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 1:1. 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
Conclusions: this study emphasized the importance of NPH as a cause of CRF in Egyptian children with a prevalence of 15%. It clarified its insidious course, manifestations and paucity of alarming signs. Also, it reported 3 cases with the rare Senior Loken syndrome. High index of suspicion for NPH is needed during evaluation of children and adolescents with refractory anemia, polyuria, isothenuria, growth retardation or unexpiained renal impairment. We recommend renal US to be an essential part of the diagnostic approach of cases suspected to have NPH, but the absence of renal medullary cysts does not exclude the diagnosis
ABSTRACT
Nephrocalcinosis [NC] is the deposition of calcium and oxalate or phosphate in the renal tubules, tubular epithelium or renal interstitial tissue. It is being recognized more frequently since the introduction of ultra sonographic imaging. The sonographic appearance of NC is characterized by presence of echo- dense deposits in renal medulla, cortex or both. This study was conducted to define the underlying etiology of NC in Egyptian infants and children. Thirty two cases with NC were studied in Alexandria University Children's Hospital during the period [January 2001 to January 2004]. The ages of studied cases varied between I month and 9 years with male to female ratio of 1:3:1. Mean age at diagnosis was 2.8 +/- 2.7 years. Thorough clinical, imaging and metabolic evaluations were done to all cases. Sonographic evidences of bilateral medullary NC were evident in 87.5% of cases, combined medullary and cortical NC occurred in 9.4 % of cases, while cortical NC was found in only one case [3.13%]. Abdominal X-ray detected NC in only 34.4% of patients. Clinical presentations of NC were polyuria, polydipsia or dehydration in 62.5%, metabolic acidosis in 53%, urinary tract infection in 47%, psychomotor retardation [44%] failure to thrive [37.5%], abdominal or loin pain [31%], gross or microscopic hematuria [25%] and spontaneous passage of stones [12.5%]. Nephrolithiasis was associated with NC in 79% of the cases. Family history of renal stones was reported in 25% of cases compared to 10% in controls. , , Infants with NC [group I] had normal anion gap [AG], increased mean serum levels of calcium [Ca] and I chloride and decreased mean level of blood pH but without reaching statistical significance. Serum ; potassium, HCO3, urinary specific gravity [SG], citrate/creatinine and magnesium/ creatinine ratios were significantly reduced in group I, while urinary pH and Calcreatinine ratio were significantly elevated [p= 0.02,0.001 respectively]. Infant mortality was 41.2% due to recurrent sepsis. Blood urea, creatinine [Cr] and AG were high in patients older than one year of age [groups II and III], while HCO3 and Cr clearance were significantly lower than the control values [p<0.005]. Serum uric acid in cases older than 5 years [group III] was significantly higher than the control group. Urinary 24 hour calcium and oxalate output were significantly high in groups II and III [p=0.0001, 0.02 respectively] while urinary output of citrate, magnesium and phosphate were significantly lower in these cases compared to controls [p<0.005]. , Nephrocalcinosis was due to metabolic diseases in 75% of the cases and due to iatrogenic hypervitaminosis D [HVD] in 25%. Metabolic errors were distal renal tubular acidosis [RTA-I] in 37.5%, renal idiopathic hypercalciuria [IHC] in 25% and primary hyperoxaluria [PHyOx] in 12.5%. Hypercalciuria ' was the commonest urinary abnormality detected in 87.5% of cases, being due to RTA-I in 42%, IHC in I 29% and HVD in 29%. Hyperoxaluria was present in 723% of cases due to PHyOx. Hypocitraturia and hypomagnesuria were found in 75% and 66%of cases respectively. Etiology of NC in infants was RTA-I in 64.7% and HVD in 35.3%. The commonest cause sf NC in cases > 1 year of age was IHC [53%]. None of the studied cases showed resolution of NC during the years of follow-up [1.8 +/- 0.9 years]
Conclusions: the diagnosis of NC requires a thorough evaluation to identify the underlying offending factor. Different etiological factors may interplay to produce NC; but metabolic errors played the major role in the current study [75%], while iatrogenic HVD was responsible for 25% of the cases. The metabolic causes of NC were RTA-I, IHC and PHyOx. Hypercalciuria was the most common urinary abnormality detected in 87.5% of cases. The deficiency of the urinary calcium crystallization inhibitors manifested by hypocitraturia in 75%of cases and hypomagnesuria in 66% were associated possibly contributing risk factors in most of the cases. Ultrasonography is superior to abdominal X-ray and CT in early detection of NC