.

Fibroblast growth factor 23 and soluble Klotho in patients with autosomal dominant polycystic kidney disease.

AIM: This study aimed to examine the roles of fibroblast growth factor 23 (FGF23) and soluble Klotho in phosphate metabolism in autosomal-dominant polycystic kidney disease (ADPKD) patients. METHODS: We measured these two factors and phosphate metabolism parameters in 80 patients with ADPKD and 53 patients with non-diabetic chronic kidney disease (CKD). RESULTS: The mean serum FGF23 level in the ADPKD group was significantly (twofold) higher than in the non-diabetic CKD patients, but the mean soluble Klotho level in the ADPKD group was significantly lower in the non-diabetic CKD group. The mean serum phosphate levels of the two groups were similar. The estimated glomerular filtration rate (eGFR) was approximately 45 mL/min per 1.73 m2 in both groups, and their serum vitamin D metabolite levels were in the normal range. CONCLUSION: The serum FGF23 levels were significantly higher and soluble Klotho levels significantly lower in the ADPKD group than in the non-diabetic CKD group matched for eGFR, and these findings may be associated with resistance of renal phosphate excretion.