Initial renal histology and early response predict outcomes of Brazilian lupus nephritis patients.

OBJECTIVE: We analyzed baseline and follow-up characteristics related to poorer renal outcomes in a Brazilian cohort of admixture race patients with lupus nephritis. METHODS: Overall, 280 outpatients with a diagnosis of systemic lupus erythematosus and previous kidney biopsy of lupus nephritis were recruited from August 2015 to December 2018 and had baseline laboratory and histologic data retrospectively analyzed; patients were then followed-up and data were recorded. The main outcome measure was the estimated glomerular filtration rate at last follow-up. Secondary analyses assessed the impact of initial kidney histology and treatment in long-term kidney survival. RESULTS: Median duration of lupus nephritis was 60 months (interquartile range: 27-120); 40 (14.3%) patients presented progressive chronic kidney disease (estimated glomerular filtration rate <30 and ≥10 ml/min/1.73 m2) or end-stage kidney disease at last visit. Adjusted logistic regression analysis showed that class IV lupus nephritis (odds ratio 14.91; 95% confidence interval 1.77-125.99; p = 0.01) and interstitial fibrosis ≥25% at initial biopsy (odds ratio 5.87; 95% confidence interval 1.32-26.16; p = 0.02), lack of complete or partial response at 12 months (odds ratio 16.3; 95% confidence interval 3.74-71.43; p < 0.001), and a second renal flare (odds ratio 4.49; 95% confidence interval 1.10-18.44; p = 0.04) were predictors of progressive chronic kidney disease. In a Kaplan-Meier survival curve we found that class IV lupus nephritis and interstitial fibrosis ≥25% were significantly associated with end-stage kidney disease throughout follow-up (hazard ratio 2.96; 95% confidence interval 1.3-7.0; p = 0.036 and hazard ratio 4.96; 95% confidence interval 1.9-12.9; p < 0.0001, respectively). CONCLUSION: In this large cohort of admixture race patients, class IV lupus nephritis and chronic interstitial damage at initial renal biopsy together with non-response after 1 year of therapy and relapse were associated with worse long-term renal outcomes.

PP019 The role of renal markers in women with and without preeclampsia: Evaluation of urinary excretion of podocytes and proteins.

INTRODUCTION: Preeclampsia (PE) is an important cause of glomerulopathy. Assessment of renal markers during pregnancy may have a predictive value for glomerular disease later in life. The early detection of PE may prevent the complications of this syndrome. OBJECTIVES: Assess the glomerular involvement in PE and in normal pregnancy by evaluating renal markers such as podocyturia and proteinuria. METHODS: Case-control study with 39 pregnant women after 20 weeks of gestation (control group - CG with n=25 and PE with n=14), we assessed podocyturia (cytospin method) and proteinuria (albuminuria, urine protein:creatinine - PCR, urinary retinol protein - RBP and albumin/creatinine ratio - ACR). (Grant FAPESP 08/56338-1) RESULTS: Mean±standard deviation of age and mean gestational age of CG were 26.9±6.4years and 37.1±5.0weeks and of PE, 26.4±6.9 and 30.6±5.6, respectively (p=0.001). No statistical differences were found between podocyturia in CG and PE although it was more frequent in this last group (p=0.258). Podocyte cells and parietal epithelial cells were detected in the slides. Mean±standard deviation of urinary RBP (p=0.017), albuminuria (p=0.002) and UAC ratio (p=0.006) of CG were 0.4±0.7mg/L, 7.3±6.9mg/L and 8.2±6.7mg/g and of PE, 2.0±4.4mg/L, 2267.4±2130.8mg/L (p=0.002) and 3778.9±4296.6mg/g (p=0.006), respectively. Mean value±standard deviation of urine PCR in PE was 6.7±6.1g/g (p=< 0.001). CONCLUSION: Urinary RBP, PCR, albuminuria and UAC ratio were elevated in PE in comparison to CG indicating its glomerular involvement but there was no correlation between those renal parameters and podocyturia. RPC and UAC ratios were good predictors of PE, but not podocyturia. Either podocyte cells as parietal epithelial cells were detected in the urine, these findings may indicate a non-invasive marker for renal disease activity but more studies are required to determine its role in PE.

PP090. The contribution of podocyturia to the evaluation of ongoing glomerular disorder in pregnant women with kidney graft (preliminary results).

INTRODUCTION: Progressive proteinuria and glomerulosclerosis characterize chronic allograft nephropathy. However, the causes are not fully elucidated. Injury of parietal epithelial cells in glomeruli, the podocytes, is the initiating cause of many renal diseases, leading to proteinuria with possible progression to glomerulosclerosis. Podocytes are highly specialized cells, with an important role in maintaining the glomerular filtration barrier and producing growth factor for mesangial cells and endothelial cells. With their foot processes they cover the glomerular basement membrane, and form slit diaphragms with neighboring podocytes. The potential role of podocytes in the failing transplanted kidney is unknown. OBJECTIVES: To evaluate podocyturia as a functional marker in pregnant women with kidney grafts. METHODS: Twenty pregnant women with kidney grafts had their urine samples cytocentrifugated and evaluated by indirect immunofluorescence. The slide was incubated for 45' at room temperature with fluorescein (FITC) anti-rabbit IgG secondary antibody (Sigma-Aldrich, EUA). Then Vectashield (mounting medium for fluorescence) with DAPI (4'6-diamino-2-fenilindol dihidrocloreto) were applied H-1200 (Vector laboratories, inc, USA). The podocytes and the total number of cells were counted in 15 fields photographed under 400x magnification with a digital camera coupled to an epifluorescence microscope DM1000 (Leica, Germany) connected to a computer. The results were expressed as podocyte/total cells (%) per area of higher cell concentration (hot spots) in the field of 400x detected by staining of nuclei and cytoplasm. (Grant FAPESP 08/56338-1). RESULTS: The mean age of the women was 26years. The urinalysis was performed at the third trimester of gestation; 11 did not exhibit urinary podocytes and 9 had podocyturia. There was also a relationship between blood pressure levels, proteinuria and the excretion of podocytes. CONCLUSION: Urinary podocyte number, blood pressure and proteinuria were associated. We observed that urinary podocyte excretion occurs in pregnant women with kidney transplant almost synchronously with higher systolic and diastolic blood pressure and higher mean levels of proteinuria. The detection of podocyturia in these women could be useful for early diagnosis and follow-up of glomerular injury, eventually preeclampsia. It may be also associated to its severity or activity, although additional studies are necessary to confirm these aspects.

[Glomerulonephritis associated with hepatitis c virus infection]. / Glomerulonefrite associada à infecção pelo vírus da hepatite C.

We report 4 patients with glomerulonephritis (GN) associated with hepatitis C virus (HCV) infection seen between August 1993 and July 1996. Two of them were male and median age was 41 years. Anti-HCV was detected by enzyme-immunoassay and HCV-RNA by PCR. Serum cryoglobulins, 24-hour proteinuria, and erythrocyte dismorphism were also determined. Viremia, cryoglobulinemia, hematuria and proteinuria were observed in all patients. Liver biopsies revealed inflammatory activity in 3 cases, and renal biopsies revealed membranoproliferative glomerulonephritis in 3 patients and mesangial proliferative glomerulonephritis in 1 patient. Two patients are on specific therapy for HCV infection (IFN in combination with ribavirin) and have presented clinical and laboratory improvement. The occurrence of active liver disease and viremia concurrent with urinary alterations suggests viral involvement in renal disease, a conclusion supported by the by improvement of urinary alterations observed after treatment for HCV. We conclude that the search for viral markers in patients with GN is important since their detection could change the therapeutic approach.

Prevalence of hepatitis C virus antibodies in primary glomerulonephritis in Brazil.

The association between hepatitis B virus and membranous glomerulonephritis and membranoproliferative glomerulonephritis (MPGN) was first described in 1971. Recently, a similar association between hepatitis C virus (HCV) and glomerulonephritis (GN) has been reported. We investigated the prevalence of hepatitis C serum antibodies (anti-HCV) in patients with primary GN followed up at our Nephrology Outpatient Clinic between March 1993 and November 1995. The diagnosis of primary GN was established after excluding the presence of connective tissue disease, diabetes, infectious disease, and malignancy. Anti-HCV antibodies were detected by a second-generation enzyme immunosorbent assay and HCV RNA by polymerase chain reaction. Of 81 patients with primary GN, 24 had membranous glomerulonephritis, 17 MPGN, 15 minimal-change disease, 12 focal-segmental glomerulosclerosis, 9 diffuse proliferative GN, and 4 IgA nephropathy. Anti-HCV were detected in 2 cases (2.5%), both were HCV RNA positive and had a polyclonal mixed cryoglobulinemia (IgM-IgG). These 2 cases both came from the group of 17 patients with MPGN. Biochemical investigation in these patients revealed persistent elevation of serum aminotransferase activity, and a liver biopsy specimen in 1 of them showed evidence of chronic active hepatitis. We conclude that in our setting the prevalence of anti-HCV among patients with primary GN is low, being higher (11.8%) only if we consider the patients with MPGN as the reference group. Further studies are necessary to clarify this association and to determine appropriate therapy for these patients.

alpha-Interferon therapy for HBV-related glomerulonephritis.

We report a case of a patient with hepatitis B virus (HBV)-related membranous glomerulonephritis (MGN) who showed improvement after interferon-alpha (IFN-alpha) therapy. A 35-year-old man with nephrotic syndrome and HBV antigens received a 24-week course of IFN-alpha. At the end of therapy there was an elevation in the level of plasma aminotransferase and an increase in proteinuria, which were followed by antigen/antibody seroconversion. This "flare-up" before seroconversion suggests an increase in disease activity in the liver and kidney, demonstrating in vivo HBV involvement in MGN.

Specific and nonspecific aspects of humoral immune response in leprosy.

1. We have studied some generic and specific aspects of the humoral immune response in 96 patients with leprosy (29 paucibacillary and 67 multibacillary individuals). We determined serum immunoglobulins (IgM, IgG and IgA), CH50, C1q, C3 and C4, circulating immune complexes (CIC), C-reactive protein (CRP), rheumatoid factor (RF) and antinuclear antibodies. No specific pattern of general humoral immune changes could be observed. 2. The specific immune response was studied by the detection of specific IgM anti-M. leprae antibodies. An immunoradiometric assay (IRMA) and an ELISA were compared for clinical effectiveness. IRMA showed greater sensitivity for the serodiagnosis of leprosy as compared to ELISA (88.1% vs 58.2% for multibacillary patients and 20.7% vs 10.3% for paucibacillary leprosy patients). Specificity was 96% for IRMA and 97% for ELISA. 3. Our results indicate that nonspecific changes in the humoral immune response are of little value in assessing leprosy patients and that immune assays for the detection of specific anti-M. leprae antibodies may be of value in the diagnosis, study and follow-up of these patients.

Specific and nonspecific aspects of humoral immune response in leprosy

1. We have studied some generic and specific aspects of the humoral immune response in 96 patients with leprosy (29 paucibacillary and 67 multibacillary individuals). We determined serum immunoglobulins (IgM, IgG and IgA), CH50, C1q, C3 and C4, circulating immune complexes (CIC), C-reactive protein (CRP), rheumatoid factor (RF) and antinuclear antibodies. No specific pattern of general humoral immune changes could be observed. 2. The specific immune response was studied by the detection of specific IgM anti-M. leprae antibodies. An immunoradiometric assay (IRMA) and an ELISA were compared for clinical effectiveness. IRMA showed greater sensitivity for the serodiagnosis of leprosy as compared to ELISA (88.1 percent vs 58.2 percent for multibacillary patients and 20.7 percent vs 10.3 percent for paucibacillary leprosy patients). Specificity was 96 percent for IRMA and 97 percent for ELISA. 3. Our results indicate that nonspecific changes in the humoral immune response are of little value in assessing leprosy patients and that immune assays for the detection of specific anti-M. leprae antibodies may be of value in the diagnosis, study and follow-up of these patients

Renal abnormalities in leprosy.

We have evaluated laboratory and clinical manifestations of renal disease in 96 patients with leprosy, looking for a sensitive and early marker for detection and possibly follow-up of nephropathy in these patients. Microscopic hematuria was observed in 21.9% of the cases (with dysmorphic erythrocytes in 71.4% of them). Abnormal microalbuminuria and urinary beta 2-microglobulin were found in 15.8 and 19.8% of the cases, respectively. We have observed a high frequency of hematuria, abnormal microalbuminuria and elevation of urinary beta 2-microglobulin in these patients still with normal serum creatinine.

Osteomalacia secondary to renal tubular acidosis in a patient with primary Sjögren's syndrome.

We report a case of a 41-year-old woman whose disease manifested as osteomalacia and whose etiological investigation revealed renal tubular acidosis secondary to primary Sjögren's syndrome. Proximal tubular dysfunction was also present and was documented by increased urinary excretion of beta-2-microglobulin and retinol-binding protein. The patient showed clinical and laboratory improvement after treatment with oral potassium citrate, calcium supplements and steroids.