Nationwide questionnaire survey on the management of chronic kidney disease for general practitioners in Japan.

BACKGROUND: In 2019, a nationwide questionnaire survey on the management of chronic kidney disease (CKD) was circulated to general practitioners (GPs) throughout Japan by The Japan Physicians Association. The aim was to assess the current state of CKD medical care in the country and evaluate the utilization of CKD-specific guidelines in the treatment by GPs. METHODS: The voluntary survey targeted all members of Japan Physicians Association, a nationwide organization consisting primarily of 15,000 GPs in clinics throughout the country. GPs were divided into groups: 171 GPs using and 414 GPs not using the guidelines. Comparisons between the groups' responses were made using propensity score matching and component cluster analysis. RESULTS: Overall responses revealed that the estimated glomerular filtration rate's utilization rate was high (95.1%). However, evidence-practice gaps in urine protein quantification and anemia remedy were prominent. There were significantly favorable answers in terms of CKD management in the user group compared with those in the non-user group, except for the questions about a urine check at the first visit, stopping the use of renin-angiotensin system inhibitors, and the target blood pressure for elderly CKD patients. The differences suggest that utilization of the CKD guidelines has improved CKD management practices by GPs. CONCLUSIONS: Further promotion of CKD guidelines utilization (28% in this survey) is considered valid for CKD medical education.

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.

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.

Effect of Luseogliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, and Dipeptidyl-Peptidase 4 Inhibitors on the Quality-of-Life and Treatment Satisfaction of Patients With Type 2 Diabetes Mellitus: A Subanalysis of a Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT Study).

INTRODUCTION: The effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) on quality of life (QOL) and treatment satisfaction have not been directly compared. This sub-analysis of a randomized-controlled trial with an SGLT2i, luseogliflozin, and DPP-4is compared their effects on QOL and treatment satisfaction of patients. METHODS: This study recruited 623 patients with type 2 diabetes mellitus who were drug-naïve or treated with antidiabetic agents other than SGLT2is and DPP-4is. The patients were randomized into luseogliflozin or DPP-4i group and followed for 52 weeks. This sub-analysis assessed QOL and treatment satisfaction using Oral Hypoglycemic Agent Questionnaire (OHA-Q) version 2 in the drug-naïve subgroup who were drug-naïve at baseline and with monotherapy with luseogliflozin or DPP-4i throughout the observation period (256 patients) at 24 and 52 weeks and in the add-on subgroup who were treated with OHAs other than SGLT2is and DPP-4is (204 patients) at baseline, 24 and 52 weeks. RESULTS: In the drug-naïve subgroup, total (50.8 ± 8.2 in luseogliflozin group and 53.1 ± 10.0 in DPP-4i group, p = 0.048) and somatic symptom scores (22.4 ± 5.0 in luseogliflozin group and 24.4 ± 5.8 in DPP-4i group, p = 0.005) at 52 weeks (but not at 24 weeks) were significantly higher in DPP-4i group than in luseogliflozin group. In add-on subgroup, changes in total (3.3 ± 7.8 in luseogliflozin group and 0.9 ± 7.6 in DPP-4i group, p = 0.030) and treatment convenience (1.2 ± 3.9 in luseogliflozin group and - 0.6 ± 4.2 in DPP-4i group, p = 0.002) from baseline to 24 weeks (but not at 52 weeks) were significantly greater in luseogliflozin group than in DPP-4i group. The QOL related to safety or glycemic control was comparable between the groups. CONCLUSIONS: Physicians should pay attention to side effects of SGLT2is to maintain the patients' QOL when SGLT2is are initiated or added-on. Add-on of luseogliflozin increased patients' QOL more than DPP-4is. Considering patients' QOL and treatment satisfaction is important for selecting SGLT2is or DPP-4is. TRIAL REGISTRATION: UMIN000030128 and jRCTs031180241.

Xenotransplanted embryonic kidney provides a niche for endogenous mesenchymal stem cell differentiation into erythropoietin-producing tissue.

Recent findings have demonstrated that stem cells can differentiate into mature tissue when supplied with a niche containing factors identical to those in the normal developmental program. A niche for the development of an organ can be provided by xenotransplantation of a similar developing organ. However, this process has many technical, safety, and ethical concerns. Here, we established xenotransplantation models that control endogenous mesenchymal stem cell (MSC) differentiation into mature erythropoietin (EPO)-producing tissue in a niche provided by a developing xenometanephros. Transplantation of rat metanephroi into mouse omentum, and similarly pig metanephroi into cat omentum, led to the recruitment of host cells and EPO production. EPO-expressing cells were not differentiated from integrating vessels because they did not coexpress endothelial markers (Tie-2 and VE-cadherin). Instead, EPO-expressing cells were shown to be derived from circulating host cells, as shown by enhanced green fluorescent protein (EGFP) expression in the grown transplants of chimeric mice bearing bone marrow from a transgenic mouse expressing EGFP under the control of the EPO promoter. These results suggest that donor cell recruitment and differentiation in a xenotransplanted developing organ may be consistent between species. The cells responsible for EPO expression were identified as MSCs by injecting human bone marrow-derived MSCs and endothelial progenitor cells into NOD/SCID mice. Furthermore, using metanephroi from transgenic ER-E2F1 suicide-inducible mice, the xenotissue component could be eliminated, leaving autologous EPO-producing tissue. Our findings may alleviate adverse effects due to long-lasting immunosuppression and help mitigate ethical concerns.

Obesity-related glomerulopathy and the nephron complement.

Obesity-related glomerulopathy (ORG) is a secondary form of glomerular disease that can occur in individuals with obesity. However, the absolute risk for an obese individual to develop progressive renal deterioration is low. Therefore, obesity alone appears to be insufficient to develop such severe renal injury, and there are likely other factors that contribute to the development of this entity. The glomerular hyperfiltration found in patients with ORG has been postulated to lead to structural abnormalities in glomeruli, such as glomerulomegaly and focal segmental glomerular sclerosis, in a manner analogous to that described in patients with reduced renal mass. In fact, recent studies suggest that a reduction in nephron mass is implicated in patients with ORG and synergistically contributes to the development of this renal complication together with obesity-induced changes in renal hemodynamics.

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.

Distribution of glomerular density in different cortical zones of the human kidney.

Our studies have demonstrated that a low glomerular density in renal biopsies is a plausible predictor of a worse renal outcome in patients with primary glomerular diseases. However, there remains a concern regarding the diversity that may exist in the distribution of glomerular density within the same kidney. This study therefore aimed to determine the differences in the glomerular density between anatomically different cortical zones of the human kidney. A total of 89 autopsy kidneys were analyzed to accurately measure the glomerular density in different parts of the renal cortex. As a whole, compared to the glomerular density in the superficial cortex (3.0 ± 0.7/mm(2)), the average glomerular density in the juxtamedullary cortex (2.2 ± 0.6/mm(2)) was approximately two-thirds. The glomerular density showed maximal 3.5-fold variations between individuals and was inversely correlated with the mean glomerular volume in both cortical areas. A low glomerular density of the superficial cortex was predominantly associated with the increase of global glomerulosclerosis. On the other hand, a low glomerular density of the juxtamedullary cortex was predominantly associated with an increase in the kidney weight. Thus, there are significant zonal differences in the distribution of the glomerular density in human kidneys independent of the potential variations observed between individuals.

Clinical features and long-term renal outcomes of Japanese patients with obesity-related glomerulopathy.

BACKGROUND: Studies have suggested that obesity-related glomerulopathy (ORG) is one of the important disease entities leading to end-stage renal disease. However, information is limited regarding the clinical features and renal outcomes of Japanese ORG patients. METHODS: Among the patients whose renal biopsy was performed at our institute during the past 10 years, we identified 28 ORG patients. Among them, the renal prognosis of the 20 patients with more than 2 years of follow-up was further analyzed. The clinical features at biopsy and the renal outcomes were compared with those of other ORG cohorts. RESULTS: The average values at diagnosis were a body mass index of 32.0 kg/m(2), eGFR of 65 ml/min/1.73 m(2), and urinary protein excretion of 1.7 g/day. These features were less serious than those of the US cohort or the Spanish cohort and were compatible with those of the Chinese cohort. At the last observation, seven patients (35%) showed a 50% increase in their serum creatinine, and two patients (10%) had a 100% increase in serum creatinine and/or end-stage renal disease (end point). A multivariate analysis identified the time-averaged proteinuria during follow-up as an independent factor that was associated with the slope of renal function. The annual rate of patients reaching the end point in the US cohort, the Spanish cohort and the current cohort were 6.7, 6.9 and 1.6% per year, respectively. CONCLUSION: The long-term outcomes of Japanese ORG patients include progression to renal failure, emphasizing the importance of an accurate early diagnosis of this entity.

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.

PGD2-CRTH2 pathway promotes tubulointerstitial fibrosis.

Urinary excretion of lipocalin-type PGD(2) synthase (L-PGDS), which converts PG H(2) to PGD(2), increases in early diabetic nephropathy. In addition, L-PGDS expression in the tubular epithelium increases in adriamycin-induced nephropathy, suggesting that locally produced L-PGDS may promote the development of CKD. In this study, we found that L-PGDS-derived PGD(2) contributes to the progression of renal fibrosis via CRTH2-mediated activation of Th2 lymphocytes. In a mouse model, the tubular epithelium synthesized L-PGDS de novo after unilateral ureteral obstruction (UUO). L-PGDS-knockout mice and CRTH2-knockout mice both exhibited less renal fibrosis, reduced infiltration of Th2 lymphocytes into the cortex, and decreased production of the Th2 cytokines IL-4 and IL-13. Furthermore, oral administration of a CRTH2 antagonist, beginning 3 days after UUO, suppressed the progression of renal fibrosis. Ablation of IL-4 and IL-13 also ameliorated renal fibrosis in the UUO kidney. Taken together, these data suggest that blocking the activation of CRTH2 by PGD(2) might be a strategy to slow the progression of renal fibrosis in CKD.

[A case of acute kidney injury during warfarin therapy].

The patient was an 82-year-old female. She had been treated with warfarin for atrial fibrillation that developed after a heart valve replacement operation. She was admitted because of a progressive loss of renal function together with persistent microscopic hematuria and proteinuria. Although the renal biopsy showed only focal mononuclear cell infiltration and mild mesangial expansion in the glomeruli, the occlusive red blood cell casts were remarkable in the tubules and were accompanied by inflammatory and edematous changes in the surrounding interstitial area. After the adjustment of an excessively extended prothrombin time, her renal function gradually improved in parallel with the marked decrease in the microhematuria. It was assumed that an acute kidney injury observed in this case was caused by the occlusive red blood cell casts as a result of abnormal hemorrhage in the glomeruli due to focal glomerulonephritis and a warfarin overdose. The present case, therefore, suggests that a warfarin overdose is a potential risk factor for acute kidney injury in the presence of coexisting glomerular injury.

Overall Efficacy and Safety of Sodium-Glucose Cotransporter 2 Inhibitor Luseogliflozin Versus Dipeptidyl-Peptidase 4 Inhibitors: Multicenter, Open-Label, Randomized-Controlled Trial (J-SELECT study).

INTRODUCTION: Evidence of a direct comparison between dipeptidyl-peptidase 4 inhibitors (DPP-4is) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) remains lacking, and no clear treatment strategy or rationale has been established using these drugs. This study aimed to compare the overall efficacy and safety of DPP-4is and the SGLT2i luseogliflozin in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with T2DM who had not used antidiabetic agents or who had used antidiabetic agents other than SGLT2is and DPP-4is were enrolled in the study after written informed consent had been obtained. The enrolled patients were subsequently randomly assigned to either the luseogliflozin or DPP-4i group and followed up for 52 weeks. The primary (composite) endpoint was the proportion of patients who showed improvement in ≥ 3 endpoints among the following five endpoints from baseline to week 52: glycated hemoglobin (HbA1c), weight, estimated glomerular filtration rate (eGFR), systolic blood pressure, and pulse rate. RESULTS: A total of 623 patients were enrolled in the study and subsequently randomized to either the luseogliflozin or DPP-4i groups. The proportion of patients who showed improvement in ≥ 3 endpoints at week 52 was significantly higher in the luseogliflozin group (58.9%) than in the DPP-4i group (35.0%) (p < 0.001). When stratified by body mass index (BMI) (< 25 or ≥ 25 kg/m2) or age (< 65 or ≥ 65 years), regardless of BMI or age, the proportion of patients who achieved the composite endpoint was significantly higher in the luseogliflozin group than in the DPP-4i group. Hepatic function and high-density lipoprotein-cholesterol were also significantly improved in the luseogliflozin group compared with the DPP-4i group. The frequency of non-serious/serious adverse events did not differ between the groups. CONCLUSION: This study showed the overall efficacy of luseogliflozin compared with DPP-4is over the mid/long term, regardless of BMI or age. The results suggest the importance of assessing multiple aspects regarding the effects of diabetes management. TRIAL REGISTRATION NUMBER: jRCTs031180241.

The effect of metanephros transplantation on blood pressure in anephric rats with induced acute hypotension.

BACKGROUND: The kidney is an important organ for maintaining blood pressure. We have previously reported that transplanted metanephroi can reproduce some kidney functions. The aim of the present study was to determine the metabolic function of transplanted metanephroi with particular reference to maintaining blood pressure. METHODS: Male Wistar rats were transplanted with metanephroi (transplanted group, n = 28), following unilateral nephrectomy. For comparison, we performed unilateral nephrectomy without transplantation in 32 rats (non-transplanted group, n = 18; haeminephrectomy control group, n = 14). The remaining kidney was removed 2 weeks after the initial operation, while control rats had a sham operation. Hypotension was induced by intravenous infusion of diltiazem hydrochloride or rapid withdrawal of blood. Mean arterial blood pressure (MAP) was invasively monitored and plasma renin activity (PRA) was analysed at multiple time points. Renin expression by metanephroi was evaluated by real-time polymerase chain reaction and immunohistochemistry. RESULTS: Metanephroi in the transplanted group expressed renin messenger RNA. Metanephros transplantation significantly raised PRA and maintained MAP compared with the non-transplanted group. No significant differences between the transplanted and control groups were found with respect to PRA or MAP. PRA was positively correlated with metanephroi weight as well as MAP in the transplanted group. CONCLUSION: The present study shows that transplantation of metanephroi produces PRA and contributes to raising MAP in a rat model of acute hypotension.

Metanephros transplantation inhibits the progression of vascular calcification in rats with adenine-induced renal failure.

BACKGROUND/AIM: Recent research has shown that transplanted metanephroi form primitive vascularized kidneys with histologically recognizable renal features. The aim of the present study was to determine the metabolic function of transplanted metanephroi in rats with chronic renal failure (CRF), with particular reference to secondary hyperparathyroidism and vascular calcification. METHODS: CRF was induced in 11-week-old male Wistar rats by maintaining them on a 0.75% adenine diet for 4 weeks, followed by normal diet for an additional 2 weeks. At the end of adenine loading, whole metanephroi from embryonic day 15 rats were transplanted into the omentum and epididymis of the transplantation group. Vascular calcification was evaluated 2 weeks after metanephroi transplantation. RESULTS: Metanephros transplantation significantly reduced vascular calcium and phosphorus content and suppressed the progression of vascular calcification as indicated by von Kossa staining of the media of the thoracic aorta. However, no significant differences between the adenine-fed control and transplantation groups were found regarding the serum levels of 1,25(OH)2D3, calcium or phosphorus or the calcium × phosphorus product. CONCLUSION: The present study has shown that transplantation of metanephroi suppresses the progression of vascular calcification via a mechanism that is independent of calcium-phosphorus dynamics.

Diffuse tubulointerstitial nephritis associated with ANCA-negative pauci-immune glomerulonephritis.

Tubulointerstitial nephritis (TIN) is histopathologically characterized by the infiltration of leukocytes, edema, and fibrosis of the renal interstitium with or without tubulitis and vasculitis. TIN is not usually accompanied by specific glomerular lesions. We herein report the case of a 65-year-old male with a diagnosis of non-small cell lung carcinoma that showed acute renal failure, together with proteinuria and microscopic hematuria. The renal biopsy findings showed severe and diffuse TIN, despite the fact that glomerulonephritis (GN) with cellular crescents was only focally identified. In this case, the GN was of the pauci-immune type, but the serum tests for anti-neutrophil cytoplasmic antibodies were negative. No disorders known to be associated with TIN were detected. The pathogenesis involved in this unusual presentation of a concomitant occurrence of TIN and pauci-immune GN is currently unclear.

A case of idiopathic membranoproliferative glomerulonephritis with a transient glomerular deposition of nephritis-associated plasmin receptor antigen.

The differential diagnosis of acute poststreptococcal glomerulonephritis (APSGN) and idiopathic membranoproliferative glomerulonephritis (MPGN) is sometimes difficult, as they share several key features in their laboratory and histological findings, especially during the acute phase of the diseases. We herein report an idiopathic case of MPGN in which the glomerular deposition of nephritis-associated plasmin receptor (NAPlr), a recently identified nephritic antigen for APSGN, was demonstrated. A 24-year-old postpartum woman developed nephrotic syndrome and hypocomplementemia. Although she showed no apparent findings of a prior infection, her serum titer of antistreptolysin O antibody was elevated. Renal biopsies were performed twice at intervals of 6 months, both of which showed findings fully consistent with those of MPGN. Of note, fluorescent immunostaining for NAPlr was positive in the glomeruli of the first biopsy but not in the second. Despite the use of a corticosteroid, hypocomplementemia persisted for more than 1 year. It was therefore suggested that a streptococcal infection may have influenced the development of glomerular injury in this idiopathic case of MPGN.

Comparison of the 2013 and 2019 Nationwide Surveys on the Management of Chronic Kidney Disease by General Practitioners in Japan.

In 2019, the Japan Physicians Association conducted a second nationwide survey on the management of chronic kidney disease (CKD) among the Japanese general practitioners (GPs). We aimed to clarify the changes in the state of CKD medical care by GPs since the 2013 survey. The 2013 and 2019 surveys included 2214 and 601 GPs, respectively, who voluntarily participated. The two surveys were compared, using propensity score matching to balance the background of the responded GPs. For the medical care of CKD, the frequency of urine or blood examination, use of estimated glomerular filtration rate (eGFR) value for CKD management, and continuous use of renin-angiotensin system inhibitors for their reno-protective effects were significantly higher in 2019 than in 2013 (all: p < 0.001). The medical cooperation in CKD management, the utilization of the clinical path for CKD management and the measurement of the eGFR during the medical health checkup were significantly increased in 2019, compared to those in 2013. More GPs felt dissatisfied with the components of CKD treatment by nephrologists (p < 0.001). The two surveys confirmed improvements in the level of medical care for CKD and a strengthening in cooperation. However, the dissatisfaction with the consultation with nephrologists did not necessarily improve.

Glomerular density-associated changes in clinicopathological features of minimal change nephrotic syndrome in adults.

BACKGROUND: Differences in nephron number and/or glomerular size between individuals, in relation to intrauterine growth retardation or low birth weight, have been suggested to affect the clinical course of minimal change nephrotic syndrome (MCNS) in children. However, no previous study has investigated the potential influences of these histological variables on the clinical course of adult patients with MCNS. METHODS: The glomerular density (GD; the number of non-sclerotic glomeruli per renal cortical area) and the glomerular volume (GV) were evaluated using renal biopsy specimens from adult patients with a histological diagnosis of MCNS (n = 50). Relationships between these variables and clinicopathological features, including the initial response to corticosteroid therapy, were analyzed. RESULTS: Both the GD (1.5-6.5/mm(2)) and the GV (1.2-4.4 × 10(6) µm(3)) showed about 4-fold variations, and a close inverse correlation was observed between these two variables. Notably, the MCNS patients with a low GD showed a trend towards having similar clinicopathological characteristics as patients with a histological diagnosis of focal segmental glomerular sclerosis, as compared to the MCNS patients with a high GD. In addition, during the initial treatment with corticosteroids, the number of patients achieving complete remission was significantly lower in the MCNS patients with a low GD than that in the MCNS patients with a high GD. CONCLUSION: These results suggest that the GD in renal biopsies may be an important determinant of the glomerular size variability, and can therefore influence the clinical phenotype, such as the response to corticosteroid therapy, in adult patients with MCNS.

Low glomerular density is a risk factor for progression in idiopathic membranous nephropathy.

BACKGROUND: The adverse histological features predicting a progressive loss of renal function in idiopathic membranous nephropathy (IMN), before the establishment of impaired renal function with advanced glomerulosclerosis and/or interstitial fibrosis, are still poorly understood. The present study examined the relationship between the glomerular density (GD; non-sclerotic glomerular number/renal cortical area of biopsy) and the renal prognosis in IMN patients, especially in those without any apparent renal dysfunction at the time of diagnosis. METHODS: The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed in the 65 IMN patients with an estimated glomerular filtration rate (eGFR) of ≥ 60 mL/min/1.73 m(2) (mean, 80 mL/min/1.73 m(2)) at biopsy. RESULTS: The individual values for GD ranged from 1.6 to 6.5/mm(2) with 4-fold variation. A lower GD was associated with progression based on a ≥ 50% reduction in eGFR or reaching to end-stage renal disease. An association between a lower GD and progression was observed, especially in patients with persistent proteinuria of ≥ 1 g/day at follow-up. In contrast, any patients who achieved proteinuria of <1 g/day at follow-up did not show progression regardless of their GD levels. In addition, among the various clinicopathological factors observed, the GD was the only factor at biopsy that independently predicted the slope of the renal function during the observation periods. CONCLUSION: These results suggest that low GD is a plausible risk factor for progression in IMN patients, especially in those that do not achieve a remission of proteinuria during the follow-up.