Faculty Bibliography

The pathophysiology of stone disorder in older adults, as compared to their younger counterparts, has not been thoroughly investigated. This article examines the differences in serum and urine chemistries between groups that are younger and older than 60 years of age. The principal finding is that stone formation occurs at lower urinary supersaturations in older patients, suggesting that other unexplored factors are significant contributors. The authors then review the possible effect of age on the morbidity of stone disease and the implications of stone disease for the development and management of osteoporosis

Human immunodeficiency virus-associated nephropathy (HIVAN), characterized by heavy proteinuria, rapidly progressive renal failure, 'collapsing' glomerulopathy, and tubulointerstitial abnormalities, is the most common finding in HIV-infected patients undergoing a renal biopsy and predominantly affects blacks. We describe the clinical features and renal pathologic findings of 12 intravenous drug users (IVDUs) coinfected with HIV and hepatitis C virus (HCV) who were selected for renal biopsy because they presented with features different from typical HIVAN, including hypertension, microscopic hematuria, and cryoglobulinemia. There were seven black and five Hispanic patients. Eleven patients had immune complex glomerulonephritis (ICGN); one had glomerulosclerosis with immune complex deposits. Ten individuals had evidence of past hepatitis B viral infection, but none had persistent hepatitis B surface antigenemia. No other underlying cause for immune complex glomerulonephritis was identified. Renal biopsy showed membranoproliferative glomerulonephritis in five patients, mesangial proliferative glomerulonephritis in five, membranous nephropathy in one, and 'collapsing' glomerulopathy with immune complex deposits in one. Hepatitis C virus RNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in the renal tissue and/or serum of nine of the 11 patients tested, and also in the renal biopsy tissue of four of eight patients with clinical and pathologic features of typical HIVAN without immunofluorescence evidence of immune complex deposits. One patient presented with renal failure, five patients developed end-stage renal disease (ESRD) requiring hemodialysis (mean time, 6.5 months), and six had stable renal function after a mean follow-up of 29.1 months (range, 2 to 72 months). Liver function abnormalities were present in seven of the 12 individuals, including four of the six patients who developed renal failure. These findings indicate that in some patients coinfected with HIV and HCV, the development of ICGN may dominate the clinical course of the disease. The occurrence of ICGN among black patients at risk for HIVAN may be related to the relatively high prevalence of HCV infection among IVDUs in this group

The mechanisms by which the benzothiadiazide class of diuretics inhibit electroneutral NaCl absorption are not fully understood. We studied the mechanisms of thiazide action in perfused loops of distal colon in anesthetized male Sprague-Dawley rats. Hydroflumethiazide (1 mM) reversibly inhibited greater than 40% of Na, Cl, and water absorption. Prior exposure of the colon to the carbonic anhydrase inhibitor methazolamide (0.1 mM) prevented the effects of hydroflumethiazide and metolazone, a thiazide-like drug, on colonic absorption. In Ussing flux chambers, addition of hydroflumethiazide to both the mucosal and serosal bathing solutions (but not to the mucosal solution alone) caused marked decreases in Na and Cl absorption. Such inhibition only occurred at concentrations of hydroflumethiazide (0.1 and 1.0 mM) that inhibited greater than 90% of carbonic anhydrase activity in homogenized colonic mucosa. We conclude that an important mechanism by which thiazides inhibit NaCl absorption in the rat distal colon is by inhibition of mucosal carbonic anhydrase. In tissues containing this enzyme, this mechanism of thiazide effect on ion flux must be considered

Alterations in extracellular pH cause reciprocal changes in NaCl absorption in the rat and rabbit ileum. The presence of cholera toxin-induced secretion does not affect pH action measured by in vivo perfusion of the rat ileum. We examined the interaction of pH and cyclic adenosine monophosphate-induced secretion in the rabbit ileum. We found that alterations in arterial pH did not affect ileal absorption in the rabbit in the presence of cholera toxin-induced secretion. This was true whether transport was studied during in vivo ileal perfusion of anesthetized rabbits or by measuring Na+ and Cl- fluxes across isolated, short-circuited tissues in the Ussing chamber. The effects of pH also were blocked when normal rabbit ileum was exposed to 1 mmol/L dibutyryl cyclic adenosine monophosphate in vitro. By contrast, alterations in bathing solution pH affected ileal absorption in the rat in the presence and absence of cyclic adenosine monophosphate. Similarly, exposure to cyclic adenosine monophosphate did not affect the response of the rat colon to PCO2. These findings suggest that the apparently independent effects of pH and cyclic adenosine monophosphate in the rat ileum are not universal. In tissues such as the rabbit ileum, the mechanisms of pH and cyclic adenosine monophosphate action may have biochemical or physiological pathways in common