Faculty Bibliography

Sucralfate is used in the treatment and prophylaxis of peptic ulcer disease. One possible mechanism of action is the binding of bile acids. Because the absorption of dietary fat and cholesterol is dependent on the presence of bile acids in the small intestines, sucralfate therapy may produce changes in serum lipoprotein composition qualitatively similar to bile acid sequestrants, such as cholestyramine, which reduce serum cholesterol levels. Although changes in total serum cholesterol have not been reported in sucralfate efficacy studies, the effect of sucralfate on serum lipoprotein composition has not been specifically addressed. The purpose of this study was to prospectively examine the effect of sucralfate on serum lipids and lipoproteins in normal volunteers. Eight healthy volunteers (six men, two women) were recruited for this 10-week study. Drugs known to affect cholesterol levels were not permitted before or during the study. Diet composition during the study period was unaltered from before the study. Subjects took 1 g sucralfate orally 1 hour before meals and at bedtime (four times a day) for 8 weeks, followed by a 2-week washout period. Fasting blood samples were obtained at baseline and weekly, and were analyzed for serum total and HDL cholesterol and for triglycerides. Levels of LDL cholesterol were estimated. After eight weeks of sucralfate, HDL cholesterol increased from baseline by 2.5 mg/dL (6.6%, from 37.6 +/- 9.5 to 40.1 +/- 8.69 mg/dL), and LDL cholesterol decreased by 7.6 mg/dL (6.4%, from 134 +/- 28.1 to 125.4 +/- 34.1). Total cholesterol decreased by 3.5 mg/dL (1.8%, from 192.9 +/- 34.3 to 189.4 +/- 37.2 mg/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

To test our hypothesis that a circulating factor(s) may be causing the renal salt and urate wasting in patients (pts) with intracranial diseases, we exposed rats to the plasma of these patients and studied sodium and lithium transport. We selected 21 neurosurgical pts, 13 of whom had increased fractional excretion (FE) of urate, and 14 age and sex-matched controls. Plasma from pts and controls were injected IP (0.5 mL) and infused, 0.2 ml prime and 1.8 mL at 0.01 mL/min, to Sprague Dawley rats anesthetized with Inactin. Renal transport of sodium (Na), lithium (Li) and potassium (K) was determined. There were higher mean +/- SEM for FENa, 0.59 +/- 0.07% vs 0.29 +/- 0.05%, P < 0.01, FELi, 36.6 +/- 1.9% vs 24.0 +/- 1.6%, P < 0.001 and K excretion rates, 1.69 +/- 0.13 vs 1.31 +/- 0.09 mumol/min, p < 0.02, in rats infused with plasma of pts as compared to controls, respectively. FENa decreased with increasing dilution of plasma of 2 pts with ICD. There was no difference in mean weight of rats, blood pressure, urine flow rate or insulin clearance between pts and controls. These data suggest that pts with ICD have a plasma factor(s) which decreases net Na, Li and K reabsorption.

Hyperkalemia is a commonly encountered problem in dialysis patients with end-stage renal disease. In this study we evaluated the effect of mineralocorticoid therapy (MCT; fludrocortisone 0.1-0.3 mg per os daily) on serum potassium of hyperkalemic end-stage renal disease patients. Consecutive monthly clinical and biochemical profiles 3-6 months before and after MCT were compared. Twenty-one patients with a mean age (+/- SE) of 54 +/- 4 years (11 male and 10 female) were studied. Two patients were dropped from this study because they required a change in prescription of dialysis after starting MCT. Mean serum potassium levels significantly fell (p < 0.001) during the post-MCT period (4.9 +/- 0.1 mEq/l) compared with potassium levels during the pre-MCT (5.6 +/- 0.1 mEq/l) period. All patients except 1 showed a reduction in serum potassium levels after MCT. Pre- and post-MCT values were not different for body weight, mean blood pressure, blood urea nitrogen, serum glutamic-oxaloacetic transaminase, lactate dehydrogenase, sodium, chloride, bicarbonate, creatinine and albumin. Since the majority of the patients were anuric (n = 15), a decrease in serum potassium values in the post-MCT period was not due to loss of potassium in the urine. MCT appears to decrease serum potassium values in patients with end-stage renal disease by extrarenal mechanisms. We conclude that MCT can be used safely to lower serum potassium in patients with end-stage renal disease.

Based on our demonstration of a high incidence of hypouricemia, tubular urate transport abnormality, and cerebral atrophy in patients with acquired immunodeficiency syndrome (AIDS), we performed prospective renal clearance studies in 29 consecutive neurosurgical patients with intracranial diseases of multiple etiologies to test our hypothesis that patients with intracranial disorders had defective tubular urate transport. Similar studies were performed in 21 age-matched controls. None of the subjects had serum creatinine greater than 123.8 mumol/L (1.4 mg/dL), sickle cell or liver diseases, or received intravenous fluid or uricosuric drugs at the time of study. Seven patients had no surgical procedures, 12 were studied after a neurosurgical procedure, and 10 had preoperative and postoperative studies. Ten had more than one postoperative study. Twelve had 24-hour urine collections. We found that 18 of 29 patients had elevated fractional excretion (FE) of urate greater than 10%. There was no difference in preoperative and postoperative FE urate by nonpaired t test for all patients and by paired t test in the 10 patients who had preoperative and postoperative studies performed. Seven patients had hypouricemia, defined as serum urate less than or equal to 0.18 mmol/L (3 mg/dL). Only one had hyponatremia (serum sodium less than 130 mmol/L). Urate excretion averaged 3.6 +/- 0.32 mmol (603 +/- 52.7 mg)/24 h, suggesting that the hypouricemia was not due to decreased urate production. None of the medications or surgical procedures could be considered to have caused the urate transport abnormality, nor was it associated with any specific intracranial location or type of disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypouricemia in coexistence with hyponatremia often differentiates the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) from most other causes of hyponatremia. We report clearance studies in 5 cases of hyponatremia and hypouricemia that were not due to SIADH. One had metastatic pancreatic carcinoma with ascites, edema, hypoalbuminemia and hypophosphatemia. Two had adenocarcinoma of the lung with metastasis to the brain in 1, 1 had disseminated cryptococcus and 1 had Hodgkin's disease. None received radiation or known nephrotoxins at least 4 months prior to study. None had serum creatinine greater than 106.1 mumol/l (1.2 mg/dl). Two had postural hypotension and hyponatremia that responded to saline therapy. Fluid restriction corrected the hyponatremia in all patients, but the hypouricemia, high fractional excretion (FE) of urate, and high urine sodium concentration persisted. In 2 patients studied, ADH was appropriately suppressed after volume repletion but there was a defect in free water clearance due to high renal solute excretion. In contrast to patients with SIADH who correct their defect in renal urate transport with correction of hyponatremia by water restriction, our patients appear to have a persistent renal urate transport defect and abnormality in sodium conservation. Elevated FE urate of greater than 10% after correction of hyponatremia can thus differentiate these patients from SIADH. The diametrically opposing goals of fluid therapy emphasize the importance of differentiating one group from the other.

Clinical evaluations of hypouricemia in patients with the acquired immunodeficiency syndrome (AIDS) have shown that it is a common disorder resulting from defective renal handling of uric acid. We prospectively studied renal urate handling in 23 patients and reviewed the records of 73 consecutive patients with AIDS or AIDS-related complex (ARC), who were seen in our AIDS clinic between March 1985 and April 1988, to determine the incidence, significance, and, when possible, the cause of hypouricemia. Hypouricemia was defined as serum urate less than or equal to 0.18 mmol/L (3 mg/dL). Renal clearance studies were performed in 23 patients, 10 hypouricemic and 13 nonhypouricemic. Eight patients (six with hypouricemia) underwent central venous pressure (CVP) monitoring, which was performed for clinical signs and symptoms of extracellular volume depletion. Fourteen (eight with hypouricemia) had daily urine urate measured. Hypouricemia was found in 21 (21.9%) of 96 patients. It was more common in females and intravenous (IV) drug abusers, and was associated with more opportunistic illnesses, particularly mycobacterium avium intracellulare (MAI) and cytomegalovirus (CMV) infections. Hypouricemia occurred in three patients with ARC and 18 patients with AIDS and was associated with cerebral atrophy in all 12 hypouricemic and 14 of 28 nonhypouricemic patients who had cranial computed tomography (CT) scans. During a comparable follow-up period, 71.4% of the hypouricemic as compared with 38.7% of nonhypouricemic patients died. Eleven developed hypouricemia as outpatients. Fractional excretion of uric acid (FEua) was elevated in the eight patients with CVP less than 1 cm of water, and in 10 of 10 with and nine of 13 without hypouricemia, despite CVP less than 1 cm water in eight.(ABSTRACT TRUNCATED AT 250 WORDS)

We performed prospective and retrospective studies of 96 consecutive patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) to determine the incidence, pathogenesis, and clinical significance of hyponatremia, defined as serum sodium levels less than or equal to 130 mmol/L on more than one occasion. Thirty (31.3%), six with ARC and 24 with AIDS, had hyponatremia, and it developed in 20 as outpatients. Age, gender, duration of illness, and weight loss did not differ between groups. The hyponatremic patient had more opportunistic illnesses, including Pneumocystis carinii pneumonia and cytomegalovirus infections, and had a mortality of 70% as compared to 36.4% of the patients without hyponatremia. The probability of 50% survival after diagnosis of human immunodeficiency virus (HIV) infection in the hyponatremic group was 11.5 months, as compared to 39 months for those without hyponatremia, p less than 0.001. The probability of 50% survival after development of hyponatremia was 4.5 months and the median length of time to development of hyponatremia was 12.5 months after diagnosis of HIV infection. Eighty-eight percent had hypovolemia and 12% normovolemia. Seventeen of 21 with hypovolemia had no evident source of fluid loss. Two had Addison's disease, and 15 had unexpectedly high urine sodium concentration without evidence of renal or adrenal insufficiency. Hyponatremia occurs commonly in ambulatory patients with ARC or AIDS, appears in patients with higher mortality and morbidity, and does not represent a terminal event. Most patients had hypovolemia and unexpectedly high urine sodium concentration, suggesting defective renal sodium conservation.