Increased serum aluminum. An independent risk factor for mortality in patients undergoing long-term hemodialysis.

The annual mortality rate among patients receiving long-term hemodialysis has been rising over the past decade. The prevalences of known risk factors such as older age, male sex, duration of dialysis, presence of diabetes, coronary artery disease, or hypertension do not seem to have changed during this time. However, evidence suggests that an increased body aluminum level may have an adverse effect on survival even in the absence of overt aluminum toxic reaction. Therefore, we evaluated the correlation between serum aluminum levels and mortality in 10 646 patients undergoing long-term hemodialysis. Mortalities were 18% higher for patients with serum aluminum levels between 1520 and 2220 nmol/L and progressively increased to 60% higher for patients with aluminum levels above 7410 nmol/L. Serum aluminum level was an important predictor of survival even after other known risk factors had been controlled. These data strongly suggest that patients undergoing long-term hemodialysis should have periodic surveillance of the serum aluminum levels, and in those patients who have plasma levels of 1520 to 2220 nmol/L or higher, one should seriously consider discontinuing aluminum salts and giving therapy to decrease body aluminum level if it is found to be increased.

Vestibular toxicity of gentamicin. Incidence in patients receiving long-term hemodialysis therapy.

Twenty-three patients on long-term hemodialysis regimens who received gentamicin sulfate were reviewed retrospectively to assess the incidence of ototoxicity and to identify potential risk factors. Dosage of gentamicin sulfate was 1.0 to 1.5 mg/kg intravenously three times weekly. Serum gentamicin levels were monitored in 21 cases. Seven patients developed signs and symptoms of vestibular dysfunction. Statistically significant differences were found between the ototoxic and nonototoxic groups with respect to age (P less than .001), total dose (milligrams per kilogram) (P less than .001), and duration of therapy (P less than .001). The total dose per kilogram of body weight contributed most heavily to ototoxicity, and regression analysis suggests that the critical cumulative dose is about 17.5 mg/kg. The two groups did not differ with respect to mean peak and valley serum levels. We conclude that this population is at high risk of developing gentamicin-related vestibular dysfunction specifically when the cumulative dose exceeds 17.5 mg/kg.

Bacteremic infection in hemodialysis.

This is a retrospective study of 133 episodes of bacteremic infection in 112 hemodialysis patients. The frequency of bacteremic infection was 9.5% in patients with chronic renal failure and 10.9% in patients with acute renal failure. In patients with acute renal failure, pneumonia and intra-abdominal abscess were the most frequent sources of septicemia. Sepsis was usually due to Gram-negative organisms and mortality was high. In patients with chronic renal failure, infection of the shunt or fistula was the most common cause, was frequently due to Staphylococcus organism, and had a more favorable survival rate. Gram-negative septicemia from a nonaccess source in patients with chronic renal failure was associated with a higher mortality. Bacterial endocarditis and septic pulmonary emboli occurred in 3.6% of septic episodes and 0.35% of patients at risk and had very low mortality. A low threshold for obtaining blood cultures and early antibiotic treatment are believed to be important in the treatment of bacteremic infections in patients undergoing long-term hemodialysis.

Comparing the urea reduction ratio and the urea product as outcome-based measures of hemodialysis dose.

The urea reduction ratio (URR) and normalized treatment ratio (Kt/V) are related quantities that have become accepted measures of hemodialysis dose. Recent studies, however, have suggested that they combine two elements, both favorably associated with clinical outcome, as a single ratio. These elements, Kt and V, may offset each other, producing a complex quantity that does not reflect a true relationship between dialysis exposure and clinical outcome. This project explored and compared the associations of the URR and the ¿urea clearance x time¿ product (Kt) with mortality in a large sample of hemodialysis patients (37,108 patients) during 1998. Survival analyses using conventional techniques were the primary analytic tools. The relationship between URR and survival was U-shaped or J-shaped, with greater relative mortality at both extremes of the URR distribution than at its middle. Thus, identifying a threshold for adequate dialysis was not possible unless one considers also a threshold for overdialysis. Conversely, the association between Kt and outcome was much simpler, reflecting progressive improvement over the range of Kt evaluated here. These analyses suggest that such measures as URR and Kt/V are compound and complex, and that a simpler, more direct, measure, such as the Kt, should be considered to describe hemodialysis dose.

Quality-of-life evaluation using Short Form 36: comparison in hemodialysis and peritoneal dialysis patients.

Short Form 36 (SF-36) is a well-documented health-related quality-of-life (HRQOL) instrument consisting of 36 questions compressed into eight scales and two primary dimensions: the physical and mental component scores. This tool was used to evaluate QOL among peritoneal dialysis (PD) and hemodialysis (HD) patients. The results of 16,755 HD and 1,260 PD patients (728 continuous ambulatory PD [CAPD] and 532 continuous cycling PD [CCPD]) completing an SF-36 during 1996 were analyzed. Three analyses of variance were performed, consisting of (1) no adjustment, (2) case mix (age, sex, race, and diabetes), and (3) case mix plus laboratory parameters. PD patients were younger (P < 0.001), a larger fraction were white (P < 0.001), fewer had diabetes (P < 0.001), and had lower serum albumin concentrations (P < 0.001) and higher creatinine, hemoglobin, and white blood cell count values (P < 0.001) than HD patients. Diabetes was present in a larger fraction of CCPD than CAPD patients (P < 0.001). HD and PD patients scored similarly for scales reflecting physical processes. PD patients scored higher for mental processes, but only after statistical adjustment for the laboratory measures. Scores on scales reflecting physical processes were worse, and those reflecting mental processes were better among CCPD than CAPD patients. HD and CAPD scores were similar. CCPD patients perceived themselves as more physically impaired but better adjusted than HD or CAPD patients. These descriptive data show that perception of QOL among PD and HD patients is similar before adjustment, but PD patients score higher for mental processes with adjustment. CCPD patients score worse for physical function and better for mental function than either CAPD or HD patients. We cannot, however, exclude the influence of therapy selection.

Thoughts about judging dialysis treatment: mathematics and measurements, mirrors in the mind.

This article considers the contributions of the urea kinetic parameters, , Kt/V and nPCR, to beliefs about judging dialysis treatment. The values calculated from any set of data depend on the model (eg, 1 pool, 2 pool, or so forth) and the mathematics used to derive the values. Yet, the medical community debates the value of Kt/V at which patients should be treated even as they debate the mathematics by which Kt/V should be calculated. The resulting ambiguities about proper targets and methods may actually frustrate large-scale clinical quality enhancement initiatives. The casual use of mathematical models can mislead unwary clinicians and compromise quality enhancement. For example, the observation that a high Kt/V is associated with a high nPCR leads to the widespread belief that improving Kt/V must substantially improve nutritional status. The association, however, results mainly, if not solely, from mathematical coupling rather than biological cause and effect. The misguided belief could contribute to ineffective treatment of malnourished patients. Complicated mathematical models are useful tools for describing and evaluating evolving concepts about the physical properties of dialysis and for estimating the effects of new therapies. However, the changing nature of concepts, and therefore the mathematical models designed to support them, makes clinical care ideas that attempt to shoehorn old concepts into new equations. It is the result of the dialysis treatment, not the mathematical path by which it is achieved, that is associated with improved patient health. Consequently, clinical care should be guided by simple measurements that reflect the outcome of the treatment, not by mathematical parameters.

Race and diabetes as death risk predictors in hemodialysis patients.

Case mix and laboratory predictors of death risk were evaluated in 17,185 hemodialysis patients. The laboratory variables most closely associated with the increased death risk borne by diabetic patients (relative to non-diabetics) and White patients (relative to non-Whites) were identified. The analyses of laboratory death risk predictors were similar to those previously reported. Serum albumin concentration is the most powerful death risk predictor among all of the variables, both case mix and laboratory. Statistical models including only case mix variables reveal both race (RRWhites = 1.42) and diabetes (RRdiabetes = 1.43) as significant predictors. Adding creatinine, albumin, and BUN concentrations to the model eliminated diabetes as a significant predictor. Creatinine and albumin accounted for most of the change. Adding only creatinine eliminated race. The data suggest that reduced visceral and somatic protein mass and/or metabolism may be important determinants of mortality in dialysis patients. Because differences in the concentrations of creatinine and albumin explain much of the risk associated with being White or diabetic, differences in nutritional status may explain the reduced survival observed in those groups. Therefore, clinicians should not simply accept without question the notion that diabetics and Whites are doomed to inferior survival.

Cardiovascular disease in uremic patients on hemodialysis.

In conclusion, patients on chronic maintenance dialysis have an increased incidence of death from cardiovascular disease. Hypertension plays a major role, and these patients must be carefully monitored for complete control of blood pressure. Adequacy of ultrafiltration to maintain normal extracellular volume is an essential part of the dialytic treatment. Hypertensive patients should be screened for excessive renin secretion because of its possible role in unresponsive hypertension in patients on dialysis. Nephrectomy should be used when necessary, where dialysis and antihypertensive medication have not adequately controlled blood pressure. Patients must be monitored for the presence of pericardial disease to avoid subsequent pericardial effusion and the development of constrictive pericarditis with its adverse effect on myocardial function. When constrictive pericarditis is present, it obviously should be relieved by appropriate surgery. Efforts should be made to minimize cardiac output in hemodialysis patients. Whether or not routine transfusions to maintain a higher hematocrit are indicated is a question that cannot yet be answered. However, patients with marginal cardiovascular function who are accepted on hemodialysis and must have an arteriovenous shunt should be supported in any manner to minimize an increase in cardiac output. Early and aggressive treatment of known episodes of sepsis is important in the elimination of valvular endocarditis in this patient population. Perhaps one of the finer indicators of adequacy of hemodialysis will be K rate and peak immunoreactive insulin levels. Continued abnormality of these parameters may contribute to cardiovascular disease. Clearly, further study of the effect of abnormal carbohydrate metabolism on lipid metabolism is in order. Serum triglyceride, serum cholesterol and lipid electrophoretic pattern should be followed to evaluate the beneficial effects of drug therapy and changes in dialytic technique on the development of cardiovascular disease. Careful monitoring of calcium, phosphorus, bone films and parathyroid hormone levels is indicated to assess parathyroid status. The use of aluminum binders and parathyroidectomy to prevent vascular and myocardial calcification is important in the therapy of these patients. The use of cardiac catheterization, coronary artery arteriography, and possibly cardiac vascular repair, should be considered in the chronic hemodialysis patient with coronary artery disease if he is otherwise well. Adequacy of hemodialysis perhaps can be evaluated through its effect on all of the above parameters. Whether or not changes in artificial kidney treatments can correct the final vascular disease remains to be seen.

Which mathematical model to study uremic toxicity? National Cooperative Dialysis Study.

Mathematical modelling advantages and limitations to study dialysis adequacy are evaluated, the use of the single pool urea model in the guidance of the National Cooperative Dialysis Study (NCDS) is described, and therapeutic control results from the Control phase of the NCDS are reported. The relevance of using urea as a target compound and the practicality of modelling its levels in clinical settings using a single pool model are discussed. The NCDS involves intensive participation of 8 geographically separate centers to control BUN at two weekly time averaged concentrations (50 +/- 5 and 100 +/- 5 mg/dl) using standard clinical dialyzers and two different lengths of dialysis (3 and 4.5 hr) in the presence of .8-1.4 g/kg/day protein intake. Control phase data on 195 patients indicates a remarkable level of clinical precision and method reproducibility as well as a high degree of patient compliance. Patient urea volumes averaged 39.8 +/- 8.9 liters, net rates of daily protein catabolism were 1.06 +/- .17 g/kg; daily weight gain: .96 +/0 .43 kg; and dialyzer clearances to maintain patients in the control phase for 3 to 6 months were 168 +/- 44 ml/min. Clearances required to randomize patients into four experimental groups ranged 40-250 ml/min. Less than 1/4 of dialyzers were larger than 1.8 m2 and were not specific to any experimental group.

Testosterone therapy in hemodialysis patients.

30 patients undergoing regular, three times weekly hemodialysis were treated with large doses of intramuscular testosterone with evaluation of hematopoiesis before and after treatment. A control group of 30 patients not using the drug was evaluated in similar fashion. The presence or absence of native kidneys was the most important factor determining hematocrit level and transfusion requirements in these patients, whether treated with testosterone or not. The mean hematocrit was lower and the transfusion requirements were higher in bilaterally nephrectomized patients. A significant increase in hematocrit occurred in testosterone treated nephric patients, but untreated nephric patients also had a significant rise. Important adverse side effects occurred with testosterone. Anephric patients did not increase hematocrit levels with or without testosterone.