Robert G. Narins

Thrombotic Microangiopathy and Renal Failure Associated with Antineoplastic Chemotherapy

Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.

Bicarbonate Therapy for Organic Acidosis: The Case for Its Continued Use

Critics of bicarbonate therapy for life-threatening lactic acidosis have argued that the treatment is not only ineffective but that it also worsens morbidity and mortality. We critically examine the six major arguments used to condemn alkali treatment. We highlight the shortcomings of frequently cited uncontrolled human studies, experiments in animals, and in-vitro chemical analyses not clearly related to the human condition. The damaging hemodynamic effects of acidemia, which centralizes blood volume while depressing myocardial contraction (thereby causing hemodynamic collapse), are discussed and offered in support of alkali therapy. We also emphasize the extreme sensitivity of patients with acidosis to further small decreases in serum bicarbonate concentration or increases in arterial PCO2. In short, we have found no basis by which to condemn the use of alkali and believe that those who have scorned its use have yet to demonstrate its danger clearly. Until that time, sodium bicarbonate should remain the standard of therapy for this life-threatening condition.

Diagnostic strategies in disorders of fluid, electrolyte and acid-base homeostasis

Our understanding of the physiology and biochemistry of acid-base and fluid-electrolyte regulations has greatly expanded in recent years. Key physiologic principles have emerged that now permit rational diagnosis and therapy of clinical disorders of serum electrolyte concentration. This paper describes diagnostic strategies based upon these principles. The etiology of the myriad factors in hyponatremia is best derived by first measuring serum tonicity and then assessing extracellular fluid volume. The hyper-, iso- and hypotonic hyponatremia are defined, and the hypotonic group is subclassified into hypo-, iso- and hyper volemic forms. The hypernatremias are best categorized by their state of volume expansion. Classification into the hypo-, hyper- and isovolemic hypernatremias simplifies their diagnosis. Metabolic acidoses are classified in terms of the anion gap. Clinical and chemical aspects of increased and normal anion gap acidoses are described. Metabolic alkaloses require a source of new bicarbonate and its retention by the kidney. The means by which new alkali is synthesized and urinary loss prevented serve to effectively classify the alkaloses. Hypokalemic syndromes are defined in terms of associated changes in body potassium. The potassium-depleted states are further subclassified by whether normotension or hypertension is associated. Hyperkalemia is produced by redistribution of cellular and extracellular potassium or by increased body potassium. Defects in the renin-angiotensin-aldosterone-distal renal tubule effector arm usually underlie hyperkalemic states, which are than classified in terms of this regulatory hormonal cascade. Classifications for disordered serum concentrations of calcium, magnesium, phosphorus and uric acid are presented. Hormonal, metabolic and renal regulatory factors form the basis for an organized approach to these disorders.

Hypokalemia and cardiovascular disease

A growing body of experimental, epidemiologic and physiologic evidence testifies to the hazards of hypokalemia and other electrolyte disorders that can complicate the chronic use of diuretic drugs in patients with cardiovascular disease. This study reviews the complex renal and extrarenal mechanisms that regulate potassium balance in normal persons with special attention to the role of stress-related hormones. Disturbances of potassium balance are common in patients taking diuretics; indeed, the potential number of people in this country at risk of diuretic-related hypokalemia approaches 9 million. The magnitude of this problem is of particular concern, because of the compelling data that link hypokalemia in such patients to electrical instability of the heart and to a fatal outcome after an acute cardiac injury. Therefore, aggressive correction of hypokalemia is warranted in patients with cardiovascular disorders.

The role of the anion gap in detecting and managing mixed metabolic acid-base disorders

Mixed metabolic-respiratory acid-base disorders may be diagnosed when the respiratory compensation for a primary metabolic acidosis or alkalosis is inappropriate or when there is inappropriate metabolic compensation for a primary respiratory disorder. The magnitude of the primary change in HCO3 concentration (in metabolic disorders) defines the limits of compensation. We emphasized the importance of the equality of the increment in the anion gap (delta AG) and the decrement in the serum bicarbonate concentration (delta HCO3) in diagnosing a simple high AG metabolic acidosis. The close relationship between these two changes in simple high AG acidoses is reviewed. When the delta HCO3 is greater than the delta AG, we suggest that a mixed high AG and hyperchloraemic acidosis is present. Other possible interpretations of these chemical changes are discussed. When the delta HCO3 is less than the delta AG, a mixed metabolic alkalosis and metabolic acidosis is likely to be present, but other additional explanations of this combination are also reviewed. Thus, guidelines are presented as a basis for the use of the delta AG and delta HCO3 for diagnosing and managing mixed metabolic acid-base disorders.

Natriuretic Effect of Calcium-Channel Blockers in Hypertensives

This double-blind, randomized, crossover trial characterizes the acute natriuretic response to calcium-channel blockers (CCB) and investigates the role of hemodynamic and hormonal factors in mediating the natriuresis. Thirteen male subjects with essential hypertension received a single oral 20-mg dose of nifedipine or 120 mg of diltiazem. Renal functional and hemodynamic measurements were performed prior to and hourly for 4 hours following medication. Subjects then received these medications for 4 weeks at which time the above studies were repeated. Urinary sodium excretion increased within 60 minutes of CCB administration and the natriuresis was sustained for 4 hours. Cumulative sodium loss during the 4 hours of study was greater with nifedipine (43 +/- 12 mmol) than with diltiazem (18 +/- 6 mmol) (P less than 0.05). Despite natriuresis, urinary potassium excretion was decreased by both agents. Even though both drugs decreased the mean arterial pressure, inulin and paraaminohippurate (PAH) clearances were not altered. Plasma aldosterone concentrations decreased, plasma catecholamine concentrations increased, whereas plasma-renin activity was unchanged with both drugs. Body weight, glomerular filtration rate (GFR), renal plasma flow, plasma-renin activity, plasma aldosterone, and catecholamine concentrations were unchanged following 4 weeks of therapy. The acute natriuretic response after 4 weeks of therapy was similar to the response noted after the first dose. This study concludes that CCB are acutely natriuretic. Despite systemic hypotension, renal hemodynamics are unaltered during CCB therapy. Suppression of aldosterone as well as direct tubular effects of these drugs may mediate the natriuresis. Chronic therapy with CCB does not modify the acute natriuretic response to these agents.

Cimetidine-Induced Acute Renal Failure

Abstract Acute, partially reversible interstitial nephritis and azotemia developed in two patients after cimetidine treatment. Renal biopsy in Patient 2 showing acute interstitial nephritis and the...

Parathyroid Carcinoma in a Chronic Hemodialysis Patient

G. Gopal Krishna, MD, Section of Nephrology, Temple University Hospital, 3401 North Broad Street, Philadelphia, PA 19140 (USA) Dear Sir, Hyperparathyroidism and parathyroid hyperplasia invariably accompany chronic renal failure [1]. However, parathyroid carcinoma rarely occurs in this setting. Indeed, our survey of the English language literature revealed only one patient developing this lesion during chronic renal failure [2]. We report a second patient manifesting such an association. A 64-year-old white female developed end-stage renal disease in 1976 secondary to idiopathic chronic interstitial nephritis. Her serum calcium at that time was 9 mg/dl (1.97 mmol/l), phosphorus 7.9 mg/dl (2.55 mmol/l) with a normal albumin concentration. Despite therapy with phosphate-binding agents, serum phosphate levels remained greater than 6 mg/dl (1.94 mmol/l). Over the next several years she developed multiple bone fractures (ribs, ankle and hip) from severe secondary hyperparathyroidism. Beginning in September 1983, serum calcium levels ranged from 10 to 11 mg/dl (2.50–2.74 mmol/l). Parathyroid hormone (PTH) levels (C-terminal assay) in February 1985 were greater than 10,000 pg/ml (normal 0–340 pg/ml). At parathyroidectomy in May 1985, the two inferior glands were hyperplastic while both superior glands revealed malignant changes with infiltration of adjacent thyroid tissue (fig. 1). Immunoperoxidase studies using monoclonal antibodies, positive for PTH and negative for thyroglobulin, confirmed that the tumor indeed originated from parathyroid tissue. No metastatic foci were identified in the seven paratracheal lymph nodes resected. As of June 1988 the patient is in a stable condition with no clinical evidence of metastatic disease. Parathyroid carcinoma is a rare cause of hyperparathyroidism, accounting for only 1–3% of patients with

Delayed onset of hemothorax: an unusual complication of subclavian access for hemodialysis.

Subclavian catheterization for acute hemodialysis has become routine in many institutions. Immediate complications of this technique are dramatic and easily recognized, whereas late complications are less common, frequently insidious and tend to be more severe. We report the delayed occurrence of a right hemothorax following two hemodialysis treatments with a left subclavian access. Pertinent literature is reviewed.

Diuretic use in critical care.

Diuretics have found wide application in critical care medicine. The use of mannitol and loop diuretics in a variety of life-threatening disorders is reviewed. The combined venodilatory and natriuretic effects of bumetanide, furosemide and ethacrynic acid relieve congestive symptoms in pulmonary edema. Although commonly administered to prevent development of acute tubular necrosis or in varying stages of evolving disease, few data are available to demonstrate the efficacy of mannitol or loop diuretics. An approach to the oliguric patient with acute tubular necrosis is described. The dangers of hyponatremia are reviewed, and the rational use of loop diuretics and hypertonic saline is outlined. The 3 loop-active agents inhibit calcium reabsorption in the thick ascending limb of Henles loop and therefore have proved useful in treating hypercalcemia. A practical approach to the diuretic-saline treatment of severe hypercalcemia is outlined. The kaliuretic effect of loop diuretics can be used to advantage in patients with acute or chronic hyperkalemia. A guide to such therapy is described.