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Background: Progression of aortic calcification is associated with all-cause and cardiovascular mortality in hemodialysis patients. Blood calciprotein particle (CPP) levels are associated with coronary artery calcification and were reported to be inhibited when using citric acid-based bicarbonate dialysate (CD). Therefore, this study aimed to examine the effect of CD on the progression of the aortic arch calcification score (AoACS) and blood CPP levels in hemodialysis patients., Methods: A 12-month retrospective observational study of 262 hemodialysis patients was conducted. AoACS was evaluated by calculating the number of calcifications in 16 segments of the aortic arch on chest X-ray (minimum score is 0; maximum score is 16 points). The patients were divided into the following groups according to their baseline AoACS: grade 0, AoACS = 0 points; grade 1, AoACS 1-4 points; grade 2, AoACS 5-8 points; grade 3, AoACS 9 points or higher. Patients on bisphosphonates or warfarin or with AoACS grade 3 were excluded. Progression, defined as ΔAoACS (12-month score - baseline score) > 0 points, was compared between the CD and acetic acid-based bicarbonate dialysate (AD) groups before and after adjusting the background using propensity score matching., Results: The AoACS progression rate was significantly lower in the CD group than in the AD group (before matching: P = 0.020, after matching: P = 0.002). Multivariate logistic regression analysis showed that CD was significantly associated with AoACS progression (odds ratio 0.52, 95% confidence interval 0.29‒0.92, P = 0.025)., Conclusion: CD may slow the progression of vascular calcification in hemodialysis patients., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Purpose: Central fibrous areas (CFAs) are small, hyalinotic, monotonous nodular areas observed in glomerular vascular pole lesions. We attempted to clarify the relationship between CFA formation and age in healthy kidneys and in those affected by immunoglobulin A (IgA) nephropathy., Methods: Zero-hour biopsy specimens from living renal donors (135 cases) and IgA nephropathy biopsy specimens (67 cases) were collected retrospectively. We observed each biopsy specimen and determined the total number of glomeruli, total level of glomerulosclerosis, number of observable glomerular vascular poles, number of glomeruli with CFAs, serum creatinine level, and estimated glomerular filtration rate (eGFR). Additionally, we calculated the glomerular sclerosis rate (GSR), vascular pole appearance rate (PAR), and CFA rate (CFAR) to evaluate the relationship between these factors and patient age., Results: There was a significant negative correlation between patient age and eGFR for both the zero-hour (p < 0.0001 in Spearman, p = 0.0009 in multiple regression, the same hereafter) and IgA (p = 0.0022, p = 0.0001) groups. In the zero-hour group, we observed a significant positive correlation between patient age and GSR (p = 0.0001, p < 0.0001); however, there was no such correlation in the IgA group. In both groups, there was a significant positive correlation between patient age and CFAR (zero-hour group: p = 0.0003, p = 0.0091, IgA group; p < 0.0001, p = 0.0004). The slope of the regression line of the IgA group formula was also significantly higher than that of the zero-hour group formula (p < 0.01)., Conclusion: These findings indicate that CFA may be a useful indicator of kidney aging, especially in patients with kidney disease caused by IgA nephropathy., (© 2022. The Author(s).)

Background: Tonsillectomy and steroid pulse therapy (TSP) for immunoglobulin A nephropathy (IgAN) is frequently employed in many Japanese institutions; however, performing this invasive treatment in patients with mild IgAN is controversial. This study aimed to evaluate the appropriate treatment for IgAN patients with mild proteinuria., Methods: In this retrospective cohort analysis, 122 IgAN patients with mild proteinuria (0.5-1.0 g/day) and estimated glomerular filtration rate of ≥ 60 mL/min/1.73 m 2 were classified into three groups as follows: patients treated with TSP (n = 32), oral prednisolone (oPSL, n = 33), and conservative therapy (CONS, n = 47). The clinical and histological backgrounds, 5-year remission rates of urinary findings, and 10-year renal survival rates were analyzed., Results: The backgrounds were similar among the three groups. The remission rates of hematuria, proteinuria, and both were significantly higher for TSP and oPSL than for CONS; however, they were similar for TSP and oPSL. In the multivariate Cox regression analysis, TSP and oPSL were independent factors for the remission of urinary findings compared with CONS; however, the relapse rates of urinary abnormalities were similar among the three groups. No patient progressed to end-stage renal disease (ESRD) within 10 years. Adverse effects of corticosteroid therapy were significantly more frequent in oPSL than in TSP., Conclusion: In IgAN patients with mild proteinuria and stable renal function, similar to oPSL, TSP showed higher remission rates of hematuria and/or proteinuria than CONS, and no case progressed to ESRD regardless of the treatment methods. Therefore, appropriate treatments should be carefully considered for each patient., (© 2021. Japanese Society of Nephrology.)

Background: Steroid pulse therapy with tonsillectomy is known as a major treatment for IgA nephropathy (IgAN). However, its protocol was different among institutions and the effects of varying the number of steroid pulses remain unclear., Methods: From a total of 1,174 IgAN patients in a multicenter retrospective cohort analysis in Japan, 195 patients were treated by tonsillectomy combined with corticosteroid. They were divided into four groups based on the number of administered steroid pulses from 0 to three (TSP0-3), and remission of urinary abnormalities and renal survival until 1.5-fold increase in serum creatinine level from baseline were analyzed among the four groups and between TSP1 and TSP3., Results: Among the four groups, renal function was relatively good when the estimated glomerular filtration rate was approximately 80-90 mL/min/1.73m 2 and proteinuria was relatively mild (< 1.0 g/gCre). The ratio of patients who developed renal dysfunction was < 5% in all groups, and the cumulative renal survival rate by Kaplan-Meier analysis was similar among groups (log-rank test, p = 0.37), despite varying clinical backgrounds and treatments. After adjustment of the background variables between TSP1 and TSP3, the remission rates of urinary abnormalities were similar and the renal survival rate also remained similar (66.8 vs. 85.4%, p = 0.45)., Conclusions: In patients with mild proteinuria and good renal function, the number of steroid pulses did not affect the renal outcome in steroid pulse therapy with tonsillectomy. The adaptation and protocols, such as the number of steroid pulses, should be determined for each IgAN patient's background.

Background: Preventing progression to end-stage renal disease (ESRD) in advanced IgA nephropathy (IgAN) patients with impaired renal function remains challenging. We analyzed the efficacy of tonsillectomy combined with steroid pulse therapy (TSP)., Methods: In this retrospective analysis, IgAN patients with proteinuria > 0.5 g/day and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 were divided into three groups: patients treated with TSP (TSP group; n = 23), oral prednisolone (oPSL group; n = 41), and conservative therapy (CONS group, n = 51). We analyzed the clinical and histological backgrounds, remission of urinary findings, and renal survival rate to a 25% decline in eGFR from baseline, and incidence of ESRD., Results: There were significant differences in the patients' backgrounds among the groups. Therefore, we adjusted the background using propensity score marching between TSP group and oPSL or CONS group. The 5-year remission rate of hematuria was significantly higher in the TSP group than in the oPSL group, and that of both hematuria and proteinuria was significantly higher in the TSP group than in the CONS group. The 10-year renal survival rate was significantly higher in the TSP group than in the oPSL and CONS groups. In a multivariate Cox regression analysis, TSP was found to be an independent factor for the 25% decline in eGFR in entire cohort. The adverse effect frequency in the TSP group was similar to the CONS group., Conclusions: TSP can effectively induce remission of urinary abnormality and improve the prognosis without frequent adverse effects in IgAN patients with impaired renal function.

Background: The clinical characteristics and treatment of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) after initiating chronic hemodialysis remain unknown., Methods: We retrospectively enrolled 11 adult patients with AAV receiving chronic hemodialysis in our hospital from 2000-2016. We collected data describing each patient's clinical findings and treatment before and after initiating hemodialysis. Patients with AAV with and without post-hemodialysis AAV relapse were compared statistically., Results: The average observation period was 6.8 ± 4.1 years, and the interval between diagnosis and initiating chronic hemodialysis was 1.9 ± 2.6 years. Before initiating chronic hemodialysis, five patients (45%) experienced 12 AAV relapses, with diagnoses made serologically or symptomatically. After initiating chronic hemodialysis, four patients experienced nine relapses, with no significant difference between the number of relapses and the number of patients experiencing relapse (p = 0.067 and 0.083, respectively). For patients' entire clinical courses before initiating chronic hemodialysis, the average steroid dose was 11.6 ± 6.9 g/y. Comparing before and after initiating chronic hemodialysis, the steroid dose decreased significantly to 3.3 ± 1.4 g/y after initiating chronic hemodialysis (p = 0.0012). Two of 11 patients died of serious infections after initiating chronic hemodialysis., Conclusions: Our results showed that the number of relapses tended to be lower despite a significantly different lower amount of steroid after initiating hemodialysis compared with before initiating hemodialysis, and the burn-out phenomenon specific to uremic patients was inferred. We believe that early tapering of steroids should be considered to avoid death rather than focusing only on relapse.

In the Original publication, the authors found few errors in the text.

Chronic glomerulonephritis is the second most common reason, after diabetic nephropathy, for initiation of dialysis in Japan and IgA nephropathy (IgAN) is the most prevalent form of chronic glomerulonephritis. In the half century since IgAN was initially reported, our understanding of the long-term prognosis, clinical and histological features, pathogenesis of onset and progression, risk factors for progression, and appropriate treatment under different clinical and histological conditions, has steadily increased. Strong experimental and clinical evidence, the Clinical Practice Guidelines for IgA Nephropathy in Japan, the Oxford Classification, and the Kidney Disease Improving Global Outcomes guidelines have all contributed to the appropriate treatment of IgAN. Several intensive therapies, such as tonsillectomy, steroid therapy, and their combinations, can result in clinical remission, and prevent the progression to end stage renal disease (ESRD). However, some IgAN patients still progress to ESRD even when treated with intensive therapies. In this review, we discuss the clinical and histological features of IgAN, focusing primarily on our previous reports, and our opinions on therapeutic strategies for IgAN.

Background: Global sclerosis has been reported as the risk factor of IgAN. In Oxford classification, global sclerosis was correlated with tubulointerstitial (T) lesions. Therefore, in patients with T lesions, renin-angiotensin system inhibitors (RASI) might be effective by decreasing glomerular hyperfiltration and hypertension. However, these beneficial effects of RASI have not been reported., Methods: In this retrospective cohort study, we divided 87 IgAN patients with T1/2 lesions into two groups: RASI group (n = 47, treated with RASI) and APA group (n = 40, treated with anti-platelet agents). We analyzed the background of each group, the serial changes of blood pressure and the amount of proteinuria (U-Prot), progression to end-stage renal disease, and the risk factors for progression., Results: After propensity score matching, 22 cases from each group were selected, and clinical and histological characteristics were similar. Serial changes of blood pressure had been significantly decreased in RASI group (p = 0.0029), but not in the APA group. Proteinuria was tended to decrease in RASI group, though it was not significant (1.14-0.47 g/gCre) and it was similar in APA group (0.95-0.85 g/gCre). 20 year renal survival rate was 59.5% in RASI group, whereas 21.3% in APA group (p = 0.0119). In multivariate Cox regression analysis, RASI was an independent factor to prevent from progression to ESRD (HR 5.91, p = 0.0039)., Conclusion: RASI has shown a significant beneficial effect on histologically advanced IgAN patients with T lesions. These results are compatible with the previous studies that reported the beneficial effects of RASI on clinically advanced IgAN patients.

Background: Recently, a new classification has been established for membranoproliferative glomerulonephritis (MPGN). However, the effect of the new classification on MPGN treatment is not fully understood., Methods: We conducted a retrospective study of 87 patients with biopsies diagnosed as MPGN. We reclassified 87 MPGN patients diagnosed between 1977 and 2014 at our hospital, according to the new classification, and analyzed both primary immune complex (IC)- and Alternative pathway (AP)-mediated MPGN [corrected] in terms of clinicopathological features, treatment, and renal prognosis., Results: Proteinuria was abundant in the IC-mediated MPGN group (p = 0.0063), and the serum albumin level was significantly lower in the IC-mediated MPGN group (p = 0.0186). The serum C3 value was significantly lower in the CP-mediated MPGN group (p = 0.0317). Serum CH50 values were also lower in the CP-mediated MPGN group (p = 0.0404). However, glomerular deposition of C3 showed no significant differences in immunofluorescence findings. The 148.6-month renal survival rate was similar in both groups (p = 0.445)., Conclusion: These results suggested no significant differences in complement activation of the solid phase in local glomeruli and therefore equivalent in renal prognosis [corrected].

Background: The objective of this study is to determine whether initial steroid therapy is actually effective for the treatment of iMN, and we examined a 40% reduction in estimated glomerular filtration rate (eGFR) and remission rates., Methods: This was a retrospective study between 1993 and 2013. First, we divided patients with iMN having a urinary protein level of ≥1 g/gCre into two groups: those who had received steroid therapy (Group S 1 ; n = 52) within 6 months of diagnosis and those who had received supportive therapy (Group H 1 ; n = 31). Second, we compared 20 cases using propensity score matching (Group S 2 , Group H 2 ). Third, we compared patients with a urinary protein level of 1-3.5 g/gCre (Group S 3 , n = 18; Group H 3 , n = 19) and those with a urinary protein level ≥3.5 g/gCre (Group S 4 , n = 34; Group H 4 , n = 12). The primary endpoint was a 40% reduction in eGFR, and the secondary endpoint was the achievement of complete remission (CR)., Results: In Group S 1 and Group H 1 , a 40% reduction in the eGFR was observed at the end of 5 years in 18 and 17% of the patients, respectively (P = 0.93); at the end of 10 years, these rates had increased to 43% and 50%, respectively (P = 0.88). The CR rates at the end of 5 years were 58% and 32%, respectively (P = 0.02), while the rates at 10 years were 65 and 39%, respectively (P = 0.02). No difference in renal outcomes was observed between Group S 1 and Group H 1 . No significant differences were observed between Group S 2 and Group H 2 , between Group S 3 and Group H 3 , or between Group S 4 and Group H 4 ., Conclusion: Initial steroid therapy is not superior to supportive care within the first 6 months after diagnosis in terms of a 40% reduction in eGFR.

Background: Treatment of IgA nephropathy (IgAN) in Japan has recently changed, from oral prednisolone (oPSL) to tonsillectomy plus steroid pulse (TSP) therapy. However, a few studies have compared their efficacy and safety., Methods: IgAN patients diagnosed in our institution between 1991 and 2013, treated with TSP or oPSL, aged ≥16 years, with ≥1 g/day proteinuria, and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m 2 , and no other renal disease were selected. Baseline clinical and histological findings, clinical outcomes, and adverse events were compared. Clinical remission (CR) was defined as <0.3 g/day proteinuria and <5 urinary red blood cells per high-powered field., Results: Sixty-six patients were identified; after propensity score adjustment, 26 patients were selected in each group. CR rates were significantly higher at 12 (30.8 % vs. 3.9 %), 36 (47.3 % vs. 7.9 %), and 72 (57.8 % vs. 20.1 %) months (p < 0.01), and the renal survival rate, defined as the development of a 25 % reduction from baseline eGFR, was significantly higher at 12 (96.2 % vs. 69.2 %), 36 (96.2 % vs. 61.5 %), and 72 (96.2 % vs. 41.0 %) months in the TSP than the oPSL group (p < 0.001). Multivariate analysis showed that TSP was the only independent factor associated with CR (hazard ratio, 3.58; 95 % confidence interval, 1.32-10.91, p = 0.01). The number of patients with adverse events was significant lower in TSP group than in oPSL group (11.5 % vs. 34.6 %, p = 0.04)., Conclusions: CR rates are higher; protection of renal function and prevention from adverse events were superior with TSP than with oPSL in patients with IgAN and moderate-to-severe proteinuria.

Background: We previously demonstrated the efficacy of single-dose 6-monthly rituximab infusions in 25 adults with steroid-dependent minimal-change nephrotic syndrome. Herein, we assessed the safety of rituximab treatment and its effect in ameliorating the adverse effects of prednisolone (PRED) in a larger study sample., Methods: We treated 54 adult patients with four single-dose 6-monthly infusions of rituximab (375 mg/m(2) BSA per dose). We compared the adverse effects of PRED (osteoporosis, hypertension, and diabetes mellitus) between the first rituximab infusion (baseline) and the end of the 24-month observation period. In addition, we examined the adverse effects of rituximab during the same period., Results: The PRED dose was significantly lower at 24 months than at the baseline. The bone density was significantly higher at 24 months as compared to the baseline value (Z score -1.8 vs. -1.1; p < 0.05). Blood pressure at 24 months was significantly lower than that at the baseline (120.9/74.4 vs. 111.8/70.3 mm Hg; p < 0.05). Eight patients with diabetes mellitus showed improved glycemic control at 24 months as compared to that at the baseline. There were no severe adverse effects of rituximab. However, mild infusion reactions occurred in 31 patients (57%). The frequency of the infusion reactions decreased significantly with every successive infusion., Conclusion: Rituximab treatment was effective and safe in patients with steroid-dependent nephrotic syndrome, allowed reduction of the PRED dose, and ameliorated the adverse effects of PRED. It may be preferentially used in patients at a risk of the adverse effect of PRED.

Background: The effects of hematuria on the outcome of IgA nephropathy (IgAN) remain unknown and treatment of IgAN with severe hematuria is controversial., Methods: Eighty-eight IgAN patients with proteinuria <0.5 g/day and who had not received corticosteroids, immunosuppressive agents, or undergone a tonsillectomy were divided into two groups: (1) patients with low (<20/high-power field [HPF]) urinary red blood cell (U-RBC) counts (L-RBC group, n = 48); and (2) patients with high (≥20/HPF) U-RBC counts (H-RBC group, n = 40). Clinical and histological findings, renal survival rate and risk factors for progression were analyzed., Results: The male ratio and blood pressure were significantly higher in the L-RBC group. Median proteinuria, mean estimated glomerular filtration rate and histological findings according to Oxford classifications were similar. During the 5 years after renal biopsy, the median amount of proteinuria remained at <0.5 g/day or g/g creatinine in both groups, and the median U-RBC decreased to <10/HPF in both groups without any intensive therapy. The 15-year renal survival rate, estimated using the Kaplan-Meier method, was 100 % in the H-RBC group, but decreased to 83.4 % in the L-RBC group, although it was not significant. The treatment of inhibitors of renin-angiotensin system (RAS inhibitors) decreased the risk for progression by Cox regression analysis (hazard ratio: 0.14, p = 0.027)., Conclusion: Severe hematuria at the time of biopsy naturally improved without any intensive therapy, and there were no negative effects of hematuria on the outcome of IgAN with mild proteinuria. Its prognosis was relatively good, and the treatment of RAS inhibitors might prevent from progression.

Background: High uric acid level is a known risk factor for deterioration of renal function in chronic kidney disease (CKD), but its influence on the progression of IgA nephropathy (IgAN) remains unclear., Methods: Adult IgAN patients (n = 611) were classified according to CKD stage. Renal survival rates and clinical and histological findings were compared between patients with high (H-UA) and normal (N-UA) uric acid levels in different CKD stages., Results: The proportion of patients with H-UA increased significantly with increasing CKD stage (stage G1, 12.3%; stage G2, 19.0%; stage G3a, 43.7%; stage G3b-4, 69.0%; P < 0.001). The 30-year renal survival rate was similar in patients with H-UA and N-UA in CKD stages G1, G2, and G3b-4, but was significantly lower in patients with H-UA than with N-UA in CKD stage G3a (24.7 vs. 51.9%; P = 0.0205). The clinical findings were similar in patients with H-UA and N-UA, but the interval from onset to biopsy differed between groups. The proportion of patients with global sclerosis was significantly higher in patients with H-UA than with N-UA in CKD stage G3a (33.3 vs. 11.4%; P = 0.0005), but the Oxford classifications were similar between groups. Multivariate Cox regression analysis identified H-UA (HR 1.36, 95% CI 1.07-1.72, P = 0.011) and a large amount of proteinuria (HR 1.38, 95% CI 1.09-1.74, P = 0.0084) as independent predictors of end-stage renal disease., Conclusions: H-UA induced global glomerular sclerosis and accelerated the progression of IgAN in CKD stage G3a.

Purpose: The susceptible age for IgA nephropathy (IgAN) is <30 years. However, IgAN sometimes develops in people aged >60 years, and its characteristics remain unknown., Methods: We divided 600 IgAN patients into three groups: advanced-age group (AAG, n=31, ≥60 years); middle-aged group (MAG, n=162, 40-59 years); and young-aged group (YAG, n=407, 20-39 years). We analyzed clinical and histological background, renal outcome, and risk of progression., Results: In the AAG, mean arterial pressure (MAP) and the number of hypertensive patients were significantly higher than in the YAG. Total protein, serum albumin, and estimated glomerular filtration rate were significantly lower, and blood urea nitrogen, proteinuria, and N-acetyl-β-D-glucosaminidase were significantly higher in the AAG than in MAG and YAG. In histological findings, interstitial fibrosis/tubular atrophy by Oxford classification and arteriosclerosis were more severe in the AAG than the in YAG. Renal survival rate analyzed by Kaplan-Meier method was significantly lower in the AAG (22.9%/19 years in the AAG vs. 69.2 and 84.9%/20 years in the MAG and YAG, p<0.0001). The patients who progressed to end-stage renal disease (ESRD) in the AAG had higher MAP and more severe proteinuria compared with the patients who did not progress to ESRD in the AAG., Conclusions: The characteristics of IgAN in advanced-age were lower renal function, high levels of proteinuria, severe interstitial change, and arteriolosclerosis caused by glomerulopathy and concomitant diseases, such as hypertension, dyslipidemia, and hyperuricemia. Prognosis was poor, and >70% developed ESRD within 20 years.

Hyperuricemia is a frequent complication of chronic kidney disease (CKD). Febuxostat is a novel xanthine oxidase inhibitor that is metabolized by many metabolic pathways in the kidney and the liver. We performed a 1-year cohort study of 73 hyperuricemic patients who had an estimated glomerular filtration rate (eGFR) below 45 ml/min and were being treated with urate-lowering therapy. In 51 patients, treatment was changed from allopurinol to febuxostat, and the other 22 patients were continued on allopurinol. The serum levels of uric acid (UA) level, creatinine, and other biochemical parameters were measured at baseline and after 3, 6, 9, and 12 months of treatment. The serum UA levels significantly decreased from 6.1 ± 1.0 to 5.7 ± 1.2 mg/dl in the febuxostat group and significantly increased from 6.2 ± 1.1 to 6.6 ± 1.1 mg/dl in the allopurinol group. The eGFR decreased 27.3 to 25.7 ml/min in the febuxostat group and from 26.1 to 19.9 ml/min in the allopurinol group. The switch from allopurinol to febuxostat was significantly associated with the changes in eGFR according to a multiple regression analysis (β = -0.22145, P < 0.05). Febuxostat reduced the serum UA levels and slowed the progression of renal disease in our CKD cohort in comparison with allopurinol.

Background: In recent years, tonsillectomy and steroid pulse (TSP) therapy have been widely performed in Japan. However, there is no consensus about the treatment protocol and indication., Methods: In this retrospective analysis, we compared patients who received tonsillectomy plus intermittent steroid pulse (SP) therapy three times in 6 months (ISP group, n = 44) with patients who received tonsillectomy plus 3 weeks of consecutive SP therapy (CSP group, n = 46) within 1 year after renal biopsy. These two different protocols were performed at two different institutions. We analyzed the clinical and histological background and clinical remission (CR), defined as disappearance of urine abnormalities at 18 months after starting treatment., Results: Before treatment, there was no significant difference in the clinical findings except for sex between the two groups. In ISP group and CSP group, mean estimated glomerular filtration rate was 82.1 ± 20.9 and 85.9 ± 19.1 ml/min/1.73 m(2), median proteinuria was 0.55 and 0.56 g/day, and median urinary red blood cells were 20 (10-20) and 20 (6-30)/high power filed. The histological (H) grade was lower in the CSP than the ISP group (p = 0.022). The remission rate of proteinuria, hematuria, and rate of CR by the Kaplan-Meier method and logrank test were significantly higher in the CSP group than in the ISP group (CSP vs. ISP group; proteinuria: 97.8 vs. 77.3 %, p < 0.001, hematuria: 97.8 vs. 75.0 %, p = 0.005, CR: 95.6 vs. 63.6 %, p < 0.001). In the Cox proportional hazard model (forced entry), SP protocol and proteinuria before treatment were significantly associated with CR [SP protocol: hazard ratio (HR) 2.50, 95 % confidence interval (CI) 1.46-4.30, p = 0.001, proteinuria: HR 0.81, 95 % CI 0.68-0.96, p = 0.013)]. However H-grade was associated with remission of proteinuria (H-grade: hazard ratio (HR) 0.56, 95 % confidence interval (CI) 0.37-0.85, p = 0.006), and this result meant histological bias affected the remission of proteinuria., Conclusions: The difference of the protocol of TSP therapy may have some effect on the CR of IgAN, though the histological bias was observed in this study. The appropriate protocol and indication of TSP therapy must be analyzed and determined in the randomized controlled trial.

Purpose: To the best of our knowledge, no study has compared intermittent steroid pulse therapy, according to Pozzi's regimen, with versus without tonsillectomy., Methods: In this retrospective cohort analysis, we compared clinical findings, histological findings according to the Oxford classification, and complete remission rates (RR), defined in terms of urinary protein excretion (U-Prot <0.3 g/g creatinine) and urinary red blood cell count (U-RBC <5/high-power field), after 1 year of treatment in patients with IgA nephropathy (IgAN), who received tonsillectomy with steroid pulse therapy (TSP group, n = 26) or steroid pulse therapy alone (SP group, n = 15)., Results: The baseline clinical and histological characteristics did not differ between the two groups. The RR for U-Prot analyzed by the Kaplan-Meier method did not differ between the groups (76.9 vs. 53.3 %). However, the RR for U-RBC was significantly higher in the TSP than in the SP group (88.4 vs. 33.3 %, log-rank test; P = 0.0008). The RRs for U-Prot and U-RBC were significantly higher in the TSP group than in the SP group (69.2 vs. 13.3 %, log-rank test; P = 0.0019). Cox's regression analysis showed that combination therapy was associated with higher RR (odds ratio, 12.5; 95 % confidence interval, 2.91-86.7; P = 0.0002)., Conclusions: Tonsillectomy combined with steroid pulse therapy achieved higher RR after 1 year of treatment, compared with steroid pulse monotherapy in patients with IgAN. The long-term effects on renal survival should be analyzed in further studies.

Background: Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established., Methods: We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed., Results: Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04)., Conclusions: C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.

Background: IgA nephropathy with nephrotic syndrome (nephrotic IgAN) is a rare form of IgAN. Its prognosis and response to steroid therapy are still controversial because the differential diagnosis between nephrotic IgAN and minimal change nephrotic syndrome with IgA depositions is sometimes confused., Methods: In this retrospective cohort analysis, we accurately diagnosed 42 cases of nephrotic IgAN (4.4%) from 954 IgAN patients, according to the Oxford classification. We analyzed the clinical and histological data, prognosis, and response to steroid therapy., Results: In nephrotic IgAN, mean estimated glomerular filtration rate (eGFR) was 51.1 ± 24.6 ml/min, proteinuria was 5.71 ± 2.56 g/day, and urinary red blood cells were 51.0 ± 37.8 high power field. Both active and chronic histological lesions were observed. Cumulative renal survival rate was significantly lower in nephrotic IgAN than in non-nephrotic IgAN (the control group consisted of 47 non-nephrotic IgAN patients diagnosed between 1995 and 1996) (log-rank test: P < 0.0001). The cases with steroid therapy significantly improved their prognosis, though their male-to-female ratio and blood pressure level measured at renal biopsy were significantly lower than in the cases without steroid therapy. Steroid therapy was particularly effective in cases with low-grade tubular atrophy and interstitial fibrosis (T-grade in Oxford classification). Without steroid therapy, lower eGFR and higher T-grade were independent risk factors for severe outcome by multivariate Cox regression., Conclusion: Nephrotic IgAN is a very severe form of IgAN, with renal dysfunction, massive hematuria, and active and chronic histopathological lesions. Renal outcome is severe; however, steroid therapy can improve prognosis in cases with higher eGFR and lower T-grade, according to the Oxford classification.

Background: Blockade of the renin-angiotensin-aldosterone system is a therapeutic mainstay in patients with chronic kidney disease (CKD). However, the renoprotective effect of the novel direct renin inhibitor aliskiren is unknown., Materials and Methods: We performed a prospective study in 10 CKD patients. All 10 patients with persistent proteinuria (urinary protein-to-creatinin ratio 0.3-3.5 g/g), despite good blood pressure control (<130/80 mmHg) with olmesartan, were started on 150 mg/day aliskiren. Clinical parameters were examined before and after 4, 8, 12, and 16 weeks of treatment., Results: Urinary protein-to-creatinine ratio significantly decreased by about 40% at 16 weeks from baseline (P = 0.0002), although estimated glomerular filtration rate and blood pressure did not change throughout the study period. Plasma renin activity also decreased significantly from baseline (P = 0.019), although plasma aldosterone concentration did not change., Conclusions: Aliskiren combined with olmesartan reduces proteinuria in CKD patients.

Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid (UA) clearance and is associated with acute renal failure (ARF). A 17-year-old Japanese male developed ARF after anerobic exercise. Renal function improved completely after approximately 2 weeks of hydration treatment. After remission, hypouricemia became evident (1.0 mg/dL) from the initial level of UA (4.8 mg/dL) and fractional excretion of uric acid (FEUA) was >50%. His parents showed normal levels of UA and FEUA. Polymerase chain reaction of a urate anion exchanger known to regulate UA level [SLC22A12 gene: UA transporter 1 (URAT1)] demonstrated compound heterozygous mutations (Q297X and R90H). Thus, we describe a Japanese male with hypouricemia complicated by anerobic exercise-induced ARF, with definite demonstration of a genetic abnormality in the responsible gene, URAT1.

Background: The adaptation of steroid therapy and the effect of renin-angiotensin-aldosterone system inhibitors (RASIs) for advanced immunoglobulin A nephropathy (IgAN) patients with impaired renal function are still controversial., Methods: We divided 63 IgAN patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m(2) and proteinuria ≥ 0.5 g/day into two groups: the RASI group (RASI, n = 33), treated with RASIs alone; and the combination group (COMBI, n = 30), treated with corticosteroids and RASIs. We analyzed the clinical and histological background, renal survival rate, and the risk factors for progression., Results: Renal function (mean eGFR: COMBI 46.4 vs. RASI 47.0 ml/min/1.73 m(2)), the amount of proteinuria (median: COMBI 1.39 vs. RASI 1.17 g/g creatinine) and histological backgrounds were not significantly different between the groups, but urinary red blood cells (U-RBCs) were significantly higher in the COMBI group than in the RASI group (median: COMBI 30.0 vs. RASI 10.0 counts/high-power field, P = 0.0171). The serial change in proteinuria did not differ until 5 years after treatment, but U-RBCs were significantly decreased in both groups (P < 0.0001), and eGFR was significantly decreased in the RASI group (P < 0.001) but not in the COMBI group. The results for each year after treatment did not differ significantly between both groups. The renal survival rate was not significantly different between the groups. There was no independent risk factor for progression by Cox regression analysis., Conclusion: Combination therapy with steroids and RASIs was not superior to monotherapy with RASIs for advanced IgAN with impaired renal function.

Background: There are few reports analyzing the effects of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) on the long-term renal survival of advanced immunoglobulin A nephropathy (IgAN) patients., Patients and Methods: In this retrospective cohort analysis, we divided 66 IgAN patients with an estimated glomerular filtration rate (eGFR) <60 ml/min into three groups: ACEI group (n = 20, treated with ACEIs), ARB group (n = 23, treated with ARBs), and control group (n = 23, treated with antiplatelet agents), and analyzed the clinical and histological background, renal survival rate until the primary endpoint of 50% decrease of eGFR from baseline, and the secondary endpoint of progression to end-stage renal disease, and the risk factors for progression., Results: The clinical and histological background without serum IgA and C3 were not significantly different among the three groups. The renal survival rate until the primary and secondary endpoints was significantly higher in the ACEI and ARB groups than in the control group. The independent risk factors for progression were higher mean blood pressure (hazard ratio [HR] 1.76, P = 0.04), higher histological grade (HR 2.54, P = 0.0184) at baseline, and without ACEIs or ARBs (HR 7.09, P = 0.001), but decreased proteinuria and blood pressure. The risk factors with resistance to ACEIs or ARBs were higher blood pressure and lower eGFR at baseline. There was no difference regarding the survival rate and the risk for progression between ACEI s and ARBs., Conclusion: ACEIs or ARBs were effective for long-term renal survival of advanced IgAN, although proteinuria and blood pressure did not decrease.

Background/aim: No accepted therapy has been established for progressive IgA nephropathy (IgAN). The purpose of the present study was to assess low-dose steroid therapy in the treatment of patients with IgAN., Methods: A prospective trial of low-dose steroid therapy was performed in patients with IgAN with mild histological activities. Twenty-four patients in the steroid group and 24 patients in the control group were included in this study. The initial dose of prednisolone was 0.4 mg/kgBW/day (20-30 mg/day), gradually tapered to 5-10 mg/day over 24 months. The patients with mild active inflammatory lesions were treated with prednisolone. The patients assigned to the control group were treated with dipyridamole or zilazep hydrochloride in a dose of 150 or 300 mg/day., Results: In all of the patients studied, serum creatinine levels did not significantly change over 24 months. However, daily proteinuria significantly reduced after 24 months of steroid therapy (0.97 +/- 0.75 vs. 0.31 +/- 0.51 g/day, P = 0.0012), even if did not change after 24 months of anti-platelet drugs (0.89 +/- 0.49 vs. 0.68 +/- 0.69 g/day, P = 0.2289), respectively. In addition, the grade of hematuria significantly reduced after 24 months of steroid therapy (35.6 +/- 36.3 RBC/HPF vs. 13.7 +/- 28.4 RBC/HPF, P = 0.0249) and 24 months of anti-platelet drugs (30.1 +/- 37.1 RBC/HPF vs. 12.4 +/- 20.3 RBC/HPF, P = 0.0465), respectively. Systolic and diastolic blood pressures did not significantly change during treatment with steroid or anti-platelet drugs. Vascular changes (0.63 +/- 0.73) in the steroid group were lower than those (1.08 +/- 0.88) in the control group (P = 0.008)., Conclusion: Our data suggested that low-dose steroid therapy for IgAN patients with mild inflammatory lesions could reduce the amount of urinary protein excretion and prevent deterioration of renal function, provided the histological findings in the renal biopsies showed mild vascular lesions.

Background: Recent studies have shown that steroid therapy is effective for IgA nephropathy (IgAN) in patients with moderate proteinuria and active histological findings. However, the effectiveness of steroid therapy has not been determined yet in patients with advanced IgAN and impaired renal function., Methods: Sixty IgAN patients whose creatinine clearance was under 70 ml/min at the time of renal biopsy were studied retrospectively. The patients were divided into two groups according to treatment: a steroid group ( n = 20) and a nonsteroid group ( n = 40). The mean age was 39.6 +/- 14.9 years in the steroid group and 40.6 +/- 10.9 years in the nonsteroid group. The mean follow-up period was 4.5 +/- 2.2 years in the steroid group and 4.6 +/- 2.4 years in the nonsteroid group. Patients with high proteinuria and high histological activity were treated with prednisolone. Clinical and histological findings before treatment and the outcome after treatment were analyzed., Results: In the retrospective analysis, the amount of urinary protein excretion before treatment tended to be higher in the steroid group than in the nonsteroid group, but was not significantly different (2.33 +/- 1.54 vs 1.39 +/- 1.87 g/day). Histologically, the percentage of patients with crescent formation, especially that of cellular or fibrocellular crescents, was significantly higher in the steroid group than in the nonsteroid group (17.2 +/- 15.9% vs 2.3 +/- 4.5%; P < 0.0001). The grades of mesangial cell proliferation (1.65 +/- 0.55 vs 1.21 +/- 0.47; P = 0.002) and mesangial matrix increase (1.88 +/- 0.64 and 1.41 +/- 0.67; P = 0.01) were higher in the steroid group than in the nonsteroid group. In the evaluation of the outcome after treatment, the amount of urinary protein excretion at 1 year after treatment had significantly decreased in the steroid group (before treatment, 2.33 +/- 1.54 g/day; at 1 year, 1.02 +/- 0.98 g/day; P = 0.003), but the amount remained unchanged in the nonsteroid group (before treatment, 1.39 +/- 1.87 g/day; at 1 year, 1.28 +/- 2.19 g/day). The levels of serum creatinine before treatment and at 1 year after treatment were not changed in either of the groups, however, in the nonsteroid group, the level at the final observation was significantly higher than the level before treatment (2.51 +/- 3.43 vs 1.27 +/- 0.33 mg/dl; P = 0.0219)., Conclusions: In the present study, in advanced IgAN patients whose creatinine clearance was under 70 ml/min, steroid therapy effectively reduced the amount of proteinuria and maintained the serum creatinine level, if the treatment was selectively applied to patients with a moderate amount of proteinuria and active glomerular lesions such as cellular and fibrocellular crescents, and mesangial cell proliferation.