Clinical morbidity in pediatric dialysis patients: data from the Network 1 Clinical Indicators Project.

The Health Care Financing Administration (HCFA) has gathered clinical data on end stage renal disease (ESRD) patients since 1994, but details are only available on patients >/=18 years. In this report, we present morbidity data collected prospectively over 12 months from all children (1-18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD) within the six-state New England area. During this year, 17 observations were recorded on 14 HD patients (age 13.4+/- 11.3 years) and 36 observations were made on 25 PD patients (age 11.5+/-4.8 years; mean +/- SD). These patients were generally highly functional, attending school at least part time in nearly all cases. Dialysis adequacy index (DAI), defined as the delivered KT/V divided by DOQI guideline values, indicated that patients were well dialyzed (HD 1.41+/-0.1 and PD 1.10+/-0.1; mean +/- SE). When all dialysis patients were grouped and analyzed, the DAI did not correlate with number of hospitalizations, degree of anemia, serum albumin, or type of dialysis. The number of hospitalizations were greater the younger the patient (P<0.01). The need for antihypertensive medications was higher in the children maintained on HD (94%) compared to children on PD (58%) (P<0.01). Lastly, while serum ferritin did not correlate with serum iron, hematocrit or Epo dosage, it was inversely related to serum albumin (P<0.03). We conclude that, in children, (1) exceeding suggested dialysis adequacy may not improve patient morbidity, (2) the need for antihypertensive medications appears greater in children maintained on HD, and (3) inflammation may play a role in determining serum albumin independent of nutrition.

Treatment of hyperhomocysteinemia in end-stage renal disease.

Mild to moderate hyperhomocysteinemia (Hhcy) is observed in more than 90% of patients with end-stage renal disease (ESRD) undergoing maintenance dialysis and approximately 60% to 70% of chronic stable renal transplant recipients. The reported association between Hhcy and the development of arteriosclerotic cardiovascular disease may account, in part, for the disproportionate risk for cardiovascular morbidity and mortality in patients with chronic renal disease. Treatment with the recommended daily allowances of folic acid and vitamins B(6) and B(12), which consistently normalizes total homocysteine (tHcy) levels in the general population free of chronic renal disease, rarely results in the normalization of tHcy levels in patients with ESRD. A large number of investigations now have shown that even grossly supraphysiological doses of folic acid and vitamins B(6) and B(12) fail to normalize tHcy levels in more than 90% of dialysis-dependent patients with ESRD with baseline Hhcy. Conversely, such treatment consistently normalizes tHcy levels among hyperhomocysteinemic chronic stable renal transplant recipients or patients with mild to moderate renal insufficiency. A randomized, placebo-controlled, tHcy-lowering intervention trial involving approximately 4,000 chronic stable US renal transplant recipients (RO1 DK56486 01A2) will soon be underway to formally address the tenable hypothesis that tHcy-lowering treatment may reduce the risk for arteriosclerotic outcomes. Data from this trial should be applicable to patients with chronic renal insufficiency in general.

Residual renal function and mortality risk in hemodialysis patients.

Residual renal function, defined as the urinary clearance of urea and creatinine, is minimal in many patients treated with hemodialysis (HD) and tends to be ignored in most outcome studies involving HD patients. Recent studies showed that residual renal function, even at a low level, is influential in preventing mortality in the minority of patients with end-stage renal disease treated with peritoneal dialysis. This issue generally has not been examined in patients treated with HD. This prospective observational study of all 114 patients at a single community-based freestanding HD center is designed to examine the impact of residual renal function (defined as renal urea clearance and renal creatinine clearance derived from 24-hour urinary volumes) on mortality over a 2-year period. During that period, 50 deaths occurred in 114 patients. The presence of residual renal function was protective against mortality (odds ratio for death, 0.44; 95% confidence interval, 0.24 to 0.81; P = 0.008), even after adjustment for duration of dialysis treatment, age, smoking, presence of diabetes, presence of cardiovascular disease, serum albumin level, and urea reduction rate. In conclusion, the presence of residual renal function, even at a low level, is associated with a lower mortality risk in HD patients.

Treatment of hyperhomocysteinemia in hemodialysis patients and renal transplant recipients.

BACKGROUND: Hyperhomocysteinemia, a putative atherothrombotic risk factor, is observed in at least 85% of patients undergoing maintenance hemodialysis (HD), as well as 65 to 70% of renal transplant recipients (RTRs). The hyperhomocysteinemia regularly found in HD patients is largely refractory to combined oral vitamin B supplementation featuring supraphysiological doses of folic acid (FA). Relative to their HD counterparts, the hyperhomocysteinemia of RTRs appears to be considerably less refractory to treatment with high-dose FA-based vitamin B supplementation regimens, although controlled comparison data are lacking. We evaluated whether improved total homocysteine (tHcy)-lowering efficacy could be achieved in chronic HD patients with a high-dose L-5-methyltetrahydrofolate (MTHF)-based regimen, as suggested by recent uncontrolled findings, and compared the relative responsiveness of RTRs and HD patients with equivalent baseline tHcy levels, to 12 weeks of tHcy lowering with combined folate-based vitamin B treatment. METHODS: First, we blocked randomized 50 chronic, stable HD patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 25 subjects treated for 12 weeks with oral FA at 15 mg/day, or an equimolar amount (17 mg/day) of oral MTHF. All 50 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12. RESULTS: The mean percentage (%) reductions (+/- 95% confidence intervals) in predialysis tHcy were not significantly different [MTHF 17.0% (12.0 to 22.0%), FA 14.8% (9.6 to 20.1%), P = 0.444 by matched analysis of covariance adjusted for pretreatment tHcy]. Final on-treatment values (mean with 95% confidence interval) were: MTHF, 20.0 micromol/L (18.8 to 21.2); and FA, 19.5 micromol/L (18.3 to 20.7). Moreover, neither treatment resulted in "normalization" of tHcy levels (that is, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients [MTHF, 2 out of 25 (8%); FA, 0 out of 25 (0%); Fisher's exact test of between groups difference, P = 0.490]. Second, we compared the relative responsiveness of (N = 10) RTRs and (N = 39) HD patients with equivalent baseline tHcy levels (RTR range of 14.2 to 23.6 micromol/L, and HD range of 14.4 to 24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTRs received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, MTHF, in addition to 50.0 mg/day of vitamin B6 and 1.0 mg/day of vitamin B12. The mean percentage (%) reductions (+/- 95% confidence interval) in tHcy were as follows: RTR 28.1% (16.2 to 40.0%); HD 12.1% (6.6 to 17.7%, P = 0.027 for comparison of between groups differences by analysis of covariance adjusted for baseline tHcy levels). Moreover, 5 out of 10 (50.0%) of the RTR versus only 2 out of 39 (5.1%) of the HD patients had final on-treatment tHcy levels <12 micromol/L (P = 0.002 for comparison of between groups differences by Fisher's exact test). CONCLUSIONS: First, in comparison to high-dose FA, high-dose oral MTHF-based supplementation does not afford improved tHcy-lowering efficacy among HD patients. The preponderance of HD patients (that is,> 90%) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution. Second, relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering vitamin B treatment regimens featuring supraphysiological amounts of FA or the reduced folate MTHF. Accordingly, RTRs are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering vitamin B intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.

Rapid communication: L-folinic acid versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients.

BACKGROUND: The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid (FA). We evaluated whether a high-dose L-folinic acid-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients, as suggested by a recent uncontrolled report. METHODS: We block-randomized 48 chronic, stable hemodialysis patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 24 subjects treated for 12 weeks with oral FA at 15 mg/day or an equimolar amount (20 mg/day) of oral L-folinic acid (FNA) [L-5-formyltetrahydrofolate]. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12. RESULTS: The mean percentage (%) reductions (with 95% CIs) in predialysis tHcy were not significantly different [FNA = 22.1% (11.8 to 31.4%), FA = 20.7% (11.7 to 30.5%), P = 0.950 by paired t test]. Final on-treatment values (mean with 95% CI) were as follows: FNA, 15.9 micromol/L (14.0 to 18.0); FA, 16.9 micromol/L (14.8 to 18.8). Moreover, in those subjects with baseline tHcy levels >/=14 micromol/L, neither treatment resulted in "normalization" of tHcy levels (that is, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients [FNA = 2 out of 22 (9.1%); FA = 2 out of 24 (8.3%); Fisher's exact test of between groups difference, P = 1.000]. CONCLUSIONS: Relative to high-dose FA, high-dose oral L-folinic acid-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (that is,> 90%) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen.

First hemodialysis access selection varies with patient acuity.

Timely placement of a reliable permanent vascular access is essential for hemodialysis care quality; National Kidney Foundation Dialysis Outcomes Quality Improvement (NKF-DOQI) guidelines emphasize native arterio-venous (AV) fistulae as preferred access for incident patients. As part of Network One's Vascular Access Quality Improvement Project (QIP) we investigated whether patients' course to end-stage renal disease (ESRD) influenced vascular access selection. Baseline information was obtained for incident (1998) dialysis patients from 6 centers participating in the Network QIP. Patients were subdivided into 3 predefined clinical groups: KNOWN (known chronic renal disease, seen by a nephrologist, with predictable progression to ESRD), CRISIS (KNOWN but with unanticipated medical crisis precipitating ESRD), and UNKNOWN (not known to have chronic renal insufficiency or never seen by a nephrologist before developing ESRD). Two hundred forty patients were identified (median age 69.9, 42% diabetic). Only 43% of the entire population experienced an orderly progression to renal insufficiency. The most frequent initial access was a catheter (54%), followed by a fistula (29%) and a graft (16%), but selection of initial access differed significantly by patient group, with 46% of KNOWN patients receiving a fistula (P <.001). After 2 months of dialysis, the initial access supported dialysis in only 53.7% of the KNOWN patients, and in 59.4% and 45.7% of the CRISIS and UNKNOWN patients, respectively. We conclude that unpredicted, new ESRD patients are common and are less likely to receive a fistula as initial hemodialysis access. Studies should define optimum access management when dialysis requirement is unforeseen.

Residual renal function in a large cohort of peritoneal dialysis patients: change over time, impact on mortality and nutrition.

OBJECTIVE: Residual renal function contributes importantly to total solute clearance in peritoneal dialysis (PD) patients. This study was designed to examine the progression of residual renal function over time and its impact on nutrition and mortality in PD patients in the six New England states (ME, NH, VT, CT, MA, RI) comprising End Stage Renal Disease (ESRD) Network 1. DESIGN: As part of the ESRD Clinical Indicators Project, data on 990 PD patients in Network 1 were abstracted from data supplied by dialysis units in the fourth quarter of 1997. This included demographic information; dose of PD in L/day; weekly renal, dialysis, and total Kt/V urea; weekly renal, dialysis, and total creatinine clearance (CCr); serum albumin level; and mortality and transplantation information. Data collection was repeated in the second and fourth quarters of 1998 and in the second quarter of 1999. PATIENTS: 990 PD patients in Network 1. OUTCOME MEASURES: The change in total and renal solute clearances over time, the relationship between renal clearance and mortality, and the relationship between renal clearance and nutritional status, as represented by serum albumin. RESULTS: Over the 2-year period, mean weekly renal Kt/V urea and weekly renal CCr dropped significantly. To examine the effect of residual renal function on mortality, patients were divided into high and low (above and below the median) weekly renal Kt/V urea and weekly renal CCr groups. Patients above the median levels of both weekly renal Kt/V urea and weekly renal CCr had a significantly decreased risk of dying during the observation period, after controlling for age, gender, serum albumin level, and diabetic status [OR for high vs low renal Kt/V urea 0.54 (CI 0.34 - 0.84), OR for high vs low renal CCr 0.61 (CI 0.40 - 0.94)]. The mean weekly renal Kt/V urea was significantly and directly correlated with the mean serum albumin level by Spearman rank correlation (R = 0.133, p < 0.001), as was the mean weekly renal CCr (R = 0.115, p < 0.001). CONCLUSIONS: Residual renal function is an important contributor to total solute clearance in PD patients. Even at low levels it is linked to decreased mortality and better nutritional status.

Outcome data on pediatric dialysis patients from the end-stage renal disease clinical indicators project.

Network 1 (New England) initiated the Clinical Indicator Project to survey dialysis adequacy (Kt/V), nutrition (serum albumin level), and anemia management in patients maintained on chronic dialysis. Because little information is available in children, data were specifically recorded covering these variables in patients (age, 1 to 18 years) maintained on either hemodialysis (HD) or peritoneal dialysis (PD). During the 18 months of data collection, 29 observations were recorded on 23 HD patients (age, 14.3 +/- 3.6 years), and 43 observations were made on 30 PD patients (age,10.6 +/- 4.7 years). Kt/V correlated inversely with the age of the patient (HD, P < 0.004; PD, P < 0.0007). Although serum albumin level was not associated with dialysis adequacy in HD patients, there was a strong inverse relationship between albumin level and Kt/V in PD patients (P < 0.002). Hematocrit values were not significantly different in the two groups (HD, 31.0% +/- 5.5% versus PD, 32.9% +/- 4.8%) and could not be correlated with weekly erythropoietin dose. Weekly erythropoietin dose was directly related to patient age in both groups (HD, P < 0.05; PD, P < 0.02). The weekly erythropoietin dosage needed to maintain the hematocrit was greater in HD patients (HD, 11,211 +/- 7,484 U versus PD, 3,790 +/- 1,968 U; P < 0.0001). We conclude that (1) smaller children in both groups tend to have a greater Kt/V, (2) Kt/V greater than 2.75 in PD patients may not improve nutrition per se and could result in increased albumin losses, and (3) erythropoietin dosing appears to correlate best with patient size (age) rather than degree of anemia.

Controlled comparison of L-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients.

BACKGROUND: The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid. We evaluated whether a high-dose L-5-methyltetrahydrofolate-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients. METHODS AND RESULTS: We block-randomized 50 chronic, stable hemodialysis patients on the basis of their screening predialysis tHcy levels, sex, and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d (FA group) or an equimolar amount (17 mg/d) of oral L-5-methyltetrahydrofolate (MTHF group). All 50 subjects also received 50 mg/d of oral vitamin B(6) and 1.0 mg/d of oral vitamin B(12). The mean percent reductions (+/-95% CIs) in predialysis tHcy were not significantly different: MTHF, 17.0% (12.0% to 22.0%); FA, 14.8% (9.6% to 20.1%); P=0.444 by matched ANCOVA adjusted for pretreatment tHcy. Final on-treatment values (mean with 95% CI) were MTHF, 20.0 micromol/L (18.8 to 21.2 micromol/L); FA, 19.5 micromol/L (18.3 to 20.7 micromol/L). Moreover, neither treatment resulted in "normalization" of tHcy levels (ie, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients: MTHF, 2 of 25 (8%); FA, 0 of 25 (0%); Fisher's exact test of between-groups difference, P=0.490. CONCLUSIONS: Relative to high-dose folic acid, high-dose oral L-5-methyltetrahydrofolate-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (ie, >90%) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution.

Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients.

BACKGROUND: Mild hyperhomocysteinemia is common among maintenance hemodialysis (HD) patients and renal transplant recipients (RTR) and may contribute to the excess incidence of arteriosclerotic outcomes experienced by both patient groups. Relative to their RTR counterparts, the hyperhomocysteinemia of HD patients seems to be considerably more refractory to treatment with high-dose folic acid (FA)-based B-vitamin supplementation regimens, although controlled comparison data are lacking. METHODS: We compared the relative responsiveness of (n=10) RTR and (n=39) HD patients with equivalent baseline total homocysteine (tHcy) levels (i.e., RTR range=14.2-23.6 micromol/L; HD range=14.4-24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTR received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, L-5-methyltetrahydrofolate, in addition to 50.0 mg/day of vitamin B6, and 1.0 mg/day of vitamin B12. RESULTS: The mean percent (%) reductions (+/-95% confidence interval) in tHcy were: RTR=28.1% (16.2-40.0%); HD=12.1% (6.6-17.7%), P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels. Moreover, (50.0%) of 10 of the RTR versus only (5.1%) of 39 of the HD patients had final on-treatment tHcy levels <12 micromol/L; P=0.002 for comparison of between-groups differences by Fisher's exact test. CONCLUSION: Relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering B-vitamin treatment regimens featuring supraphysiological amounts of FA or the reduced folate, L-5-methyltetrahydrofolate. Accordingly, RTR are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering B-vitamin intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.

Effect of aminoglycoside use on residual renal function in peritoneal dialysis patients.

Residual renal function (RRF) is a major contributor to total solute clearance in peritoneal dialysis (PD) patients, and maintenance of RRF has been linked to decreased morbidity and mortality in PD. There have been few clinical studies examining the impact of factors that potentially affect RRF in PD. This is a prospective observational study that examines the effects of parenteral aminoglycosides, a common nephrotoxin in the general population, on RRF in a cohort of PD patients. Seventy-two patients from two Rhode Island PD units were observed over 4 years. Twenty-four-hour renal creatinine clearances and urine volumes were measured every 4 to 6 months. The patients were divided into three groups, depending on exposure to peritonitis and aminoglycoside use. Group I included patients without peritonitis who received no intravenous (IV) or intraperitoneal (IP) antibiotics. Group II included patients with peritonitis who received IV or IP penicillins, cephalosporins, vancomycin, or quinolones, but no aminoglycosides. Group III included patients with peritonitis who received IV or IP aminoglycosides for at least 3 days. Patients in group III had a more rapid decline in renal creatinine clearance (-0.66 +/- 0.58 mL/min/mon) than groups I and II (P < 0.005) and had a more rapid decline in daily urine volume (-74 +/- 62 mL/d/mon) than groups I and II (P < 0.01). We conclude that IV or IP aminoglycosides seem to increase the rapidity of decline in RRF in PD patients. In patients with solute clearance dependent on RRF, it seems reasonable to withhold aminoglycosides, especially if other antibiotics are available and appropriate.

Plasma total homocysteine and hemodialysis access thrombosis: a prospective study.

Mild hyperhomocysteinemia, a putative risk factor for atherothrombotic cardiovascular disease morbidity and mortality, may contribute to the excess incidence of atherothrombotic outcomes in the dialysis-dependent end-stage renal disease population. Hemodialysis access (fistula or graft) thrombosis is an unfortunately common and costly morbidity in this patient population. In this study, using a prospective design, the potential relationship between baseline nonfasting, predialysis plasma total homocysteine (tHcy) levels and vascular access-related morbidity was examined in a cohort of 84 hemodialysis patients with a fistula or prosthetic graft as their primary hemodialysis access. Vascular access thrombotic episodes were recorded over a subsequent 18-mo follow-up period. Forty-seven patients (56% of the total) had at least one access thrombosis during the 18-mo follow-up period (median follow-up, 13 mo; rate, 0.6 events per patient-year of follow-up). Proportional hazards modeling revealed that each 1 microM/L increase in the tHcy level was associated with a 4.0% increase in the risk of access thrombosis (95% confidence interval, 1.0 to 6.0%, P = 0.008). This association persisted after adjustment for type of access (fistula versus graft), age, gender, time on dialysis, diabetes, smoking, hypertension, nutritional status, urea reduction ratio, dyslipidemia, and the presence of previous vascular disease. Elevated tHcy levels appear to confer a graded, independent increased risk for hemodialysis access thrombosis. A randomized, controlled trial examining the effect of tHcy-lowering intervention on hemodialysis access thrombosis appears to be justified.

Antihypertensive therapy and progression of chronic renal disease.

This paper reviews findings on the relationship between blood pressure control and the progression of renal disease. Experimental studies demonstrate a correlation between systemic blood pressure and histologic glomerular injury and the delay in progression of renal disease with antihypertensive therapy, particularly with angiotensin-converting enzyme inhibitors. Recent clinical findings are reviewed, including epidemiologic data linking hypertension to subsequent renal disease, and clinical studies showing a beneficial effect on progression of renal disease with lower than usual blood pressure targets.

Clinical outcome in three patients with postpartum hemolytic uremic syndrome treated with frequent plasma exchange.

This study reviewed 3 cases of postpartum hemolytic uremic syndrome (HUS) at our hospital over a 3 year period. The 3 patients had clinical and laboratory abnormalities similar to those of 12 patients with other causes of thrombotic microangiopathy presenting during the same time span. Both groups were treated with 4-7 plasma exchange treatments/week and prednisone, 60 mg/day or its intravenous equivalent, until remission. The postpartum HUS patients had a more complicated, prolonged course; 3 of 3 required dialysis compared to 4 of 12 in the nonpostpartum group (p < 0.05), and they required more plasma exchange treatments (49 +/- 17 vs. 10 +/- 8, p = 0.0001) and a longer duration of therapy (70 +/- 31 vs. 19 +/- 17 days, p < 0.01) before remission. All postpartum HUS patients discontinued dialysis and survived whereas 4/12 nonpostpartum patients died before attaining remission. Compared to other variants of thrombotic microangiopathy, postpartum HUS requires a longer duration of therapy, but with aggressive therapy, renal and overall prognoses may be better.

Elevated fasting total plasma homocysteine levels and cardiovascular disease outcomes in maintenance dialysis patients. A prospective study.

There is an excess prevalence of hyperhomocysteinemia in dialysis-dependent end-stage renal disease (ESRD) patients. Cross-sectional studies of the relationship between elevated total homocysteine (tHcy) levels and prevalent cardiovascular disease (CVD) in this patient population suffer from severe methodologic limitations. No prospective investigations examining the association between tHcy levels and the subsequent development of arteriosclerotic CVD outcomes among maintenance dialysis patients have been reported. To assess whether elevated plasma tHcy is an independent risk factor for incident CVD in dialysis-dependent ESRD patients, we studied 73 maintenance peritoneal dialysis or hemodialysis patients who received a baseline examination between March and December 1994, with follow-up through April 1, 1996. We determined the incidence of nonfatal and fatal CVD events, which included all validated coronary heart disease, cerebrovascular disease, and abdominal aortic/lower-extremity arterial disease outcomes. After a median follow-up of 17.0 months, 16 individuals experienced at least one arteriosclerotic CVD event. Cox proportional-hazards regression analyses, unadjusted and individually adjusted for creatinine, albumin, and total cholesterol levels, total/HDL cholesterol ratio, dialysis adequacy/residual renal function, baseline CVD, and the established CVD risk factors (ie, age, sex, smoking, hypertension, diabetes/glucose intolerance, and dyslipidemia) revealed that tHcy levels in the upper quartile (> or = 27.0 mumol/L) versus the lower three quartiles (< 27.0 mumol/L) were associated with relative risk estimates (hazards ratios, with 95% confidence intervals for the occurrence of (pooled) nonfatal and fatal CVD ranging from 3.0 to 4.4; 95% confidence intervals (1.1-8.1) to (1.6-12.2). We conclude that the markedly elevated fasting tHcy levels found in dialysis-dependent ESRD patients may contribute independently to their excess incidence of fatal and nonfatal CVD outcomes.

Sodium balance in renal failure.

Sodium balance in patients with renal failure varies with the severity and clinical manifestations of renal disease. Progressive chronic renal insufficiency is typified by an adaptive increase in the sodium excretion rate per nephron as the total glomerular filtration rate declines. This increase is caused, at least in part, by the effect of atrial natriuretic peptide and other natriuretic peptides, whose release is augmented in the setting of volume expansion and renal failure. However, exogenous administration of natriuretic peptides in clinical chronic and acute renal disease does not consistently increase renal sodium excretion. As the glomerular filtration rate progressively declines towards end-stage renal disease, total renal sodium excretion eventually decreases, and extracellular volume expansion, hypertension, and edema develop. Sodium removal, induced by high dose diuretics or via convective ultrafiltration during dialysis, is necessary to decrease the extracellular volume to normal.