Focal segmental glomerulosclerosis in a boy with Dent-2 disease

Abstract

Sirs, Proximal tubular dysfunction is, in general, more common when the nephrotic syndrome is associated with focal segmental glomerulosclerosis (FSGS) than with minimal-change nephrotic syndrome. Although it has been considered that the nonselective proteinuria in FSGS causes proximal tubular cell injury with the resultant tubulointerstitial damage and scarring, Copelovitch et al. have recently postulated that the tubular dysfunction or damage is the primary renal insult and that FSGS may be a secondary epiphenomenon in some patients with congenital tubulopathies [1]. We encountered a patient who fits into this concept. The patient was a 4-year-old Japanese boy referred to us for further evaluation of significant proteinuria detected by a mass screening program for renal disease in Japan at 3 years of age. He was first referred to a local hospital where renal biopsy was performed because of persistent proteinuria for several months. Pathological diagnosis of FSGS was made (Fig. 1). His past medical history and family history were unremarkable. Physical examination on admission showed that the boy’s height was 95.2 cm (−2.4 S.D.), his weight was 15.1 kg (−1 S.D.), and his blood pressure was 102/ 68 mmHg. There were no dysmorphic features. Initial serum concentrations were all normal: sodium 139 mEq/L, potassium 3.8 mEq/L, chloride 103 mEq/L, carbon dioxide 25 mEq/L, calcium 9.9 mg/dl, phosphorous 3.8 mg/dl, albumin 4.5 g/dl, and creatinine 0.27 mg/dl. Twenty-fourhour protein excretion varied from 892 mg/day to 1,242 mg/day. Repeated urinalysis did not detect glucosuria or hematuria. From these findings, the presumptive diagnosis of idiopathic FSGS was made and the treatment consisting of steroid and cyclosporine A had been initiated without a significant reduction in the amount of proteinuria. During the treatment over the following 11 months, quantitative analysis of the low-molecular weight protein in urine, such as beta-2-microglobulin (BMG), was repeatedly performed and showed extraordinarily high values (BMG: 84,800 μg/l–185,000 μg/l, normal T, p.P509S). This same mutation has been neither previously described nor observed in 200 control chromosomes from healthy individuals. No mutations were detected in CLCN5. Our patient was diagnosed as having Dent-2 and was weaned off steroids and cyclosporine A over the following month. He is now 6 years old and otherwise healthy without any medication, although a significant amount of proteinuria is still present. K. Kaneko (*) :M. Hasui Department of Pediatrics, Kansai Medical University, 2-3-1 Shin-machi, Hirakata-shi, Osaka 573-1191, Japan e-mail: kanekok@hirakata.kmu.ac.jp