Compensatory renal growth in human fetuses with unilateral renal agenesis

To determine whether compensatory growth of the kidney occurs during fetal life we studied 20 human specimens with a unilateral kidney as an isolated defect. The mean combined kidney weight to body weight ratio x 100 in controls was 0.76 +/- 0.14 (SD) and in the solitary kidney cases (after doubling the kidney weight) was 1.26 +/- 0.35 (SD). This significant increase leads us to hypothesize that the increased weight may be due to an induced negative feedback system involving a renotropic factor. From histologic studies a uniform increase in all nephron elements was found. Why should a fetus with adequate placental clearance of metabolic wastes need increased renal size?     

Heterogeneity of bilateral renal agenesis.

Bilateral and unilateral renal agenesis may be expressions of single dominant gene. Chromosome abnormalities may be present and the renal agenesis may be part of a syndrome of multiple abnormalities. Apparently normal relatives of affected individuals should be screened by intravenous pyelography before genetic counselling given.     

The pathogenesis of Potter's syndrome of renal agenesis

Current views of the pathogenesis of Potter''s syndrome of renal agenesis are discussed. Embryological, teratological and genetic associations between kidney and limb development are reviewed. An infant is described with lobsterclaw deformity of the hands and feet, renal hypoplasia and the Potter face.     

Unilateral renal agenesis in chick embryos: a model for chronic renal insufficiency.

Although renal agenesis and dysgenesis are relatively common and significant birth defects, no animal model to date has been utilized to adequately study these developmental pathologies. Blockage of the migration of the mesonephric duct in Day 2 chick embryos results in unilateral renal agenesis (URA) on the operated side, thus providing a model of chronic renal insufficiency. Embryos with URA respond with an increase in the rate of growth of the remaining meso- and metanephric kidney. The allometric scaling of single (left) kidney weight to total body weight in control embryos is KM = 3.48M0.98 compared to KM = 3.02M1.16 in embryos with URA. In addition, embryos with URA exhibit a progressively polycystic mesonephros with distinct glomerulonephritis and expansion of the renal tubules. These renal changes are insufficient for normal urine (allantoic fluid) production and oliguria persists throughout incubation. While mortality is unaffected by URA in embryos up to Day 14 of incubation, there is a steady increase in mortality after Day 14; no chick embryo with URA lives beyond Day 18 of the 21-day incubation period.     

Urological anomalies in children with renal agenesis or multicystic dysplastic kidney

This study aimed to determine the frequency of associated urological abnormalities in children with unilateral renal agenesis (RA) or multicystic dysplastic kidney (MCDK). In total, 38 children (10 girls, 28 boys) were studied: 21 with RA and 17 with MCDK. In 14 children (37%) anomalies of the urinary tract were suspected prenatally in ultrasound studies. In the remaining 24 children the diagnosis of RA/MCDK was made postnatally: in 13 (34%) in the first 7 days of life, in 11 (29%) at the age of 8 days to 34 months, mean 10.6+/-8.05 months. Voiding cystourethrography was done in 36 (95%) children, the isotopic 99mTc-EC/DMSA scan of the kidney in 29 (67%), and urography in 8. Urological anomalies were present in 11 (29%) children: in 7 (33%) with RA and in 4 (24%) with MCDK. Vesicoureteral reflux was diagnosed in 8 children: grade II in 4, III in 3, and IV in 1 (in 1 child to duplicated, in 1 to ectopic kidney); ureterovesical junction obstruction in 2 (9.5%); and ureteropelvic junction obstruction in 1 (4.8%). Among them, 2 children demanded surgery on the contralateral urinary tract: pyeloplasty in 1, antireflux procedure in 1; while 9 children were treated conservatively. Compensatory hypertrophy of the contralateral kidney was found in 90% of children. Thus due to an increased risk of pathological changes in the single functioning kidney, lifelong nephrological care is recommended in patients with unilateral RA/MCDK.     

Arsenate-induced phytochelatins in white lupin: influence of phosphate status

White lupin ( Lupinus albus L.) is adapted to environments of low pH and low available phosphorus through the development of proteoid roots. The high-affinity phosphate/arsenate uptake system is much less sensitive to downregulation by phosphate in white lupin than in other plants. Arsenate is a phosphate analogue and its toxicity to plants is intimately linked to phosphate nutrition. The synthesis of phytochelatins (PCs) has been proposed as a detoxification mechanism for arsenic (As) in plants. The aim of this research was to study PC production by lupin plants in response to As, and the impact of the arsenate–phosphate interaction on PC production. PCs were the most abundant thiols in white lupin under high As exposure, reaching levels higher than in other plants tested. Together, glutathione (GSH) and PCs were able to complex the majority of As in shoots, while an additional PC-independent mechanism might function in roots. P deficiency increased As concentrations in plant tissues, causing an increase in PC accumulation and an increase in the average size of PCs. A direct relationship was observed between PC concentrations and the level of stress caused by As, i.e. the degree of growth inhibition in plants. This study suggests a key role for PCs and GSH in As detoxification by white lupin, especially in shoots. PC analysis may be useful as an early indicator of As exposure and as a tool to assess the degree of As stress of plants, even under P deficiency.     

Congenital hypoparathyroidism, ocular colobomata, unilateral renal agenesis and dysmorphic features.

A boy with primary hypoparathyroidism and dysmorphic features suggesting a partial DiGeorge sequence is presented. Different possibilities of genetic counseling are considered in the absence of a definitive etiological diagnosis.     

Genetic bases of renal agenesis in the ACI rat: mapping of Renag1 to chromosome 14

Unilateral renal agenesis (URA) is a common developmental defect in humans, occurring at a frequency of approximately 1 in 500–1000 births. Several genetic syndromes include bilateral or unilateral renal agenesis as an associated phenotype. However, URA frequently occurs in individuals not afflicted by these syndromes and is often asymptomatic. Although it is clear that genetic factors contribute to the etiology of URA, the genetic bases of URA are poorly defined at this time. ACI rats, both males and females, exhibit URA at an incidence of 5%–15%. In this article we characterize the incidence of URA in female and male F₁, F₂, and backcross (BC) progeny from reciprocal genetic crosses between the ACI strain and the unaffected Brown Norway (BN) strain. Through interval mapping analyses of 353 phenotypically defined female F₂ progeny, we mapped to rat Chromosome 14 (RNO14) a genetic locus, designated Renag1 (Renal agenesis 1), that serves as the major determinant of URA in these crosses. Further genotypic analyses of URA-affected female and male F₂ and BC progeny localized Renag1 to a 14.4-Mb interval on RNO14 bounded by markers D14Rat50 and D14Rat12. The data from these genetic studies suggest that the ACI allele of Renag1 acts in an incompletely dominant and incompletely penetrant manner to confer URA. James D. Shull and Cynthia M. Lachel authors contributed equally to this work.     

Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis

ICAT, inhibitor of beta-catenin and T cell factor, or Ctnnbip1, is a negative regulator of the Wnt signaling pathway that interferes with the interaction between beta-catenin and T cell factor. Some ICAT-deficient (ICAT-/-) embryos exhibit unilateral or bilateral renal agenesis. In this study, we investigated developmental processes in the ICAT-/- kidney. ICAT was highly expressed in both the ureteric bud (UB) and the surrounding metanephric mesenchymal (MM) cells in the metanephros of embryonic day E11.5-E13.5 wild-type (ICAT+/+) mouse. In the E12.5-ICAT-/- metanephros, UB branching was delayed, and a T-shaped, bifurcated UB was frequently seen; this was never seen in the E12.5-ICAT+/+ metanephros. More apoptotic MM cells were detected in the ICAT-/- metanephros than in the ICAT+/+ metanephros. These results suggest that the loss of ICAT gene function causes the arrest of UB branching and the apoptotic death of MM cells, resulting in renal agenesis.     

Minerals in renal and SHR hypertensive rats

References to individual trace minerals in hypertensive rats have been made; however, data on multiple minerals in SHR hypertensive rats is lacking. The purpose of this study was to investigate five trace minerals in normotensive, chronic renal and SHR hypertensive rats. Blood samples were drawn to measure serum levels of Ca, Fe, K, Mg, and Na. Serum K values were elevated in the chronic renal hypertensive animals. Iron levels were decreased in both the renal and SHR hypertensive animals. No difference was observed in levels of Ca, Mg, and Na between normotensive and chronic renal or SHR hypertensive rats. Further study of multiple trace minerals in experimental hypertension is recorded in order to extend these deviations.