James R. Oster

Heparin-Induced Aldosterone Suppression and Hyperkalemia

PURPOSE To review the effects of heparin and heparinoid compounds on aldosterone physiology and associated induction of hyperkalemia. MATERIALS AND METHODS A comprehensive literature search (of human and animal data) was carried out by computer and by using reference citations from primary sources. RESULTS Heparin and its congeners are predictable, potent inhibitors of aldosterone production. This inhibitory effect is specific for the zona glomerulosa; other corticosteroids are not affected. Aldosterone suppression occurs within a few days of initiation of therapy, is reversible, and is independent of either anticoagulant effect or route of administration. Decreases in aldosterone levels may occur with heparin dosages as low as 5,000 U BID. The most important, but probably not the only mechanism of aldosterone inhibition appears to involve reduction in both the number and affinity of the angiotensin-II receptors in the zona glomerulosa. Prolonged use of heparin causes marked reduction in the width of the adrenal zona glomerulosa. CONCLUSIONS Aldosterone suppression results in natriuresis and less predictably in decreased excretion of potassium. Greater than normal serum potassium levels occur in about 7% of patients, but marked hyperkalemia generally requires the presence of additional factors perturbing potassium balance (in particular, renal insufficiency, diabetes mellitus, or the use of certain medications). Heparin-induced increases in serum potassium need to be better anticipated by clinicians. Serum potassium levels should be monitored periodically in patients being given heparin for 3 or more days, and in patients at relatively high risk for hyperkalemia, the monitoring interval should probably be no greater than 4 days.

Combined Therapy with Thiazide-Type and Loop Diuretic Agents for Resistant Sodium Retention

Excerpt True resistance to a loop-type diuretic agent such as furosemide is relatively uncommon, and treatment failures can often be attributed to noncompliance either with medication or diet (1). ...

Serum Potassium Concentration in Acidemic States

It has been generally accepted that acidosis results in hyperkalemia because of shifts of potassium from the intracellular to the extracellular compartment. There is ample clinical and experimental evidence, however, to support the conclusion that uncomplicated organic acidemias do not produce hyperkalemia. In acidosis associated with mineral acids (respiratory acidosis, end-stage uremic acidosis, NH4Cl-or CaCl2-induced acidosis), acidemia per se, results in predictable increases in serum potassium concentration. In acidosis associated with nonmineral organic acids (diabetic and alcoholic acidosis, lactic acidosis, methanol and the less common forms of organic acidemias secondary to methylmalonic and isovaleric acids, and ethylene glycol, paraldehyde and salicylate intoxications), serum potassium concentration usually remains within the normal range in uncomplicated cases. A number of factors, however, may be responsible for hyperkalemia in some of these patients other than the acidemia per se. These include dehydration and renal hypoperfusion, preexisting renal disease, hypercatabolism, diabetes mellitus, hypoaldosteronism, the status of potassium balance, and therapy. The mechanism(s) of this differing effect of mineral and organic acidemias on transmembrane movement of potassium remains undefined. The prevalent hypothesis, however, favors the free penetrance of the organic anion into cells without creating a gradient for the hydrogen ions and, thus, obviating the efflux of intracellular potassium. The importance of the presence of hyperkalemia in clinical states of organic acidemias is obvious. A search for the complicating factors reviewed above should be undertaken since organic acidemias per se, should not be expected to be accompanied by elevations of serum potassium concentration. Moreover, the classical teaching that the absence of hyperkalemia during severe acidosis is indicative of severe potassium deficiency, may not be universally valid in patients with uncomplicated organic acidemias.

Renal acidosis and renal potassium handling in selective hypoaldosteronism

Abstract Selective hypoaldosteronism was demonstrated in a 60 year old black man with moderate renal insufficiency and hyperkalemic, hyperchloremic acidosis. Urine pH was appropriately low during acid loading demonstrating that the hydrogen ion gradient generating capability of the distal-most nephron was intact. In addition to impaired net acid excretion during acidosis, significant bicarbonaturia was present when serum bicarbonate concentration was normal. Desoxycorticosterone acetate (DOCA) administration improved renal potassium handling and corrected the hyperkalemia but not the acidosis or bicarbonaturia. It is concluded that the patient had idiopathic selective hypoaldosteronism and hyporeninemia and that the hyperkalemia was related to hypoaldosteronism. The patients bicarbonaturia, however, did not appear to be related to mineralocorticoid deficiency and therefore should be attributed to other factors.

A Short Duration Renal Acidification Test Using Calcium Chloride

Since the use of NH4CI – the standard agent for short duration acid loading – may be hazardous in patients with hepatic disease, the acute renal response to another acidifying agent, orally

Management of Magnesium Depletion

In addition to the well-known complexities inherent in the recognition of hypomagnesemia and/or magnesium depletion, the management of magnesium deficiency oftentimes is not straightforward and requires the understanding of several important principles. Among these is that the avoidance of ineffective undertreatment of patients with symptomatic severe depletion may require parenteral administration of quite large amounts of magnesium for several days. This point is evident in the included case example describing a patient in whom the small amounts of magnesium given initially were entirely ineffective. The use of the various protocols to provide a patient with magnesium by the parenteral route requires consideration of several factors. The purpose of this paper is to provide the practitioner with a comprehensive, clinically useful review of the oral and parenteral therapy of patients with magnesium depletion.

Pharmacokinetics of ranitidine in patients with renal failure

The pharmacokinetics of ranitidine were studied in ten patients with renal failure (creatinine clearance, 6–54 mL/min) after intravenous (IV) (50 mg) and oral doses (150 mg). After oral administration, peak plasma concentrations of 378–808 ng/mL were obtained in two to six hours. Plasma concentrations declined very slowly and concentrations greater than 100 ng/mL were obtained for 16 to 20 hours after the dose. The elimination half‐life following oral administration was 8.5 ± 2.8 hours (standard deviation [SD]), and the bioavailability of ranitidine was 43.3% ± 10.5%. After IV administration, the elimination half‐life, plasma clearance, renal clearance, and volume of distribution were 7.0 ± 1.0 hours, 170 ± 38 mL/min, 36.0 ± 25.0 mL/min, and 1.3 ± 0.4 L/kg, respectively. About 20% of the IV dose and 9% of the oral dose were recovered unchanged in urine. There was a significant correlation between the renal clearance of ranitidine and creatinine clearance (r = .74, P < .05) after IV administration. The elimination half‐life in patients with renal insufficiency is about three times greater than that reported in the literature for healthy subjects. Similarly, the plasma clearance in these patients is about 20% of that reported in healthy subjects. The results indicate that ranitidine elimination is appreciably reduced in renal failure and that an adjustment of dose in patients with renal failure is warranted. A dose of 75 mg bid may be adequate in maintaining the therapeutic plasma concentrations that are required for adequate H2‐blocking activity.

Review of the Literature: Severe Hyperphosphatemia

A patient with a markedly elevated serum phosphorus level (23.9 mg/dL) is described, followed by a brief review of severe hyperphosphatemia. Elevated serum phosphorus levels may be artifactual or true. True hyperphosphatemia is usefully subdivided according to (a) whether phosphorus is added to the extracellular fluid from a variety of exogenous or endogenous sources, or (b) whether the urinary excretion of phosphorus is reduced from either decreased glomerular filtration or increased tubular reabsorption. Severe hyperphosphatemia, defined herein as levels of 14 mg/dL or higher, is almost invariably multifactorial--usually resulting from addition of phosphorus to the extracellular fluid together with decreased phosphorus excretion. The hyperphosphatemia of the patient described herein appeared to result from a combination of dietary phosphorus supplementation, acute renal failure, acute pancreatitis, and ischemic bowel disease, complicated by lactic acidosis.

Pharmacokinetics of Ranitidine after Intravenous Administration in Hemodialysis Patients

The pharmacokinetics of ranitidine and its removal by hemodialysis were determined in 9 patients with chronic renal failure requiring hemodialysis. Ranitidine (50 mg) was administered as an intravenous bolus at the beginning of the dialysis procedure, which lasted for 4 h. The elimination half-life, plasma clearance and volume of distribution (VD area) of ranitidine in these patients were 9.0 +/- 2.6 h (mean +/- SD), 305 +/- 152 ml/min and 3.5 +/- 1.9 liters/kg, respectively. About 8% of the administered dose was removed during a single dialysis procedure. The elimination of ranitidine is appreciably reduced in these patients. These results suggest that the dose of ranitidine should be adjusted in patients with severe renal failure who are undergoing hemodialysis, and a suitable schedule for dosing such patients is suggested.

Renin-Aldosterone Responsiveness in Uncomplicated Juvenile-Type Diabetes Mellitus

The changes in plasma renin activity (PRA) and plasma aldosterone concentration (PA) in response to dietary sodium restriction and upright posture were evaluated in 7 patients with juvenile-type, insulin-dependent, uncomplicated diabetes mellitus and in 5 healthy volunteers. All patients had normal blood pressure, 24-hour urine protein excretion and endogenous creatinine clearance. Renal sodium conservation and concentrating ability were grossly normal and 5 patients so tested, had normal renal acidification. PRA and PA were normal in every subject suggesting that abnormalities of the renin-aldosterone axis are late complications of diabetes mellitus usually associated with hypertension and nephropathy or neuropathy.