Russell W. Chesney

Myopathy and Cystine Storage in Muscles in a Patient with Nephropathic Cystinosis

NEPHROPATHIC cystinosis is a lysosomal storage disorder characterized by the appearance of renal tubular Fanconis syndrome in the first year of life and by growth retardation, progressive photopho...

Long term follow-up of bone mineral status in children with renal disease.

Bone mineral content (BMC) was measured by photon absorptiometry in the non-dominant forearm of children with chronic renal failure followed for a total of 2472 months. From 48 children, 302 measurements were made, and changes which occurred in BMC over time were correlated with several factors. Patients were divided into those who had received glucocorticoids (group 1) and those who had not (group 2). Group 1 patients had a lower mean serum creatinine (Cr) (p<0.05), a lower growth velocity (p>0.02) and were more demineralized than group 2 patients. There was no correlation between BMC and height velocity or estimated creatinine clearance. BMC and height Z-score (SDS) were highly correlated. Over the period of study, group 1 patients remained shorter, had a lower height velocity, a lower BMC Z-score and a lower BMC for each serum creatinine level. Long-term therapeutic intervention with oral 1,25(OH)2D improved bone mineral status in three children in the nonsteroid group, but none of those in the steroid group. This study demonstrates that steroid administration is probably the most important factor causing bone demineralization, possibly even more important than renal failure.

Studies on renal adaptation to altered dietary amino acid intake: reduced renal cortex taurine content increases the Vmax of taurine uptake by brush border membrane vesicles

Rats were placed on a normal taurine diet (NTD), low taurine diet (LTD) or a high taurine diet (HTD) for 14 days. β-Alanine was fed to half of the animals in each group and resulted in a lowered renal cortex taurine content. Brush border membrane vesicle (BBMV) uptake of taurine was higher after β-alanine feeding and was associated with an increase in Vmax of uptake. β-Alanine feeding to HTD animals also altered the Km of uptake, possibly since the load of sulfur amino acids (6% of diet) was high. As a control, glycine (3%) feeding for 8 days along with each diet did not alter the plasma or renal cortex content; BBMV uptake as well as Km and Vmax of taurine accumulation were minimally altered. Accordingly, ingestion of a non-sulfur-containing α-amino acid did not change β-amino acid transport. This study provides evidence that whole body taurine homeostasis is maintained in the presence of a taurine-depleting agent (β-alanine feeding) by an increase in the number of Na+-taurine uptake sites.

Forms of nephrotic syndrome more likely to progress to renal impairment.

In this article, emphasis is placed on those conditions that appear as the idiopathic nephrotic syndrome but that are more likely to result in progressive renal failure. Four conditions, membranoproliferative glomerulonephritis (mesangiocapillary glomerulonephritis), mesangial proliferative glomerulonephritis, membranous nephropathy, and focal segmental glomerulocosclerosis, account for 12 to 15 per cent of cases of idiopathic nephrotic syndrome during childhood. The further aim of this article is to focus on recent progress in our understanding of these conditions and to remind readers that little is known regarding the etiology and pathogenesis of each, and that effective, clearly proven forms of treatment for each are not apparent currently.

Renal adaptation to dietary amino acid alteration is expressed in immature renal brush border membranes

The transport of ions and solutes at the epithelial surface of the renal proximal tubule increases during periods of reduced dietary intake and decreases with dietary excess. We have used the sulfur-containing β-amino acid, taurine, as a probe of this renal adaptive response to altered dietary sulfur amino acid intake to better understand the mechanisms of renal amino acid reabsorption. There exists an age-related precession of taurine uptake values by brush border membrane vesicles prepared from nursing rats from youngest to oldest. However, despite the immaturity of this transport mechanism, epithelial membranes become able to display a full renal adaptive response to altered sulfur amino acid intake sometime between the 7th and 14th day of life. This adaptive response is expressed in both “up regulation” and “down regulation” by means of a change in the initial rate of Na+-taurine cotransport. No changes in the lipid microenvironment of the membrane, as assessed by measurements of membrane fluidity, are evident. The lack of adaptation observed in 7-day-old pups may be due to immaturity of the Na+ transporting mechanism which energizes the uptake of amino acids.

Good outcome in prune-belly syndrome despite associated severe anomalies

A boy aged 4.5 years with prune-belly syndrome (PBS) and associated urethral stenosis, oligohydramnios, imperforate anus and vesicosigmoid fustula is described. In contrast to the anticipated poor prognosis, vesicostomy and divided transverse colostomy performed after birth followed by prophylaxis of infection and bicarbonate supplementation have resulted in a good outcome. The vesicosigmoid fistula might have served in utero as a “natural diversion” protecting from pressure-induced renal damage. It is suggested that the main determinant of prognosis in PBS is the presence and degree of kidney dysplasia at birth as reflected by the neonatal renal function after performance of an indicated urinary diversion procedure rather than the presence of severe associated anomalies.

Idiopathic Nephrotic Syndrome: Proliferative Nephropathy and Membranous Nephropathy

In this chapter we shall cover those disorders in children which result in a proliferative and/or membranous renal morphologic appearance. If one considers only the idiopathic nephrotic syndrome and excludes known causes of these disorders such as systemic lupus erythematosus, chronic hepatitis antigenemia, and partial lipodystrophy, three conditions should be considered: membranoproliferative glomerulo-nephritis (mesangiocapillary glomerulonephritis), mesangial proliferative glomerulonephritis, and membranous nephropathy. These three conditions account for only a small percent of the cases of the idiopathic nephrotic syndrome in childhood, occurring in less than 10% of cases in series from North America, Britain and Western Europe. It is our intention to review each of these three disorders, focusing on the major references and on recent reports which indicate the progress in our understanding of these conditions. At the outset it is essential to remember that the etiology and pathogenes is of each is poorly understood and that effective, clearly established forms of treatment for each are not presently available.