Autopsy study examining non-chronic kidney disease versus chronic kidney disease caused by hypertensive-nephrosclerosis in elderly subjects.

BACKGROUND: The aim of this autopsy study was to clarify the differences of renal histopathology between non-chronic kidney disease (CKD) and CKD caused by hypertensive-nephrosclerosis in the elderly and during the aging process. METHODS: We examined autopsy specimens from 105 elderly patients (53 male subjects; mean age, 86.2 years) including 44 patients with CKD as a result of nephrosclerosis. The analysis was divided into two groups depending on whether they had CKD. RESULTS: The incidences of arterial intimal thickening (AIT), obsolescent-type global glomerulosclerosis (OB), and interstitial fibrosis and tubular atrophy (IF/TA) were higher in the CKD group than in the non-CKD group (all p < 0.01). These factors were all correlated with each other (AIT vs. OB, r = 0.43; AIT vs. IF/TA, r = 0.25; OB vs. IF/TA, r = 0.53). IF/TA had the strongest association with hypertension and decreased eGFR. In the non-CKD group, the frequency of OB was more than 20% in subjects aged 90 years or older. However, the individuals in the non-CKD group tended to have compensatory glomerular hypertrophy with increasing age and a retained eGFR, while the CKD group was unable to obtain compensatory hypertrophy and had a lower eGFR. We also found that AIT, OB and IF/TA occurred independently of systemic atherosclerosis. CONCLUSIONS: Non-CKD in the elderly refers to the so-called aging kidney. The progression from aging kidney to CKD caused by nephrosclerosis was influenced by increases in AIT, OB and IF/TA. IF/TA was thought to be the most important downstream factor in the progression of aging kidney to CKD.

Identification of histopathological and clinical spectrum of diabetic kidney disease based on an unsupervised hierarchical clustering analysis of elderly autopsy specimens.

AIM: Diabetic kidney disease (DKD), a chronic kidney disease caused by diabetes and other comorbidities, is the leading cause of end-stage renal disease. The pathogenesis of DKD is diverse and influenced by various causes, some but not all of which cause proteinuria. Some factors such as hypertension can modify DKD. Therefore, the spectrum of DKD is difficult to elucidate and remains unsolved. This study aims to classify and characterize DKD. METHODS: We examined autopsy specimens from type 2 diabetes mellitus (DM) (n = 44) and non-DM (n = 21) groups. RESULTS: The frequency of interstitial fibrosis and tubular atrophy was higher in patients with proteinuric DKD than in those with non-proteinuric DKD. The presence of polar vasculosis was associated with hypertension in DKD. In addition, an unsupervised hierarchical clustering analysis revealed the spectrum of renal histopathology findings for more-proteinuric and less-proteinuric DKD. With changes in the diagnostic criteria for hypertension and advances in antihypertensive drugs, the pathogenesis of DKD may be changing. Furthermore, a decision tree model suggested how diabetes, hypertension, and dyslipidemia interacted in predicting the characteristics of DKD. CONCLUSION: Polar vasculosis is a good indicator of the presence of DM and hypertension. Furthermore, the histopathological and clinical spectrum of DKD were related to the interaction of diabetes, hypertension, and dyslipidemia. These histopathological and clinical results may help to show the range of patient characteristics when conducting clinical trials and could help to determine whether chronic kidney disease is caused by DM or some other cause.

Geriatric assessment of estimated glomerular filtration rate: a cross-sectional study.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is routinely calculated based on the serum creatinine level. However, the validity of such calculation in the geriatric population has not been sufficiently assessed. To examine whether the discrepancies between the eGFR determined based on the serum creatinine (eGFRcr) and that based on the serum cystatin C (eGFRcys) may be influenced to a lesser degree, by factors such as aging and muscle mass. METHODS: We measured the cystatin C and creatinine levels in 19,764 subjects (mean 77.0 years) and the eGFRcys and eGFRcr using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Japanese, and Berlin Invitation Study (BIS) equations were calculated. RESULTS: The mean measured eGFRcys and eGFRcr values by the CKD-EPI equation were 48.2 and 66.6 ml/min/1.73 m2 body surface area, respectively. The correlation between the eGFRcr (x) and eGFRcys (y) was y = 0.728x (r = 0.867; p < 0.001). Analysis of the slope among all ages could be shown by the relation, eGFRcys = (0.43 + 0.33/(1 + 10^((82-age)* - 0.046)))*eGFRcr. The correlation between the eGFRcr and eGFRcys by the Japanese equation were also similar. However, when it was calculated by the BIS equation, no drop of the slope of the linear regression line was observed with age. CONCLUSIONS: The eGFRcr was overestimated irrespective of whether the CKD-EPI or the Japanese equation was used. We could convert eGFRcr into eGFRcys by an equation using age. Estimation of eGFR including serum cystatin C was more accurate in elderly people.

Systematic review and meta-analysis for 2017 clinical practice guidelines of the Japan research committee of the ministry of health, labour, and welfare for intractable vasculitis for the management of ANCA-associated vasculitis.

OBJECTIVES: To provide evidence for the revision of clinical practice guideline (CPG) for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the Japan Research Committee for Intractable Vasculitis. METHODS: PubMed, CENTRAL, and the Japan Medical Abstracts Society were searched for articles published between January 1994 and January 2015 to conduct systematic review (SR), and the quality of evidence was assessed with GRADE approach. RESULTS: Nine randomized controlled trials (RCTs) and two non-RCTs were adopted for remission induction therapy, three RCTs and two non-RCTs for plasma exchange, and five RCTs and one non-RCT for remission maintenance therapy. A significant difference was found in efficacy and safety for the following comparisons. In the non-RCT adopted for remission induction therapy, glucocorticoid (GC) + cyclophosphamide (CY) was significantly superior to GC monotherapy regarding remission. GC + intravenous CY for remission induction therapy was superior to GC + oral CY regarding death at one year, serious adverse events, and serious infection. Concomitant use of plasma exchange for remission induction therapy of AAV with severe renal dysfunction reduced risk of end-stage renal disease versus non-users at month 3. CONCLUSION: This SR provided necessary evidence for developing CPG for the management of ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody-associated glomerulonephritis with immunoglobulin deposition.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is commonly classified as pauci-immune glomerulonephritis; however, some cases have granular immunoglobulin deposition along the glomerular capillary. The pathogenesis of immune deposits is poorly studied. METHODS: Of 66 patients diagnosed with ANCA-associated glomerulonephritis on renal biopsy, cases with immunoglobulin deposition along the glomerular capillary were identified and their clinicopathological characteristics were analyzed. We also performed myeloperoxidase (MPO) and double immunofluorescence (IF) stainings to determine the presence of immune complex antigens. RESULTS: Granular IgG deposition, IgG plus IgM deposition, and IgM deposition were observed in 15 (22.1%), 8 (11.2%), and 17 (25.0%) cases, respectively. In cases with granular IgG deposition, MPO-IgG double IF staining revealed co-localization of MPO and IgG. In cases with granular IgM deposition, MPO-IgM double IF staining did not co-localize. By electron microscopy, subepithelial deposition as well as intramembranous, subendothelial, and mesangial deposition was detected in the patients with IgG deposition. In addition, renal survival curves were not significantly different between the immunoglobulin deposition and non-deposition groups. CONCLUSIONS: Granular IgG and/or IgM deposition was observed in 60.6% of patients with ANCA-associated glomerulonephritis. In cases with IgG deposition, electron-dense deposits (EDDs) were observed at various sites in the glomerulus, and MPO and IgG immunocomplex deposition was frequently observed along the glomerular capillary. With IgM deposition, EDDs were not obvious in the glomerular basement membrane, and MPO and IgM immunocomplex was not detected. These data suggest differential mechanism between IgG deposition and IgM deposition.

Long-term outcomes of initial therapy for idiopathic membranous nephropathy.

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 S1; n = 52) within 6 months of diagnosis and those who had received supportive therapy (Group H1; n = 31). Second, we compared 20 cases using propensity score matching (Group S2, Group H2). Third, we compared patients with a urinary protein level of 1-3.5 g/gCre (Group S3, n = 18; Group H3, n = 19) and those with a urinary protein level ≥3.5 g/gCre (Group S4, n = 34; Group H4, 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 S1 and Group H1, 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 S1 and Group H1. No significant differences were observed between Group S2 and Group H2, between Group S3 and Group H3, or between Group S4 and Group H4. 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.

[Rituximab therapy in the treatment of anti-neutrophil cytoplasmic antibody (ANCA) -positive interstitial pneumonia: case report].

We report a patient treated with rituximab for interstitial pneumonia (IP) associated with microscopic polyangiitis (MPA) and who was undergoing hemodialysis. A 59-year-old woman who had been treated with tacrolimus for 1 year for rheumatic arthritis was referred to the Department of Nephrology for fatigue, fever, weight loss, and rapidly developing renal dysfunction. On the first admission, severe renal dysfunction, proteinuria, hematuria, and an elevated titer of MPO-ANCA were observed, and the woman was diagnosed with rapidly progressive glomerulonephritis because of MPA. At that point, IP was found to be present but not active. Although steroid semipulse therapy following an initial prednisolone (PSL) administration of 40 mg/day, IVCY, and plasma exchange were administered, renal dysfunction did not recover, and the patient required maintenance hemodialysis. Upon discharge, a high titer of MPO-ANCA was continuously observed. Nine months after the initiation of hemodialysis, respiratory discomfort and desaturation developed. Interstitial shadow and ground glass opacity were seen on a CT scan, and the patient was diagnosed with exacerbation of interstitial pneumonia caused by MPA recurrence. At the second admission, acute findings identified by imaging techniques had improved. However, the high titer of MPO-ANCA continued in spite of the steroid semi-pulse therapy following PSL administration, and rituximab corresponding to 200 mg/weekly for 1 month was also administered. The dose of rituximab was decreased subsequently because the patient was judged to be compromised by the hemodialysis. At the same time, internal administration of sulfamethoxazole/trimethoprim was initiated. After the rituximab treatment, MPO-ANCA antibodies gradually decreased, and the respiratory condition improved. Five months after the rituximab treatment, respiratory dysfunction recurred. Based on the CT findings and a high level of ß-D-glycan, the patient was diagnosed with ARDS due to pneumocystis pneumonia. In this case, rituximab was effective for IP due to MPA, but pneumocystis pneumonia could not be prevented in spite of prophylactic antibiotics. This case suggests that deliberative dose adjustments, careful patient observation, and prophylactic measures for infection are critical in rituximab treatment.

Caveolae may enable albumin to enter human renal glomerular endothelial cells.

Caveolae on human renal glomerular endothelial cells (HRGECs) are increased in glomerular disease and correlate with the degree of albuminuria. To assess the mechanism by which caveolae contribute to albuminuria, we investigated whether albumin enters into HRGECs through caveolae. HRGECs were incubated with Alexa Fluor 488 labeled BSA or transferrin, followed by immunofluorescence localization with antibody to caveolin-1 (Cav-1), the main structural protein of caveolae, or clathrin, the major structural protein of clathrin coated pits, to assess whether BSA colocalized with Cav-1. HRGECs were also incubated with albumin and caveolae disrupting agents, including methyl beta cyclodextrin (MBCD) and nystatin, to determine whether disrupting caveolae interfered with albumin endocytosis into HRGECs. HRGECs were also incubated with albumin after transfection with Cav-1 small interfering RNAs (siRNAs). Labeled BSA colocalized with Cav-1, but not with clathrin. In contrast, labeled transferrin colocalized with clathrin, but not with Cav-1. Incubation of HRGECs with MBCD or nystatin, or transfection with Cav-1 siRNA, significantly reduced the intracellular amounts of albumin and Cav-1, relative to normal HRGECs, as shown by western blotting and immunofluorescence. These findings indicate that albumin enters HRGECs through the caveolae, suggesting that caveolae play an important role in the pathogenesis of albuminuria by providing a pathway through which albumin can enter glomerular endothelial cells.

Atypical hemolytic uremic syndrome diagnosed four years after ABO-incompatible kidney transplantation.

Atypical hemolytic uremic syndrome (aHUS) in allograft kidney transplantation is caused by various factors including rejection, infection, and immunosuppressive drugs. We present a case of a 32 year old woman with aHUS four years after an ABO-incompatible kidney transplantation from a living relative. The primary cause of end-stage renal disease was unknown; however, IgA nephropathy (IgAN) was suspected from her clinical course. She underwent pre-emptive kidney transplantation from her 60 year old mother. The allograft preserved good renal function [serum creatinine (sCr) level 110-130 µmol/L] until a sudden attack of abdominal pain four years after transplant, with acute renal failure (sCr level, 385.3 µmol/L), decreasing platelet count, and hemolytic anemia with schizocytes. On allograft biopsy, there was thrombotic microangiopathy in the glomeruli, with a cellular crescent formation and mesangial IgA and C3 deposition. Microvascular inflammation, such as glomerulitis, peritubular capillaritis, and arteriole endarteritis were also detected. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) did not decrease and Shiga toxin was not detected. Donor-specific antibodies or autoantibodies, including anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane (anti-GBM) antibody, were negative. The patient was diagnosed with aHUS and received three sessions of plasmapheresis and methylprednisolone pulse therapy, followed by oral methylprednisolone (0.25-0.5 mg/kg) instead of tacrolimus. She temporarily required hemodialysis (sCr level, 658.3 µmol/L). Thereafter, her sCr level improved to 284.5 µmol/L without dialysis therapy. This case is clinically considered as aHUS after kidney transplantation, associated with various factors, including rejection, glomerulonephritis, and toxicity from drugs such as tacrolimus.

Comparison of a novel chemiluminescence enzyme immunoassay (CLEIA) with enzyme-linked immunosorbent assay (ELISA) for the determination of MPO-ANCA in patients with ANCA-associated vasculitis.

BACKGROUND: Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (ANCA) represents the serological hallmark of ANCA-associated vasculitis (AAV). We evaluated the analytical and diagnostic accuracy of chemiluminescence enzyme immunoassay (CLEIA) versus enzyme-linked immunosorbent assay (ELISA) for the detection of MPO-ANCA. METHODS: A total of 242 sera obtained from 51 patients with AAV and 103 patients without AAV were tested for MPO-ANCA by ELISA (NephroScholor MPOANC II) and CLEIA (the STACIA MEBLux test). Disease activity in the patients with AAV was determined based on the Birmingham Vasculitis Activity Score. We analyzed the correlations between the MPO-ANCA titers determined by the CLEIA and those determined by the ELISA, and also between the MPO-ANCA titers and the disease activity. RESULTS: The MPO-ANCA titers determined by the CLEIA (x) were strongly correlated with those determined by the ELISA (y). The correlation could be expressed by the following equation in this study: y = 1.8x + 7.7 (r = 0.96; p < 0.0001). At the cutoff value of 3.5 U/ml, the CLEIA yielded positive test results for MPO-ANCA in 73 of the 242 sera (30.2%), while at the cutoff value of 20 U/ml, ELISA yielded positive test results in 57 of the 242 sera (23.6%). The CLEIA yielded false-positive test results in 4 of the 120 sera obtained from the non-AAV patients (3.3%), whereas the ELISA yielded a false-positive result in only 1 of the 120 sera obtained from the non-AAV patients (0.8%). The sensitivity and specificity of the CLEIA for the diagnosis of AAV were 100% and 96.7%, respectively, while those of the ELISA were 94.3% and 99.2%, respectively. The sensitivity and specificity of the CLEIA for the prediction of active disease were 100% and 64.4%, respectively, while those of the ELISA were 94.3% and 73.6%, respectively. CONCLUSION: The false positivity rate of the CLEIA for MPO-ANCA tended to be high as compared with that of the ELISA. Also, according to the correlation coefficient between the results of the CLEIA and the ELISA calculated in this study, it is necessary to pay attention to the differences in the sensitivity and specificity between CLEIA and ELISA.

A novel autoantibody against moesin in the serum of patients with MPO-ANCA-associated vasculitis.

BACKGROUND: Antineutrophil cytoplasmic autoantibody (ANCA) directed against myeloperoxidase (MPO), a diagnostic criterion in MPO-ANCA-associated vasculitis (MPO-AAV), does not always correlate with disease activity. Here, we detected autoantibodies against moesin, which was located on the surface of stimulated endothelial cells, in the serum of patients. METHODS: The anti-moesin autoantibody titer was evaluated by ELISA. Seventeen kinds of cytokines/chemokines were measured by a Bio-Plex system. RESULTS: Serum creatinine in the anti-moesin autoantibody-positive group was higher than that in the negative group. Additionally, interferon (IFN)-γ, macrophage chemotactic peptide-1 (MCP-1), interleukin (IL)-2, IL-7, IL-12p70, IL-13, granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor were significantly higher in the positive group. Furthermore, IL-7 and IL-12p70 levels correlated with the anti-moesin autoantibody titer. Based on these findings and the binding of anti-moesin IgG to neutrophils and monocytes, we detected the secretion of cytokines/chemokines such as IFN-γ, MCP-1 and GM-CSF from these cells. CONCLUSIONS: The anti-moesin autoantibody existed in the serum of patients with MPO-AAV and was associated with the production of inflammatory cytokines/chemokines targeting neutrophils with a cytoplasmic profile, which suggests that the anti-moesin autoantibody has the possibility to be a novel autoantibody developing vasculitis via neutrophil and endothelial cell activation.

Statins stabilize the renal function of IgA nephropathy.

BACKGROUND: The renoprotective pleiotropic effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has recently been reported by several investigators. However, the effect of statins on IgA nephropathy (IgAN) is still unknown. METHODS: We selected 24 IgAN patients who had newly started statin therapy and were not treated with steroids and immunosuppressive agents during the observation period. We analyzed and compared clinical findings 1 year before and after treatment. RESULTS: Mean age was 50.5 ± 9.91 years and mean blood pressure was 90.9 ± 10.8 mmHg. Renal function was slightly deteriorated, serum creatinine was 1.03 (0.71-1.24) mg/dL and estimated glomerular filtration rate (eGFR) was 55.8 ± 22.8 mL/min. Lipid metabolism was poorly controlled [total cholesterol 247.7 ± 35.7 mg/dL, low-density lipoprotein cholesterol 151.5 (140.8-172.8) mg/dL, and triglyceride 163.0 (126.3-243.8) mg/dL]. Mild urinary abnormality was observed [proteinuria: 0.50 (0.22-1.29) g/g creatinine, urinary red blood cells 1.0 (0.2-5.0) per high power field]. After 1 year of statin treatment, lipid control was significantly better than at baseline. Proteinuria was not significantly decreased but renal function was improved. eGFR changed from a -5.9% decrease to a 2.4% increase (p = 0.0098). CONCLUSION: Our results indicated that statins stabilized the renal function of IgAN patients independent of their reduction of proteinuria.

Long-term damage assessment in patients with microscopic polyangiitis and renal-limited vasculitis using the Vasculitis Damage Index.

OBJECTIVES: The Vasculitis Damage Index (VDI) is used to define the degree of damage occurring in patients with systemic vasculitis. We conducted a retrospective study of 30 patients with microscopic polyangiitis (MPA) and renal-limited vasculitis (RLV). METHODS: The clinical data and VDI of the 30 patients enrolled in the study were collected and assessed for a period of 5 years. RESULT: The VDI score, which was 2.5 at 1 year after the initial diagnosis, increased gradually to 4.3 at 5 years post-diagnosis. The degrees of musculoskeletal and ocular damage significantly increased during the 5-year period (p = 0.001 and p = 0.002, respectively). The most frequent damage items in the VDI were cataract (13 %), hypertension (12 %), diabetes mellitus (9 %), and osteoporosis (6 %). The VDI score was significantly higher in the groups of patients who showed relapse or MPA than in the groups of patients who did not show relapse or RLV at 5 years (p = 0.02 and p = 0.03, respectively). In addition, a significant correlation was found between the VDI score at 5 years and the Birmingham Vasculitis Activity Score at diagnosis (p = 0.04, r = 0.4). CONCLUSION: The VDI was found to be a useful tool for determining the severity of damage caused by disease and the effects of treatment. The individual contributions of the VDI items may also be applied to treatment decisions.

Usefulness of assessment of the Clinical Frailty Scale and the Dementia Assessment Sheet for Community-based Integrated Care System 21-items at the time of initiation of maintenance hemodialysis in older patients with chronic kidney disease.

INTRODUCTION: We examined whether the Clinical Frailty Scale (CFS), a widely adopted tool for stratifying the degree of frailty, and the Dementia Assessment Sheet for Community-based Integrated Care System 21-items (DASC-21), a simple tool for simultaneous assessment of impaired cognition and impaired ADL, at the time of initiation of hemodialysis is useful tool of older patients for the outcome and prognosis. METHODS: Data for 101 patients aged 75 years or older (mean age, 84.3 years) with ESRD who were initiated on hemodialysis and could be followed up for a period of 6 months were reviewed. RESULTS: The 6-month survival curves showed a significantly higher number of deaths in the frailty (CFS≥5) group than in the normal to vulnerable (CFS<5) group (p<0.01). The CFS level was also significantly higher (6.5±1.5) in patients who died within 6 months of dialysis initiation as compared with that (4.6±1.7) in patients who survived (p<0.01). On the other hand, the total score of DASC-21 was related to need for inpatient maintenance dialysis (p<0.01). The total score on the DASC-21 were found as showing significant correlations with the CFS level. The IADL outside the home was identified in the DASC-21 sub-analyses as being correlated with CFS. CONCLUSIONS: The CFS and the DASC-21 appeared to be a useful predictive tool of outcome and prognosis for older patients being initiated on hemodialysis. Assessment by the CFS or the DASC-21 might be useful for selecting the renal replacement therapy by shared decision-making and for advance care planning.

Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults.

BACKGROUND: Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to selective immunomodulating regimens is necessary for these cases. METHODS: To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion. RESULTS: A significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion [25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001]. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse. CONCLUSIONS: Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.

Evaluation of the newly proposed simplified histological classification in Japanese cohorts of myeloperoxidase-anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in comparison with other Asian and European cohorts.

The prognostic value of renal biopsy in anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is widely recognized; however, there is no consensus regarding its pathological classification. Berden et al. proposed a new classification of glomerulonephritis in ANCA-associated vasculitis (AAV) categorized into focal, crescentic, mixed, and sclerotic classes and showed its prognostic value in 100 international multicenter cohorts for 1- and 5-year renal outcomes. In order to evaluate whether this new classification has predictive value and reproducibility in Japanese AAV cases, 87 cohorts with only microscopic polyangiitis in 3 limited centers in Japan were analyzed. In addition, those from Japan, Europe (Berden's cohorts) and China were compared in a recent report.

Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis.

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.

Anti-glomerular basement membrane disease developing 3 years after the development of Sweet syndrome and 1 year after the development of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

A 73-year-old Japanese woman, with a history of Sweet syndrome diagnosed 3 years earlier and anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis diagnosed 1 year earlier, presented with an episode of rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement membrane (GBM) disease. At the time of diagnosis of the ANCA-associated vasculitis 1 year earlier, serological testing yielded a negative result for anti-GBM antibody. However, at the present visit, serology for anti-MPO antibody was negative, while that for anti-GBM antibody was positive. This is the first report of anti-GBM disease developing sequentially after Sweet syndrome and ANCA-associated vasculitis. This case may provide clues to the potential immunological links among these three distinct conditions.

Relationship between the urinary Na/K ratio, diet and hypertension among community-dwelling older adults.

The association between the urinary sodium (Na)/potassium (K) ratio and hypertension is well recognized. We investigated whether the urinary Na/K ratio might be associated with hypertension in community-dwelling older adults and whether the association was influenced by habitual dietary patterns. We enrolled a total of 684 older adults (mean age, 76.8 years) and conducted health examinations at Kusatsu, Japan, in 2021. The urinary Na/K ratio was found to be independently associated with systolic blood pressure (SBP) (p < 0.0001), years of education (p = 0.0027), number of cohabitants (p = 0.0175), estimated glomerular filtrate rate (eGFR) (p = 0.0244), and Geriatric Depression Scale short-version (GDS15) score (p = 0.0366). In addition, an unsupervised hierarchical clustering analysis revealed a spectrum of habitual dietary patterns for higher and lower values of the urinary Na/K ratio. The decision tree indicated that the urinary Na/K ratio was associated with the history of milk consumption. A positive history of daily milk consumption predicted a mean urinary Na/K ratio of 2.8, and a negative history of daily milk consumption predicted a mean urinary Na/K ratio of 3.3. Furthermore, the frequency of fruit and vegetable consumption also predicted the urinary Na/K ratio. The relationship between the urinary Na/K ratio and hypertension was influenced by the frequency of consumption of milk, fruits, and vegetables in the subjects. This finding might be due to the influence of education and/or depression. The results suggested the importance of nutritional education in the development of hypertension.