No abstract

This prospective follow-up study of 422 19-yr-old subjects born very preterm in The Netherlands was performed to determine whether intrauterine growth retardation (IUGR) predisposes to abnormal GFR and microalbuminuria in adolescents. GFR (ml/min per 1.73 m 2 ) was estimated using the Cockcroft-Gault equation, and albumin-creatinine ratio (mg/mmol) was calculated in a cohort of 19-yr-old subjects born very preterm (gestational age <32 wk) in 1983. Birth weights were adjusted for gestational age and expressed as standard deviation scores (sds) as a measure of IUGR. All subjects had normal renal function. Birth weight (sds) was associated negatively with serum creatinine concentration (mol/L) (␤ ‫؍‬ ؊1.0 mol/L, 95% confidence interval [CI]: ؊1.9 to ؊0.2), positively with GFR (␤ ‫؍‬ 3.0, 95% CI: 1.7 to 4.2), and negatively with the logarithm of albumin-creatinine ratio (␤ ‫؍‬ ؊0.05, 95% CI: ؊0.09 to ؊0.01) in young adults born very preterm. IUGR is associated with unfavorable renal functions at young adult age in subjects born very premature. These data suggest that intrauterine growth-retarded subjects born very premature have an increased risk to develop progressive renal failure in later life.

Various aberrations of cell biology have been reported in polycystic kidney diseases and in cystic renal dysplasias. A common theme in these disorders is failure of maturation of renal cells which superficially resemble embryonic tissue. Apoptosis is a feature of normal murine nephrogenesis, where it has been implicated in morphogenesis, and fulminant apoptosis occurs in the small, cystic kidneys which develop in mice with null mutations of bcl-2. Therefore, we examined the location and extent of apoptosis in pre- and postnatal samples of human polycystic and dysplastic kidney diseases using propidium iodide staining, in situ end-labeling and electron microscopy. In dysplastic kidneys cell death was prominent in undifferentiated cells around dysplastic tubules and was occasionally found in cystic epithelia. The incidence of apoptosis was significantly greater than in normal controls of comparable age both pre- and postnatally. In the polycystic kidneys there was widespread apoptosis in the interstitium around undilated tubules distant from cysts, in undilated tubules between cysts and in cystic epithelia. The level of apoptosis compared to controls was significantly increased postnatally. A similar increase of cell death was also noted in the early and late stages of renal disease in the polycystic cpk/cpk mouse model. We speculate that deregulation of cell survival in these kidneys may reflect incomplete tissue maturation, and may contribute to the progressive destruction of functional kidney tissue in polycystic kidneys and the spontaneous involution reported in cystic dysplastic kidneys.

Congenital analbuminaemia is a rare disorder with remarkably mild signs and symptoms at all ages. Although often thought to be innocent, this disorder may have important clinical complications.

Current models of autosomal recessive polycystic kidney disease (ARPKD) fail to demonstrate biliary abnormalities in association with renal cysts. We therefore studied a new murine model of ARPKD in which dual renal tubular and biliary epithelial abnormalities are present. Affected homozygous animals typically die 1 month postnatally in renal failure with progressively enlarged kidneys. Renal cysts shift in site from inner cortical proximal tubules at birth to collecting tubules 20 days later, as determined by segment-specific lectin binding. Increased numbers of mitosis were demonstrated in proximal and collecting tubular cysts. In addition, epithelial hyperplasia was demonstrated morphometrically in the intra- and extrahepatic biliary tract of affected animals. The number of intrahepatic biliary epithelial cells was increased by 50% on postnatal day 5 and by 100% on postnatal day 25 (P < 0.01). Despite an increased frequency of "chaotic" portal areas in mice with renal cysts, no intrahepatic cysts or shape abnormalities of the biliary lumen were detected using biliary casts and morphometry. Additionally there was nonobstructive hyperplastic dilatation of the extrahepatic biliary tract which was linked in all animals to the presence of renal cysts. The hyperplastic abnormalities in both renal and biliary epithelium make this new mouse strain a good model for the study of the dual organ cellular pathophysiology of ARPKD.