Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Structural modeling for Oxford histological classifications of immunoglobulin A nephropathy.

In immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria, eGFR, mean arterial pressure (MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy (ST) and renin-angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the model's goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity and active crescent (C) had an attenuating indirect effect via ST. Segmental sclerosis (S) had an attenuating indirect effect via eGFR and mesangial hypercellularity (M) had accelerative indirect effect for RFD via proteinuria. Moreover, M and C had accelerative indirect effect via proteinuria, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR or MAP at biopsy, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.

Use of a 2-year continuing professional development programme to change Japanese physicians' attitudes to learning primary care: a qualitative study.

OBJECTIVE: To evaluate changes in the learning attitudes of primary care physicians. DESIGN: Qualitative study through one focus group interview with the programme's participants. Analysis of the focus group content using the Steps for Coding and Theorization method. SETTING: Japan. PARTICIPANTS: Eight primary care physicians who completed a 2-year continuing professional development (CPD) programme using a problem-based learning (PBL) approach, focused on acquiring the skills needed to practise as primary care physicians in the community. RESULTS: Participants described positive changes in their attitudes and behaviours as a result of the training programme. These changes were grouped into three main themes: 'changes in learning methods regarding medical practice', 'encounters with diverse perspectives and values, and confidence gained from those encounters', and 'showing one's attitude towards learning and its influence on others'. The experienced practitioners participating in this study reported that the programme helped them apply their skills more broadly; for example, searching the literature for psychosocial aspects of practice and engaging more comfortably with diverse perspectives. They reported the positive impact of their learning on their coworkers. CONCLUSION: A 2-year CPD programme using PBL can influence primary care physicians' attitudes and learning-related behaviours. Further research is needed to determine which specific aspects of the programme are the most effective and whether the changes in attitudes and behaviours described affect patient care.

Long-Term Renal Survival in Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis With Complement C3 Deposition.

INTRODUCTION: Recent studies have revealed the pivotal role of complement activation in the pathogenesis of antineutrophil cytoplasmic antibody-associated glomerulonephritis (ANCA-GN). This study investigated the clinicopathologic and prognostic significance of glomerular C3 deposition in the renal histopathology of patients with ANCA-GN. METHODS: We retrospectively identified 142 patients with ANCA-GN from 6 hospitals in Japan (2004-2020). C3 deposition was defined as C3 staining ≥1+ on a scale of 0 to 2+ using direct immunofluorescence (IF). The primary composite end points included a 30% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), and death. We compared clinicopathologic features and long-term outcomes between patients with and without C3 deposition. RESULTS: C3 deposition was observed in 56 of 142 kidney biopsy samples (39.4%). Patients with C3 deposition had a lower serum C3 level (P = 0.002). During a median follow-up of 2.9 (interquartile range: 0.2-5.7) years, 69 events occurred and the cumulative event-free survival rate at 5 years was significantly lower in the C3-positive group than in the C3-negative group (log-rank: P = 0.002). In multivariable analysis, C3 deposition was significantly associated with the composite end points after adjusting for age, sex, baseline eGFR, serum C3 level, treatment, and the percentage of normal glomerulus, cellular crescents, global sclerosis, and interstitial damage (adjusted hazard ratio [HR] = 2.02, 95% confidence interval: 1.20-3.40, P = 0.008). CONCLUSION: This study revealed that ANCA-GN patients with glomerular C3 deposition on IF had worse renal and overall survival rates.

How a problem-based learning approach could help Japanese primary care physicians: a qualitative study.

OBJECTIVES: This study aimed to identify training needs among primary care physicians in Japan who had no formal primary care training. METHODS:  We conducted a focus group interview with seven Japanese primary care physicians who had not previously undergone specialist training in primary care and had been recruited to a family medicine training program that used a problem-based learning approach. At the start of the program, the physicians attended the interview. The discussion was recorded, and the transcribed interview was analyzed using the Steps for Coding and Theorization method. RESULTS:  Three main themes emerged. First, there is a lack of standard re-education programs for physicians who move away from their specializations into primary care. Second, there is insufficient training on primary care in undergraduate and postgraduate medical education in Japan. Third, continuing professional development programs should cover the communication skills, attitudes, and behaviors necessary for primary care practice. CONCLUSIONS:  This study clarified the needs to be addressed in our training program for primary care physicians involved in retraining in primary care. It is important to consider how to best include the communication skills, attitudes, and behaviors necessary for primary care among the topics covered in the program. As the program undergoes further iteration, it will be important to check whether it meets the needs of primary care practitioners. It will be necessary to investigate the needs of re-education programs for more physicians in many areas, and to emphasize the importance of primary care re-education in these abilities in undergraduate and postgraduate medical education.

Negative impact of proteinuria on circulating myeloid dendritic cells.

BACKGROUND: A decrease in absolute numbers (abs.) of circulating dendritic cells (DCs) and recruitment into target organs has been reported, but whether the level of proteinuria associates with circulating DC abs. has not been clarified. METHODS: We conducted a cross-sectional study of 210 patients with kidney disease aged 21-96 years who were admitted to our hospital for kidney biopsy in 2007-2010. For accuracy, the level of proteinuria was thoroughly measured by 24-h urine collection from patients in their admitted condition. The abs. of total DCs (tDCs), myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) was measured by three-color fluorescence-activated cell sorting (FACS). Patients were divided into four groups based upon the quartile of each DC abs. and one-way ANOVA, and multivariable-adjusted regression analyses were performed. RESULTS: Quantile analysis showed that the level of daily proteinuria decreased with increasing blood mDC abs., with mean proteinuria levels (g/day) of 2.45, 1.68, 1.68, 1.10 for those in mDC abs. quartiles ≤ 445, < 686, < 907, ≥ 907 cells/102 µL (p = 0.0277), respectively. Multivariate-adjusted regression analysis revealed that the mDC abs. was negatively associated with proteinuria (95% CI - 57.0 to - 8.5) and positively associated with male gender (95% CI 66.2-250.5). Independent associations were also shown between pDCs abs. and estimated glomerular filtration rate (eGFR) (95% CI 0.14-2.67) and C-reactive protein (95% CI - 49.4 to - 9.9) and between tDCs abs. and male gender (95% CI 54.5-253.6) and C-reactive protein (95% CI - 80.5 to - 13.4). CONCLUSION: We first reported that circulating mDC abs. has a negative association with the level of proteinuria.

A grading system that predicts the risk of dialysis induction in IgA nephropathy patients based on the combination of the clinical and histological severity.

Histological classification is essential in the clinical management of immunoglobulin A nephropathy (IgAN). However, there are limitations in predicting the prognosis of IgAN based on histological information alone, which suggests the need for better prognostic models. Therefore, we defined a prognostic model by combining the grade of clinical severity with the histological grading system by the following processes. We included 270 patients and explored the clinical variables associated with progression to end-stage renal disease (ESRD). Then, we created a predictive clinical grading system and defined the risk grades for dialysis induction by a combination of the clinical grade (CG) and the histological grade (HG). A logistic regression analysis revealed that the 24-h urinary protein excretion (UPE) and the estimated glomerular filtration rate (eGFR) were significant independent variables. We selected UPE of 0.5 g/day and eGFR of 60 ml/min/1.73 m2 as the threshold values for the classification of CG. The risk of progression to ESRD of patients with CG II and III was significantly higher than that of patients with CG I. The patients were then re-classified into nine compartments based on the combination of CG and HG. Furthermore, the nine compartments were grouped into four risk groups. The risk of ESRD in the moderate, high, and super-high-risk groups was significantly higher than that in the low-risk group. Herein, we are giving a detailed description of our grading system for IgA nephropathy that predicted the risk of dialysis based on the combination of CG and HG.

A Case of Hepatic Glomerulosclerosis with Monoclonal IgA1-κ Deposits.

Glomerular immunoglobulin A (IgA) deposition is a common finding in hepatic glomerulosclerosis; thus, this disease is also called hepatic IgA nephropathy. However, only a small number of patients with hepatic IgA nephropathy have active glomerular lesions, so functional decline is slow in most cases. In this report, we describe a 60-year-old man who developed nephrotic syndrome and progressive renal impairment during follow-up for alcoholic liver cirrhosis. A renal biopsy showed a membranoproliferative glomerulonephritis-like pattern; diffuse double-contours of the glomerular basement membrane and focal active glomerular lesions with moderate-to-severe endocapillary proliferation and fibrocellular crescents. Immunofluorescence findings revealed granular staining for monoclonal IgA1-κ and C3 on the peripheral capillary walls. Laboratory examinations did not reveal any definitive evidence of myeloproliferative disorders. Therefore, this case may represent a previously unrecognized etiology of renal injury in relation to liver cirrhosis that is characterized by monoclonal IgA1-κ deposits and proliferative glomerulonephritis.

Fluctuation in Serum Sodium Levels Related to Ipragliflozin Administration in a Patient with Diabetic Nephropathy and Sequela of Traumatic Brain Injury.

A 46-year-old diabetic man underwent the removal of a hematoma caused by traumatic brain injury. After surgery, severe hyponatremia occurred. The subsequent administration of NaCl and fludrocortisone improved his laboratory findings. The patient was transferred to our hospital, and his insulin therapy was replaced by teneligliptin. One week later, ipragliflozin treatment was initiated and induced an immediate increase in the serum sodium levels. NaCl and fludrocortisone were therefore discontinued. However, hyponatremia recurred after ipragliflozin withdrawal due to a urinary tract infection. NaCl and fludrocortisone were initiated again, and the laboratory data improved. We herein report a case of serum sodium fluctuation related to ipragliflozin administration.

Tonsillectomy reduces recurrence of IgA nephropathy in mesangial hypercellularity type categorized by the Oxford classification.

BACKGROUND: In patients with IgA nephropathy (IgAN), recurrence after steroid pulse therapy is associated with reduced renal survival. However, the predictors of recurrence have not yet been clarified. METHODS: All patients who received 6-month steroid pulse therapy from 2004 to 2010 in our four affiliated hospitals and achieved a reduction of proteinuria to <0.4 g/day 1 year after treatment were retrospectively evaluated. The primary outcome was proteinuria ≥1.0 g/day during follow-up or additional antiproteinuric therapy. Two histological classifications were evaluated, the Oxford Classification with a split system and Japanese histological grades (HGs) with a lumped system. RESULTS: During a median follow-up of 3.4 years, 27 (26.7 %) of the 101 patients showed recurrence. Multivariate analysis showed that HG was the only significant predictor of recurrence, with HG 2+3+4 vs HG 1 having a hazard ratio of 7.38 (95 % confidence interval 1.52-133). Furthermore, in patients with mesangial hypercellularity according to the Oxford Classification, cumulative rate of recurrence-free survival was greater in patients with steroid therapy plus tonsillectomy compared with those who received steroid therapy alone (Log-rank test, P = 0.022). However, this association was not observed in patients without mesangial hypercellularity. CONCLUSIONS: HG is a novel predictor of recurrence after steroid pulse therapy in patients with IgAN. Moreover, the combination of steroid pulse therapy plus tonsillectomy may indicate a lower risk of recurrence in patients with mesangial hypercellularity, as defined by the Oxford Classification.

Clinicopathological characteristics of patients with immunoglobulin A nephropathy showing acute exacerbations after favorable long-term clinical courses.

BACKGROUND: Sometimes, acute and progressive proteinuria increases occur in patients with IgA nephropathy (IgAN) after favorable long-term clinical courses of >10 years, but their clinical and histological characteristics are not well understood. METHODS: We retrospectively selected 20 IgAN patients who had been followed for >10 years after their initial biopsies ((1st)Bx) and underwent second biopsies ((2nd)Bx), because their proteinuria increased to >1 g/day. Eight patients with acute exacerbations (Group A) showed acute proteinuria increases after long periods of mild proteinuria. Their clinicopathological characteristics were analyzed as a case series and were compared with those in Group B that comprised 12 patients with persistent proteinuria. RESULTS: Group A experienced acute proteinuria increases and significant hematuria increases compared with the -1-year (P = 0.006) and -3-year (P = 0.010) time points before the (2nd)Bx, which contrasted to the clinical course in Group B. In Group A, glomerulosclerosis (GS) and the arteriosclerosis score did not differ between the (2nd)Bx and the (1st)Bx, and most patients (88 %) showed cellular and/or fibrocellular crescents within the (2nd)Bx. Compared with Group B, the (2nd)Bx revealed that the percentage of cellular and/or fibrocellular crescents (P = 0.001) was significantly higher, whereas the percentage of GS (P = 0.012) and the arteriosclerosis score (P = 0.020) were significantly lower in Group A. CONCLUSION: Rapid proteinuria and hematuria increases, and acute histological lesions characterize acute exacerbations in IgAN after favorable long-term clinical courses.

A Case of Concurrent MPO-/PR3-Negative ANCA-Associated Glomerulonephritis and Membranous Glomerulopathy.

We report a case in which antineutrophil cytoplasmic antibody- (ANCA-) associated glomerulonephritis and membranous glomerulopathy (MGN) were detected concurrently. The patient showed rapidly progressive renal deterioration. A renal biopsy showed crescentic glomerulonephritis, together with marked thickening and spike and bubbling formations in the glomerular basement membranes. Indirect immunofluorescence examination of the patient's neutrophils showed a perinuclear pattern. Enzyme-linked immunosorbent assays revealed that the ANCA in this case did not target myeloperoxidase (MPO) or proteinase 3 (PR3) but bactericidal-/permeability-increasing protein, elastase, and lysosome. The relationship between these two etiologically distinct entities, MPO-/PR3-negative ANCA-associated glomerulonephritis and MGN, remains unclear.

A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy.

BACKGROUND: The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). METHODS: Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. RESULTS: During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01-8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. CONCLUSIONS: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

The role of a low glomerular density and being overweight in the etiology of proteinuria in CKD patients without known glomerular diseases.

BACKGROUND: Among the proteinuric patients with chronic kidney disease (CKD) who undergo a renal biopsy, we sometimes encounter those who cannot be classified as having a known primary or secondary glomerular disease. The pathogenesis and pathophysiology of these CKD patients have not been sufficiently elucidated. METHODS: We recruited 34 proteinuric patients without known glomerular diseases. The glomerular volumes (GV) of the biopsy specimens from those patients were determined by a morphometric analysis. Glomerular hypertrophy (GH) was defined as having more than 3.6 × 10(6) µm(3). The patients were divided in two groups: those with GH (Group 1) and those without GH (Group 2). We compared the clinical and pathological parameters between Group 1 and Group 2, and among the three groups of patients: non-obese, overweight and obese group. RESULTS: The patients with Group 1 had significantly higher values for the proportion of males, the body mass index (BMI), uric acid and significantly lower values for the glomerular density (GD). Of note, a multivariate regression analysis revealed that sex, the BMI and GD were significant factors correlated with the mean GV. The values for the mean GV were significantly higher in the overweight and obese groups as compared to the non-obese group, and the values for the GD were significantly lower in the obese group than in the non-obese group. CONCLUSIONS: We identified a subgroup of patients who were characterized as having a high BMI and GV, and a low GD among the proteinuric CKD patients without known glomerular diseases.

Overestimation of the risk of progression to end-stage renal disease in the poor prognosis' group according to the 2002 Japanese histological classification for immunoglobulin A nephropathy.

BACKGROUND: The current (2012) histological classification of immunoglobulin A nephropathy was established using a case-control study of 287 patients. However, the risk of progression to end-stage renal disease (ESRD) has not been validated for the previous (2002) classification. This study aimed to determine whether the previous classification could identify the risk of long-term renal outcome through re-analysis of the 2012 cohort. METHODS: On the basis of the 2002 classification, namely 'good prognosis', 'relatively good prognosis', 'relatively poor prognosis', and 'poor prognosis', we examined the clinical data at the time of biopsy, the correlation between the 2002 classification and long-term renal outcomes, and a patient-by-patient correlation between the 2002 and 2012 classification systems. This was performed by analyzing samples from the 287 patients used to establish the 2012 classification. RESULTS: The rate of decline of estimated glomerular filtration rate was greater and the odds ratio of progression to ESRD was higher in the 'poor prognosis' group. In contrast, the odds ratio for renal death was comparable between the groups described as 'relatively poor prognosis' and 'relatively good prognosis' in the 2002 classification. Many patients in the 2002 classification were classified with a lower histological grade in the current classification, but none were classified with a higher grade. CONCLUSIONS: The 2002 classification could also identify the risk of progression to ESRD. However, it was overestimated for patients in the 'poor prognosis' group in the 2002 classification, as that group included patients with milder histological damage.

Factors related to the glomerular size in renal biopsies of chronic kidney disease patients.

BACKGROUND: Glomerular enlargement is an important process that preserves the optimal surface area of glomerular capillaries under both physiological and pathological conditions. However, information is limited regarding how the glomerular size is defined, especially in chronic kidney disease (CKD) patients. METHODS: A total of 206 renal biopsy specimens obtained from two different patient cohorts with or without a diagnosis of glomerulonephritis (non-GN group and IgAN group) were examined. The mean glomerular volume was estimated from the outer capillary area of individual glomeruli, and the clinicopathological factors at biopsy that were associated with the mean glomerular volume were analyzed in each group. RESULTS: The mean glomerular volume showed maximal 5.8 and 7.9-fold variations between individuals in the non-GN and IgAN groups, respectively. In both groups, the body mass index and glomerular density (non-sclerotic glomerular number per renal cortical area of the biopsy) were consistently identified as independent factors that were associated with the mean glomerular volume. In addition, the multivariate analyses using the glomerular density/body mass index ratio showed a more close association with the mean glomerular volume than the analyses using each measure separately. CONCLUSION: These results suggest that factors presumably reflecting both body consumption and nephron number have close relationships with the glomerular size, regardless of mechanism(s) underlying the injury. The most relevant factor affecting glomerular size may be a balance between these two measures.

A histologic classification of IgA nephropathy for predicting long-term prognosis: emphasis on end-stage renal disease.

BACKGROUND: A multicenter case-control study on IgA nephropathy (IgAN) was conducted to develop an evidence-based clinicopathologic classification of IgAN for predicting long-term renal outcome. METHODS: Two hundred and eighty-seven patients including those with isolated hematuria or very mild proteinuria were enrolled. During a median follow-up of 9.3 years after biopsy, 49 patients (17%) progressed to end stage renal disease (ESRD). The associations between pathological variables and the need for chronic dialysis was examined by multivariate logistic regression analysis separately in patients who required dialysis earlier than 5 years (Early Progressors) and those who required dialysis within 5 to 10 years (Late Progressors) after biopsy. RESULTS: Independent pathological variables predicting progression to ESRD were global sclerosis, segmental sclerosis and fibrous crescents for Early Progressors, and global sclerosis and cellular/fibrocellular crescents for Late Progressors. Four histological grades, HG 1, HG 2, HG 3 and HG 4, were established corresponding to <25%, 25-49%, 50-74% and =75% of glomeruli exhibiting cellular or fibrocellular crescents, global sclerosis, segmental sclerosis or fibrous crescents. Eleven (7%) patients in HG 1, 12 (16%) in HG 2, 13 (31%) in HG 3 and 13 (68%) in HG 4 progressed to ESRD. Multivariate logistic analysis revealed that the risk of progression to ESRD was significantly higher in HG 2, 3 and 4 than in HG 1 (odds ratio, 2.4, 5.7 and 27.6 vs. 1.0). CONCLUSIONS: Our evidence-based histologic classification can identify the magnitude of the risk of progression to ESRD and is useful for predicting long-term renal outcome in IgAN.

The predictive value of attenuated proteinuria at 1 year after steroid therapy for renal survival in patients with IgA nephropathy.

BACKGROUND: The relationship between the urinary protein excretion (UPE) initially achieved after steroid therapy and the long-term renal outcome of IgA nephropathy (IgAN) has not been clarified. We investigated the threshold UPE at 1 year after steroid therapy which predicts a favorable renal survival. METHODS: We enrolled 141 IgAN patients who received 6 months of steroid therapy. The endpoint was defined as a 50 % increase in serum creatinine from baseline. The spline model was used to define the threshold UPE predicting renal survival. RESULTS: Thirteen patients (9.2 %) reached the endpoint at a median follow-up of 3.8 years. When evaluating the relative hazard ratio (HR) of the UPE at 1 year for the endpoint, we found an inflection point at 0.40 g/day on the spline curve. The multivariate Cox model revealed that, in addition to the Disappeared category of UPE (range <0.30 g/day), the Mild category (range 0.30-0.39 g/day) was associated with more reduced risk of the endpoint [HR 0.02, 95 % confidence intervals (CI) 0.00-0.29] relative to the Severe category (range ≥1.00 g/day), whereas the Moderate category (range 0.40-0.99 g/day) was not. The estimated glomerular filtration rate <60 ml/min/1.73 m(2) was also an independent predictor of the endpoint. When renal survival was adjusted with pathological parameters in the Cox model, UPE <0.40 g/day was still an independent favorable predictor (HR 0.08, 95 % CI 0.01-0.45). CONCLUSIONS: In IgAN patients receiving 6 months of steroid therapy, the achievement of proteinuria <0.4 g/day at 1 year could be a therapeutic indicator for a favorable renal outcome.

Successful treatment of adult IgA nephropathy with nephrotic-level proteinuria by combination therapy including long-term coadministration of mizoribine.

A 41-year-old male patient was admitted to our hospital due to massive proteinuria and hematuria. His 24-hour urinary protein excretion and the number of urinary erythrocytes were 3.91 g/day and 50-99/high-power field, respectively. A renal biopsy showed a severe pathological pattern of immunoglobulin A nephropathy (IgAN) that involved marked endocapillary proliferation and segmental sclerosis (Oxford-MEST score: M0, E1, S1, T0). Because he had nephrotic-level proteinuria with severe pathological findings, which are tonsillectomy and corticosteroid pulse therapy-resistant characteristics, he received mizoribine for a long period as part of the combination therapy using corticosteroid, tonsillectomy, dipyridamole, warfarin and renin-angiotensin-aldosterone system blockers. Twelve months after the beginning of treatment, his urinary findings were normal. In this report, we describe the pathological findings and successful treatment course, and discuss the potential effects of long-term coadministration of mizoribine for adult IgAN treatment.

The long-term antiproteinuric effect of eplerenone, a selective aldosterone blocker, in patients with non-diabetic chronic kidney disease.

INTRODUCTION: There is still insufficient data concerning the clinical effects of eplerenone, a selective aldosterone blocker, in patients with non-diabetic chronic kidney disease (CKD). METHODS: This study included non-diabetic CKD patients with urinary protein excretion (UPE) of 1.0 g/gCr or more in spite of long-term treatment with renin-angiotensin system (RAS) inhibitors. The clinical effects of eplerenone (25-50 mg/day) were investigated for 12 months. RESULTS: Eplerenone treatment was associated with a 38% reduction in UPE after 12 months. There was only a slight increase in the serum potassium level. The reduction of proteinuria was observed more prominently in patients with modestly impaired renal function than in those with preserved renal function at baseline. CONCLUSION: The long-term administration of low-dose eplerenone was effective and safe for the treatment of non-diabetic CKD patients who showed persistent proteinuria in spite of therapy with RAS inhibitors.