Alan Wasserstein

Disorders of calcium and magnesium homeostasis

The components of calcium and magnesium balance and the factors responsible for the maintenance of the serum concentration of these cations are reviewed. Within this framework, the causes and treatment of disturbances of the serum concentration are discussed. Hypercalcemia is usually a reflection of increased bone resorption and/or gut absorption with the kidney playing a secondary role. Hypocalcemia is usually due to either a disturbance in the parathyroid hormone-adenylate cyclase system or a disturbance in vitamin D metabolism. As vitamin D is required for expression of the action of PTH at bone and as PTH is a prime regulator of vitamin D metabolism, the absence of either component results in important disturbances in calcium balance. In contrast to calcium homeostasis, the kidney plays a major role in the determination and regulation of serum magnesium. The major causes of hypermagnesemia therefore are associated with loss of renal function, and hypomagnesemia is frequently due to renal magnesium wasting.

Sleep Apnea in Hemodialysis Patients: The Lack of Testosterone Effect on Its Pathogenesis

After the discovery of sleep apnea in 2 patients receiving chronic maintenance hemodialysis, we decided to survey all 29 male patients undergoing outpatient dialysis for symptoms suggestive of sleep apnea. 12 of 29 (41%) had positive clinical histories. 8 of these patients consented to undergo all-night polysomnography. 6 were found to have sleep apnea which was primarily obstructive in type. Recent information has implicated testosterone administration in the development of obstructive sleep apnea. Therefore, polysomnography was performed in 5 of the patients both on and off weekly testosterone injections which they were receiving to stimulate erythropoiesis. There was no change in sleep complaints or a decrease in the number of apneas and hypopneas off therapy. Sleep apnea should be considered in symptomatic male dialysis patients. Its causation is presently unknown but it does not appear to be solely related to the administration of testosterone.

Effects of oxcarbazepine on sodium concentration and water handling

Oxcarbazepine, a keto‐analogue of carbamazepine, was recently approved in the United States for the treatment of seizures of partial onset. Some patients treated with oxcarbazepine showed the development of hyponatremia, which in most instances was asymptomatic. Understanding the mechanisms by which oxcarbazepine can lead to a reduction of serum sodium levels could have therapeutic implications for the few patients in whom symptomatic hyponatremia develops. In this study, we evaluated sodium and water handling in patients with epilepsy and in healthy subjects titrated over 3 weeks to a maximum daily oxcarbazepine dose of 2,400mg. All subjects were evaluated in a hospital setting after an overnight fast and after an acute water‐load test performed before oxcarbazepine exposure and after maintenance on the medication for 3 weeks. Before oxcarbazepine exposure, the percentage of water load excreted was normal as both groups excreted more than 80% of the administered water load. After the intake of oxcarbazepine, the water load resulted in a reduction of the serum sodium and free water clearance without a concomitant increase in the arginine vasopressin serum levels. Most subjects in both groups failed to excrete 80% or more of the water load, suggesting that the effect of oxcarbazepine is physiological. We found that, after the water load, serum sodium and free water clearance were diminished in both groups without a concomitant increase in the arginine vasopressin serum levels. These findings indicate that oxcarbazepine‐induced hyponatremia is not attributable to the syndrome of inappropriate secretion of antidiuretic hormone. Possible mechanisms include a direct effect of oxcarbazepine on the renal collecting tubules or an enhancement of their responsiveness to circulating antidiuretic hormone.

Physical Examination versus Normalized Pressure Ratio for Predicting Outcomes of Hemodialysis Access Interventions

PURPOSE The ratio of intragraft venous limb pressure (VLP) to systemic pressure (S) has been proposed to help determine the endpoint of hemodialysis access interventions. It was hypothesized that physical examination of the access could be used in the same way and these techniques were compared as predictors of outcome. PATIENTS AND METHODS With use of a quality-assurance database, records from 117 hemodialysis access interventions were retrospectively reviewed. Only interventions in grafts were included. The database included physical examination (to establish thrill, thrill with slight pulsatility [TSP], pulse with slight thrill [PST], and pulse) at three locations along the graft (proximal, midportion, and distal), normalized pressure ratio calculated with S from a blood pressure cuff (S(cuff)) and S within the graft with outflow occluded (S(direct)), graft configuration and location, indication, operator, and time to next intervention (outcome of primary patency). Only procedures with complete follow-up data were included in the analysis (n = 97; declotting, n = 51; prophylactic percutaneous transluminal angioplasty [PTA], n = 46). Statistical analysis was performed with use of Cox proportional-hazards regression. RESULTS Graft configuration, location, side, VLP, S(direct), and S(cuff) did not affect outcomes. An operator effect was noted for two physicians and was adjusted for in all analyses. Pressure ratios were weak predictors of outcome (VLP/S(direct), P =.07; VLP/S(cuff), P =.08) and suggested that patency increased with increasing pressure ratio, contrary to earlier studies. Procedure type predicted outcome (declotting, median patency of 50 days; PTA, median patency of 105 days; P =.01). Thrill at distal physical examination was predictive of outcome (P =.04) and even more so when thrill and TSP combined were compared with PST and pulse combined (P =.03). Similar but less-pronounced effects were seen at midportion and proximal physical examinations. CONCLUSIONS The presence of a thrill or slightly pulsatile thrill at the distal (venous) end of a dialysis graft is the best predictor of outcome after percutaneous intervention. Based on the present study, the authors believe that physical examination of dialysis access should supplant pressure measurements as an endpoint of intervention and should serve as an essential component of quality assurance of access interventions.

Effectiveness of a Two-Part Educational Intervention to Improve Hypertension Control: A Cluster-Randomized Trial

Study Objective. To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control.

Nephrolithiasis: Acute management and prevention

The primary care physician has a responsibility not only to recognize and treat acute stone passage but to ensure that the patient with recurrent stones has metabolic evaluation and appropriate preventive care. Renal colic is typically severe, radiates to the groin, is associated with hematuria, and may cause ileus. About 90% of stones that cause renal colic pass spontaneously. The patient with acute renal colic should be treated with fluids and analgesics and should strain the urine to recover stone for analysis. Highgrade obstruction or failure of oral analgesics to relieve pain may require hospitalization; a urinary tract infection in the setting of an obstruction is a urologic emergency requiring immediate drainage, usually with a ureteral stent. Several approaches are available when stones do not pass spontaneously, including extracorporeal shock wave lithotripsy, percutaneous lithotripsy, and ureteroscopic laser lithotripsy. Calcium stone disease has a lifetime prevalence of 10% in men and causes significant morbidity. Renal failure is unusual. Stone types include calcium oxalate, uric acid, struvite, and cystine. Stone analysis is particularly important when a noncalcareous constituent is identified. The majority of patients with nephrolithiasis will have recurrence, so prevention is a high priority. High fluid intake is a mainstay of prevention. Metabolic evaluation will indicate other appropriate preventive measures, which may include dietary salt and protein restriction, and use of thiazide diuretics, neutral phosphate, potassium citrate, allopurinol, and magnesium salts. Dietary calcium restriction may worsen oxaluria and negative calcium balance (osteoporosis).

Pulmonary Hypertension Among End-Stage Renal Failure Patients Following Hemodialysis Access Thrombectomy

Purpose: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy.Methods: A retrospective case-control study was performed. Cases (n = 88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n = 100, group 1), and controls with ESRD but no prior thrombectomy procedures (n = 117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression.Results: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n = 23), 10% (n = 9) and 16% (n = 14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p = 0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n = 49), 10% (n = 12) and 4% (n = 5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR = 1.5), although this failed to reach statistical significance (p = 0.14).Conclusion: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial hypertension. Patients with ESRD are more likely to have pulmonary hypertension.

Reprocessing of Hemodialyzers: A Critical Appraisal

The reprocessing of hemodialysis equipment was originally developed to conserve scarce resources and to reduce the time necessary to construct early dialyzers. Although most dialyzers in current use are marketed as disposable items, the majority of dialysis facilities in the United States reprocess these devices and use them multiple times on the same patient. Recent studies have shown that certain reprocessing techniques confer improved biological properties on dialyzers compared with new membranes as prepared by manufacturers. Several studies have suggested that these biological properties may lead to improved clinical outcomes. However, critics of dialyzer reprocessing argue that it may expose patients to risks that produce increased morbidity and mortality. This article critically reviews the available scientific information regarding reprocessing hemodialyzers.

L-Carnitine Supplementation in Dialysis: Treatment in Quest of Disease

L‐Carnitine (LC) administration has been recommended for specific indications in dialysis patients, including epoetin‐resistant anemia, intradialytic hypotension, cardiomyopathy, fatigue, muscle weakness, and exercise performance; it may ameliorate insulin resistance, inflammation, and protein wasting. Use of LC for anemia and intradialytic hypotension has been approved for reimbursement by the Centers for Medicare and Medicaid Services. Yet, the data to support these recommendations are inadequate and have not been bolstered over several decades. LC administration continues to appeal to nephrologists because its use in dialysis patients has an attractive rationale, it addresses problems that persist despite dialysis, it is safe, and the existing literature does not refute its use. Nevertheless, definitive trials to justify LC administration have not been conducted and are increasingly unlikely to be funded. In an era of shrinking resources and bundling of dialysis services, the use of LC in dialysis patients will, appropriately, diminish.

Toward a Romantic Science: The Work of Oliver Sacks

Excerpt Medicine is the oldest of the arts and the oldest of the sciences, writes neurologist Oliver Sacks. But the growth of the science has threatened the art. There is a subtle opposition betwee...