Clinicopathological study of juvenile nephronophthisis

ABSTRACT

Juvenile nephronophthisis [NPH] is an important cause of chronic renal failure [CRF] in children and adolescents. It is inherited as an autosomal recessive trait. To the best of our knowledge there have been no detailed clinicopathological studies in Egypt or Arab countries on this disease. The aim of this work was to study NPH in Egyptian children. Eighteen cases with NPH were studied in Alexandria University Children's Hospital during the period from March 2001 to January 2004. They were subjected to thorough clinical, ophthalmological, and laboratory evaluation. Radiological skeletal survey, abdominal ultrasonography [US] and thin-section abdominal computed tomography [CT] were done in all cases. The diagnosis of NPH was based on typical clinical presentation, laboratory and sonographic evidences of chronic tubulointerstitial renal disease, not related to urologic abnormality, and progressing to chronic renal insufficiency [CRI] or CRF. Confirmation of the diagnosis was done by histological and ultrastructural examination of the renal biopsy in all cases. The mean age of cases was 11.3 +/- 2.6 years, and male to female ratio was 11. The chief complaints in studied cases were polyuria, polydipsia, nocturnal enuresis and growth retardation noted at a mean age of 5.5 +/- 1.8 years. Poor urinary concentration, anemia and chronic renal insufficiency or failure were noted in all cases during hospitalization. Eight cases had end stage renal failure [ESRF] and required chronic dialysis. The mean age at ESRF was 10 +/- 2 years. The mean value of creatinine clearance in NPH cases was 24 +/- 15 mL/min/1.73 m[2]BSA versus 106 +/- 8 mL/min/1.73 m[2]BSA in control group [p=0.001]. Out of 121 children with CRF or CRI registered during the period of the study in Alexandria University Children's Hospital 15% were due to NPH. The prevalence of this disease among dialysis population aged 5 - 15 years was 18%. Inheritance of NPH in familial cases was compatible with autosomal recessive transmission. Three of the studied cases [16.7%] had retinal dystrophy in addition to the manifestations of NPH, Two cases sf them had a picture similar to childhood onset retinitis pigmentosa, while the other case had a retinal dystrophy indistinguishable from Leber's congenital amaurosis. These findings were consistent with the diagnosis of Senior Loken syndrome which is a rare autosomal recessive syndrome that combines NPH and tapetoretinal degeneration. Renal sonographic examinations revealed renal hyperechogenicify and poor corticomedullary differentiation in all cases, reduced renal size in 44% of cases, and medullary cysts in 39% of cases. Thin-section CT scans revealed the medullary cysts in 50% of the cases. No cysts in other abdominal organs or hepatic fibrosis were detected either by US or CT in studied cases. Apart from the rachitic-like changes noted in 4 cases with ESRF; no other skeletal abnormalities were found by radialogical surveys. Histological examination of renal biopsies revealed pronounced tubular atrophy with marked thickening of the tubular basement membrane [TBM] and microcyst formation in all cases. It was accompanied with diffuse interstitial fibrosis and focal interstitial infiltration by chronic inflammatory cells. Ultrastructurally, the TBM displayed abrupt transition from thin to markedly thickened Iamellated areas