Physical activity levels in patients on hemodialysis and healthy sedentary controls.

BACKGROUND: Patients on dialysis have reduced exercise tolerance compared with age-matched sedentary controls. The reasons for this debility have not been fully elucidated, but physical inactivity could be a contributing factor. The purpose of the current study was to determine whether patients on hemodialysis are less active than healthy sedentary controls and to explore clinical correlates of physical activity level in a group of hemodialysis patients. METHODS: Thirty-four hemodialysis patients and 80 healthy sedentary individuals participated in the study. Physical activity was measured for seven days with a three-dimensional accelerometer and with an activity questionnaire. RESULTS: Vector magnitude values from the accelerometer for the dialysis and control subjects were 104,718 +/- 9631 and 161,255 +/- 6792 arbitrary units per day, respectively (P < 0.0001, mean +/- SEM). The estimated energy expenditure values derived from the questionnaire were 33.6 +/- 0.5 kcal/kg/day and 36.2 +/- 0.5 kcal/kg/day (P = 0.002). The difference between patients on dialysis and controls increased with advancing age. Among the dialysis subjects, some measures of nutritional status correlated with physical activity level, including serum albumin concentration (r = 0.58, P = 0.003), serum creatinine concentration (r = 0.37, P = 0. 03), and phase angle derived from bioelectrical impedance analysis (r = 0.40, P = 0.02). CONCLUSIONS: Patients on hemodialysis are less active than healthy sedentary controls, and this difference is more pronounced among older individuals. There is an association between the level of physical activity and nutritional status among patients on dialysis. These findings are of great concern, given the trend toward increasing age in incident dialysis patients and the well-known association between inactivity and increased mortality in the general population.

The technology of dialyzer reuse.

Dialyzer reuse has become an integral part of chronic hemodialysis in the United States of America because it has large economic benefits which allow the use of expensive, biocompatible membranes, and the delivery of adequate dialysis therapy in the face of continued inflation of costs and fixed reimbursement. The conflict between patient safety and provider economic benefit has been resolved by the development of recommended practice guidelines by the Association for the Advancement of Medical Instrumentation. When followed carefully, disinfection of dialyzers for multiple reuse by the same patient is relatively safe and effective in eliminating infection, pyrogen reactions, and other potential complications associated with germicide use. However, despite all precautions, there appears to be consequences of certain germicides, such as formaldehyde, that are difficult to eliminate, such as anti-N antibody. The development of heat or heat and 1.5% citric acid would appear to eliminate all these problems, and offers a safe, effective, and cost saving method for reuse of polysulfone dialyzers. Allegations of increased mortality with certain germicides, reuse techniques, and treatment settings, as well as the contribution of reuse to inadequate dialysis remain unproven and require further investigation.

Roxithromycin disposition in patients on continuous ambulatory peritoneal dialysis.

Roxithromycin is a macrolide antibiotic with a spectrum of activity similar to erythromycin. Roxithromycin has been shown to have a favourable pharmacokinetic profile with more reliable absorption and higher, prolonged plasma and tissue concentrations compared with erythromycin. The pharmacokinetics and dialysis clearance of roxithromycin were studied in twelve patients with end-stage renal disease on continuous ambulatory perionteal dialysis. Following a single 300 mg oral dose, multiple blood, dialysate and urine samples were collected over 48 h and assayed for roxithromycin by a microbiological method. Peak plasma concentrations were attained between 0.5 and 5 h, and ranged from 2.3 to 6.8 mg/L. The mean elimination half-life was 20.6 +/- 8.7 h, compared with 10 to 14 h previously reported in healthy volunteers given a single 300 mg dose. Plasma clearance relative to bioavailability (Clp/F) ranged from 37.3 to 118.3 mL/min. The percentage of the dose recovered in the dialysate and net dialysis clearance were low, ranging from 1.0 to 3.1% and 0.9 to 1.8 mL/min, respectively. Only 1% of the dose was recovered in the urine. These results demonstrate that roxithromycin is not substantially removed by continuous ambulatory peritoneal dialysis, and its elimination is prolonged in renal failure, possibly due to impaired nonrenal elimination.

CAPD prescription in current clinical practice.

A total of 132 patients from 15 dialysis centers were studied. Analyses were made of each drained dialysate exchange over 24 hours to determine total peritoneal urea clearance (KpT, liters/day), and a 24-hour urine was collected to determine total renal urea clearance (KrT, liters/day) and the sum of KpT+KrT or KprT, liters/day. Body water volume (V, L) was estimated from gender and surface area, and daily fractional urea clearance (KprT/V) was calculated. Normalized protein catabolic rate (PCRN, grams/kilogram/day) was also calculated from the urea data. Major results were the following: KrT comprised 25% of KprT; the mean KprT/V was 0.28, but ranged from 0.10-0.50; an equivalent thrice-weekly hemodialysis KT/V was calculated from the KprT/V values and showed mean KT/V = 1.07, but 67% of values were less than 1.0. In contrast, the Health Care Finance Administration (HCFA) consensus criteria indicated 91% of prescriptions were adequate. These data indicate the need for clinical outcome studies with KprT/V randomized over the range 0.20-0.30 to better define the domain of adequate CAPD.

Increasing incidence of human immunodeficiency virus-associated nephropathy at San Francisco General Hospital.

A survey of consultations to the Division of Nephrology at San Francisco General Hospital from 1982 to 1988 found only seven cases of proven or possible renal disease matching that described for human immunodeficiency virus (HIV)-associated nephropathy (nephrotic proteinuria, rapidly progressive renal insufficiency, and focal and segmental glomerulosclerosis [FSGS] histologically). In the period from April 1, 1988 (the conclusion of the original survey) through December 31, 1990, a roughly 11-fold increase in the incidence of such cases among referrals of HIV-infected patients to the Division occurred compared with the initial experience. The patients were nearly exclusively black men, only about half of whom had intravenous drug abuse (IVDA) as an HIV risk factor. This striking increase was associated with a progressive increase in the number of black patients with acquired immunodeficiency syndrome (AIDS) in San Francisco, and in the percentage of patients with an AIDS diagnosis discharged from San Francisco General Hospital (SFGH) who were black. These data support other evidence indicating a particular vulnerability of blacks to this form of renal disease and help to reconcile data from our division with the experience reported from other centers.

Renal involvement in patients infected with HIV: experience at San Francisco General Hospital.

A spectrum of renal abnormalities has been described in patients infected with the human immunodeficiency virus (HIV) with or without signs of the acquired immunodeficiency syndrome (AIDS). In particular, attention has been focused on a nephropathy characterized clinically by nephrotic proteinuria and rapidly advancing renal insufficiency, and histologically by focal and segmental glomerulosclerosis (FSGS). To evaluate the relationship between HIV infection and structural renal disease, we reviewed all consultations between January 1982 and March 1988 to the Division of Nephrology at San Francisco General Hospital (SFGH), a municipal hospital treating approximately one-third of AIDS cases in San Francisco. Seventy-three consultation requests were received during this period regarding patients with AIDS (48), AIDS-Related Complex (23), or asymptomatic HIV infection (2). Of these, 27 gave evidence of structural renal disease (Group I): 14 had chronic renal insufficiency, in 10 of whom nephrotic proteinuria was also present. However, progression of renal insufficiency to end-stage renal disease (ESRD) in this group did not follow the rapid course described for HIV-associated nephropathy. Renal tissue was examined in 11 Group I patients and showed FSGS in four and a variety of acute and chronic glomerular and tubulointerstitial changes in the others. In 46 Group II patients, consultation was requested for acute renal failure or fluid, electrolyte, and acid-base disturbances. We also reviewed 91 consecutive autopsies performed in patients dying with AIDS at SFGH between 1981 and 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Teicoplanin pharmacokinetics and bioavailability during peritoneal dialysis.

The pharmacokinetics of teicoplanin in serum and dialysate were examined in a crossover study after intravenous and intraperitoneal administration of a 3 mg/kg dose to five anuric patients who were undergoing continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were obtained for 30 and 15 days, respectively, and were assayed microbiologically. The principal pharmacokinetic parameters after intravenous administration were as follows: total body clearance, 2.76 +/- 1.08 ml/min; elimination half-life, 377 +/- 109 hours; volume of distribution at steady state, 1.04 +/- 0.18 L/kg. Only 9% +/- 6% of the intravenous dose was recovered in the dialysate and the net peritoneal clearance was 0.25 +/- 0.21 ml/min. Bioavailability values, which were assessed by use of three methods after intraperitoneal administration and while dialysate was retained in the peritoneal cavity for 5 hours (dwell time), were 0.77 +/- 0.21, 0.78 +/- 0.05, and 0.76 +/- 0.08. Changes in bioavailability with dwell time were also examined. A dosing guide, which accounts for changes in bioavailability with dwell time, is presented.

Effects of a magnesium-free dialysate on magnesium metabolism during continuous ambulatory peritoneal dialysis.

While the use of magnesium-containing compounds is usually contraindicated in dialysis patients, the risk of toxicity from hypermagnesemia can be reduced by lowering the magnesium concentration in dialysate. We examined the effects of a magnesium-free dialysate on both serum magnesium level and the peritoneal removal rate of magnesium over 12 weeks in 25 stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). After 2 weeks, the serum magnesium level decreased from 2.2 to 1.9 mg/dL (0.9 to 0.8 mmol/L) (P less than .02) and the peritoneal removal rate increased from 66 to 83 mg/d (2.8 to 3.5 mmol/d) (P less than .05), with both values remaining stable thereafter. There was a strong association between these parameters (r = -0.62, P less than .05), suggesting that the serum magnesium level decreased as a result of the initial increased peritoneal removal rate. For an additional 4-week period, a subgroup of nine patients received magnesium-containing, phosphate binding agents instead of those containing only aluminum. During this phase, serum inorganic phosphorus was well controlled. The serum magnesium level increased only from 1.8 to 2.5 mg/dL (0.7 to 1.0 mmol/L) (P less than .05), due in great part to the concomitant 41% rise in peritoneal magnesium removal from 91 to 128 mg/d (3.8 to 5.3 mmol/d) (P less than .05). No toxicity was noted during the entire 16-week study period, nor did serum calcium change. Thus, serum magnesium levels remained within an acceptable range as magnesium-containing phosphate binders were given through the use of magnesium-free peritoneal dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of the kidneys in the metabolism of circulating mevalonate in humans.

Previous studies in several animal species have demonstrated that the kidneys are the primary site of mevalonate metabolism by the oxidative or shunt pathway. To determine the role of the human kidney in mevalonate oxidation, we studied mevalonate shunt activity in patients undergoing hemodialysis for varying degrees of renal failure. Surprisingly, at least half of the uremic patients and even anephric patients had normal ability to oxidize mevalonate by the shunt pathway. In addition, we found a strong negative correlation (R = -0.94) between mevalonate shunt activity and serum phosphorus levels in uremic patients. The resulting inhibition of mevalonate oxidation by high serum phosphorus levels was reversed by lowering the serum phosphorus in one patient. Finally, a positive correlation was found between mevalonate oxidation and serum PTH levels. The results of this study suggest that, in humans, extrarenal tissues can be major contributors to mevalonate oxidation. It is therefore probable that in humans, in contrast to other animals, the kidney is not the primary site of mevalonate metabolism by this oxidative pathway. Finally, the strong negative correlation between serum phosphorus levels and the ability of uremic patients to oxidize mevalonate suggests a regulatory role for the phosphate ion in the mevalonate shunt pathway.

Plasma cholesterol metabolism in end-stage renal disease. Difference between treatment by hemodialysis or peritoneal dialysis.

Plasma cholesterol metabolism was investigated in normotriglyceridemic patients with end-stage renal disease treated by hemo- or continuous ambulatory peritoneal dialysis (CAPD), and compared with that in a control group with normal renal function. A reversed net transport of free cholesterol from plasma to cultured fibroblasts, as well as greatly reduced levels of plasma cholesterol esterification and cholesterol ester transfer rates to low and very low density lipoproteins (LDL and VLDL), was found in the hemodialysis group compared to the controls. The LDL and VLDL contained increased amounts of free cholesterol and inhibited cholesterol ester transfer when recombined with control plasma. The LDL triglyceride content was doubled in the hemodialysis group, whereas cholesterol esters were decreased. Patients treated by CAPD, in marked contrast, had cholesterol metabolic rates that were within the normal range, as well as normal lipoprotein composition.

Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis.

Albumin and protein removal rates were studied in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In nine patients simultaneous studies of albumin distribution and turnover were performed. Total albumin loss was 4.23 +/- 1.42 g/1.73 m2/24 hr; total protein removed was 8.79 +/- 4.21 g/1.73 m2/24 hr. Although these values were well within the range for severe nephrosis, serum albumin concentration remained nearly normal, 3.7 +/- 0.5 g/dl. Plasma albumin mass, 120.0 +/- 25.2 g/1.73 m2, and total albumin mass, 249 +/- 29.1 g/1.73 m2, did not differ from those of the control group. Compared with the control group, patients had reduced albumin catabolism, 9.76 +/- 1.74 g/1.73 m2/24 hr versus 13.8 +/- 0.77 g/1.73 m2/24 hr (P less than 0.001). Within the patient group albumin synthesis increased with increased albumin loss. Serum albumin concentration correlated negatively with albumin losses (P less than 0.001). The CAPD patients maintained albumin homeostasis through decreased albumin catabolism and increased synthesis. All major albumin pools were maintained despite massive albumin loss.

Tuberculosis in patients with end-stage renal disease.

Ten patients with proved disease caused by Myocobacterium tuberculosis were identified over a 10 year period in a population of 172 adult patients undergoing long-term dialysis. The incidence of tuberculosis was 12 times greater than that prevailing in the general community during the period of the study and could not be accounted for solely by demographic factors. Diagnosis was obscured because the symptoms were nonspecific and attributable to uremia, intermediate strength (5 TU) tuberculin tests were often negative, the roentgenographic appearance of pulmonary disease was often atypical, and there was more frequent extrapulmonary involvement. Impaired cellular immunity due to advanced renal failure may predispose to the increased incidence of tuberculosis and the greater frequency of extrapulmonary disease observed. Treatment was safe and effective in these patients using 300 mg of isoniazid and 8 to 10 mg/kg of ethambutol daily. Eight patients survived longer than one year following the diagnosis of tuberculosis, and all were clinically cured. No deaths were directly attributed to tuberculosis. A high index of suspicion and aggressive evaluation may be necessary to diminish the significant mortality described previously in association with disseminated disease.

The effect of infusion of mannitol-sodium bicarbonate on the clinical course of myoglobinuria.

Twenty patients who had evidence of myoglobinuria were treated with intravenous infusions of mannitol and sodium bicarbonate. Nine patients (group 1) responded with higher urine output, and continued infusion improved renal function; none required dialysis and all survived. Eleven patients (group 2) did not respond to the infusion, and required an average of 5.3 (range, 0 to 11) dialyses; one patient died. There was no significant difference in initial BUN level, creatinine level, BUN/creatinine ratio, or fractional sodium excretion level between the two groups. However, group 2 patients had a significantly higher creatine phosphokinase (CPK) level, serum phosphate level, and hematocrit reading initially than did group 1, indicative of more severe muscle injury and hemoconcentration. These results demonstrate that some patients with myoglobinuria will respond to infusion of mannitol and sodium bicarbonate. This treatment may be effective in altering the clinical course of myoglobinuric acute renal failure.

Peritoneal clearance and total body elimination of vancomycin during chronic intermittent peritoneal dialysis.

Vancomycin is a useful antimicrobial agent in patients undergoing chronic hemodialysis treatment; its efficacy in chronic peritoneal dialysis (CPD) has not been established. Serum (VS) and peritoneal fluid (VPF) vancomycin concentrations were measured in two CPD patients with staphylococcal peritonitis. Half-life of VS agreed with the half-life of VPF in each patient, and the VS/VPF ratio was 1.27 in both patients. Distribution volumes were 37.2 and 58.7 l, values approximating total body water in these patients. VS and VPF persisted in the therapeutic range (greater than 5 microgram/ml) for more than 16 days. In one patient, mean peritoneal clearacne was 9.8 ml/min, and overall drug clearance averaged 2.3 ml/min; in the other patient, overall clearance was 2.1 ml/min. These results indicate that therapeutic vancomycin levels can be maintained for more than 16 days with a single 1 g intravenous dose in patients receiving intermittent CPD, as is the case for hemodialysis patients. Because of this, parenteral vancomycin is useful in the treatment of staphylococcal peritonitis in CPD patients.

Nitrogen balance during intermittent dialysis therapy of uremia.

Daily measurements of nitrogen balance were made at two levels of protein intake in five patients undergoing chronic intermittent dialysis therapy. During ingestion of high (1.4 g/kg of body wt) protein intake, nitrogen balance was positive on nondialysis days and negative on dialysis days, so that cumulative balance for the week of study was not different from zero. During ingestion of low (0.5 g/kg) protein intake, nitrogen balance was approximately zero on nondialysis days but was again negative on dialysis days, so that cumulative balance for this period was negative. The negative nitrogen balance observed on dialysis days was associated with a higher rate of urea nitrogen generation (Gu, g/24 hr, determined by a kinetic model of urea nitrogen in dialysis patients) that was most evident in the hours immediately following dialysis. Net protein catabolic rate (PCR, g/24 hr), derived from total nitrogen mass balance equations, correlated very closely with Gu:Gu = 0.154 PCR - 1.7, r = 0.96. This relationship agreed well with previous observations made in nondialyzed uremic patients under more steady-state conditions. These studies demonstrate that nitrogen balance is negative on dialysis days regardless of protein intake, and that Gu is higher on dialysis days. The negative nitrogen balance could result from amino acid loss in dialysate and from increased protein catabolism stimulated by loss of glucose into dialysate.