Luiz Antonio Ribeiro de Moura

The Classification of Glomerulonephritis in Systemic Lupus Erythematosus Revisited

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving <50% of total number of glomeruli) with subdivisions for active and sclerotic lesions; class IV for diffuse glomerulonephritis (involving > or =50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

An overview on frequency of renal biopsy diagnosis in Brazil: clinical and pathological patterns based on 9617 native kidney biopsies

BACKGROUND Studies about the prevalence of renal and particularly glomerular diseases in Brazil are still scarce. METHODS We evaluated retrospectively the reports of 9,617 renal biopsies, analyzed by the same pathologist, from January 1993 to December 2007. RESULTS The 9,617 renal biopsies performed in subjects of all ages in native kidneys. 4,619 were primary glomerulopathies (GN), the most frequent was focal segmental glomerulosclerosis (FSGS, 24.6%), followed by membranous nephropathy (MN, 20.7%), IgA nephropathy (IgAN, 20.1%), minimal change disease (MCD, 15.5%), mesangioproliferative non IgAN (nonIgAN, 5.2%), diffuse proliferative GN (DPGN, 4.7%) and membranoproliferative GN (MPGN, 4.2%). Lupus nephritis was responsible for most cases which etiology was determined, i.e., 950 out of 2,046 cases (45.5%), followed by post infectious GN (18.9%), diabetic nephropathy (8.5%), benign and malignant nephroangiosclerosis (7.3%), haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura (HUS/TTP), amyloidosis (4.8%) and vasculitis (4.7%). There was a predominance of secondary GN in the North, mostly due to lupus nephritis (LN); FSGS was very common in Northeast (27.7%), Central (26.9%) and Southeast regions (24.1%); IgAN was most frequent in South (22.8%) and MN in North (29.6%); the total prevalence of MPGN was low, and its regional distribution has not changed along the years. CONCLUSION FSGS was the most frequent primary glomerular disease, followed closely by MN and IgAN. The predominance of FSGS is in accordance with recent studies all over the world that revealed its frequency is increasing. Lupus nephritis predominated among secondary GN in most regions, a finding observed in other studies.

Early presence of calcium oxalate deposition in kidney graft biopsies is associated with poor long-term graft survival

Accumulated oxalate will be excreted after renal transplantation, creating an increased risk of tubular precipitation, especially in the presence of allograft dysfunction. We evaluated calcium oxalate (CaOx) deposition in renal allograft biopsies with early dysfunction, its association with acute tubular necrosis (ATN) and graft survival. We studied 97 renal transplant patients, submitted to a graft biopsy within 3 months post‐transplant, and reanalyzed them after 10 years. We analyzed renal tissue under polarized light and quantified CaOx deposits. CaOx deposits were detected in 52.6% of the patients; 26.8% were of mild and 25.8% of moderate intensity. The deposits were more frequent in biopsies performed within 3 weeks post‐transplant (82.4 vs. 63.0%, p < 0.05) and in allografts with more severe renal dysfunction (creatinine 5.6 mg/dL vs. 3.4 mg/dL, p < 0.001). ATN incidence was also higher in patients with CaOx deposits (47% vs. 24%, p < 0.001). Twelve‐year graft survival was strikingly worse in patients with CaOx deposits compared to those free of deposits (49.7 vs. 74.1%, p = 0.013). Our study shows a high incidence of CaOx deposits in kidney allografts with early dysfunction, implying an additional risk for acute tubular injury, with a negative impact on graft survival.

Urinary Retinol-Binding Protein as a Prognostic Marker in Glomerulopathies

Tubulointerstitial involvement seems to have a decisive influence on the progression of glomerular diseases. We have prospectively evaluated the levels of urinary retinol-binding protein (urRBP), a marker of proximal tubular dysfunction, in patients with different glomerulopathies (GPs) and correlated these levels with disease progression. By studying 238 patients with GPs, we found that urRBP tend to be lower in minimal change disease, glomerular hematuria and poststreptococcal glomerulonephritis as compared to focal segmental glomerulosclerosis, membranous nephropathy and membranoproliferative glomerulonephritis. By following 149 patients for up to 10 years, we have concluded that high levels of urRBP can identify patients who will progress with loss of renal function (defined as doubling of serum creatinine level) and that a urRBP level >1 mg/l was an efficient and independent indicator of poor prognosis as shown by multivariate analysis. This prediction was possible at a time when serum creatinine and creatinine clearance were still in the normal range. Our data suggest that this laboratory test adds important clinical information to the follow-up of GPs.

Exercise Attenuates Renal Dysfunction with Preservation of Myocardial Function in Chronic Kidney Disease

Previous studies have suggested that exercise improves renal and cardiac functions in patients with chronic kidney disease. The aim of this study was to evaluate the effects of long-term aerobic swimming exercise with overload on renal and cardiac function in rats with 5/6 nefrectomy (5/6Nx). Eight Wistar rats were placed into 4 groups: Control (C), Control+Exercise (E), Sedentary 5/6Nx (NxS) and 5/6Nx+Exercise (NxE). The rats were subjected to swimming exercise sessions with overload for 30 min five days per week for five weeks. Exercise reduced the effect of 5/6Nx on creatinine clearance compared to the NxS group. In addition, exercise minimized the increase in mean proteinuria compared to the NxS group (96.9±10.0 vs. 51.4±9.9 mg/24 h; p<0.05). Blood pressure was higher in the NxS and NxE groups compared to the C and E groups (216±4 and 178±3 vs. 123±2 and 124±2 mm Hg, p<0.05). In the 200 glomeruli that were evaluated, the NxS group had a higher sclerosis index than did the NxE group (16% vs. 2%, p<0.05). Echocardiography demonstrated a higher anterior wall of the left ventricle (LV) in diastole in the NxS group compared with the C, E and NxE groups. The NxS group also had a higher LV posterior wall in diastole and systole compared with the E group. The developed isometric tension in Lmax of the heart papillary muscle was lower in the NxS group compared with the C, E and NxE groups. These results suggested that exercise in 5/6Nx animals might reduce the progression of renal disease and lessen the cardiovascular impact of a reduction in renal mass.

Up-regulation of cyclooxygenase-2 during acute human renal allograft rejection.

Abstract:  Background:  Cyclooxygenases‐1 and ‐2 (COX‐1 and COX‐2) are important in renal physiology and in many abnormal states. However, there is poor information about them during renal allograft rejection. The purpose of this study was to analyze cyclooxygenases expression in renal tissue allograft during acute rejection.

Functional and morphologic evaluation of kidney proximal tubuli and correlation with renal allograft prognosis.

Renal transplant patients with stable graft function and proximal tubular dysfunction (PTD) have an increased risk for chronic allograft nephropathy (CAN). In this study, we investigated the histologic pattern associated with PTD and its correlation with graft outcome. Forty‐nine transplant patients with stable graft function were submitted to a biopsy. Simultaneously, urinary retinol‐binding protein (uRBP) was measured and creatinine clearance was also determined. Banff’s score and semi‐quantitative histologic analyses were performed to assess tubulointerstitial alterations. Patients were followed for 24.0 ± 7.8 months. At biopsy time, mean serum creatinine was 1.43 ± 0.33 mg/dl. Twelve patients (24.5%) had uRBP ≥1 mg/l, indicating PTD and 67% of biopsies had some degree of tubulointerstitial injury. At the end of the study period, 18 (36.7%) patients had lost renal function. uRBP levels were not associated with morphologic findings of interstitial fibrosis and tubular atrophy (IF/TA), interstitial fibrosis measured by Sirius red or tubulointerstitial damage. However, in multivariate analysis, the only variable associated with the loss of renal function was uRBP level ≥1 mg/l, determining a risk of 5.290 of loss of renal function (P = 0.003). Renal transplant patients who present PTD have functional alteration, which is not associated with morphologic alteration. This functional alteration is associated to progressive decrease in renal function.

The role of electron microscopy for the diagnosis of glomerulopathies

CONTEXT Electron microscopy has been used for the morphological diagnosis of glomerular diseases for more than three decades and its value has been widely emphasized. However, recent reports have analyzed the routine use of electron microscopy critically. Its use in other areas of diagnosis such as tumor diseases has declined considerably; in addition, in view of the unavoidable financial pressure for the reduction of costs due to investigations and diagnostic routines, the selection of cases for electron microscopy has been quite rigorous. OBJECTIVE To identify the glomerular diseases that depend on electron microscopy for a final diagnosis, by means of reviewing renal biopsies performed over a 12-year period. DESIGN Prospective SETTING Hospital Ana Costa, Hospital Guilherme Alvaro and Serviço de Anatomia Patológica de Santos, Santos, São Paulo, Brazil. PARTICIPANTS 200 consecutive renal biopsies obtained from private hospitals and the teaching hospital from 1979 to 1991 were studied. MAIN MEASUREMENTS All cases were analyzed via light microscopy, immunofluorescence and electron microscopy. The diagnosis was first made via light microscopy plus immunofluorescence and then via electron microscopy. RESULTS Electron microscopy was diagnostic or essential for diagnosis in 10.0% of the cases, corresponding to 3.4% of primary glomerulopathies and 100% of hereditary glomerulopathies. Electron microscopy was contributory (useful) to the diagnosis in 5.5% of the cases, confirming the preliminary diagnosis formulated on the basis of clinical and laboratory data and light microscopy plus immunofluorescence findings. We obtained a 7.5% rate of discordant immunofluorescence, which was considered as such when negative immunofluorescence findings were not confirmed by electron microscopy. The final diagnosis with the use of light microscopy plus immunofluorescence alone was 77.0%. CONCLUSIONS It was possible to diagnose with certainty a great percentage of glomerulopathies (82.5-90% of the cases) based on the light microscopy and immunofluorescence findings alone. Electron microscopy was essential for the diagnosis of hereditary nephropathies.

Effect of eicosapentaenoic acid on the progression of chronic renal failure in rats

Eicosapentaenoic acid (EPA) can induce a shift in prostaglandin and leukotriene synthesis. The effects of EPA supplementation of the diet on the progression of chronic renal failure (CRF) were evaluated in a model of 5/6 renal mass ablation in rats. After 30 or 60 days of CRF, elevation in single-nephron glomerular filtration rate due to an increase in glomerular plasma flow and hydraulic pressure was observed. These hemodynamic alterations were followed by a rise in proteinuria and glomerular sclerosis. EPA treatment for 30 or 60 days did not substantially modify the hemodynamic or morphological profiles induced by renal mass ablation. In the present non-immune model of CRF, preglomerular vasodilation with glomerular hyperperfusion and hypertension were responsible, at least in part, for the presence of proteinuria and glomerular sclerosis. No additional vasodilation was observed in the present model of CRF, and, thus, hemodynamic effects induced by EPA did not modify renal damage, in contrast to the EPA effects observed in immune-mediated models of CRF.

Ligation of the left renal vein in epm1-wistar rats: functional and morphologic alterations in the kidneys, testes and suprarenal glands

OBJECTIVE The ligation of the left renal vein (LLVR) in man is a controversial procedure in view of the risks of lesion to the renal parenchyma. With the objective of studying the morphologic and functional alterations caused by these lesions, we conducted experimental research with rats. MATERIAL AND METHODS 64 male adult EPM1-WISTAR rats were used, divided into 8 groups-4 for LLRV and four for control. Each LLRV group and corresponding control group were sacrificed progressively on the 7th, 15th, 30th and 60th day after the initial surgery. RESULTS We found morphofunctional alterations only in animals that underwent LLRV in the four periods of sacrifice. The proteinuria creatinine in serum, testosterone in serum and serum corticosterone in serum showed practically no alteration in relation to the normal values for rats. Statistically significant severe histological lesions were found in the kidneys and testes of the LLRV groups. Lesions in the suprarenal glands were also present in these groups, but no sufficient to demonstrate statistical significance. CONCLUSION Based on these results we can conclude that the ligation of the left renal vein is a procedure of high risk in these animals.