A unique evolution of the kidney phenotype in a patient with autosomal recessive Alport syndrome.

Alport syndrome is due to mutations in one of the genes encoding (α3,4,5) type IV collagen resulting in defective type IV collagen, a key component of the glomerular basement membrane (GBM). The GBM is initially thin and, with ongoing remodeling, develops a thickened basket-woven appearance. We report a unique case of a 9-year-old boy who underwent biopsy for hematuria and proteinuria, diagnosed as IgA nephropathy, with normal GBM appearance and thickness. Because of a family history of hematuria and chronic kidney disease, he subsequently underwent genetic evaluation, and a mutation of α3 type IV collagen (COL4A3) was detected. Additional studies of the initial biopsy demonstrated abnormal type IV collagen immunostaining. A repeat biopsy 4 years later showed characteristic glomerular basement membrane morphology of Alport syndrome and scarring consistent with sequelae of IgA nephropathy. This is the first description of this unusual transition from an initial normal appearance of the glomerular basement membrane to the classic Alport phenotype.

Nitric oxide does not mediate promotion of cellular potassium release by phenolphthalein in COS-7 cells.

1. It has been proposed that phenolphthalein exerts its laxative effect via an intracellular cascade that begins with the activation of nitric oxide synthase (NOS) and ends with an inhibition of NaCl and water reabsorption from the colon. Phenolphthalein also promotes the release of potassium from cells, but it is not known how this is related to its effect on sodium and water uptake. 2. An established in vitro system was used to examine the role of nitric oxide (NO) in phenolphthalein-induced release of (86)Rb(+) from COS-7 cells. 3. Sodium nitroprusside, an NOS-independent NO source, was unable to mimic the effects of phenolphthalein and N(G)-nitro-L-arginine methyl ester, an NOS inhibitor, was unable to block the effect of phenolphthalein. 4. It is concluded that NO generation is not required for phenolphthalein-stimulated potassium release. It is proposed that the effect of phenolphthalein on cellular potassium release is mechanistically distinct from the effect on NaCl and water uptake by colonocytes.

Development of IgA nephritis following cat scratch disease in a 13-year-old boy.

We describe a 13-year-old boy who presented with hematuria and intermittent low-grade proteinuria at the time when he was diagnosed with cat scratch disease. Two months before presentation, he had a negative urinalysis during a routine physical evaluation. He continued to have microscopic hematuria for the next 6 months, when he developed gross hematuria and recurrence of low-grade proteinuria. The renal biopsy showed evidence of mild/moderate IgA nephropathy. We speculate that the immunological changes associated with cat scratch disease in this patient may have triggered the development of IgA nephropathy. A history or serological evidence of infection with Bartonella henselae may need to be sought in patients presenting with IgA nephritis.

Regulation of 86Rb+ ion transport across polarized human colonocytes by bis-phenolic compounds.

1. Phenolphthalein, a well-known laxative, stimulates the secretion of Na+ and Cl- ions and accompanying water into the intestinal tract. Measurement of 86Rb+ efflux from several, but not all, cell types indicates that phenolphthalein also results in release of cellular K+ ions. 2. In the present study, the transport of 86Rb+ across human colonocyte cells (T84) cultured on trans-well inserts was examined. The T84 cells were cultured until they developed tight junctions and a high trans-epithelial resistance. 3. Results show that phenolphthalein applied to the apical, but not the basolateral, surface of cells causes the release of 86Rb+ from the apical surface. Basolateral treatment of cells with phenolphthalein had no effect on the release of 86Rb+. 4. Simultaneously with the increased 86Rb+ efflux, indirect evidence of enhanced Na+/K+-ATPase activity was also observed. 5. Although ouabain inhibited the increased Na+ pump activity, it did not affect apical 86Rb+ release. 6. As evidenced by near steady state 86Rb+ uptake data, the increased Na+/K+-ATPase activity was insufficient to restore intracellular concentrations of K+ in the presence of phenolphthalein. 7. 4,4(9-Fluorenylidene)diphenol, a homologue of phenolphthalein, had a similar effect on 86Rb+ transport by T84 cells. 8. These results indicate a primary stimulation of 86Rb+ efflux from the apical surface of polarized T84 cells by apically applied bis-phenolic compounds. 9. A secondary stimulation of the basolateral Na+/K+-ATPase is thought to result from intracellular Na+ increase, as documented in several other cell types exposed to bis-phenolic compounds, although not directly measured in these experiments. 10. The results also indicate that bis-phenolic compounds interact specifically with some apical but not basolateral membrane structures in regulating 86Rb+ efflux from polarized T84 cells.