Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients.

BACKGROUND: Cardiovascular diseases are the most common causes of death among chronic hemodialysis patients, yet the risk factors for these events have not been well established. METHODS: In this cross-sectional study, we examined the relationship between several traditional cardiovascular disease risk factors and the presence or history of cardiovascular events in 936 hemodialysis patients enrolled in the baseline phase of the Hemodialysis Study sponsored by the U.S. National Institutes of Health. The adjusted odds ratios for each of the selected risk factors were estimated using a multivariable logistic regression model, controlling for the remaining risk factors, clinical center, and years on dialysis. RESULTS: Forty percent of the patients had coronary heart disease. Nineteen percent had cerebrovascular disease, and 23% had peripheral vascular disease. As expected, diabetes and smoking were strongly associated with cardiovascular diseases. Increasing age was also an important contributor, especially in the group less than 55 years and in nondiabetic patients. Black race was associated with a lower risk of cardiovascular diseases than non-blacks. Interestingly, neither serum total cholesterol nor predialysis systolic blood pressure was associated with coronary heart disease, cerebrovascular disease, or peripheral vascular disease. Further estimation of the coronary risks in our cohort using the Framingham coronary point score suggests that traditional risk factors are inadequate predictors of coronary heart disease in hemodialysis patients. CONCLUSIONS: Some of the traditional coronary risk factors in the general population appear to be also applicable to the hemodialysis population, while other factors did not correlate with atherosclerotic cardiovascular diseases in this cross-sectional study. Nontraditional risk factors, including the uremic milieu and perhaps the hemodialysis procedure itself, are likely to be contributory. Further studies are necessary to define the cardiovascular risk factors in order to devise preventive and interventional strategies for the chronic hemodialysis population.

Continuous renal replacement therapies: an update.

Continuous renal replacement modalities have found widespread use and acceptance over the last decade. The various modalities differ in the kind of access (arteriovenous v venovenous); in the application of convective clearance (continuous hemofiltration), diffusive clearance (continuous hemodialysis), or a combination of both (continuous hemodiafiltration); and in the location where the replacement fluid enters the circuit (predilution v postdilution). Continuous therapies incorporate several advantages, such as improved hemodynamic stability, the possibility for unlimited alimentation, optimal fluid balance, and gradual urea removal without fluctuations. However, it has not yet been shown whether these advantages have a significant impact on outcome and prognosis, the ultimate measure of treatment efficiency. Major disadvantages of continuous therapies are the ongoing necessity for continuous anticoagulation, immobilization of the patient, and possible side effects from lactate-containing replacement fluid or dialysate. Continuous renal replacement procedures have certainly made the management of critically ill patients easier. In particular, oligoanuric patients with diuretic resistant volume overload and hemodynamically unstable patients with acute renal failure and concomitant sepsis or multiorgan failure appear to benefit most from continuous treatment. The role of continuous hemofiltration as a method of removing serum cytokines in septic patients without renal failure is still controversial and needs further clinical assessment. Due to slow efficacy, continuous renal replacement is indicated only in rare circumstances for intoxication; this therapy also is of rather limited use in severe hyperkalemia or acidosis. Noncritically ill patients with uncomplicated renal failure (eg, due to the use of dye or antibiotics) should be treated with intermittent hemodialysis or peritoneal dialysis. Furthermore, intermittent hemodialysis is preferable in patients with hemorrhagic diathesis because it can be easily performed without anticoagulants.

Peritoneal dialysis: an evolving understanding.

Since continuous ambulatory peritoneal dialysis (PD) was introduced in 1978 by Popovich and Moncrief, the use of peritoneal dialysis as effective renal replacement therapy has expanded on an international level. Improvements in technology and technique have lessened the incidence of infectious complications, although strategies continue to evolve to improve technical success. As technical challenges have been met, increasing attention has been turned to PD dose. Retrospective studies have strongly suggested that patient outcome is related to the amount of toxin removal. Recently, prospective data confirm that morbidity and mortality are strongly associated with dialysis adequacy. The important contribution of residual renal function to total toxin clearance is now recognized and implies a need to adjust dialysis dose to maintain adequate clearance as residual renal function declines. Reasonable, yet arbitrary, targets for dialysis clearances can now be asserted as Kt/V of 2.0 per week and weekly creatinine clearance of 60 L/wk. These current guidelines indicate a need to individualize dialysis dose to achieve target clearances and improved outcome. Current data also indicate that malnutrition is highly prevalent in the PD population and is associated with poor clinical outcomes, including decreased survival. Deterioration in nutritional status begins before the initiation of dialysis, and it seems that worse nutritional status at the start of dialysis is a strong predicator of poor outcome. These findings suggest that earlier initiation of dialysis, before a significant decline in nutritional status occurs, is warranted to maintain good nutrition and optimize outcome.

A proposed glossary for dialysis kinetics.

Quantification of the dialysis dose and assessment of nutritional status and response to nutritional therapy have become standard parts of the management of the chronic dialysis patient. Although advances in these areas have led to a more rational basis for therapy, certain misconceptions and points of confusion appear to have occurred. Recognizing the importance of a standard nomenclature to the development of concepts and the communication of research findings, we have attempted to compile a list of terms that are commonly used in the field of dialysis. New terms have been proposed for current ones that do not seem adequate. In addition, we have discussed potential methodologies for obtaining more accurate data for dialysis kinetics and for precise monitoring of nutritional intake and status. It is hoped that this glossary will stimulate discussion that will lead to refinements in terminology and concepts that will, in turn, improve research and practice in nephrology. It is anticipated that many of these definitions and recommendations will be modified or superseded as the management of patients with renal failure continues to advance.

Health-related quality of life associated with recombinant human erythropoietin therapy for predialysis chronic renal disease patients.

The investigators evaluated the impact of recombinant human erythropoietin (r-HuEPO) therapy on health-related quality of life (HRQL) in predialysis chronic renal disease patients with anemia. Eighty-three patients were entered into a randomized, parallel-group, open-label clinical trial with follow-up evaluations over 48 weeks. Forty-three patients were assigned to r-HuEPO treatment, and 40 patients were assigned to an untreated control group. Hematocrit levels were measured at baseline and monthly. HRQL was assessed at baseline and at weeks 16, 32, and 48. The HRQL assessment included measures of physical function, energy, role function, health distress, cognitive function, social function, home management, sexual dysfunction, depression, and life satisfaction. Significant improvements in hematocrit levels were observed in the r-HuEPO-treated group (P < 0.0001), and no changes were seen in the untreated group. Correction of anemia (hematocrit > or = 36) occurred in 79% of r-HuEPO-treated patients and 0% of control patients. Significant improvements in assessments of energy (P < 0.05), physical function (P < 0.05), home management (P < 0.05), social activity (P < 0.05), and cognitive function (P < 0.05) were found for the r-HuEPO-treated group. No changes were observed in the control group, except for a decrease in physical function (P < 0.05). Between-group differences favoring the r-HuEPO-treated group were found for energy (P < 0.05) and physical functioning (P < 0.05). In patients receiving r-HuEPO, significant improvements were seen in hemotocrit levels, and these increases resulted in improvements in HRQL.

Adequacy of continuous ambulatory peritoneal dialysis: morbidity and mortality in chronic peritoneal dialysis.

Mortality for hemodialysis patients tends to be in excess of 20% per year, and it is generally agreed that outcome for continuous ambulatory peritoneal dialysis patients is comparable. Several investigators have suggested recently that continuous ambulatory peritoneal dialysis, as commonly practiced, may not provide adequate therapy, especially for larger patients and for those with no residual renal function. Unfortunately, a dose-response curve relating the amount of dialysis delivered and clinical outcome for continuous ambulatory peritoneal dialysis patients has not been constructed. Several methods of quantifying the dose of peritoneal dialysis are described. Both cross-sectional and longitudinal studies are reviewed. The conclusions of these studies are of limited value, however, because of their retrospective nature and the limited number of patients enrolled. Nevertheless, in aggregate, these studies suggest that survival may be improved by higher doses of dialysis. They also suggest that while malnutrition is relatively common in this patient population, higher doses of Kt/V are associated with higher protein intake (as measured by protein catabolic rate). Serum albumin is recognized as a strong predictor of clinical outcome and the protein catabolic rate may correlate directly with Kt/V, but there are studies that support and others that refute a correlation between Kt/V and serum albumin. Definitive answers to these questions are likely to be available in the near future. Two large multicenter studies are currently under way. Preliminary results may be available in the near future.

Solute clearance in continuous venovenous hemodialysis. A comparison of cuprophane, polyacrylonitrile, and polysulfone membranes.

Critically ill patients with ARF and MOSF were treated with continuous venovenous hemodialysis (CVVHD). The BSM 22 delivery system (CGH Medical, Denver, CO) and four different dialyzer membranes were used. Vascular access was achieved with a dual lumen catheter placed percutaneously into a large vein. Heparin was used for anticoagulation, and commercially available peritoneal dialysis fluid was used as dialysate. At a fixed blood flow rate of 100 ml/min, the dialysate inflow and outflow rates were regulated to control azotemia and fluid balance. Blood side and dialysate side clearances for urea nitrogen, creatinine, bicarbonate, and lactate were measured. All dialyzer membranes studied provided high urea nitrogen clearance approximating dialysate outflow rate and resulting in excellent control of azotemia. Some of the dialyzer membranes also had high creatinine and bicarbonate clearances. Bicarbonate loss was balanced by lactate uptake with all dialyzers. It is concluded that CVVHD is an efficient and safe therapy for acute renal failure, capable of maintaining nitrogen balance in patients with protein catabolic rates up to 2 g/kg/day. Urea nitrogen clearance is dependent upon dialysate outflow rate rather than the dialyzer membrane type or dialyzer flow geometry, and may prove to be the modality of choice for therapy of acute renal failure in unstable patients with MOSF.

Suppression of renal vein renin profiles by mannitol prophylaxis: implications in the evaluation of renovascular hypertension.

Renal arteriography with concomitant renal vein renin profiling remains the diagnostic standard for evaluating the anatomic and physiologic significance of stenotic renal artery lesions in hypertensive patients. False-negative renal vein renin profiles with failure of lateralization in patients with anatomically apparent high-grade stenosis complicate the diagnostic process. Mannitol is frequently administered prophylactically to minimize the risk of dye nephropathy in these patients. Yet, the potential effects of mannitol on renal vein renin profiling in man have not been previously reported. Seven patients with renovascular hypertension were studied prospectively to determine changes in renal vein renin profiles before and after mannitol prophylaxis. Despite captopril stimulation, all patients demonstrated significant renin suppression leading to the loss of renin lateralization in patients with unilateral renovascular hypertension. In 60% of the patients, renal vein renin ratios fell to below the standard 1.5 to 1 ratio after mannitol infusion. In patients with bilateral renovascular disease, the least stenotic side suppressed completely, while the more stenotic side suppressed partially. Percent suppression analysis showed a mean suppression of 56.8% on the stenotic side versus 8.2% on the noninvolved side (P less than 0.002). In every study, suppression equaled or exceeded 32% on the involved side and was less than this on the noninvolved side. Thus, the degree of renin suppression following mannitol infusion may prove to be an important tool in the diagnosis of clinically significant stenotic lesions. The mechanism of mannitol-induced suppression remains undefined, but appears independent of volume expansions or dilutional effects. The inhibitory effects of mannitol on renin profiles can obscure the diagnosis of underlying renovascular hypertension.

Intradialytic parenteral nutrition in chronic hemodialysis patients.

The effects of intradialytic parenteral nutrition (IDPN) were studied in chronic hemodialysis (CHD) patients who had a normalized protein catabolic rate (PCRN) of less than or equal to 0.8 g/kg/day, and KT/V = 0.94 +/- 0.04. Intradialytic parenteral nutrition was administered during thrice weekly CHD for 3-6 months, and consisted of essential and nonessential amino acids (42.5 g), glucose (125 g), and lipid emulsion (50 g). Blood urea nitrogen, creatinine, total protein, albumin, transferrin, pre-albumin, total lymphocyte count, anthropometrics, protein catabolic rate, 3 day historic dietary protein intake, and dietary energy intake (DEI) were measured at baseline, before IDPN, during IDPN, and at completion of IDPN. Six of nine enrolled patients completed the study. Reasons for withdrawal included nausea and hyperglycemia or hypoglycemia. DPI normalized for body weight (DPIN) increased significantly from 0.75 +/- 0.1 to 1.02 +/- 0.18 (p = 0.02). Increases in PCRN (0.57 +/- 0.18 to 0.78 +/- 0.2) and DEI (1495 +/- 266 to 1681 +/- 358) did not reach statistical significance. More aggressive IDPN or a longer study period may be necessary to assess this form of nutritional intervention.

Urea kinetic analysis and clinical outcome on CAPD. A five year longitudinal study.

The present study, along with some recent studies, suggests that there is an organic link between the amount of dialysis a patient receives and his/her nutritional status. The latter, as reflected by serum albumin, is predictive of survival on CAPD. It is clear, therefore, that urea kinetic analysis is a powerful tool for prescribing and monitoring therapy in CAPD patients.

Successful treatment of postparathyroidectomy hypocalcemia using continuous ambulatory intraperitoneal calcium (CAIC) therapy.

Severe, recalcitrant hypocalcemia and hungry bone syndrome can complicate parathyroidectomy in end-stage renal disease patients. Treatment with prolonged and massive doses of intravenous calcium, with calcitriol supplementation, is often necessary, but potentially dangerous and may prolong hospitalization. Three CAPD patients (including 1 with malabsorption) were safely treated by adding 1 to 3 ampules (10-30 mL) of 10% calcium gluconate solution to each bag of dialysate for up to 29 months. Continuous ambulatory intraperitoneal calcium (CAIC) therapy was initiated postoperatively and continued on an outpatient basis until the patients' hungry bone syndrome resolved and serum calcium normalized. Complications such as visible dialysate precipitation or an increased rate of peritonitis were not observed. Mean total calcium uptake was approximately 137 to 226 mg/exchange. We conclude that CAIC therapy is a safe, effective treatment both for CAPD patients with postparathyroidectomy hypocalcemia with hungry bone syndrome, as well as in patients with hypocalcemia secondary to malabsorption.

Carpal tunnel syndrome in dialysis patients: comparison between continuous ambulatory peritoneal dialysis and hemodialysis populations.

Carpal tunnel syndrome (CTS) has been reported with increased frequency in hemodialysis (HD) patients. A comparative study of patients on continuous ambulatory peritoneal dialysis (CAPD) has not been previously reported. To delineate the significance of dialytic modality and access-related risk factors, this study investigated the incidence and patient characteristics of CTS in CAPD v HD populations. One hundred and fifty one patients (HD n = 90, CAPD n = 61) were evaluated by questionnaire, physical examination, and nerve conduction studies. Age, gender, renal diagnosis, access, diabetic history, and duration of dialysis were determined. Eight of 57 CAPD and 15/83 HD patients had CTS. chi 2 testing revealed no significant difference in incidence (P = 0.7). It is concluded that CTS occurs with similar incidence in CAPD and HD populations. Dialytic modality and access are not likely to be factors in the development of CTS. Rather, CTS is a metabolic complication of end-stage renal failure.

Solute transport in continuous hemodialysis: a new treatment for acute renal failure.

A pumpless dialysis technique which combines continuous convection and diffusion was studied in 15 critically ill acute renal failure patients. Fluid identical in composition and purity to that used in peritoneal dialysis was continuously circulated (single-pass) at 16.6 cc/min through the dialysis compartment of a 0.43 m2 flat plate PAN membrane dialyzer. Whole blood clearances for urea, creatinine and phosphate averaged 25.3 +/- 4.4 cc/min, 24.1 +/- 5.5 cc/min and 21.3 +/- 5.6 cc/min, respectively. Over the range of blood flows studied (50 to 190 cc/min) clearances of these solutes were independent of blood flow rate but rather were determined by both dialysate flow rate and ultrafiltration rate. In contrast net fluxes of calcium and sodium were correlated only with ultrafiltration rate. Bicarbonate loss was 0.52 +/- 0.11 mEq/min; K+ balance varied with dialysate K+; glucose uptake from dialysate was 107 +/- 24.0 mg/min. In fresh non-clotting dialyzers, mean ultrafiltration rate was 8.1 cc/min. At QBi of 70 to 190 cc/min, dialysate and blood solute equilibrate yielding a total clearance equal to the dialysate outflow, or 25 cc/min, that is, the sum of dialysate flow rate plus ultrafiltration rate. In comparison to currently used continuous arteriovenous hemofiltration (CAVH), the exceptionally-high solute clearances obtained with continuous hemodialysis constitute a significant improvement in continuous renal replacement therapy.