Horácio Ajzen

A Controlled Trial of Pulse Cydophosphamide Versus Pulse Methylprednisolone in Severe Lupus Nephritis

We carried out a prospective randomized trial comparing pulse cyclophosphamide and pulse methylprednisolone in 29 patients with severe lupus nephritis in activity. Patients were assigned to one of two regimens: monthly pulse cyclophosphamide (0.5-1.0 g/m 2 body surface area) for 4 months, followed by bimonthly doses for 4 months and quarterly doses for 6 months (14 patients) or pulse methylprednisolone (10-20 mg/kg weight) initially for 3 consecutive days and thereafter in the same intervals as the alternative regimen (15 patients). The mean follow-up was 15 months. Two patients in the cyclophosphamide group and three in the methylprednisolone group died. Renal failure (doubling of serum creatinine) developed in four patients in the cyclophosphamide group compared with five patients in the methylprednisolone group. Cumulative probability of not doubling serum creatinine was similar for cyclophosphamide and methylprednisolone groups (0.66 vs 0.69, respectively, P > 0.20, after 18 months). Cumulative probability of survival without renal failure was also not significantly different (0.61 and 0.63, respectively, P > 0.20, after 18 months). These results suggest that pulse cyclophosphamide is as effective as pulse methylprednisolone in preserving renal function in patients with severe lupus nephritis.

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.

Cost-Effectiveness Analysis of the Treatment of End-Stage Renal Disease in Brazil

Cost-effectiveness analysis compared four treatments of end-stage renal disease in Brazil: continuous ambulatory peritoneal dialysis (CAPD), in-center hemodialysis (HD), cadaver donor transplantation (CD-Tx), and living related donor transplantation (LR-Tx). After 2 years, the costs per year of survival were CAPD,

Effectiveness of Oral Energy-Protein Supplementation in Severely Malnourished Hemodialvsis Patients

12,134; HD,

Prediction of steroid responsiveness in the idiopathic nephrotic syndrome using urinary retinol-binding protein and beta-2-microglobulin

10,065; CD-Tx,

Urinary Retinol-Binding Protein as a Prognostic Marker in the Treatment of Nephrotic Syndrome

6,978; and LR-Tx,

Renal Abnormalities in Leprosy

3,022. The HD cost was lower than CAPD partially because of the reuse of hemodialyzers in Brazil. Although less cost-effective, both dialysis treatments yielded more years of survival after 2 years. This analysis reveals a trade-off between cost per year of survival and years of survival.

FREQUENT ABNORMALITIES OF RENAL FUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS

■ Objective: To evaluate the effect of an oral energy-protein supplementation on the nutritional status of severely malnourished uremic hemodialysis patients. ■ Design: A cohort study of malnourished patients orally supplemented for 4 months. ■ Setting: A satellite hemodialysis unit at the Escola Paulista de Medicina, Sao Paulo, Brazil. ■ Patients: In a population-based sample, 14 of 123 chronic severe malnourished patients selected by clinical and anthropometric criteria initiated the study. Ten patients completed the trial. ■ Interventions: In addition to the instructed diet, each patient received a flavored oral powder supplement containing egg albumin, corn and coconut oils, hydrogenated fat, and malto-dextrin, providing 800 kcal and 19.6 g protein/d. ■ Main outcome measures: The following parameters were obtained: 3-day dietary diaries, protein catabolic rate (PCR), body weight (BW), triceps skinfold thickness (TSF), midarm circumference (MAC), body mass index, body fat (BF), percentage of body fat (PF), lean body mass (LBM), midarm muscle area (MAMA), and hematological and biochemical indices. ■ Results: At the end of the study, significant increases in total energy (27 ± 6 to 43 ± 6 kcal/kg/d) and protein consumption (1.07 ± 0.4 to 1.57 ± 0.4 g/kg/d) were observed. Significant increases were also observed in BW (48.9 ± 8.4 to 50.4 ± 8.9 kg), MAC (23 ± 2.6 to 23.8 ± 2.5 cm), TSF (6.5 ± 3.1 to 7.9 ± 3.6 mm), and BF (7.2 ± 2.8 to 8.6 ± 3.3 kg). There were no modifications in LBM and MAMA. Changes in BW correlated significantly with changes in PF ( r = 0.47; P r = 0.63; P ■ Conclusion: The oral supplement was well tolerated and was effective in improving the nutritional status of malnourished hemodialysis patients.

Idiopathic focal segmental glomerulosclerosis and HLA antigens

OBJECTIVES To determine the prevalence of early proximal tubular dysfunction, measured by urinary excretion of retinol-binding protein (RBP) and beta-2-microglobulin (B2M), in patients with the idiopathic nephrotic syndrome and to investigate the value of these tests in predicting steroid responsiveness. DESIGN Before-after trial with 8-week treatment period. SETTING Tertiary referral center. PATIENTS Sequential sample of 37 patients with the idiopathic nephrotic syndrome caused by minimal change disease, focal segmental glomerulosclerosis, or mesangial proliferative glomerulonephritis. INTERVENTION All patients were treated with prednisone as one dose of 1 to 1.5 mg/kg body weight per day for 8 weeks. MEASUREMENTS Urinary RBP was measured by an immunoenzymometric assay and B2M, by an enzyme-linked immunosorbent assay. Remission of the nephrotic syndrome after steroid treatment was the main outcome variable. RESULTS Elevated levels of urinary RBP and B2M before treatment were detected in 65% and 75% of the patients, respectively. Median urinary RBP and B2M, before treatment, were significantly higher in the steroid-unresponsive group than in the responsive group (P less than 0.01). In the steroid-responsive group, urinary RBP and B2M levels decreased significantly after remission (P less than 0.01). In the steroid-unresponsive group, the likelihood ratios for urinary RBP greater than 4000 micrograms/g creatinine and for B2M greater than 3000 micrograms/g creatinine were 3.8 and 3.0, respectively. The probability was 100% that values of RBP of less than 1300 micrograms/g creatinine and B2M of less than 130 micrograms/g creatinine were from steroid-responsive patients. Multivariate analysis confirmed that higher urinary levels of RBP and B2M were associated with a lower likelihood of steroid responsiveness, independent of age and histologic diagnosis. CONCLUSIONS Proximal tubular dysfunction is frequent in patients with the idiopathic nephrotic syndrome. Pretreatment urinary RBP and B2M levels may be helpful in identifying nephrotic patients who are more likely to be responsive to steroids.

Nephrotoxicity of Low-Osmolality Contrast Media

We studied the urinary levels of retinol-binding protein (urRBP), an index of proximal tubular dysfunction, in patients with nephrotic syndrome before and approximately 2 months after the beginning of steroid therapy as a predictor of response to therapy which included for some patients courses of immunosuppressive drugs. Those patients with minimal-change disease, mesangial proliferative glomerulonephritis, and focal-segmental glomerulosclerosis who had normal pretreatment urRBP levels were responsive to treatment; occasionally, responsive patients had an initially elevated urRBP level which normalized during treatment. Contrariwise, those patients with abnormally high levels of urRBP which did not normalize during treatment did not respond to treatment. The chance of a patient with minimal-change disease, mesangial proliferative glomerulonephritis, or focal-segmental glomerulosclerosis and a pretreatment urRBP level equal to or >1.0 mg/l being resistant to steroid treatment is 30 times that of a patient with a urRBP level <1.0 mg/l and even higher, if we consider the levels obtained during treatment.