Faculty Bibliography

PURPOSE: We determined whether a network of 7 comprehensive kidney stone treatment centers supported by specialized stone management software and laboratory resources could achieve reductions in urine supersaturation comparable to those in a single research clinic devoted to metabolic stone prevention. MATERIALS AND METHODS: Supersaturation values for calcium oxalate, calcium phosphate and uric acid in 24-hour urine samples were calculated from a set of kidney stone risk factor measurements made at a central laboratory site for the network and research laboratory for the clinic. Individual results and group outcomes were presented to each center in time sequential table graphics. The decrease in supersaturation with treatment was compared in the network and clinic using analysis of variance. RESULTS: Supersaturation was effectively reduced in the network and clinic, and the reduction was proportional to the initial supersaturation value and increase in urine volume. The clinic achieved a greater supersaturation reduction, higher fraction of patient followup and greater increase in urine volume but the treatment effects in the network were, nevertheless, substantial and significant. CONCLUSIONS: Given proper software and laboratory support, a network of treatment centers can rival but not quite match results in a dedicated metabolic stone research and prevention clinic. Therefore, large scale stone prevention in a network system appears feasible and effective

BACKGROUND: Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level. METHODS: In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration. RESULTS: For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild. CONCLUSIONS: In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration

Purpose: We determined the validity of urine supersaturation assessed from 2, 24-hour urine collections from outpatients eating uncontrolled diets and receiving care at a network of treatment sites that uses a central laboratory. We compared supersaturation to stone composition to determine whether supersaturation values correlate with composition. Materials and Methods: Two 24-hour urine samples collected from 183 patients at 6 treatment sites were shipped to a single central laboratory. Complexations and crystallizations in vitro from aging during the transport step were interrupted by pH change in acid and alkaline directions. Relevant analytes were measured, and supersaturation was calculated for calcium oxalate calcium phosphate as brushite and uric acid. Stone analysis was done at various laboratories. Results: Urine supersaturation values correlated well with stone composition. Higher calcium phosphate and uric acid supersaturation was noted when stones contained higher amounts of calcium phosphate and any uric acid, respectively. In a validation study values of relevant urine materials were unchanged after 48 hours of aging. Conclusions: Despite the need for sample transport, resulting in the inevitable aging of samples, and variations in diet and details of sample collection, supersaturation values measured in only 2, 24-hour urine collections accurately reflected stone composition. This finding indicates that supersaturation values are reasonably stable in most patients during the months to years required for stones to form. In addition, samples collected in standard practice settings and sent to a central laboratory may accurately reflect these supersaturation values

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