Assessing the evolution of atherosclerotic renal artery stenosis.
Explore the source record for details and available documents.
Arteriosclerosis↗
Biomedical subjects
R D Toto
Publications and source records attributed to R D Toto.
Creatinine clearance as a measure of GFR in screenees for the African-American Study of Kidney Disease and Hypertension pilot study.
Serum creatinine and endogenous creatinine clearance (CrCl) are widely used measures of renal function. This study compares the precision, bias, and sources of error in using different CrCl measures to estimate the glomerular filtration rate (GFR) in 118 men and women screened for the African-American Study of Kidney Disease and Hypertension (AASK) pilot study. We measured serum creatinine, 24-hour CrCl, and CrCl during timed clearance periods conducted simultaneously with an 125I-iothalamate GFR study. Serum creatinine was measured using two different kinetic rate Jaffe methods (CX3 and Hitachi). After standardization for body surface area, the different measures of renal function available for each individual were compared with the 125I-iothalamate GFR simultaneous to the CrCl. In a subset of 50 participants, the CrCl measures were compared with a follow-up GFR (fGFR). The mean 125I-iothalamate GFR was 65.2 (SD, 26.4), with a range of 11 to 122 mL/min/1.73 m2. The mean +/- SD percentage differences from the GFR were -9%+/-22% for the Cockcroft-Gault estimated CrCl, 1%+/-29% for the 24-hour CrCl, and 8%+/-16% for the CX3 simultaneous CrCl. The Hitachi method overestimated serum creatinine and underestimated GFR. Compared with an fGFR, the mean +/- SD differences were 2%+/-19% for the first GFR, -6%+/-20% for the Cockcroft-Gault estimated CrCl, 10%+/-28% for the 24-hour CrCl, and 14%+/-29% for the CX3 simultaneous CrCl. Thus, the increased precision with which the timed CrCl predicted its simultaneous GFR did not extend to improved ability to predict a future GFR. The fractional excretion of creatinine, measured as the ratio of the CX3 simultaneous CrCl to 125I-iothalamate clearance, increased with decreasing GFR but was lower than expected (mean +/- SD of 1.21+/-0.16 for GFRs between 20 and 40 mL/min/1.73 m2). The lower fractional excretion explains why the 24-hour and Cockcroft-Gault CrCls did not overestimate GFR, but the reasons for this lower excretion are uncertain. Creatinine assay specificity and calibration are important sources of variability that must be examined in any CrCl measure of GFR. We conclude that despite requiring substantially more time and effort, neither the outpatient 24-hour urine nor the timed CrCl offered increased precision over a calculation based on serum creatinine, sex, age, and weight in predicting GFR.
Black People↗
Racial differences in the renal response to blood pressure lowering during chronic angiotensin-converting enzyme inhibition: a prospective double-blind randomized comparison of fosinopril and lisinopril in older hypertensive patients with chronic renal insufficiency.
This study was undertaken to compare the effects of chronic angiotensin-converting enzyme (ACE) inhibition on blood pressure (BP) and renal hemodynamics in older black and nonblack hypertensive patients with chronic renal insufficiency. A multicenter, placebo lead-in double-blind, parallel group study was performed to compare the antihypertensive efficacy and renal hemodynamic response to the once-daily ACE inhibitor fosinopril (n = 14) and lisinopril (n = 13) over a 22-week period. The study goal was to lower diastolic blood pressure (DBP) to 90 mm Hg or less. Furosemide was added after 6 weeks if blood pressure goal was not achieved. At outpatient clinics at university medical centers, 27 older hypertensive patients (> or = 45 years; 12 blacks, 15 nonblacks; 19 male, eight female) with DBP of 95 mm Hg or higher and 4-hour creatinine clearance 20 to 70 mL/min/1.73 m2 were studied. Changes (delta) from baseline in BP, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured. Mean systolic blood pressure (SBP) and DBP decreased significantly and to a similar extent in randomized groups: fosinopril (mean +/- SEM) delta DBP at 6 weeks was -13 +/- 2 (P < 0.0001; 95% CI, -16 to -9) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -9); lisinopril delta DBP at 6 weeks was -14 +/- 6 (P < 0.0001; 95% CI, -10 to -18) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -12 to -21). GFR and RPF did not change significantly in either group. BP was significantly reduced and to a similar extent in blacks and nonblacks: for blacks, delta DBP at 6 weeks was -11 +/- 3 (P < 0.05; 95% CI, -0.01 to -9) and at 22 weeks was -16 +/- 2 (P < 0.0001; 95% CI, -11 to -20); for nonblacks, delta DBP at 6 weeks was -14 +/- 1 (P < 0.0001; 95% CI, -12 to -17) and at 22 weeks was -12 +/- 2 (P < 0.0001; 95% CI, -16 to -8). Eight patients (five blacks and three nonblacks) required an addition of furosemide after 6 weeks to reach the DBP goal of < or = 90 mm Hg at 22 weeks. GFR was not significantly altered for either racial group at 6 weeks; however, at 22 weeks; however, at 22 weeks, GFR decreased significantly in blacks (delta GFR, -16 +/- 5; P < 0.006; 95% CI, -26 to -5) and tended to increase in nonblacks (delta GFR, 7 +/- 6; P > 0.25). delta GFR correlated directly with the delta RPF (delta GFR = 0.0611* delta RPF -2.35 +; r = 0.68; P < 0.003). There was no correlation between delta MAP and delta GFR or delta RPF in blacks or nonblacks. We conclude that chronic ACE inhibition with fosinopril and lisinopril alone or in combination with furosemide lowers BP in older blacks and nonblacks with hypertension and chronic renal insufficiency. Racial differences in the renal hemodynamic response to chronic ACE inhibition were noted and appear to be independent of diuretic use and the magnitude of BP lowering.
Aged↗
Evaluation of serum creatinine for estimating glomerular filtration rate in African Americans with hypertensive nephrosclerosis: results from the African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study.
Measurement of GFR is considered the standard for estimating renal function. However, standardized accurate GFR methodology is expensive and cumbersome; therefore, estimates of GFR based on serum creatinine concentration have been employed. The purpose of the study presented here was to assess the accuracy and precision of using serum creatinine measurements to estimate GFR in the screen cohort of The African-American Study of Kidney Disease and Hypertension (AASK) Pilot Study. GFR was estimated by four methods: 100/serum creatinine, Cockcroft-Gault equation, creatinine clearance from 24-h urine collection, and a new regression equation derived from the pilot study data. These methods were compared with renal clearance of 125I-iothalamate GFR (GFR1) in 193 hypertensive (diastolic blood pressure > or = 95 mm Hg) African-American screen (142 men, 51 women). A second GFR (GFR2) was performed in 98 screen who were eligible (GFR1 25-70 mL/min per 1.73 m2) for the pilot study. Accuracy was assessed by the difference of 125I-iothalamate GFR-estimated GFR (delta GFR), and precision was estimated from the combined root mean squared error (CRMSE) and the coefficient of determination (r2). The results for accuracy (+/- SD) and precision were as follows: (1) 100/Scr, delta GFR = -0.76 +/- 16.5, CRMSE = 16.5, r2 = 0.69; (2) Cockcroft-Gault, delta GFR = 9.56 +/- 14.9, CRMSE = 17.7, r2 = 0.66; 3) 24-h creatinine clearance, delta GFR = 0.79 +/- 20.7, CRMSE = 20.7, r2 = 0.49; 4) New equation delta GFR = -0.08 +/- 12.8, CRMSE 12.7, r2 = 0.75. In comparison, a second GFR (GFR2, N = 98) had delta GFR = 1.36 +/- 8.48, CRMSE 8.6, r2 = 0.75. Estimates based on 100/SCr and the new equation were the most precise. It was concluded that GFR estimated by serum creatinine is superior to outpatient 24-h urine creatinine clearance in this population. Serum creatinine values can be used to provide a reasonably accurate estimate of GFR in hypertensive African Americans.
Adult↗
Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.
Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.
Adult↗
Effect of ramipril on blood pressure and protein excretion rate in normotensive nondiabetic patients with proteinuria.
Angiotensin-converting enzyme inhibitors reduce proteinuria in both normotensive and hypertensive patients with proteinuric renal disease. However, the mechanism of the antiproteinuric effect has not been clarified. We performed a prospective, double-blind, placebo-controlled, randomized crossover trial to test the hypothesis that the antiproteinuric effect of ramipril was due to an improvement in glomerular permselectivity independent of blood pressure and glomerular filtration rate. The effect of low-dose (1.25 mg/d) and high-dose (5 mg/d) ramipril was assessed in 15 normotensive nondiabetic patients with proteinuria (> 150 mg/d). The study was divided into four 12-week periods: placebo, high- or low-dose ramipril, crossover to low- or high-dose ramipril, and placebo. Blood pressure, glomerular filtration rate, renal plasma flow rate, urinary protein excretion rate, and plasma angiotensin II levels were measured at the end of each period. Mean arterial pressure, urine protein to creatinine ratio, and albumin excretion rate decreased significantly during low- and high-dose ramipril. Glomerular filtration rate and renal plasma flow rate were not changed significantly. Plasma angiotensin II levels decreased with both low- and high-dose ramipril. There were no episodes of hypotension and only one subject developed cough during ramipril that did not require discontinuation of the study drug. In conclusion, administration of ramipril in both low and high doses lowered blood pressure and reduced proteinuria in this cohort of normotensive patients with a variety of proteinuric renal diseases. The antiproteinuric effect of ramipril is probably mediated by a reduction in glomerular capillary pressure.
Adolescent↗
Treatment of dyslipidemia in chronic renal failure.
Dyslipidemia in end-stage renal disease is a common problem and may contribute to the high rates of morbidity and mortality in this population. Recent studies indicate that defective lipolysis is a major factor in the development of this disorder which is characterized by increased levels of very-low-density-lipoprotein remnant particles, hypertriglyceridemia and occasionally hypercholesterolemia. There are no prospective long-term studies on the effect of lipid-lowering treatment on morbidity and mortality related to dyslipidemia. Therefore, at present pharmacologic treatment of hyperlipidemia should be undertaken in patients with severe hypertriglyceridemia (> 500 mg/dl) or hypercholesterolemia (LDL > 130 mg/dl) who are at high risk for coronary artery disease. This review discusses the pathogenesis of dyslipidemia, common clinical patterns of hyperlipidemia and various nonpharmacologic and pharmacologic treatment options.
Combined Modality Therapy↗
Accuracy of urea removal estimated by kinetic models.
The most accurate method for assessing the dialysis dose delivered during high efficiency/flux hemodialysis has not been established. Most current indices of dialysis dose are based on blood-side urea measurements, and thus estimate urea removal. Unfortunately, these methods may lead to inappropriately short dialysis during high flux or high efficiency dialysis, perhaps because of inaccuracies in estimating the amount of urea removal. It is unknown whether these clearance-based approaches can accurately predict either absolute or fractional net urea removal, the latter being equivalent to the solute removal index (SRI). Therefore, we compared the urea removal calculated by five blood-side kinetic methods: (1) urea reduction ration, (2) 1-pool, (3) 2-pool models, and the (4) Smye and (5) Daugirdas formulae. These were compared with the gold standard measurement by direct dialysate quantification. Eight stable patients receiving high-flux hemodialysis were studied over four sessions each. BUN was measured at 0, 45 minutes, 90 minutes, end dialysis, one hour after dialysis (equilibrium value), and 48 hours later. Total body water was determined from the dialysate urea removal; the urea generation rate was calculated using one hour post-dialysis and 48-hour BUN values. Both the total body water and urea generation rate were provided to the 1- and 2-pool models to optimize accuracy. The urea reduction ratio overestimated SRI. The 1-pool model overestimated both absolute urea removal and SRI in 28 of 32 sessions. The 2-pool model slightly underestimated both absolute urea removal and SRI. In contrast, the Smye and Daugirdas formulas accurately estimated SRI.(ABSTRACT TRUNCATED AT 250 WORDS)
Female↗
"Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis.
Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether "strict" [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus "conventional" (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate. Eighty-seven non-diabetic patients (age 25 to 73; 68 black, 58 male) with long-standing hypertension (DBP > or = 95 mm Hg), chronic renal insufficiency (GFR < or = 70 m/min/1.73 m2) and a normal urine sediment were studied. DBP was pharmacologically lowered to < or = 80 mm Hg (3 of 4 consecutive measurements at 1 to 4 weeks intervals) after which patients were randomized. DBP and GFR (renal clearance of 125I-iothalamate) were measured at baseline, at three months and every six months post-randomization. The rate of decline in GFR (GFR slope, in ml/min/1.73 m2/year), estimated by the method of maximum likelihood in a mixed effects model, was the primary outcome variable. In a secondary analysis, 50% reduction in GFR (or a doubling of serum creatinine) from baseline, ESRD and death were combined.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Metabolism of low density lipoproteins in nephrotic dyslipidemia: comparison of hypercholesterolemia alone and combined hyperlipidemia.
High levels of low-density lipoprotein cholesterol (LDL) (hypercholesterolemia) are commonly present in the nephrotic syndrome. Another pattern of dyslipidemia in nephrotic patients is an elevation of both cholesterol and triglyceride levels (combined hyperlipidemia). It has been postulated that the underlying cause of nephrotic dyslipidemia is an hepatic overproduction of apolipoprotein B (apo B)-containing lipoproteins. To examine this hypothesis, the metabolism of LDL-apo B was compared between nephrotic patients with hypercholesterolemia and with combined hyperlipidemia. Thirteen patients (7 with hypercholesterolemia, and 6 with combined hyperlipidemia) underwent measurements of turnover rates of autologous LDL apo B. The results were compared to normolipidemic controls and to patients with primary combined hyperlipidemia previously studied in our laboratory. Nephrotic patients with hypercholesterolemia generally had: (a) lower fractional catabolic rates of LDL apo B than normolipidemic healthy individuals; (b) LDL particles enriched in cholesterol; but (c) no overproduction of LDL apo B. In contrast, patients with combined hyperlipidemia were found to have: (a) high fractional catabolic rates for LDL apo B compared to normolipidemic controls; (b) cholesterol-poor LDL particles; and (c) markedly elevated production rates for LDL. Also, for the group as a whole, there was a positive correlation between plasma triglyceride levels and fractional catabolic rates. These data indicate that the metabolism of LDL is strikingly different between the two forms of nephrotic dyslipidemia. Although there may be common mechanisms contributing to LDL levels in nephrotic patients, there also appears to be a divergence of mechanisms depending on whether hypertriglyceridemia is associated with hypercholesterolemia.
Adolescent↗
Conventional measurement of renal function utilizing serum creatinine, creatinine clearance, inulin and para-aminohippuric acid clearance.
Inulin and para-aminohippuric acid clearances, determined by the conventional method of continuous intravenous infusion with blood and urine sample collections, are the gold standards for estimating glomerular filtration rate and renal plasma flow, respectively. Creatinine clearance provides a reasonably good estimate of glomerular filtration rate but is still subject to errors in accuracy and precision. However, novel methods employing cimetidine to block renal tubular creatinine secretion hold promise for improving the accuracy of estimates. More importantly, a large (and growing) number of studies have consistently demonstrated that estimating glomerular filtration rate by creatinine clearance calculated from the Cockcroft-Gault formula is better than measuring creatinine clearance with a 24-h urine collection. Until newer, more simple methods are developed, calculating creatinine clearance using fasting serum creatinine level, body weight, age and sex provides a reasonable and clinically useful bedside measure of glomerular filtration rate for the practising clinician.
Creatinine↗
Intravenous immunoglobulin-induced osmotic nephrosis.
Intravenous immunoglobulin preparations are being used for an increasing number of indications in clinical medicine. To minimize adverse reactions, sugar additives such as sucrose are added to some preparations to serve as stabilizing agents. We describe a patient treated with an immunoglobulin preparation containing sucrose who developed a fully reversible form of acute renal failure with histologic changes characterized by vacuolization and swelling of renal proximal tubular cells. We believe the high concentration of sucrose in the immunoglobulin preparation resulted in osmotic injury to the renal tubules. Such changes, which are identical to those described in humans and experimental animals given intravenous infusions of hypertonic sucrose, have come to be known as osmotic nephrosis. Risk factors for the development of this lesion are renal insufficiency and volume depletion. The risk for such injury can be minimized by further diluting the immunoglobulin preparation and slowing the infusion rate.
Aged↗
Treatment of hypertension in nondiabetic renal disease.
Over the past two decades the incidence of stroke and myocardial infarction in hypertensive populations has decreased, yet the incidence of end-stage renal disease attributed to hypertension has increased. This apparent paradox has raised questions about the adequacy of blood pressure control in hypertensive patients with renal disease. Chronic renal failure is commonly associated with hypertension, and is often severe and difficult to control, particularly in patients with hypertensive nephrosclerosis. The optimal level of blood pressure control in these patients has not been established. Long-term diastolic blood pressure control to a level lower than 90 mm Hg is associated with stable or improving renal function in hypertensive nephrosclerosis and with slowing of the deterioration in renal function from other causes of renal failure. Moreover, recent studies indicate that when blood pressure control is achieved and maintained at a level of about 130/86 mm Hg (systolic/diastolic), deterioration in renal function can be halted even in black patients with hypertensive nephrosclerosis. Therefore, in hypertensive nephrosclerosis we attempt to control diastolic blood pressure at 80 to 85 mm Hg. Newer antihypertensive agents such as calcium channel blockers and angiotensin-converting enzyme inhibitors contribute to lowering blood pressure and preserving renal function. However, they have yet to be proven superior to conventional agents in double-blind randomized clinical trials in humans with hypertensive nephrosclerosis. Importantly, minoxidil is still relied on for aggressive control of blood pressure in many patients with hypertensive nephrosclerosis.
Antihypertensive Agents↗
Renal insufficiency due to angiotensin-converting enzyme inhibitors.
Angiotensin-converting enzyme (ACE) inhibitors represent a major therapeutic breakthrough for treatment of hypertension, congestive heart failure and various chronic renal diseases. They are effective generally well tolerated and safe for most patients. However, acute renal insufficiency or overt renal failure occurs in some patients with underlying critical renal artery stenosis (RAS), hypertensive nephrosclerosis, autosomal dominant polycystic kidney disease, diabetes mellitus, and chronic congestive heart failure. Diuretic-induced sodium depletion and underlying chronic renal insufficiency are the major predisposing factors for renal insufficiency in all of these patient populations. Renal insufficiency is usually asymptomatic, nonoliguric, associated with hyperkalemia, and in nearly every case completely reversible after discontinuation of the offending agent. Moreover, it can usually be managed in the outpatient setting by discontinuation of the ACE inhibitor, concomitant diuretic or both. An asymptomatic increase in serum creatinine in patients administered ACE inhibitors should raise the possibility of RAS; however, more common renal diseases should be considered. The decision to pursue testing for RAS should be done on an individual basis; moreover, it is imperative that patient willingness to undergo invasive procedures including angioplasty and/or surgery should be determined prospectively.
Acute Kidney Injury↗
Gentamicin clearance during hemodialysis: a comparison of high-efficiency cuprammonium rayon and conventional cellulose ester hemodialyzers.
The advent of high-efficiency hemodialyzers has afforded improved efficiency of urea clearance; however, increased clearance of other substances, particularly antibiotics, also may occur, necessitating changes in clinical practice. Accordingly, we compared the efficiency of gentamicin removal using two different hemodialyzers, a conventional saponified cellulose ester (CD 135) and a high-efficiency cuprammonium rayon dialyzer (TAF 175L), in eight hospitalized patients undergoing antibiotic therapy for suspected or proven gram-negative infection. The rate of dialysis, estimated as the ratio of dialyzer urea clearance (K) to urea distribution volume (V) (K/V urea), and the total elimination rate constant (k) of gentamicin were measured during 17 hemodialysis treatments. The K/V urea for the two dialyzers, TAF 175L and CD 135, was 0.390 +/- 0.024 hr-1 and 0.413 +/- 0.129 hr-1 (P = NS), respectively. The TAF 175L hemodialyzer was almost twice as efficient in removing gentamicin as the CD 135: TAF 175, k = 0.263 +/- 0.024 hr-1; CD 135, k = 0.132 +/- 0.027 hr-1 (P < 0.001). Moreover, the rate of dialysis (K/V urea) was correlated with k of gentamicin for the TAF 175L dialyzer (r2 = 0.50, P < 0.02) but not for the CD 135 dialyzer. We conclude that dialyzer characteristics and the rate of dialysis (K/V urea) should be taken into consideration when determining the dosage of gentamicin in patients on hemodialysis.
Adult↗
Mechanisms and treatment of dyslipidemia of renal diseases.
Dyslipidemia is commonly observed in nephrotic syndrome, in chronic renal failure, and after renal transplantation. The patterns of dyslipidemia, however, differ among these three conditions, and the origins and mechanisms responsible for abnormalities in lipoprotein metabolism in each are not well understood. Whether these dyslipidemias contribute to the development of atherosclerosis and coronary heart disease is uncertain, but it is probable that they do. Important questions are whether an attempt should be made to treat the various renal dyslipidemias, and if so, by what means. Also of current interest are dyslipidemias in the nephrotic syndrome, chronic renal failure (uremia), and the post-renal transplantation state.
Animals↗
Tumor lysis syndrome.
Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hyperkalemia, hypocalcemia, and acute renal failure in patients with rapidly growing cancers (especially Burkitt's lymphomas with extensive abdominal bulk). It may be preventable with allopurinol therapy combined with aggressive intravenous fluid therapy aimed at establishing an ongoing alkaline diuresis. In most cases renal failure is completely reversible; however, fatal hyperkalemia and volume overload may develop. Therefore, aggressive management with hemodialysis often is necessary to maintain life support while tumor burden is controlled with cytoreductive therapy. Early recognition and management by a team approach in the intensive care unit where careful monitoring is available serves to forestall severe renal failure, thereby improving short-term prognosis in susceptible patients.
Adult↗
Sympathetic overactivity in patients with chronic renal failure.
BACKGROUND: Hypertension is a frequent complication of chronic renal failure, but its causes are not fully understood. There is indirect evidence that increased activity of the sympathetic nervous system might contribute to hypertension in patients with end-stage renal disease, but sympathetic-nerve discharge has not been measured directly in patients or animals with chronic renal failure. METHODS: We recorded the rate of postganglionic sympathetic-nerve discharge to the blood vessels in skeletal muscle by means of microelectrodes inserted into the peroneal nerve in 18 patients with native kidneys who were undergoing long-term treatment with hemodialysis (of whom 14 had hypertension), 5 patients receiving hemodialysis who had undergone bilateral nephrectomy (of whom 1 had hypertension), and 11 normal subjects. RESULTS. The mean (+/- SE) rate of sympathetic-nerve discharge was 2.5 times higher in the patients receiving hemodialysis who had not undergone nephrectomy than in the normal subjects (58 +/- 3 vs. 23 +/- 3 bursts per minute, P < 0.01). In contrast, the rate of sympathetic-nerve discharge was similar in the patients receiving hemodialysis who had undergone bilateral nephrectomy (21 +/- 6 bursts per minute) and the normal subjects. The rate of sympathetic-nerve discharge in the patients receiving hemodialysis who had not undergone nephrectomy was also significantly higher (P < 0.01) than that in the patients with bilateral nephrectomy, and it was accompanied in the former group by higher values for vascular resistance in the calf (45 +/- 4 vs. 22 +/- 4 units, P < 0.05) and mean arterial pressure (106 +/- 4 vs. 76 +/- 14 mm Hg, P < 0.05). The rate of sympathetic-nerve discharge was not correlated with either plasma norepinephrine concentrations or plasma renin activity. CONCLUSIONS: Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.
Angiotensin II↗