scholarly journals Clinicopathologic Features of Infection-Related Glomerulonephritis with IgA Deposits: a French Nationwide Study

2020 ◽  
Author(s):  
Elodie Miquelestorena-Standley ◽  
Charlotte Jaulerry ◽  
Marie-Christine Machet ◽  
Nolwenn Rabot ◽  
Christelle Barbet ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Outcome Data ◽  
Renal Outcome ◽  
Tubular Atrophy ◽  
Short Delay ◽  
Adult Men ◽  
Staphylococcus Infections ◽  
Endocapillary Proliferative Glomerulonephritis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. Methods: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. Results: Twenty-seven patients (23 men, mean age: 62±15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of >4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

Clinical features and outcome of infection-related glomerulonephritis with IgA deposits

2020 ◽  
Author(s):  
Elodie Miquelestorena-Standley ◽  
Charlotte Jaulerry ◽  
Marie-Christine Machet ◽  
Nolwenn Rabot ◽  
Christelle Barbet ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Outcome Data ◽  
Renal Outcome ◽  
Chi Square ◽  
Tubular Atrophy ◽  
Adult Men ◽  
Chi Square Test ◽  
Endocapillary Proliferative Glomerulonephritis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is being more widely recognized but the precise epidemiology and outcome is lacking, particularly in Europe. We aimed to assess clinical, pathologic and outcome data of IRGN-IgA. Methods Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were retrospectively collected. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed correlation between histological presentation and outcome using the Chi square test (qualitative data) and Kruskal-Wallis test (quantitative data). Results Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Most of them had a Staphylococcus aureus infection (77.8%) and 44.4% were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine >4 mg/dL, and 16% had a hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis with tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression, found in 17.8% of the cases, was most frequently observed in biopsies with acute or subacute pattern and associated with a shorter delay between infection and renal biopsy compared to segmental and focal staining. After a median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. Conclusions Infection-related glomerulonephritis with IgA deposits is usually associated with Staphyloccus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.

scholarly journals Evaluation of the Oxford classification in immunoglobulin A vasculitis with nephritis: a cohort study and meta-analysis

2020 ◽  
Author(s):  
Bingxin Yu ◽  
Sufang Shi ◽  
Wanyin Hou ◽  
Lijun Liu ◽  
Jicheng Lv ◽  
...  
Keyword(s):  
Cohort Study ◽  
Interstitial Fibrosis ◽  
Meta Analysis ◽  
Immunoglobulin A ◽  
Renal Outcome ◽  
Oxford Classification ◽  
Tubular Atrophy ◽  
The Oxford Classification ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Similarities in clinicopathological presentations in immunoglobulin A (IgA) nephropathy and IgA vasculitis with nephritis (IgAVN) raise the question of the utility of the Oxford classification in the latter. The aim of this study was to evaluate the Oxford classification in IgAVN. Methods We conducted a retrospective cohort study and meta-analysis following systematic searching of the MEDLINE and Excerpta Medica Database (EMBASE) databases between January 2009 and September 2019. We modeled the association of 30 and 50% decline in estimated glomerular filtration rate or end-stage renal disease with pathologic lesions of the Oxford classification including mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C). Results were pooled using random-effects meta-analysis. Results The cohort study included 132 patients, and only T lesion was an independently risk factor in IgAVN. The meta-analysis yielded six retrospective studies with 721 patients and 139 endpoints. In multivariate model, T lesion was significantly associated with renal outcome (hazard ratio = 2.45, P = 0.007). M and C lesions could not predict renal outcome without evidence of heterogeneity. E and S lesions could not predict renal outcome with evidence of heterogeneity (I2 = 66.6%; P = 0.01, and I2 = 65.8%; P = 0.03, respectively). Subgroup analysis showed that the possible reasons to the heterogeneity were from usage of immunosuppressant, sample size and follow-up time. Conclusions The study suggests that the Oxford classification could not be fully validated in IgAVN. Higher portion of immunosuppressant especially before renal biopsy might be the main confounder for the predictive value of Oxford classification in IgAVN.

scholarly journals Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study

2020 ◽  
Author(s):  
Ming Xia ◽  
Di Liu ◽  
Liang Peng ◽  
Yan Li ◽  
Haiyang Liu ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Coagulation System ◽  
Renal Outcome ◽  
Immunoglobulin A Nephropathy ◽  
Tubular Atrophy ◽  
Coagulation Parameters ◽  
T Score ◽  
Stage Renal Disease

Abstract Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function. Methods: This retrospective study included N=291 patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction. Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s). Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.

P0417THE ABSENCE OF C3 DEPOSIT IN MEMBRANOUS NEPHROPATHY IS ASSOCIATED WITH SPONTANEOUS REMISSION

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina Rabasco ◽  
Ana Martínez ◽  
Rosa Ortega ◽  
Mario Espinosa
Keyword(s):  
Membranous Nephropathy ◽  
Interstitial Fibrosis ◽  
Immunosuppressive Treatment ◽  
Spontaneous Remission ◽  
Glomerular Sclerosis ◽  
Tubular Atrophy ◽  
Positive Group ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background and Aims Membranous nephropathy (MN) is the most common cause of biopsied nephrotic syndrome in adults. Recently, it has been reported that the pathogenesis of MN may be associated with an activation of the complement system. The pathway of activation is not clearly established. The intensity of C3 deposition could be a good marker of this activation in MN as has been shown in other diseases (IgA nephropathy, crescentic GN). The aim of this study is to evaluate clinical-pathological data in a cohort of patients with MN and the significance of glomerular C3 staining as a possible predictor of renal outcomes. Method We analysed patients with idiopathic MN biopsied in our department between January 2000 and December 2019, excluding those who had no material for IF (n = 115). The patients were divided into positive (87 cases) and negative (28 cases) based on glomerular C3 deposition. We assessed the clinical and histological characteristics and the percentage of spontaneous remission (SR) and end-stage renal disease (ESRD). Results A total of 115 patients with MN were followed with a median follow-up of 65 (25-161) months. We found no differences in baseline characteristics between both groups, with the exception that patients with C3 deposit had less albumin at the time of biopsy that negative patients [2.4 (2-2.9) vs 2.8 (2.3-3.1) g/dl, P=0.011)]. Patients with C3-negative had a higher percentage of SR than patients with C3-positive (75 vs 24%, P = 0.000) and less need for immunosuppressive treatment (18 vs 56%, P =0.001). At the most recent follow-up, C3-positive group had higher creatinine [1.42 (0.8-1.7) vs 0.97 (0.71-1) mg/dl, P=0.045] and proteinuria [1.64 (0.08-3.2) vs. 0.62 (0.05-0.79) g / 24h, P = 0.039]. Regarding histology, we found no differences in glomerular sclerosis, tubular atrophy and interstitial fibrosis. The renal survival analysis showed no statistically significant differences between both groups (P = 0.091). We analysed a subgroup of patients (n = 23) with antibodies against the phospholipase receptor on blood at the time of the biopsy (13/23 were positive). 84% of this positive group presented C3-positive in the renal biopsy vs 25% of the C3-negative group (P =0.008). Conclusion Patients without C3 staining show a higher rate of SR and less need for immunosuppressive treatment than patients with C3-positive. These results would support the theory that complement activation in this entity can play an important role. It is possible that these patients with negative C3 deposit represent a MN with evolution to SR and in these patients and that these patients do not need immunosuppressive treatment.

A Pathological Scoring System to Predict Renal Outcome in Diabetic Nephropathy

2015 ◽  
Vol 41 (4-5) ◽  
pp. 337-344 ◽  
Author(s):  
Junichi Hoshino ◽  
Koki Mise ◽  
Toshiharu Ueno ◽  
Aya Imafuku ◽  
Masahiro Kawada ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Biopsy ◽  
Scoring System ◽  
Proportional Hazards ◽  
Interstitial Fibrosis ◽  
Predictive Ability ◽  
Cox Proportional Hazards ◽  
Renal Outcome ◽  
Tubular Atrophy ◽  
Stage Renal Disease

Background: With the association between diabetic nephropathy (DN) and renal outcome being increasingly clear, we aimed at creating a new DN pathological scoring system that could predict the renal outcome. Methods: We studied 205 patients with DN confirmed by renal biopsy, sometime between March 1985 and January 2010, who met the inclusion criteria. Renal biopsy included clinical parameters and Tervaert classifications. Hazard ratios (HRs) for death-censored end-stage renal disease (ESRD) were estimated by adjusted Cox proportional-hazards regression. The overall pathological risk score (D-score) was calculated by summing the products of beta coefficient and bootstrap-inclusion fractions, its predictive utility evaluated by Kaplan-Meier methods and c-statistics for a 10-year risk of ESRD. Results: The D-scores of glomerular classes 1, 2A, 2B, 3, and 4 were, respectively, 0, 3, 4, 6, and 6. Those of interstitial fibrosis and tubular atrophy classes 0, 1, 2, and 3 were 0, 7, 9, and 11, and those of interstitial inflammation classes 0, 1, and 2 were 0, 3, and 4, respectively. The D-score of hyalinosis class 2 was 3 and that of arteriosclerosis class 2 was 1. So, a patient's D-score could be 0-25. HRs for ESRD in patients with D-score ≤14, 15-18, 19-21, and 22-25 were, respectively, 1.00 (reference) 16.21 (95% confidence interval (CI), 1.86-140.90), 19.78 (95% CI, 2.15-182.40), and 45.46 (95% CI, 4.63-446.68) after adjusting for clinical factors. The c-statistics suggested a better predictive ability for a 10-year renal death with models that included the D-score. Conclusion: Prediction of DN patients' renal outcome was better with the D-score than without it. Patients with a D-score ≤14 had excellent renal prognosis.

Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy

2018 ◽  
Vol 35 (6) ◽  
pp. 1009-1016 ◽  
Author(s):  
Yu An ◽  
Changming Zhang ◽  
Feng Xu ◽  
Wei Li ◽  
Caihong Zeng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Renal Injury ◽  
Cox Regression ◽  
Interstitial Fibrosis ◽  
Glomerular Sclerosis ◽  
Tubular Atrophy ◽  
Cox Regression Analysis ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Recent data suggest that miR-196a is predominantly expressed in the kidney and plays an inhibitory role in the progress of renal interstitial fibrosis (IF). However, the predictive value of miR-196a in diabetic nephropathy (DN) remains unknown. We validated the role of urinary miR-196a in the progression of renal injury in a cohort of patients with type 2 diabetes mellitus. Methods Our study included 209 patients with biopsy-proven DN. The mean follow-up time was 54.03 ± 32.94 months. Histological lesions were assessed using the pathological classification established by the Renal Pathology Society. Percentages of IF and tubular atrophy were assessed using the Aperio ScanScope system. We measured the correlation of urinary miR-196a with clinical and pathological parameters using the Spearman’s correlation test. The influence of urinary miR-196a on renal outcomes was assessed using Cox regression analysis. Results Urinary miR-196a levels correlated positively with proteinuria (ρ = 0.385, P &lt; 0.001), duration of diabetes mellitus (ρ = 0.255, P &lt; 0.001) and systolic blood pressure (ρ = 0.267, P &lt; 0.001). The baseline estimated glomerular filtration rate (eGFR) and hemoglobin level showed a negative correlation with urinary miR-196a (ρ = −0.247, P &lt; 0.001 and ρ = −0.236, P = 0.001, respectively). Pathologically, urinary miR-196a levels correlated with glomerular sclerosis and IF in patients with DN. Urinary miR-196a was significantly associated with progression to end-stage renal disease [hazard ratio (HR) 2.03, P &lt; 0.001] and a 40% reduction of baseline eGFR (HR 1.75, P = 0.001), independent of age, gender, body mass index, mean arterial pressure and hemoglobinA1c level. However, urinary miR-196a did not improve predictive power to proteinuria and eGFR in DN patients. Conclusions Increased urinary miR-196a was significantly associated with the progression of renal injury and might be a noninvasive prognostic marker of renal fibrosis in DN patients.

Immune-mediated tubulointerstitial nephritis

2018 ◽  
Author(s):  
Liviu Segall ◽  
Adrian Covic
Keyword(s):  
Immune Complex ◽  
Lupus Erythematosus ◽  
Interstitial Fibrosis ◽  
Tubular Atrophy ◽  
Immunoglobulin G4 ◽  
Immune Mediated ◽  
Inflammatory Bowel ◽  
Complex Deposition ◽  
Stage Renal Disease ◽  
End Stage

Immune-mediated tubulointerstitial nephritides (TINs) are generally encountered in the context of systemic or extrarenal autoimmune diseases, such as sarcoidosis, Sjögren syndrome, systemic lupus erythematosus, inflammatory bowel disease, TIN and uveitis (TINU) syndrome, and immunoglobulin G4-related disease. The pathogenesis of these TINs is complex and more or less unclear; it usually involves leucocyte activation, autoantibodies, immune complex deposition, complement activation, and release of inflammatory cytokines and growth factors. Tubulointerstitial inflammation most commonly has a chronic pattern, although acute forms of TIN may also occur. Furthermore, inflammation may be granulomatous (as in sarcoidosis or Crohn’s disease) or non-granulomatous. Immunofluorescence staining can sometimes reveal immune complex deposits and even antitubular basement membrane autoantibodies. Systemic immunosuppressive therapies are almost always required to prevent progression to irreversible interstitial fibrosis, tubular atrophy, and end-stage renal disease.

scholarly journals Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis

2018 ◽  
Vol 48 (6) ◽  
pp. 465-471 ◽  
Author(s):  
Steven Menez ◽  
Zdenka Hruskova ◽  
Jennifer Scott ◽  
Sarah Cormican ◽  
Min Chen ◽  
...  
Keyword(s):  
Renal Disease ◽  
Proportional Hazards ◽  
Interstitial Fibrosis ◽  
Cox Proportional Hazards ◽  
Immunosuppressive Drug ◽  
Renal Outcome ◽  
First Year ◽  
Published Data ◽  
Tubular Atrophy ◽  
Stage Renal Disease

Background: The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Methods: Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Results: Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15–34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9–19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17–82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Conclusions: Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

scholarly journals Maximum Glomerular Diameter and Oxford MEST-C Score in IgA Nephropathy: The Significance of Time-Series Changes in Pseudo-R2 Values in Relation to Renal Outcomes

2019 ◽  
Vol 8 (12) ◽  
pp. 2105 ◽  
Author(s):  
Hiroshi Kataoka ◽  
Takahito Moriyama ◽  
Shun Manabe ◽  
Keiko Kawachi ◽  
Yusuke Ushio ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Immunoglobulin A ◽  
Information Criterion ◽  
Characteristic Analysis ◽  
Tubular Atrophy ◽  
Prognostic System ◽  
Renal Outcomes ◽  
C Statistic ◽  
Stage Renal Disease ◽  
End Stage

The progression of immunoglobulin A nephropathy (IgAN) is currently assessed using the Oxford MEST-C score, which uses five indicators (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and the presence of crescents) but has not yet included any risk factors related to glomerular size. Therefore, we tested whether adding another indicator, maximal glomerular diameter (Max GD), would improve the prognostic ability of this scoring system. The data of 101 adult patients diagnosed with IgAN between March 2002 and September 2004 were reviewed. We used McFadden’s pseudo-R2 and the corrected Akaike information criterion to assess model fit and the concordance (C)-statistic to assess discriminatory ability. A 10 μm increase in Max GD was significantly associated with a composite outcome (≥50% decline in the estimated glomerular filtration rate or end-stage renal disease). The receiver operating characteristic analysis determined the cut-off for high vs. low Max GD at 245.9 μm, and adding high Max GD to the MEST-C score significantly improved the model’s discrimination of renal outcomes at 5 and ≥10 years. Thus, including the Max GD in the Oxford classification of IgAN might increase its robustness and provide a more comprehensive prognostic system for clinical settings.

scholarly journals Renoprotective Effects of ETA Receptor Antagonists Therapy in Experimental Non-Diabetic Chronic Kidney Disease: Is There Still Hope for the Future?

2018 ◽  
pp. S55-S67 ◽  
Author(s):  
I. VANĚČKOVÁ ◽  
S. HOJNÁ ◽  
M. KADLECOVÁ ◽  
Z. VERNEROVÁ ◽  
L. KOPKAN ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cell Injury ◽  
Interstitial Fibrosis ◽  
Experimental Studies ◽  
Tubular Atrophy ◽  
Eta Receptor ◽  
Life Threatening ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions.

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