Faculty Bibliography

In 1988, a consensus conference was held at the National Institutes of Health to develop guidelines for prevention and treatment of kidney stones. The recommendations regarding the medical evaluation of stone formers and treatment directed at stone prevention are reviewed. The relevance of those 1988 guidelines is evaluated for continued pertinence. Most of the recommendations promulgated in the consensus statement remain useful today. One significant change is the current consensus that dietary calcium restriction is no longer considered appropriate therapy, as there is no evidence that it actually prevents stones and has as a consequence the potential to worsen bone demineralization

PURPOSE: An increased risk of nephrolithiasis has been associated with the ingestion of grapefruit juice in epidemiological studies. To our knowledge the basis of this effect of grapefruit juice has not been studied previously. We studied the effect of grapefruit juice consumption on urinary chemistry and measures of lithogenicity. MATERIALS AND METHODS: Ten healthy men and women between ages of 25 and 40 years participated. Each subject drank 240 ml. of tap water at least 3 times daily for 7 days during the control period. This period was followed by a second 7 days experimental period during which they drank 240 ml. of grapefruit juice 3 times daily. In each 7-day period urine was collected for 24 hours during the last 3 days. Urine chemical analysis was performed, supersaturations of calcium oxalate, calcium phosphate and uric acid were calculated and urinary lithogenicity was measured. RESULTS: Urine volume and creatinine excretion were the same during the control and experimental periods. Grapefruit juice ingestion was associated with an increase in mean oxalate excretion plus or minus standard deviation of 41.1 +/- 9.2 to 51.9 +/- 12.0 mg. per 24 hours (p = 0.001) and in mean citrate excretion of 504.8 +/- 226.5 to 591.4 +/- 220.0 mg. per 24 hours (p = 0.01). There was no net change in the supersaturation or upper limit of metastability of calcium oxalate, calcium phosphate or uric acid. Crystal aggregation and growth inhibition by urinary macromolecules was not affected by grapefruit juice ingestion. CONCLUSIONS: Offsetting changes in urine chemistry caused by the ingestion of grapefruit juice led to no net change in calculated supersaturation. No changes in lithogenicity were demonstrated. The results do not demonstrate an effect of grapefruit juice for increasing lithogenicity. The basis of the observations of epidemiological studies remain unexplained

BACKGROUND: Iron deficiency remains a common cause of hyporesponsiveness to epoetin in hemodialysis patients. However, considerable controversy exists regarding the best strategies for diagnosis and treatment. METHODS: As part of a multicenter randomized clinical trial of intravenous versus subcutaneous administration of epoetin, we made monthly determinations of serum iron, total iron binding capacity, percentage transferrin saturation, and serum ferritin. If a patient had serum ferritin <100 ng/mL or the combination of serum ferritin <400 ng/mL and a transferrin saturation <20%, he/she received parenteral iron, given as iron dextran 100 mg at ten consecutive dialysis sessions. We analyzed parenteral iron use during the trial, the effect of its administration on iron indices and epoetin dose, and the ability of the iron indices to predict a reduction in epoetin dose in response to parenteral iron administration. RESULTS: Eighty-seven percent of the 208 patients required parenteral iron to maintain adequate iron stores at an average dose of 1516 mg over 41.7 weeks, or 36 mg/week. Only two of 180 patients experienced serious reactions to intravenous iron administration. Two thirds of the patients receiving parenteral iron had a decrease in their epoetin requirement of at least 30 U/kg/week compared with 29% of patients who did not receive iron (P = 0.004). The average dose decrease 12 weeks after initiating iron therapy was 1763 U/week. A serum ferritin <200 ng/mL had the best positive predictive value (76%) for predicting a response to parenteral iron administration, but it still had limited clinical utility. CONCLUSIONS: Iron deficiency commonly develops during epoetin therapy, and parenteral iron administration may result in a clinically significant reduction in epoetin dose. The use of transferrin saturation or serum ferritin as an indicator for parenteral iron administration has limited utility

PURPOSE: We measured the concentration and solubility of cystine in urine from patients with cystinuria or calcium stones and from normal subjects to determine whether urine cystine supersaturation can be calculated from a standard nomogram of solubility versus pH or needs to be measured directly. We also evaluated whether increasing pH of the 24-hour collection recovered enough crystallized cystine to increase cystine supersaturation. MATERIALS AND METHODS: Cystine concentration, pH and usual stone risk factors were measured on 50 ml. aliquots of 24-hour collections from 24 patients with cystinuria, 22 calcium stone formers and 15 normal subjects. After 48 hours of incubation with sodium bicarbonate, a second aliquot was taken from the 24-hour collection for cystine concentration. The original urine at its ambient pH was incubated with an excess of cystine crystals for 24, 48, 72 or 96 hours at 37C to determine solubility and kinetics of equilibration. RESULTS: Cystine solubility varied so widely at any pH range that no predictive nomogram could be relied on for calculating supersaturation. Addition of sodium bicarbonate to the 24-hour urine significantly increased cystine concentration. Urine from stone formers had higher cystine solubility than urine from normal subjects. CONCLUSIONS: Clinical management of cystinuria can be improved by direct measurement of cystine solubility because it varies widely at any given pH. Increasing 24-hour collection pH with sodium bicarbonate additionally improves accuracy of supersaturation measurement by recovering crystallized cystine

BACKGROUND:Although the methods for the appropriate management of patients with hyperkalemia are well established, no criteria for hospital admission of patients with this common electrolyte disorder have been promulgated. OBJECTIVES/OBJECTIVE:To examine the current practices regarding hospitalization of patients with hyperkalemia and to consider appropriate criteria for admission. PATIENTS AND METHODS/METHODS:We evaluated a consecutive series of patients hospitalized for hyperkalemia and excluded patients who developed hyperkalemia after admission. For comparison, we selected a series of patients with a similar degree of hyperkalemia who were treated as outpatients. Hyperkalemia was classified as minimal, moderate, or severe. The causes of hyperkalemia were identified, and the therapeutic maneuvers used were ascertained. Although the study did not have the power to determine the relative safety of the 2 therapeutic approaches, we compared the outcomes of the 2 groups of patients. RESULTS:The inpatient group consisted of 11 patients who were admitted for the treatment of hyperkalemia, and we identified 12 patients who received outpatient therapy for hyperkalemia. The patients in the 2 treatment groups were similar with respect to age and the values of serum urea nitrogen, creatinine, and potassium prior to the identification of hyperkalemia. The mean +/-SD potassium concentrations at baseline were 5.4+/-0.7 mmol/L in the inpatients and 5.5+/-0.5 mmol/L in the outpatients. The mean +/-SD potassium concentration in the inpatients was 6.7+/-0.8 mmol/L at the time of hospital admission, compared with 6.7+/-0.5 mmol/L in the outpatients at the time that hyperkalemia occurred. Similar proportions of both groups (6 of 11 inpatients and 7 of 12 outpatients) had moderate or severe hyperkalemia. CONCLUSIONS:Patients admitted to the hospital were clinically indistinguishable from patients treated as outpatients. The justification for the decision to admit patients to the hospital or to treat them as outpatients was often not evident. We suggest criteria for hospitalization, which include severe hyperkalemia (> or =8.0 mmol/L, with changes other than peaked T waves on the electrocardiogram), acute worsening of renal function, and supervening medical problems.

To determine the role of carbonic anhydrase (CA) in colonic electrolyte transport, we studied Car-2(0) mice, mutants deficient in cytosolic CA II. Ion fluxes were measured under short-circuit conditions in an Ussing chamber. CA was analyzed by assay and Western blots. In Car-2(0) mouse colonic mucosa, total CA activity was reduced 80% and cytosolic CA I and membrane-bound CA IV activities were not increased. Western blots confirmed the absence of CA II in Car-2(0) mice. Normal mouse distal colon exhibited net Na(+) and Cl(-) absorption, a serosa-positive PD, and was specifically sensitive to pH. Decrease in pH stimulated active Na(+) and Cl(-) absorption whether it was caused by increasing solution PCO(2), reducing HCO(-)(3) concentration, or reducing pH in CO(2)/HCO(-)(3)-free HEPES-Ringer solution. Membrane-permeant methazolamide, but not impermeant benzolamide, at 0.1 mM prevented the effects of pH. Car-2(0) mice exhibited similar basal transport rates and responses to pH and CA inhibitors. We conclude that basal and pH-stimulated colonic electrolyte absorption in mice requires CA I. CA II and IV may have accessory roles

The first episode of nephrolithiasis provides an opportunity to advise patients about measures for preventing future stones. Low fluid intake and excessive intake of protein, salt and oxalate are important modifiable risk factors for kidney stones. Calcium restriction is not useful and may potentiate osteoporosis. Diseases such as hyperparathyroidism, sarcoidosis and renal tubular acidosis should be considered in patients with nephrolithiasis. A 24-hour urine collection with measurement of the important analytes is usually reserved for use in patients with recurrent stone formation. In these patients, the major urinary risk factors include hypercalciuria, hyperoxaluria, hypocitraturia and hyperuricosuria. Effective preventive and treatment measures include thiazide therapy to lower the urinary calcium level, citrate supplementation to increase the urinary citrate level and, sometimes, allopurinol therapy to lower uric acid excretion. Uric acid stones are most often treated with citrate supplementation. Data now support the cost-effectiveness of evaluation and treatment of patients with recurrent stones

PURPOSE: In general high urine supersaturation with respect to calcium oxalate, calcium phosphate or uric acid is associated with that phase in stones. We explore the exceptions when supersaturation is high and a corresponding solid phase is absent (type 1), and when the solid phase is present but supersaturation is absent or low (type 2). MATERIALS AND METHODS: Urine supersaturation values for calcium oxalate, calcium phosphate and uric acid, and other accepted stone risk factors were measured in 538 patients at a research clinic and 178 at stone prevention sites in a network served by a single laboratory. RESULTS: Of the patients 14% lacked high supersaturation for the main stone constituent (type 2 structural divergence) because of high urine volume and low calcium excretion, perhaps from changes in diet and fluid intake prompted by stones. Higher calcium excretion and low urine volume caused type 1 divergences, which posed no clinical concern. CONCLUSIONS: Type 1 divergence appears to represent a condition of low urine volume which raises supersaturation in general. Almost all of these patients are calcium oxalate stone formers with the expected high supersaturation with calcium oxalate as well as high uric acid and calcium phosphate supersaturations without either phase in stones. Type 2 divergence appears to represent an increase in urine volume and decrease in urine calcium excretion between stone formation and urine testing