Patrícia Ferreira Abreu

NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele

Mutations in NPHS2, encoding podocin, have been identified in childhood onset focal and segmental glomerulosclerosis (FSGS). The role of NPHS2 in adult disease is less well defined. We studied 30 families with FSGS and apparent autosomal recessive inheritance and 91 individuals with primary FSGS. We screened family members for NPHS2 mutations. NPHS2 mutations appeared to be responsible for disease in nine of these families. In six families, the affected individuals were compound heterozygotes for a nonconservative R229Q amino acid substitution. This R229Q variant has an allele frequency of 3.6% in a control population. In these families, R229Q was the only mutation identified on one of the two disease-associated NPHS2 alleles. We used in vitro-translated podocin and purified nephrin to investigate the effect of R229Q on their interaction and found decreased nephrin binding to the R229Q podocin. These data suggest that this common polymorphism contributes to the development of FSGS. Chromosomes bearing the R229Q mutation share a common haplotype defining an approximately 0.2-Mb region. R229Q appears to enhance susceptibility to FSGS in association with a second mutant NPHS2 allele. Identification of R229Q mutations may be of clinical importance, as NPHS2-associated disease appears to define a subgroup of FSGS patients unresponsive to corticosteroids.

Estudo prospectivo de 2151 pacientes com doença renal crônica em tratamento conservador com abordagem multidisciplinar no Vale do Paraíba, SP

INTRODUCTION Chronic Kidney Disease (CKD) is common, severe and treatable. Its detection involves low cost tests. AIM To evaluate the effect of a multidisciplinary (nephrologist, social worker, nurse, nutritionist, and psychologist) intervention comparing clinical and laboratory parameters in patients with CKD. METHODS A prospective study with 2,151 patients attended at the State Center for Kidney Diseases of the Vale do Paraiba, São Paulo, from February 2008 to March 2011. The kidney function was measured using albuminuria and estimated glomerular filtration rate (eGRF) using the MDRD formula The clinical outcomes were the occurrence of cardiovascular disease (CAD), hospitalization episodes, need of renal replacement therapy (RRT) and death. RESULTS Participants had a mean (range) age of 62 years (14-101), a mean follow-up of 546 days (90-1540) and the majority was in the stage 3 of CKD (59%). The most common primary diagnoses were hypertension (41.2%) and diabetes (32.4%). Mean blood pressure values at the beginning and at the end of treatment were 143 ± 26 mmHg x 87 ± 14 mmHg and 123 ± 16 mmHg x 79 ± 9 mmHg, respectively (p < 0.001); the eGRF decreased from 58.5 ± 31 ml/min. to 56.3 ± 23 ml/min (p < 0.01). Mean value of proteinuria decreased from 1.04 ± 1.44 g/day to 0.61 ± 1.12 g/day, p < 0.001, and the fasting glicemia decreased from 137 ± 73 mg/dl to 116 ± 42 mg/dl. One hundred and twenty-two patients (5.7%) had a CAD episode, the hospitalization rate was 6.6% (n = 143 patients), 7.3% patients died (n = 156), and 1.1% (n = 23) patients needed to start RRT. The risk of cardiovascular events, hospitalization, or death was inversely related to eGRF, and the rates of these events were low compared with the international literature. CONCLUSION The multidisciplinary care with well defined targets is effective for the preservation of renal function and reduction in morbidity and mortality of CKD patients.

Abnormalities of renal function in the elderly

OBJECTIVE To investigate the glomerular and proximal tubular renal function and the prevalence of urinary abnormalities in the elderly. DESIGN Cross-sectional study. SETTING General community in the city of São Paulo. PARTICIPANTS A population-based sample of 200 elderly subjects was randomly selected. Of these, 81 subjects (45 females and 36 males; mean +/- SD age: 73.7 +/- 6 years) accepted to undergo laboratory examination and were included in the study. MAIN OUTCOME MEASURES 24-h creatinine clearance (CCr), microalbuminuria, urinary retinol-binding protein (urRBP), leukocyturia, hematuria and total proteinuria. RESULTS CCr was lower than 80 ml/min/1.73 m2 in 68% of the subjects. The median (range) CCr was 65 ml/min/1.73 m2 (21-112) in males and 77 ml/min/1.73 m2 (27-107) in females (p = 0.14). No individual had serum creatinine greater than 1.5 mg/dl. urRBP determination was normal in 79 of 81 subjects. The prevalence of microalbuminuria (> 20 micrograms/ml) was 31% (n = 25, 19 men and 6 women). These individuals presented higher mean systolic blood pressure (147 +/- 20 vs. 135 +/- 22 mmHg, p = 0.02) and mean serum creatinine (1.13 +/- 0.20 vs. 0.96 +/- 0.20 mg/dl, p < 0.01) than those without microalbuminuria. The prevalence of leukocyturia (> 10,000/mm3), hematuria (> 10,000/mm3) and total proteinuria (> or = 0.3 mg/dl) was 19%, 28% and 5% in males and 33%, 27% and 4% in females. CONCLUSIONS Glomerular dysfunction and urinary abnormalities are frequent features in the elderly, however, proximal tubular dysfunction is uncommon in this population.

Glomerulonephritis associated with hepatitis C virus infection

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.