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Prediction of Steroid Responsiveness in the Idiopathic Nephrotic Syndrome Using Urinary Retinol-binding Protein and Beta-2-Microglobulin

Ricardo Sesso, MD; Alze P. Santos, MD; Sonia K. Nishida, MSc; Michael J. Klag, MD, MPH; Joao T. Carvalhaes, MD; Horacio Ajzen, MD; Oswaldo L. Ramos, MD; and Aparecido B. Pereira, MD
[+] Article, Author, and Disclosure Information

Grant Support: By the Rockefeller Foundation (International Clinical Epidemiology Network—INCLEN), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), and the Instituto Paulista de Estudos e Pesquisas em Nefrologia e Hipertensao. Dr Sesso was supported by a CNPq fellowship. Dr. Klag is an Established Investigator of the American Heart Association.

Request for Reprints: Ricardo Sesso, MD, The Johns Hopkins Medical Institutions, The Welch Center for Prevention Epidemiology and Clinical Research, 600 North Wolfe Street, Carnegie 292, Baltimore, MD 21205.

Current Author Addresses: Drs. Sesso and Klag: The Johns Hopkins Health Institutions, 600 North Wolfe Street, Carnegie 292, Baltimore, MD 21205.

Drs. Santos, Ajzen, Ramos, and Pereira and Ms. Nishida: Division of Nephrology, Escola Paulista de Medicina, Rua Botucatu 740, Sao Paulo, SP, 04023, Brazil.

Dr. Carvalhaes: Department of Pediatrics, Escola Paulista de Medicina, Rua Botucatu 740, Sao Paulo, SP, 04023, Brazil.

© 1992 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1992;116(11):905-909. doi:10.7326/0003-4819-116-11-905
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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 < 0.01). In the steroid-responsive group, urinary RBP and B2M levels decreased significantly after remission (P < 0.01). In the steroid-unresponsive group, the likelihood ratios for urinary RBP greater than 4000 μg/g creatinine and for B2M greater than 3000 μg/g creatinine were 3.8 and 3.0, respectively. The probability was 100% that values of RBP of less than 1300 μg/g creatinine and B2M of less than 130 μg/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.





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