Francesco Del Greco

Hemodynamic Studies in Chronic Uremia

Hemodynamic functions and blood volume were observed in patients with chronic uremia. Thirty-one patients had clinical features of circulatory congestion and 37 did not. The degree of anemia and acidosis was comparable in both groups. However, creatinine clearance was significantly lower in patients with circulatory congestion. Both groups of patients had greater blood pressure, heart rate, plasma volume, and total peripheral resistance than normal. Resting cardiac output was abnormally decreased in 19% of the patients with circulatory congestion and in 14% of patients without features of circulatory congestion. There was no correlation between blood volume and blood pressure. Intravenous digitalization of seven of the patients with circulatory congestion produced clinical and hemodynamic improvement in only two. Hemodialysis effected an increase in cardiac output and a decrease in total peripheral resistance in six patients with congestion. In seven patients without circulatory congestion after dialysis there was a fall in plasma and blood volume, associated with a slight decrease in cardiac output. It is suggested that congestion of the circulation in chronic uremia results from a variety of hemodynamic, myocardial, and metabolic alterations, rather than from any single abnormality.

N-Acetylprocainamide pharmacokinetics in functionally anephric patients before and after perturbation by hemodialysis.

NAPA pharmacokinetics were studied in 6 functionally anephric patients. Distribution and nonrenal elimination of this drug were found to be the same as in individuals with normal renal function but renal clearance was reduced, resulting in a mean elimination t½ of 41.9 hr (6.2 hr in normal subjects). Renal clearance of NAPA correlated well with ClCr. Dialysis removed NAPA from both red blood cells and plasma and increased ClTapproximately fourfold. Dialysis itself resulted in a 77% reduction in Cls that limited the total amount of NAPA removed by this procedure. This reduction in Cls was sustained for at least 3 hr after dialysis and attenuated rebound in plasma NAPA concentrations.

Hemodialysis for severe procainamide toxicity: clinical and pharmacokinetic observations.

A 67‐yr‐old woman who ingested approximately 7 gm procainamide developed severe hypotension, renal insufficiency, and life‐threatening cardiac toxicity, Hemodialysis doubled the rate of procainamide elimination and increased fourfold the clearance of NA PA , the N‐acetylated metabolite of procainamide. Observations of procainamide and N‐acetylprocainamide (NAPA) plasma levels during the patients recovery suggest that lethargy and profound hypotension can be expected when these levels total 60 µg/ml and that severe cardiac toxicity should be anticipated with levels totaling 42 µg/ml or more. Hemodialysis also permitted investigation of the effects of hypotension on the pharmacokinetics of these compounds. The apparent volume of procainamide distribution was reduced from a normal value of 2 L/kg to 0.76 L/kg, and that of NAPA from 1.4 L/kg to 0.63 L/kg. The elimination t½ of procainamide was prolongedfrom the normal of 3 hr to 10.5 hr, and that of NAPA from 6 to 35.9 hr. Procainamide absorption was also slowed in this clinical setting, causing procainamide plasma levels to continue rising for some time after toxicity was first recognized.

Renal disease associated with toxic epidermal necrolysis (Lyell's disease)

Abstract A woman with toxic epidermal necrolysis and severe renal involvement is described. Serial renal biopsies were compatible with membranoproliferative glomerulonephritis. The pathophysiology and renal manifestations of toxic epidermal necrolysis are reviewed, and several previously unreported cases of toxic epidermal necrolysis with renal involvement are discussed. In several cases, changes were consistent with membranous or membranoproliferative glomerulonephritis, lending support to the concept of toxic epidermal necrolysis as an immunologic disease.

Kidney Function after Renal Revascularization for Hypertension

Kidney function was evaluated in 53 patients with renal arterial hypertension before and after renal revascularization and was correlated with changes in blood pressure. Data were derived from an analysis of personal observations and of findings reported by others.Revascularization produced a significant decrease in blood urea nitrogen and serum creatinine in 13 azotemic patients. It did not significantly affect glomerular filtration rate when normal in 20 patients, but caused a rise in renal blood flow in three patients. Improvement in renal function was more closely correlated with preoperative functional status than with cure of hypertension.Glomerular filtration rate and renal blood flow increased significantly in the revascularized kidney, but decreased in the contralateral kidney. Urine flow and sodium concentration in the revascularized kidney rose to levels equal to, or greater than, those in the contralateral kidney. The preoperative disparity in urine osmolality between kidneys was narrowed, whereas the concentration of nonresorbable urine solute became equal to, or lower than, that of its mate postoperatively. In most cases, the Howard test reverted to negative. The tubular rejection fraction ratio of sodium became normal or suggested contralateral renal arterial disease. The only functional differences between patients whose hypertension was cured and those whose blood pressure failed to respond to revascularization related to glomerular filtration rate and the Howard test.Impairment of function of the contralateral uninvolved kidney was rarely observed after surgery. The revascularized kidney frequently exhibited excessive natriuresis and diuresis, independent of changes in systemic blood pressure or glomerular filtration rate.

Dialysis in Treatment of Neomycin Overdosage

Abstract A 39-year-old woman developed severe nephrotoxicity secondary to neomycin overdosage. A moderately high dialysance of neomycin was demonstrated. Hemodialysis is an effective method of ther...

Pressor Response to Angiotensin II in Hypertension Correlation with Plasma Renin Activity and Response to Norepinephrine and Metaraminol

Abstract The pressor response to angiotensin II infused intravenously was studied in 8 normal subjects and 44 patients with primary and secondary hypertension. The mean dose of angiotensin II required to increase diastolic blood pressure by 20 mm. Hg was significantly lower in 24 patients with essential hypertension than in control subjects and 11 patients with renovascular hypertension. Mean plasma renin activity in peripheral venous blood was similar in control subjects and patients with essential hypertension and significantly higher in patients with renovascular hypertension. The pressor dose of angiotensin II was directly correlated with peripheral plasma renin activity. However, norrnotensive control subjects and patients with essential hypertension with similar values of plasma renin activity exhibited markedly different sensitivity to angiotensin II. Further, the pressor response to norepinephrine and metaraminol paralleled that to angiotensin both in patient groups and in individual cases. The results suggest that the pressor response to angiotensin II in hypertensive patients is related not only to the level of circulating endogenous angiotensin but also to nonspecific hyperreactivity in essential hypertension and nonspecific hyporeactivity in renovascular hypertension.

Electrolyte and electrocardiographic changes in the course of hemodialysis

Abstract The electrocardiographic patterns associated with forty-six consecutive hemodialyses performed on twenty-one uremic patients were correlated with changes in plasma electrolytes. Electrocardiographic patterns resulting from organic heart disease frequently made interpretation of electolyte imbalance hazardous. Conversely, distortion of electrocardiographic patterns produced by electrolyte imbalance obscured patterns caused by underlying organic heart disease. Changes in the configuration of the T wave and RS-T segment constituted the majority of electrocardiographic abnormalities. The distortion of the RS-T segment in the predialysis tracings obscured established patterns of left ventricular hypertrophy and strain and of remote myocardial infarction. Arrhythmias were observed in six instances in five patients. In three, arrhythmias subsided spontaneously, while in three others, normal sinus mechanism was restored only after potassium was added to the dialysis rinsing fluid. The occurrence of arrhythmias in the course of hemodialysis emphasizes their probable chemical origin and indicates that the procedure may harm cardiac function. Although the electrocardiogram is of little value for assessing specific electrolyte disturbances in the uremic patient, it contributes greatly to the safe conduct of hemodialysis.

Hypertension in terminal renal failure: Observations pre and post bilateral nephrectomy

Abstract The clinical course of 16 patients, 13 hypertensive and 3 normotensive, with terminal renal failure and undergoing periodic hemodialysis has been observed before and after bilateral nephrectomy. Eight patients on dialysis for 3.5–18 months developed features of accelerated hypertension resistant to multiple drug therapy and ultrafiltration dialysis. Serum renin activity was markedly increased in 6 patients, and within normal range in 2. Hemodynamic studies performed in 5 patients with increased renin activity, revealed expanded plasma volume, near normal cardiac index and increased peripheral resistance. Following bilateral nephrectomy to control hypertension, blood pressure decreased significantly in all 8 patients. During 1.5–21.5 months of anephric state, 2 patients became normotensive, and 6 patients were moderately hypertensive. However, hypertension was readily controllable in 4 of these patients by ultrafiltration dialysis alone. The other 2 patients required reduced amounts of methyldopa also. Post nephrectomy, cardiac output was significantly greater and peripheral resistance was significantly less than pre nephrectomy. Five patients on dialysis for 4–16 months had hypertension which was readily controllable by drug therapy and dialysis. Serum renin activity was normal in 4 patients, and moderately increased in 1. Hemodynamic studies in 4 patients with normal renin activity, showed expanded plasma volume, normal cardiac index and peripheral resistance. Bilateral nephrectomy was performed electively in preparation for possible renal transplantation. During 3.5 to 48 months of anephric state, 3 patients became normotensive and 1 remained hypertensive. Post nephrectomy, plasma volume decreased significantly, while cardiac index and peripheral resistance remained unchanged. Three patients on dialysis for 1–5 months were normotensive and had normal values of serum renin activity. After elective bilateral nephrectomy in preparation for possible renal transplantation, all 3 patients remained normotensive. Assays of serum renin activity were performed at varying intervals post nephrectomy in 13 patients. Renin half-time disappearance rate ranged from 140 to 360 min in 4 patients. Renin activity was still present in the sera from 2 patients, a female and a male, 1 to more than 3 yr respectively, after bilateral nephrectomy. This activity was abolished by adding human antirenin to the sera before incubation.

Acute renal failure followed by protracted, slowly resolving chronic uremia

Abstract A case of acute tubular necrosis which resulted in prolonged renal insufficiency accompanied by severe complications is described. After 1 yr partial spontaneous recovery of renal function occurred with improvement in the patients neuropathy, anemia and secondary hyperparathyroidism. The possible mechanisms for this unusual course are discussed.