Dialysis catheter-induced superior vena cava syndrome and downhill esophageal varices.

Superior vena cava stenosis is a well-documented complication of central venous dialysis catheters. Rarely, this obstruction can lead to the formation of downhill esophageal varices. We present a case of esophageal varices as a complication of dialysis catheter-induced superior vena cava stenosis, which became symptomatic after the placement of an upper extremity arteriovenous graft and resolved with percutaneous angioplasty and stenting of the superior vena cava stricture.

Implications for the role of endogenous nitric oxide inhibitors in hemodialysis hypotension.

Hypotensive episodes during hemodialysis in patients with end-stage renal disease in the absence of inadequate maintenance of the plasma volume, pre-existence of cardiovascular disease, or autonomic nervous system dysfunction is accompanied by increase in the plasma concentrations of the end-products of nitric oxide metabolism, above the levels expected based on the reduction of urea. Factors that can influence the synthesis of nitric oxide or the regulation of the effects of this free radical in patients with chronic renal failure are reviewed. Convergence of these factors and their interactions during the hemodialysis procedure are discussed as the basis for the generation of excessive amounts of nitric oxide that serves as an important contributing factor in the development of symptomatic hypotension.

A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease.

BACKGROUND: Paricalcitol is a vitamin D analog approved for the prevention and treatment of secondary hyperparathyroidism associated with chronic renal failure. This study was designed to evaluate the long-term efficacy and safety of paricalcitol. Additional analysis evaluated the effects of paricalcitol in hypocalcemic and hyperphosphatemic subpopulations. PATIENTS AND METHODS: One hundred sixty-four end-stage renal disease (ESRD) patiesnts on hemodialysis were treated in an open-label, multicenter study lasting up to 13 months in duration. After a baseline or washout period, an initial starting dose of 0.04-0.393 microg/kg was given 2-3 times per week. This dose was adjusted at the discretion of the investigator according to the patient's intact parathyroid hormone level (iPTH), calcium level, and calcium-phosphorus (Ca x P) product. The therapy was intended to reproduce expected clinical use of paricalcitol. Patients represented a wide cross-section of the ESRD population, and were not excluded from the study based on age or underlying disease. RESULTS: The mean paricalcitol dose level throughout the study was 0.10 microg/kg. The mean iPTH levels (baseline mean 628.3 +/- 27.65 pg/ml) decreased rapidly during the first 4 months of therapy, and reached the designated target range (100-300 pg/ml) by month 5 (mean 295.3 +/- 25.69 pg/ml). A maximum mean decrease in iPTH level of 409 +/- 35.01 pg/ml was seen at month 13. Throughout the course of the study, the mean normalized calcium level was maintained well within the normal range (9.44-9.94 mg/dl). The mean phosphorus level was maintained in an acceptable range throughout the study (5.92-6.53 mg/dl). Mean Ca x P product was maintained between 52 and 65. Mean alkaline phosphatase levels decreased significantly from baseline with a maximum mean decrease of 62 +/- 17.3 U/l observed at month 9. In 34 initially hypocalcemic patients (mean of 7.7 mg/dl) iPTH levels decreased from baseline, on average, by 443 +/- 81.86 pg/ml while mean calcium levels rose by 1.2 +/- 0.23 mg/dl to reach the normal range. In 35 initially hyperphosphatemic patients (mean of 8.0 mg/dl) iPTH levels decreased, on average, by 515 +/- 103.31 pg/ml with an associated mean decrease in phosphorus of 0.57 +/- 0.52 mg/dl. Adverse events that were considered by the investigator to have a possible. probable, or definite relationship to study drug occurred in 26% of patients. Other than expected temporary effects of hypercalcemia and hyperphosphatemia. the only possible trends for causally-related adverse events were for nausea/vomiting and metallic taste. CONCLUSIONS: This long-term study of paricalcitol demonstrates that it rapidly and effectively suppresses iPTH levels in a wide spectrum of ESRD patients and caused no unexpected adverse events.

Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D(2)) in dialysis patients with secondary hyperparathyroidism: a sequential comparison.

Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P: < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting that intravenous 1alphaD(2) therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.

Reversible sequestration of nitric oxide by hemoglobin during hemodialysis in end-stage renal disease.

BACKGROUND: During hemodialysis, patients whose plasma concentrations of nitric oxide (NO) products increase reportedly experience hypotension. Therefore, whether NO bound to hemoglobin (Hb) could contribute to various clinical and laboratory changes during hemodialysis was explored in patients with end-stage renal disease (ESRD). METHODS: Ten patients were studied during 3 hemodialysis treatments with samples of blood analyzed for RBC nitrosyl Hb (HbNO), L-arginine, asymmetric dimethylarginine (ADMA), plasma nitrite+nitrate (NOx), and buffy coat NO synthase (NOS) activities. RESULTS: HbNO before and during hemodialysis varied considerably. Those with higher predialysis levels had lower HbNO values during dialysis, whereas HbNO levels in those with lower levels before dialysis increased. Plasma NOx did not correlate with HbNO, but change in HbNO in the first hour and change in NOx in the first 2 hours correlated with drop in diastolic and systolic blood pressures (BP), respectively. HbNO concentrations increased in patients with >35% drop in systolic BP, whereas in those with <35% drop, HbNO concentrations decreased. HbNO levels adjusted by the hematocrit showed a drop in HbNO for the <35% group and a >3-fold increase in the >35% group. HbNO levels were higher in men than in women, and levels and changes correlated with the hematocrit, skin temperatures, plasma ADMA, arginine, and buffy coat NOS. CONCLUSIONS: In patients with >35% drop in systolic BP, NO was scavenged by Hb in the circulating RBCs, undoubtedly attenuating the degree of hypotension. These data indicate that the amount of NO that is scavenged or released by Hb in the circulating RBCS during dialysis is highly variable and reversible. Various predialysis factors relate to the concentration of HbNO before and during dialysis, which in turn influence clinical findings that occur during the interdialytic period.

An enzyme hydrolyzing methylated inhibitors of nitric oxide synthase is present in circulating human red blood cells.

N(G),N(G)-dimethyl-L-arginine (asymmetric dimethylarginine or ADMA) and N(G)-monomethyl-L-arginine (L-NMMA) are post-translationally synthesized amino acids of nuclear proteins. Upon release during protein turnover, they are not used in protein synthesis, but are excreted or metabolized by dimethylarginine dimethylaminohydrolase (DDAH) found in many tissues. DDAH is present in monocytic and polynuclear cells of blood, but no report has appeared of its presence in red blood cells (RBCs). Because methylated arginines can inhibit nitric oxide synthase (NOS) and elevations are reported in several diseases, we explored whether RBCs express this enzyme. DDAH is present in RBCs as supported by hydrolysis of both ADMA and L-NMMA, but not symmetric dimethylarginine, and by immunoprecipitation/Westem blot using a specific monoclonal antibody to human DDAH. In a pilot study of end-stage renal disease (ESRD) patients, RBC DDAH activity with ADMA as substrate correlated inversely with age (p = 0.005) and enzyme activities were higher in patients with greater diastolic blood pressure drops during hemodialysis (p = 0.02). Similar correlations were found with white cell DDAH activity. Thus, human RBCs can hydrolyze methylated arginines. These findings indicate the RBC could be used to assess the status of DDAH in various disease states.

Intermittent doxercalciferol (1alpha-hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism.

Hypercalcemia and hyperphosphatemia frequently necessitate vitamin D withdrawal in hemodialysis patients with secondary hyperparathyroidism. In short-term trials, doxercalciferol (1alpha-hydroxyvitamin D(2) [1alphaD(2)]) suppressed intact parathyroid hormone (iPTH) effectively with minimal increases in serum calcium and phosphorus (P) levels. This modified, double-blinded, controlled trial examined the efficacy and safety of 1alphaD(2) use in 138 hemodialysis patients with moderate to severe secondary hyperparathyroidism by using novel dose titration; 99 patients completed the study. Hemodialysis patients with secondary hyperparathyroidism were enrolled onto this study, consisting of washout (8 weeks), open-label 1alphaD(2) treatment (16 weeks), and randomized, double-blinded treatment with 1alphaD(2) or placebo (8 weeks). Oral 1alphaD(2) was administered at each hemodialysis session, with doses titrated to achieve target iPTH levels of 150 to 300 pg/mL. Baseline iPTH levels (897 +/- 52 [SE] pg/mL) decreased by 20% +/- 3.4% by week 1 (P: < 0.001) and by 55% +/- 2.9% at week 16; iPTH levels returned to baseline during placebo treatment but remained suppressed with 1alphaD(2) treatment. In 80% of the patients, iPTH level decreased by 70%, reaching the target level in 83% of the patients. Grouping patients by entry iPTH level (<600, 600 to 1,200, and >1,200 pg/mL) showed rapid iPTH suppression in the group with the lowest level; greater doses and longer treatment were required in the group with the highest level. During open-label treatment, serum calcium and P levels were 9.2 +/- 0.84 (SD) to 9.7 +/- 1.05 mg/dL and 5.4 +/- 1.10 to 5.9 +/- 1.55 mg/dL, respectively. During double-blinded treatment, serum calcium levels were slightly greater with 1alphaD(2) than placebo, but P levels did not differ. During double-blinded treatment, 3.26% and 0.46% of serum calcium measurements exceeded 11.2 mg/dL with 1alphaD(2) and placebo, respectively (P: < 0.01); median level was 11.6 mg/dL during hypercalcemia. Intermittent oral 1alphaD(2) therapy effectively suppresses iPTH in hemodialysis patients with secondary hyperparathyroidism, with acceptable mild hypercalcemia and hyperphosphatemia.

Normal circulating adult human red blood cells contain inactive NOS proteins.

Human red blood cells (RBCs) are considered to play a significant role in both blood pressure (BP) regulation and tissue oxygenation, because they can bind as well as release previously bound nitric oxide (NO) from hemoglobin (Hb) and other intracellular components. Two reports indicate that the human RBC possesses nitric oxide synthase (NOS) activity-by the accumulation of nitrite across a membraned chamber in one and by the hydrolysis of labeled L-arginine, presumably to labeled L-citrulline, in the other. Furthermore, NOS proteins have been identified by immunoblot in RBCs. If true, the presence of NOS activity would convert the human RBC to a donor with limited ability to bind exogenously generated NO. In considering the importance of the question of the presence or not of NO synthetic capacity of this cell in BP regulation and tissue perfusion, whether human RBCs are, indeed, able to hydrolyze L-arginine to L-citrulline, the coproduct of NO was explored. RBC samples collected from control subjects were assayed for NOS activity by incubation of homogenized cellular fractions with labeled tritiated L-arginine in the presence of 0.5 mmol/L NADPH. By this method, the amino acid coproduct of NO, tritiated L-citrulline, would be recovered in the supernatant after removal of unused substrate by cationic resin treatment. At first, activity appeared to be present in the RBC supernatant but not in the pellet. However, activity was not suppressed by known inhibitors of NOS, whereas activity was suppressed by norvaline, an inhibitor of arginase activity with no known effect on NOS. By contrast, RBC arginase activity was not inhibited by N(omega)-nitro-L-arginine, NG-methyl-L-arginine, or aminoguanidine, known inhibitors of NOS, but was inhibited by norvaline. The label recovered by thin-layer chromatography was determined not to be tritiated L-citrulline but was instead tritiated L-ornithine, the product of arginase activity. Thus the enzymatic hydrolysis of L-arginine was not caused by NOS but was a result of the action of the enzyme arginase, which abounds in this cell. However, proteins interacting with antibodies to the endothelial and inducible isoforms of NOS were detected in human RBCs by immunoblot. Together, these findings indicate that human RBCs collected from normal adult individuals possess proteins that react with monoclonal antibodies to the Inducible and endothelial isoforms of NOS, but the proteins are without catalytic activity.

Biphasic changes in nitric oxide generation in hemodialyzed patients with end-stage renal disease treated with recombinant human erythropoietin.

BACKGROUND: Use of recombinant human erythropoietin (rHuEpo) in patients with end-stage renal disease (ESRD) improves anemia and reduces the need for blood transfusions. However, one third of patients on rHuEpo develop hypertension, aggravation of preexistent hypertension, or other complications. Nitric oxide (NO) plays a role in blood pressure (BP) regulation. Whether rHuEpo treatment in ESRD is accompanied by alterations in NO production was explored in patients undergoing hemodialysis. METHODS: Of 121 consecutive patients in a hemodialysis clinic, 107 were treated with rHuEpo and 14 were untreated. Plasma was collected before and after hemodialysis for quantification of nitrite and nitrate (NOx). Findings were correlated with various routinely monitored parameters. RESULTS: Predialysis NOx levels were lower in the treated than the untreated group; postdialysis NOx levels were virtually the same. Thus, the change was less in the treated group. Urea reduction ratios (URR) and ultrafiltrate volumes were similar. The mean predialysis systolic BP was higher in the treated group than in the untreated group. The dose of rHuEpo did not correlate with the plasma NOx or the predialysis BPs. No correlation was found between NOx levels and Hb or gender. Of the 107 treated patients, 12 had an increased postdialysis NOx without differences in ultrafiltrate volumes or URR. This group had higher total serum calcium levels, faster pulses, and greater BP reductions than other treated patients. No difference was found in the use of calcium-channel blockers and serum phosphorus and intact parathyroid hormone concentrations did not differ significantly among these groups. CONCLUSIONS: Intermittently hemodialyzed ESRD patients treated with rHuEpo accumulate less NOx in the plasma before dialysis but generate more NOx during dialysis than untreated patients. About 11% of treated patients generated excessive amounts of NOx, thereby maintaining plasma concentrations at the predialysis level or higher. This group experienced significant hemodynamic consequences characteristic of the excessive action of NO.

Hemodialysis hypotension: interaction of inhibitors, iNOS, and the interdialytic period.

Hypotension during hemodialysis in end-stage renal disease (ESRD) not explained by excessive ultrafiltration has been linked to an apparent increase in the synthesis of nitric oxide (NO). The authors tested whether the induction of NO synthase (iNOS) by cytokines or differences in the concentrations of inhibitors of NOS or both could account for variability in the amount of NO synthesized during hemodialysis. Plasma levels of an inhibitor of NOS, asymmetric dimethylarginine (ADMA), L-arginine, the substrate for NOS, the end-products N02+N03, iNOS activity in circulating buffy coat cells, and their interdialytic changes were measured in 10 patients during three treatments. Predialysis (0') levels of ADMA were markedly elevated with a mean of 0.008+/-0.002 micromol/mL of deproteinized plasma, compared to controls where ADMA is present in trace amounts. ADMA levels from 30 minutes to the end of dialysis correlated directly with the drop in blood pressure (BP), with levels being much higher in patients with severe hypotension. Postdialysis ADMA levels correlated directly with the 0' systolic BP and the drop in BP at the next dialysis treatment. NOS activity was detected in two thirds of the predialysis buffy coat samples, and appeared to increase as dialysis progressed. 0' iNOS activity correlated inversely with the 0' BP, but activities did not differ based on percent drop in BP. iNOS activity in the 0' samples correlated inversely with the time since the last dialysis, reflecting the greater accumulation of dialyzable inhibitors of NOS as the interval is prolonged. The interdialytic change in iNOS activity correlated inversely with the drop in BP. The isoform detected immunochemically in the buffy coat samples had an Mr of 130 kDa and was reactive with antihuman iNOS. Thus, iNOS is already induced in the cells of the buffy coat in many intermittently hemodialyzed ESRD subjects, but its expression may be masked by inhibitors. After 60 minutes of dialysis (too brief a time for the de novo induction of iNOS,) the appearance of or increase in iNOS activity suggests that an inhibitor had been removed. Because ADMA levels are associated with higher predialysis systolic BPs that result in a greater severity of hypotension, reduction in ADMA concentrations would appear to play a major role in the resumption of NO synthesis by various isoforms.

Hypotension during hemodialysis: role for nitric oxide.

Hypotensive episodes during hemodialysis are a frequent complication in patients with end-stage renal disease. The possibility that nitric oxide (NO), a major regulator of cardiovascular hemodynamics, could be a factor was explored. Pre and postdialysis plasma samples from 17 hemodialysis patients were analyzed for the stable end products of NO,nitrite + nitrate (NO2 + NO3), by the Greiss method. Predialysis NO2 + NO3 levels were significantly higher in end-stage renal disease than in nine age-matched controls (44.08 +/- standard error of mean 5.74 versus 18.67 +/- 3.56 uM, P = 0.017). In more than half of the patients, postdialysis values dropped markedly, whereas in others the value change was far less; several rose above predialysis values. Depending on the nitrite + nitrate reduction ratio (pre minus postdialysis NO2 + NO3 divided by the predialysis value) patients were separated into two groups, A (n = 9 where nitrate + nitrate reduction ratio was > 0.5 and B (n = 8 where nitrate + nitrate reduction ratio was < 0.5). Whereas the mean predialysis NO2 + NO3 values between groups A and B did not differ significantly, postdialysis levels fell from a predialysis mean of 50 uM to 12 uM in group A but rose from 37 uM to 45 uM in group B. The difference between the postdialysis values of group A and group B was significant (P = 0.0264). In group B, mean systolic blood pressure dropped more than in group A, (57.8 mm Hg compared with 21.2 mm Hg, P = 0.0078). When measured by analysis of variance for repeated measures, skin and core temperatures and blood pressures were lower in group B than in group A. The volume of the ultrafiltrate was removed and dialysis duration and mean weight loss did not differ. Thus, in group B, apparently NO formation increased during hemodialysis exceeding the rate of removal or metabolism of the end products, whereas in group A, NO2 + NO3 removal or metabolism was without apparent increase in the formation of NO. The basis for this difference is unknown. Because vasodilation is a major effect of NO, the strong association of severe reduction in blood pressures and increased NO synthesis in subset B suggests a role for NO in hypotensive episodes during hemodialysis.

Nutrition in the critical care settings of renal diseases.

Acute catabolic events during the course of renal dysfunction lead to exacerbation of nutritional abnormalities often present in these patients. Whether the renal failure is acute or chronic, the nutritional management of these patients is extremely challenging. Traditional methods of nutritional assessment must be extrapolated to include the effects of the renal dysfunction and renal replacement therapy being used. Cases of patients with acute renal failure, chronic renal failure with an acute insult, pancreas-kidney transplant recipient with delayed graft function, and a liver transplant recipient who developed renal failure are reviewed with emphasis on the nutritional management during the course of illness. Monitoring techniques are reviewed, and comparisons are made to other nutrition support protocols.

Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole.

Metabolism of cyclosporine is reduced by ketoconazole binding to the monooxygenase responsible for cyclosporine degradation. This isozyme of cytochrome P450, along with other similar monooxygenases, is involved in the regulation of the synthesis and degradation of important metabolic pathways of cholesterol. Monooxygenases throughout these pathways are inhibited by ketoconazole binding causing a decreased metabolism of calcitriol, bile acids, and steroid hormones, and can thereby potentiate altered lipid metabolism, bone metabolism, and weight status of transplant recipients. A group of renal transplant recipients taking ketoconazole (n=25) was compared with a matched cohort not receiving ketoconazole for metabolic changes during the first six months posttransplantation. Lower LDL cholesterol levels were seen in the ketoconazole group (109 +/- 8 mg/dl) than the no ketoconazole group (140 +/- 8 mg/dl) at one month but this difference was not sustained at six months. More bone loss occurred in the ketoconazole group as demonstrated by significant changes in bone density as well as a greater urinary appearance of bone collagen crosslink, deoxy-pyridinoline (29 +/- 4 nmol dpd/mmol creatinine and 18 +/- 4 at six months for the ketoconazole group versus the no ketoconazole group, respectively, P<0.05). Weight gain changes were different between the ketoconazole group and no ketoconazole group (6.4 +/- 1.4 kg versus 5.0 +/- 1.3 kg) at six months and an increased rate of weight gain over time in the ketoconazole group (0.02 kg/day at one month versus 0.05 kg/day at six months, P<0.007). Effectiveness of ketoconazole inhibition of cyclosporine is valuable, but inhibition of other metabolic pathways should be evaluated as well.

Factors affecting erythropoietin production and correction of anemia in kidney transplant recipients.

Anemia does not correct in many kidney transplant recipients, probably due to iron deficiency or inadequate erythropoietin (Epo) production. We evaluated effects of iron (Fe) availability on correction of anemia in renal transplant recipients and sought to characterize patterns of early Epo production by transplanted kidneys as related to peritransplant factors. In a prospective randomized trial, 51 consecutive renal transplant patients were followed for 6 months. Epo was measured on days 0, 3, 14, 48 and 168 posttransplantation. Fe status was monitored on days 14, 48 and 168. Pts were randomized at day 14 based on Fe status. Iron-deficient (FeD) patients (n = 24) were randomized to receive daily Fe supplementation (FeDs, n = 12) or no supplementation (FeDns, n = 12). Those with normal Fe status (FeN, n = 27) were followed as controls. No differences were found between groups at day 0 for Hct, Cr, Epo, age, dialysis history, or type of donor. Day 3 Creatinine and Hct were similar among groups, while Epo was significantly higher in FeD groups vs FeN (p < 0.004), and continued higher at 6 months. Though each pt improved Hct, most FeDns and FeN were anemic and Fe deficient at 6 months while all FeDs patients had corrected their anemia (p < or = 0.009) and Fe status. Four FeDs patients developed polycythemia. Epo production correlated inversely to cold ischemia time in cadaver renal allografts (p < 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Inadequate dialysis increases gross mortality rate.

The authors correlated the dialysis parameters of 613 patients on hemodialysis with their morbidity and mortality. Dialysis prescription (Kt/V) was calculated according to the dialyzer, blood flow, and dialysis time. Dialysis delivered was calculated using percentage urea reduction (PUR). Eighty patients who underwent dialysis in three units had only predialysis blood urea nitrogen (BUN) values available. Mean predialysis BUN was between 58 +/- 16 and 83 +/- 17 mg/dl. Patients with predialysis BUN > 100 mg/dl ranged from 0-22%, and those with predialysis BUN < 50 mg/dl ranged from 0-41%. Kt/V prescribed was between 0.45 and 1.75. Mean dialysis time was 191 +/- 28 min, and blood flow was 327 +/- 48 ml/min. Delivered dialysis was 78% of that prescribed. Patients who had a prescribed or delivered Kt/V < 0.8 varied from 0-44.8%. Mortality rate per year was between 11.3% and 54%. The authors attributed elevated BUN to increased protein intake or inadequate dialysis. Low BUNs may have been due to residual renal function or malnutrition. None of the dialysis parameters correlated with mortality rate except for a Kt/V < 0.8 (p < 0.001) that was directly related to mortality rate. Inadequate dialysis increases mortality rate.

Urea kinetics evaluation of hemodialysis and CAPD patients.

Urea kinetics have been used to measure adequacy of hemodialysis. The role of urea kinetics in CAPD has not been clearly established. Using urea kinetics, we studied 71 hemodialysis and 71 CAPD patients. Age was 53 +/- 12 and 45.8 +/- 12 respectively. Urea kinetics in hemodialysis were studied in the standard manner. CAPD patients collected 24 hr, dialysate fluid to measure urea, creatinine, glucose and protein. Urine was collected for 24 hr. to measure urea and creatinine. Protein catabolic rate (pcr) was calculated from the total amount of urea cleared in 24 h. Both groups of patients had similar body weight. Kt/V in CAPD (0.65 +/- 0.1) was at a level considered underdialysis for hemodialysis. In both groups, pcr increased as Kt/V increased. However, CAPD patients had levels of pcr higher than hemodialysis patients at the same level of Kt/V. BUN, serum albumin and serum potassium were significantly lower in CAPD patients. Patients who dialyze more, eat more. Differences in protein intake may be due to a more liberal diet in CAPD, patient selection, removal of middle molecules, or better control of the acidosis.

Is Na+ modeling necessary in high flux dialysis?

One important pathogenic factor in dialysis hypotension is the drop in plasma osmolality. Increasing the dialysate Na+ concentration decreases hypotensive episodes. The authors studied 39 patients being treated with high flux dialysis. During a 9 week period, the patients were on a standard Na+ dialysate (Na+ = 140 meq/L) basal period (B); 9% (Na+ = 149 meq/L) linear (L); step drop (S); and exponential drop (E). The Na+ program was changed weekly at random. The results obtained with the three Na+ modeling programs were similar. We compared the periods with and without Na+ modeling: no differences were found in weight gained interdialysis, mean blood pressure predialysis and postdialysis, and hemoconcentration. Serum Na+ levels were significantly higher predialysis and postdialysis for those patients on Na+ modeling. Hypotensive episodes and cramps decreased 50% with Na+ modeling. The amount of hypertonic and normal saline given during dialysis was markedly reduced. Na+ modeling should always be used in patients being maintained on high flux dialysis.

Is hematologic response to iron and erythropoietin in hemodialysis patients affected by other factors?

Multiple factors have been implicated in the hematologic response to erythropoietin (EPO). The authors studied 54 hemodialysis patients; 44 received 1.5 g of iron intravenously, 16 received oral iron for 12 weeks, and 24 were treated with EPO. Some patients received these treatments in sequence. The factors evaluated were serum albumin, protein catabolic rate, serologic evidence of hepatitis B or C, parathormone (PTH), and aluminum levels. Red cell production was expressed as milliliters of red blood cell increase per day per kilogram of body weight. For patients receiving EPO, hematologic response was normalized to 50 U/kg/dialysis. Of the patients on oral iron, 31% had a good response (hematocrit greater than or equal to 30%). Of the patients who received iron intravenously, 50% had a good response (hematocrit greater than or equal to 30%). All patients treated with EPO responded well, except for one patient who did not respond to doses of EPO up to 200 U/kg/dialysis. The response to intravenous iron dextran was more rapid than the response to oral iron or EPO. Nutritional factors (serum albumin and protein catabolic rate), serologic evidence of hepatitis, elevated PTH levels, or elevated aluminum levels did not significantly affect the response to iron supplementation or EPO treatment.

Evaluation of hemodialysis patients treated with erythropoietin.

We evaluated 20 hemodialysis patients who had been treated with erythropoietin (Epo). All patients had hemoglobin levels below 8.5 g/dL. They were randomized to receive either Epo (100 U/kg) or placebo three times per week for 12 weeks. All patients on Epo had a significant (P less than 0.001) elevation of hematocrit levels (19.7% v 35.7%). They also had a significant (P less than 0.05) increase in midweek predialysis blood urea nitrogen (BUN) levels, 27.8 versus 29.6 mmol/L (78 v 83 mg/dL), and serum phosphorus, 1.8 versus 2.1 mm/L (5.7 v 6.6 mg/dL). Protein catabolic rate also increased significantly (P less than 0.05). No changes were seen in the levels of serum creatinine and potassium, but episodes of hyperkalemia were more frequent in patients on Epo. No changes were seen in patients on placebo. When hematocrit increased, the clearance of blood-water for urea decreased 9%, and the clearance of creatinine, potassium, and phosphorus decreased 15%. Patients on Epo increased both their appetite and protein intake. More frequent episodes of hyperkalemia and elevated phosphorus level resulted from a combination of increased intake and decreased dialyzer clearance. We may need blood-water clearance to calculate Kt/V.