Renal Pathology Society Classification Research Articles

Polar vasculosis is associated with better kidney outcome in type 2 diabetes with biopsy-proven diabetic kidney disease: A multicenter cohort study.

This multicenter cohort study retrospectively assessed the association between polar vasculosis and the progression of diabetic kidney disease (DKD) in type 2 diabetes. We enrolled 811 patients with type 2 diabetes, biopsy-proven DKD, and proteinuria (≥0.15 g/g creatinine [g/day]). The association between polar vasculosis and other kidney lesions was explored. The outcome was DKD progression defined as a composite of renal replacement therapy initiation or 50% decline in estimated glomerular filtration rate (eGFR) from baseline. Of the 811 cases, 677 (83.5%) had polar vasculosis. In multivariate logistic regression analysis, subendothelial widening of the glomerular basement membrane, glomerulomegaly, glomerular class in the Renal Pathology Society classification ≥IIb, vascular lesions, age, eGFR, and hemoglobin A1c were positively associated with polar vasculosis, whereas interstitial fibrosis and tubular atrophy (IFTA) was negatively associated with polar vasculosis. During a median follow-up of 5.2 years, progression of DKD occurred in 322 of 677 (7.4 events/100 person-years) and 79 of 134 (11.4 events/100 person-years) cases with and without polar vasculosis, respectively. Kaplan-Meier analysis showed that polar vasculosis was associated with lower cumulative incidences of DKD progression. Multivariate Cox regression analyses showed that polar vasculosis was associated with a lower risk of DKD progression, regardless of eGFR or proteinuria subgroups. These associations between polar vasculosis and better kidney outcome were unchanged considering all-cause mortality before DKD progression as a competing event. This study showed that polar vasculosis of DKD was associated with less advanced IFTA and a better kidney outcome in type 2 diabetes with proteinuria.

Investigation of Lupus Nephritis Cases with Special Reference to Activity and Chronicity Indices

Background & Objectives: The International Society of Nephrology/ Renal Pathology Society (ISN/RPS) classification is based upon criteria which differentiate acute and chronic phases of Lupus Nephritis. Activity/Chronicity Index grants us a higher insight on the level of pathological lesions and treatment outcome by examining the reversibility of lesions .The present investigation was done in order to highlight the importance of activity and chronicity indices in the course of Lupus Nephritis.Materials & Methods: Seventy-three Kidney biopsy samples of Lupus Nephritis patients were examined. The information was recorded in a check-list and was then statistically analyzed.Results: Lupus Nephritis is importantly age-related, frequency of Lupus Nephritis increases with age until the age of 40 years; 21–40 years being the most frequent among studied patients. A prominent decline was seen after the age of 40. Regardless of age, the occurrence was more frequent in females. Class IV was most frequent in all ages and in both sexes. Both Activity and Chronicity scores were slightly higher in females. Activity Index was higher in ages of 11 to 30 years, whereas Chronicity Index was highest in 41 to 50 years of age. The highest Activity Index was reported in Class IV while the highest Chronicity Index was reported in Class V. The least Activity Index was shown in Class VI while Classes II and I had the lowest Chronicity Index. Endocapillary hypercellularity was the most frequent active lesion and tubular atrophy was the most frequent chronic lesion. It is noteworthy that fibrotic crescents were significantly less common among chronic lesions.Conclusion: Histopathological findings, clinical and para-clinical data could furnish more information on disease process, treatment, quality of life and mortality rate.

Metabolic phenotypes and risk of end-stage kidney disease in patients with type 2 diabetes.

Obesity often initiates or coexists with metabolic abnormalities. This study aimed to investigate the pathological characteristics and the independent or mutual relations of obesity and metabolic abnormalities with end-stage kidney disease (ESKD) in patients with type 2 diabetes (T2D) and associated diabetic kidney disease (DKD). A total of 495 Chinese patients with T2D and biopsy-confirmed DKD between 2003 and 2020 were enrolled in this retrospective study. The metabolic phenotypes were based on the body weight index (BMI)-based categories (obesity, BMI ≥ 25.0 kg/m2) and metabolic status (metabolically unhealthy status, ≥ 1 criterion National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) excluding waist circumference and hyperglycemia) and were categorized into four types: metabolically healthy non-obesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO). The pathological findings were defined by the Renal Pathology Society classification. Cox proportional hazards models were used to estimate hazard ratios (HRs) for ESKD. There are 56 (11.3%) MHNO patients, 28 (5.7%) MHO patients, 176 (35.6%) MUNO patients, and 235 (47.5%) MUO patients. The high prevalence of the Kimmelstiel-Wilson nodule and severe mesangial expansion were associated with obesity, whereas severe IFTA was related to metabolically unhealthy status. In the multivariate analysis, the adjusted HR (aHR) was 2.09 [95% confidence interval (CI) 0.99-4.88] in the MHO group, 2.16 (95% CI 1.20-3.88) in the MUNO group, and 2.31 (95% CI 1.27-4.20) in the MUO group compared with the MHNO group. Furthermore, the presence of obesity was insignificantly associated with ESKD compared with non-obese patients (aHR 1.22, 95% CI 0.88-1.68), while the metabolically unhealthy status was significantly associated with ESKD compared to the metabolically healthy status in the multivariate analysis (aHR 1.69, 95% CI 1.10-2.60). Obesity itself was insignificantly associated with ESKD; however, adding a metabolically unhealthy status to obesity increased the risk for progression to ESKD in T2D and biopsy-proven DKD.

Pathological validation of the Japanese Renal Pathology Society classification and challenges in predicting renal prognosis in patients with diabetic nephropathy.

BackgroundDiabetic nephropathy (DN) accounts for approximately half of all cases of chronic kidney disease (CKD) and end-stage kidney disease worldwide. The Renal Pathology Society (RPS) classification has been used to predict the renal prognosis in DN. In 2018, the Japanese Renal Pathology Society (JRPS) proposed a comprehensive classification system that included pathological changes in the kidney. The clinical significance of the JRPS classification system was comparatively evaluated in the present study.MethodsA total of 93 cases diagnosed with DN from 2009 to 2019 were enrolled. JRPS scores (J-scores) were calculated by scoring the pathological factors in the JRPS classification system and comparing them with clinical parameters.ResultsMost pathological factors constituting the J-score were significantly correlated with clinical factors. Laminated nodules were inversely correlated with estimated glomerular filtration rate. After adjusting for age, sex, body mass index, hemoglobin A1c, diabetes duration, and hypertension, CKD stage was significantly correlated with JRPS grade, nodular lesions, and exudative lesions in the multivariate logistic regression analysis. However, receiver operating characteristic curve analysis revealed that the J-score (area under the curve [AUC] = 0.639) had lower clinical significance than the traditional RPS classification system (AUC = 0.675).ConclusionThe JRPS classification can more comprehensively reflect renal changes than the RPS classification and is correlated with renal survival. When creating a new pathological classification, arteriolar hyalinosis should not be included, whereas laminated nodules should be included.

Complement Deposition Predicts Worsening Kidney Function and Underlines the Clinical Significance of the 2010 Renal Pathology Society Classification of Diabetic Nephropathy.

ObjectivesConverging evidence points towards a role of the complement system in the pathogenesis of diabetic nephropathy (DN). The classification system of diabetic kidney lesions devised by the Renal Pathology Society (RPS) in 2010 are based on the pathogenic process of DN. Therefore, we investigated the correlation between glomerular C3 deposits and RPS DN classification and the combined deleterious effects thereof on kidney function.MethodsThe study analyzed data from 217 diabetic patients who underwent renal biopsy between 2010 and 2021 and were found to have DN as the only glomerular disease. C3 deposition was considered positive if the glomerular C3 immunofluorescence intensity was at the trace or ≥1+ level. We divided DN into five glomerular lesion classes and separately evaluated the degree of interstitial and vascular involvement. The primary outcome was the composite of a ≥50% decline from the initial estimated glomerular filtration rate, end-stage renal disease, and death.ResultsNone of the patients were classified into class I, and few were classified into classes IIa (7.8%) and IV (9.2%). Most patients were classified as IIb (30.9%) and III (52.1%). C3 deposition was detected in 53.9% of patients. Multivariate logistic regression analysis showed that DN class was significantly correlated with C3 deposits [odds ratio, 1.59; 95% confidence interval (CI), 1.08–2.36; p = 0.02). During a median follow-up of 22 months, 123 (56.7%) patients reached the composite outcome. The endpoints occurred more frequently in patients with C3 deposition (69.2 vs. 42%) compared with those without C3 deposition. Patients with C3 deposition in either class IIb [hazards ratio (HR), 3.9 (95% CI, 1.14–13.17) vs. 2.46 (95% CI, 0.68–8.89)] or III [HR, 4.98 (95% CI, 1.53–16.23) vs. 2.63 (95% CI, 0.77–9.0)] had a higher risk of adverse kidney outcomes than those without C3 deposition. The prognostic accuracy of the combination of DN class and C3 deposits at 1 and 3 years was higher than that for DN class only.ConclusionsComplement deposition together with DN class predicts more rapid deterioration of kidney function in DN, which underlines the clinical significance of the DN phenotype according to the RPS classification.

IDF21-0222 Prevalence and clinical predictors of Non-diabetic kidney disease in Type 2 Diabetes with renal involvement

Background: Renal Involvement in individuals with Type-2 Diabetes (T2DM) may be due to diabetes per se i.e., Diabetes kidney disease (DKD) or to other cause other than T2DM i.e., non-Diabetic kidney disease (NDKD) and in a group of individuals may have both (DKD+NDKD). Differentiation between the same is only possible with renal biopsy. Specific treatment options are available for NDKD which could potentially change outcomes. Data regarding the proportion of subtypes of renal involvement in diabetes is limited and flawed due to biases in performing renal biopsy. Most previous studies of renal biopsies are retrospective in nature. With increasing burden of T2DM worldwide it is imperative that we to establish non-invasive markers which could help to identify those who might benefit from renal biopsy to establish diagnosis of NDKD. Aim: To determine proportion of patients with T2D with renal involvement who have DKD, NDKD or mixed disease. To identify possible clinical predictor/s which could help decision making for targeted renal biopsy to identify those with NDKD component (NDKD and mixed group). Method: We recruited consecutive patient with renal involvement (eGFR >30ml/min/m2 and/or urinary albumin: creatinine excretion >/=300mg/g. Clinical history, demography of patients, Lipid profile, Liver function test, electrolytes, serum creatinine, urea, Albumin, globulin, Uric acid, 24hr urinary protein (by autoanalyzer), Glycated hemoglobin (HbA1C) Complete blood count (CBC) (automated hematology analyzer), Urine RE/ME (dipstick method), retinopathy (Digital fundus camera) and neuropathy (VPT) were documented. Histopathological classification of renal biopsy sample was undertaken as per International Society of Nephrology and the Renal Pathology Society classification. Results: Total 110 were included of whom 31% were female. 73 patients (66.4%) had DKD 20 patients (18.2%) had NDKD and in 17 patients (15.4%) had an overlap (Mixed group). Amongst NDKD IgA nephropathy was commonest cause of NDKD (25%). Duration of diabetes (p<0.001), late age of onset (p=0.03), BMI (p=0.02), presence of hematuria (p=0.04), retinopathy (p=0.003) and neuropathy(p=0.002) were present in different proportions in the DKD vs the other two groups combined. Multivariable regression analysis however showed that only duration of diabetes was able to discriminate DKD from the other two groups. (AOR=0.9, CI 0.945 0.996, P=0.02), but it had sensitivity of 54% and specificity of 81% (AUC 0.765, P <0.001). Discussion: Almost 25% of our patients with T2DM had some evidence of NDKD (either pure NDKD or mixed) and warrants biopsy for appropriate diagnosis and management. Amongst currently used discriminators, only duration of diabetes was able to predict (not very robust) which patients needed biopsy to identify NDKD.

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04–2.60; score 2: HR 2.48, 95% CI 1.40–4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55–4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

Clinicopathologic features and prognostic factors in older patients with biopsy-proven diabetic nephropathy.

The older population has increased sharply in China. However, renal clinical and histopathological data in this population are lacking. This study investigated the clinicopathologic features and the related risk factors for long-term renal survival in older patients with diabetic nephropathy (DN). In this retrospective observational study, 74 older patients (≥ 60years old) with type 2 diabetes mellitus and biopsy-proven DN from 2007 to 2019 were included. Clinical data were extracted from electronic records. Renal biopsy specimens were semiquantitatively evaluated using the Renal Pathology Society (RPS) classification system. Cox proportional hazard analysis was used to estimate hazard ratios (HRs) for progression to end-stage renal disease (ESRD). During the median follow-up period of 22months, 24 (32%) older patients progressed to ESRD. Older patients who progressed to ESRD had poorer renal function, lower hemoglobin and albumin concentrations, more severe glomerular lesions, and higher percentages of Kimmelstiel-Wilson lesions than those who did not progress to ESRD. After adjusting for age, sex, baseline renal function, and pathological parameters, multivariate Cox proportional hazard analysis showed that RPS glomerular classification (HR 2.49, 95% confidence interval [CI] 1.03-6.04), estimated glomerular filtration rate (eGFR) (HR 0.76, 95% CI 0.58-0.99), and proteinuria (HR 3.85, 95% CI 1.44-10.27) were independent risk factors for progression to ESRD. Lower eGFR, heavier proteinuria, and more severe RPS glomerular lesions were associated with ESRD in older patients with type 2 diabetes mellitus and DN.

Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline

BackgroundWhile histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN.MethodsIn this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient’s kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence.ResultsProgression to ESKD was associated with worsening interstitial fibrosis score (p = 0.05), lower baseline eGFR (p = 0.02), higher ACR (p = 0.001), and faster eGFR decline (p < 0.001). The rate of eGFR decline did not associate with any histologic parameter. Baseline ACR was the only studied variable correlating with eGFR slope (rho = − 0.41).ConclusionsRenal histology predicts ultimate progression to ESKD, but not the rate of progression. Future work is required to identify novel predictors of rapid functional decline in patients with diabetic nephropathy.

Clinicopathological features and outcomes of diabetic kidney disease with extracapillary hypercellularity: a Japanese single-center experience.

The prognostic significance of glomerular extracapillary hypercellularity (EXHC) in diabetic kidney disease (DKD) is unclear. The aim of this study was to investigate the clinicopathological features and outcomes of DKD patients with EXHC. We studied 70 cases of renal biopsy-confirmed type 2 DKD that were diagnosed between 2004 and 2014 and compared the clinicopathological features and outcomes of 22 patients with EXHC (EXHC group) with those of 48 patients without EXHC (control group). All of the patients were Japanese. We assessed the renal biopsy specimens based on the Renal Pathology Society classification system. Clinical and laboratory data were collected at the time of the renal biopsy, and renal outcomes were assessed based on progression to end-stage renal disease (ESRD) requiring renal replacement therapy. The median duration of the observation period was 3years. In pathological features, nodular sclerosis (Kimmelstiel-Wilson lesions) was observed more frequently in the EXHC group than in the control group (63.6% vs. 35.4%, P = 0.027). There were no significant intergroup differences in clinical features or renal outcomes. Univariate and multivariate Cox regression analyses of all patients showed that a high level of proteinuria, a low initial eGFR, and severe interstitial inflammation were poor prognostic factors. EXHC is related to nodular sclerosis, which is a known risk factor for ESRD. Careful observation is needed during the follow-up of DKD patients with EXHC, although there were no significant differences in renal outcomes between the EXHC and control groups.

A Clinicopathological Study of 267 Patients with Diabetic Kidney Disease Based on the Renal Pathology Society - 2010 Classification System.

Introduction:Renal biopsy is primarily indicated in patients with diabetes mellitus (DM) with proteinuria, to diagnose non-diabetic renal disease (NDRD). However, Renal Pathology Society classification (RPSc) – 2010 has classified diabetic nephropathy (DN) into four classes of glomerular lesions with a separate scoring for tubulointerstitial and vascular lesions. Paucity of data from Indian subcontinent prompted us to plan this study to classify DN on biopsy as per the RPSc and correlate the clinical profile with histology.Materials and Methods:Patients with DM who underwent renal biopsy for various indications (between Aug 2013 and Nov 2015) were included in the study. DN on histology was classified according to RPSc. Histopathology lesions of DN were correlated with clinical and biochemical profiles.Results:Of the 267 patients studied, 252 (94.3%) were type 2 DM. NDRD alone was seen in 65 (24.34%), DN in 161 (60.3%), and NDRD with DN in 41 (15.3%). The most common indications for biopsy were rapidly progressive renal failure (76.7%) and nephrotic syndrome (16.4%). The most common glomerular class was class IV (43.5%), followed class III (41%), class II (13.3%), and class I (1.9%). The most common NDRD seen was acute interstitial nephritis (AIN) in 20.2% and is frequently associated with class III. Tubulointerstitial chronicity and not the arteriolar chronicity, was correlated with low estimated glomerular filtration rate (eGFR).Conclusions:Most patients with DN subjected to renal biopsy were in class IV, and AIN was the most common NDRD. Only tubulointerstitial chronicity correlated with low eGFR.

Morphological Indexes: Can They Predict Lupus Nephritis Outcomes? A Retrospective Study.

Lupus nephritis is a serious complication of systemic lupus erythematosus. Currently, therapy is guided by findings in the renal biopsy, following the International Society of Nephrology / Renal Pathology Society classification. Austin and Hill's histomorphological indexes are not routinely obtained. In this retrospective single-centre study, we aimed to analyze the importance and applicability of the different morphological indexes in predicting response to treatment and prognosis. Patients with kidney biopsy demonstrating lupus nephritis from the 2010 - 2016 period were included. We analyzed their demographic data, comorbidities, clinical presentation and laboratorial evaluation at the time of renal biopsy. We evaluated the following outcomes: clinical remission, renal function and proteinuria at end of follow-up. Histologic analysis was performed using the International Society of Nephrology / Renal Pathology Society classification and the morphological indexes described by Austin (Activity and Chronicity) and Hill. Univariate and multivariate statistical analysis was performed using STATA software. We analyzed 46 biopsy-proven lupus nephritis cases, with a median follow-up of 31.9 (13.2 - 45.6) months. Based on biopsy findings, 35 patients were started on immunosuppressive therapy. We observed that Class IV patients had, at presentation, lower estimated glomerular filtration rate (67.3 vs 94.6 mL/min; p = 0.02), higher proteinuria (4.26 vs 2.37 g/24 hours; p = 0.02) and a non-significantly higher C3 consumption (58.9 vs 77.4 mg/dL; p = 0.06). We did not observe correlations between International Society of Nephrology / Renal Pathology Society classification and the outcomes at the end of follow-up. In contrast, both the Hill biopsy index and Austin's Chronicity index were correlated with renal function and proteinuria at the end of follow-up. Austin's Activity index correlated with the immunological findings (C3, C4 and anti-dsDNA) at presentation. Because clinical activity poorly correlates with histologic activity, histological findings are fundamental when assessing patients with suspected lupus nephritis. The most recent International Society of Nephrology / Renal Pathology Society report supports the European League Against Rheumatism guidelines, encouraging the adoption of histomorphological indexes when evaluating lupus nephritis. Our data, showing a correlation between the renal outcomes and the indexes described by Austin and Hill, supports this view. The histomorphological indexes in lupus nephritis are easily obtainable, can predict renal outcomes and may help in the management of such patients.

Histologic predictors of renal outcome in diabetic nephropathy: Beyond renal pathology society classification.

The prognostic utility of histologic features in patients with diabetic nephropathy (DN) classified according to the Renal Pathology Society (RPS) classification is controversial. Therefore, we aimed to evaluate the relationship between histologic changes and renal outcome in DN patients.We examined the renal outcome at November 30, 2017 of 74 adult patients (median age of 54.6 years, 69% male, 81% diabetes mellitus (DM) type 2, estimated GFR (eGFR) 29.6 mL/min) with biopsy proven DN between 2010 and 2015. The primary endpoint was renal replacement therapy (RRT) initiation.Half of the patients progressed to end stage renal disease (ESRD) during follow-up; they had lower eGFR, increased proteinuria, hematuria and serum cholesterol. Regarding the pathologic features, they were more frequently in class III and IV, had higher interstitial fibrosis and tubular atrophy score (IFTA), increased interstitial inflammation, more frequent arteriolar hyalinosis and higher glomerular basement membrane (GBM) thickness. The mean kidney survival time was 2.7 (95%CI 2.1, 3.3) years. In univariate time-dependent analyses, higher RPS DN class, increased IFTA, the presence of arteriolar hyalinosis and arteriosclerosis were associated with RRT initiation.In the fully adjusted model, the clinical characteristics associated with poor renal survival were longer duration of DM, lower eGFR, increased proteinuria and higher hematuria and the only pathologic lesions to remain significant were the GBM thickness and the IFTA.In conclusion, in this European cohort, the severity of glomerular lesions evaluated with the RPS DN classification had limited utility in predicting RRT initiation. However, IFTA and GBM thickness were significantly associated with renal survival.

Donor-related diabetic nephropathy: a comprehensive clinicopathological study

Knowledge on renal involvement in kidney donors with diabetes, that is, diabetic nephropathy (DN), is limited. During the 7 years (2010-2017), 921 postperfusion biopsies were performed for living donors (14%) or deceased donors (86%). The Renal Pathology Society classification schema for DN (class 0-IV) was used. Biopsies with light microscopic changes of DN (at least class IIa) were selected for study. Eleven biopsies (1.2%) showed DN, all from deceased donors (class IIa in 8, class IIb in 2, and class III in 1 biopsy). The glomerular basement membrane thickness ranged from 439 ± 52 to 725 ± 82 nm. These biopsies also displayed arterionephrosclerosis. They were from 9 deceased donors (fulfilling clinical criteria for acceptance in all, diabetes ;[>6 years] in 8, hypertension in 6, and proteinuria [1+] in all). Follow-up biopsies (5-342 weeks after transplant) showed DN of the same class (7 biopsies), probably progression (1), or progression (3). At follow-up (15-416 weeks), all recipients were alive. One graft was lost at 76 weeks because of progressive DN. The other 10 grafts were functioning, but the serum creatinine reached 2.0 to 2.7 mg/dL in 5 of them. Although diabetes is frequent in kidney donors, donor-related DN is unusual. It is observed only in deceased donors, but the risk factors for its development are not known. Donor-related DN may be stable or progress. Whether it resolves, especially for DN in early phase, remains unknown. It may adversely impact the graft outcome with a magnitude proportional to the severity of the tissue injury in the postperfusion biopsies.

Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis.

BackgroundThis study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis.MethodsBaseline characteristics, initial (n = 301) and repeat biopsies (n = 94) and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998 to 2014 were retrospectively collected from the medical record. Clinical and morphologic variables were evaluated using a Cox proportional hazards model and multiple imputation to address missing data. Renal survival was defined as the time from initial biopsy to end-stage renal disease [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2], dialysis or transplant.ResultsA total of 218 patients had follow-up and Class IV had worse renal survival, especially in patients with active and chronic glomerular lesions {relative to non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41–2.04], Class IV-AC: HR 5.02 [95% CI 2.70–9.36]}. Interstitial inflammation grade [relative to interstitial inflammation <5%; interstitial inflammation 5–25%: HR 2.36 (95% CI 1.13–4.91), interstitial inflammation 25–50%: HR 3.84 (95% CI 1.53–9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75–15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%; IFTA 5–25%: HR 3.93 (95% CI 1.58–9.75), IFTA 25–50%: HR 4.01 (95% CI 1.37–11.70), IFTA >50%: HR 13.99 (95% CI 4.91–39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose-dependent manner. Interstitial inflammation grade and IFTA category were significant predictors of renal survival in a multivariable model adjusted for age, gender, race, ethnicity and serum creatinine.ConclusionsInterstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.

Long-term outcome in Japanese patients with lupus nephritis.

The objective of this study was to clarify the long-term outcome in patients with lupus nephritis (LN) according to the International Society of Nephrology and Renal Pathology Society classification. This retrospective analysis comprised 186 Japanese patients given a diagnosis of LN by renal specimen with a mean observation period of 12 years. Primary end point was defined as death or end-stage renal disease, and standardized mortality ratios were calculated. Five patients presented with histopathological class I, 62 with II, 21 with III or III+V, 73 with IV or IV+V and 25 with V. Fourteen deaths occurred, corresponding to an overall standardized mortality ratio of 3.59 (95% confidence interval 2.02-5.81, p < 0.0001). Kaplan-Meier analysis revealed a 10-year overall survival of 95.7%. Nephrotic proteinuria (≥3.5 g/day) at baseline was identified as an independent poor prognostic factor for overall survival in Cox regression analysis. Kaplan-Meier analysis revealed a 10-year renal survival as 94.3%. Male gender and nephrotic proteinuria at baseline were identified as independent poor prognostic factors for renal survival in Cox regression analysis. In conclusion, LN was associated with a 3.59-fold increase in mortality compared with the general population. Male gender and nephrotic proteinuria were predictive for poor renal outcome.

Toll-like receptor 9 and vascular endothelial growth factor levels in human kidneys from lupus nephritis patients

In the lupus mouse and systemic lupus erythematosus (SLE) patients, DNA fragments isolated from plasma may mimic microbial DNA and trigger Toll-like receptor 9 (TLR9) signaling with formation of autoantibodies against DNA fragments and nucleosomes. Vascular endothelial growth factor (VEGF) is a tightly regulated angiogenic cytokine in the kidney. The present study investigated glomerular and tubular expression of both TLR9 and VEGF in biopsies from human subjects with lupus nephritis (LN) and normal controls. Kidney biopsies in LN (n=8) and normal controls (n=10) were evaluated for expression of TLR9 and VEGF. The degree of kidney damage was analyzed according to the International Society of Nephrology / Renal Pathology Society classification. Immunohistochemistry was performed, and slides were incubated with antibodies against VEGF and TLR9 monoclonal antibody, stained with hematoxylin and eosin, mounted and microscopically scored at ×10 and ×20. We observed intense staining of glomeruli and tubules for TLR9 up to 3+ from patients with LN. Samples from LN subjects showed 3+ staining of glomeruli but only up to 2+ in tubules for VEGF. There was less significant staining for TLR9 and none for VEGF in controls. There was no correlation observed between LN class severity and intensity of staining for VEGF or TLR9. This is the first study that investigated combined expression of TLR9 and VEGF, which could be an important tool for understanding the role of TLR9 and VEGF in LN, with insights into the early detection and targeted treatment of this disease.

Segmental and Global Subclasses of Class IV Lupus Nephritis Have Similar Renal Outcomes

Whether renal outcomes differ between the segmental and global subclasses of diffuse proliferative (class IV) lupus nephritis is unknown. In this meta-analysis, we searched the literature in MEDLINE, EMBASE, five registries of clinical trials, and selected cohort studies and randomized, controlled trials that used the 2003 International Society of Nephrology and Renal Pathology Society classification of lupus nephritis in adult patients. Our endpoint was the composite of doubling of serum creatinine concentration or ESRD. In the eight studies included in the final analysis, the incidence of this endpoint varied between 0% and 67%. A funnel plot and Egger's test did not suggest significant heterogeneity. The meta-analysis did not support a significant difference in renal outcome between the segmental (IV-S) and global (IV-G) subclasses (relative risk for class IV-G versus IV-S, 1.08; 95% confidence interval, 0.68-1.70). Meta-regression did not suggest that ethnicity or duration of follow-up influenced the association between histologic class and renal risk. In conclusion, the rate of doubling of serum creatinine concentration or of ESRD did not differ between patients with class IV-S and those with IV-G lupus nephritis.

Proceedings From the 4th Annual Renal Pathology Society/Kidney and Urologic Foundation of America Satellite Meeting: Update in Renal Pathology

The Renal Pathology Society (RPS) hosted its 4th Annual RPS/KUFA (Kidney and Urologic Foundation of America) Satellite Meeting on September 8, 2007, in Istanbul, Turkey, in conjunction with the 21st European Congress of Pathology. The European Nephropathology Working Group cosponsored the event. The meeting was chaired by Laura Barisoni, MD, from New York University Medical Center and Alex Howie, MD, from the Royal Free Hospital in London, United Kingdom. The articles that follow represent articles generated from the invited presentations at this meeting. Since many readers of this special issue may not be familiar with the RPS, we would like to briefly introduce readers to the Renal Pathology Society. The RPS originated as the Renal Pathology Club (RPC). It was conceived by Conrad Pirani, MD, who became its first president. The founding members, many of whom made seminal contributions to other pathology subspecialties, include Peter Burkholder, MD; Jacob Churg, MD; Ramzi S. Cotran, MD; Francis Cuppage, MD; Robert H. Heptinstall, MD; David B. Jones, MD; Michael Kashgarian, MD; Richard Kempson, MD; John M. Kissane, MD; Robert McCluskey, MD; Kash Mostofi, MD; Benjamin Spargo, MD; Gary Striker, MD; Jay Bernstein, MD; Robert Lannigan, MD; and Fred Silva, MD. In 1993 the RPC transitioned to the RPS. The RPS has flourished since its inception and currently has more than 400 registered members from more than 30 countries. The RPS held a 30-year anniversary celebration in 2007, at the United States and Canadian Academy of Pathology (USCAP) meeting in San Diego, California. This afforded an opportunity to reflect upon our historic routes and to honor the founding members whose vision and pursuit of knowledge gave birth to a society structure that has provided a forum for scientific and educational activities for those who share a passion for renal pathology. The RPS fosters collaborative ventures among its membership and between the RPS and professional organizations worldwide. Two notable multi-institutional and multidisciplinary consensus efforts include the 2004 International Society of Nephrology (ISN)/Renal Pathology Society classification of lupus glomerulonephritis and the recently released 2009 Oxford classification of IgA nephropathy. The RPS has affiliations with several international societies but most significantly, the American Society of Nephrology (ASN) and the USCAP, where the RPS has multiple recurring activities at their fall and spring annual meetings, respectively. The major activities at the ASN include a 2-day renal pathology course that precedes the meeting, a clinicopathologic conference, and a renal biopsy conference, while at the USCAP, the RPS conducts a companion meeting on Sunday morning and a renal pathology evening session, to mention a few events. The RPS also supports or organizes scientific and educational events at other major meetings in the Unites States and abroad. A visit to the RPS Web site (www. renalpathsoc.org, last accessed October 3, 2009) reveals that in 2010 the RPS will be cosponsoring the first international renal pathology course to be held on June 9–12, 2010, in La Coruna, Spain, a joint venture with the European Society of Pathology Working Group and the Spanish Pathology Society. The RPS will also host its 7th Annual RPS/KUFA Satellite Symposium in conjunction with the XXVIIIth International Congress of the International Academy of Pathology on October 9, 2010, in Sao Paulo, Brazil. Since the RPS/KUPS Satellite Meeting in Istanbul, the RPS has lost 2 of its founding members, Gloria Gallo and Jay Bernstein. During their illustrious careers, these 2 individuals advanced our understanding of amyloidosis and cystic renal disease, the topics of the 2 sections of this special issue. In recognition, the RPS dedicates this issue to their memory, with eulogies presented at the beginning of each section. The first section of this special issue consists of a series of presentations on fibrillary deposits and amyloid and begins with an article by Guillermo A. Herrera, MD, and Elba A. Turbat-Herrera, MD. The authors give an overAccepted for publication November 30, 2009. From the Department of Pathology, Louisiana State University Health Sciences Center, Shreveport (Dr Bonsib); and the Department of Pathology, Loyola University Medical Center, Maywood, Illinois (Dr Picken). The authors have no relevant financial interest in the products or companies described in this article. Reprints: Stephen M. Bonsib, MD, Department of Pathology, Louisiana State University Health Sciences Center, 1505 Kings Hwy, Shreveport, LA 71130 (e-mail: sbonsi@lsuhsc.edu). Special Issue—4th Annual RPS/KUFA Satellite Meeting Proceedings

Renal Disease in Systemic Lupus Erythematosus With Emphasis on Classification of Lupus Glomerulonephritis: Advances and Implications

Systemic lupus erythematosus is an autoimmune disease with protean clinical and pathologic manifestations involving almost all organs in the body. There is a high incidence of renal involvement during the course of the disease, with varied renal pathologic lesions and diverse clinical features. A renal biopsy examined by routine light microscopy, immunofluorescence, and electron microscopy contributes toward diagnosis, prognostic information, and appropriate management. (1) To review the clinical and various pathologic features of renal lesions in systemic lupus erythematosus patients. (2) To introduce the International Society of Nephrology and Renal Pathology Society Classification of Lupus Glomerulonephritis. A literature review, illustrations with original artwork, and tabulation of clinical and pathologic data of cases obtained from the authors' renal biopsy files examined during the last 8 years were used. The International Society of Nephrology/ Renal Pathology Society-sponsored Classification of Lupus Glomerulonephritis proposes standardized definitions of the various pathologic findings, describes clinically relevant lesions, incorporates prognostic parameters, and recommends a uniform way of reporting the renal biopsy findings. Lupus glomerulonephritis is divided into 6 classes primarily based on the morphologic lesions, extent and severity of the involvement, immune complex deposition, and activity and chronicity. Special emphasis is laid on describing qualitative as well as quantitative morphologic data and to include the accompanying tubulointerstitial disease and different vascular lesions, which have prognostic and therapeutic significance. This classification is intended to facilitate a higher degree of reproducibility, resulting in better patient care and more effective future clinical and translational research. Renal biopsy findings in systemic lupus erythematosus add new and independent parameters of prognostic significance to established clinical and genetic factors.