Three-Stream, Bicarbonate-Based Hemodialysis Solution Delivery System Revisited: With an Emphasis on Some Aspects of Acid-Base Principles.

Hemodialysis patients can acquire buffer base (i.e., bicarbonate and buffer base equivalents of certain organic anions) from the acid and base concentrates of a three-stream, dual-concentrate, bicarbonate-based, dialysis solution delivery machine. The differences between dialysis fluid concentrate systems containing acetic acid versus sodium diacetate in the amount of potential buffering power were reviewed. Any organic anion such as acetate, citrate, or lactate (unless when combined with hydrogen) delivered to the body has the potential of being converted to bicarbonate. The prescribing physician aware of the role that organic anions in the concentrates can play in providing buffering power to the final dialysis fluid, will have a better knowledge of the amount of bicarbonate and bicarbonate precursors delivered to the patient.

Anticoagulation during haemodialysis using a citrate-enriched dialysate: a feasibility study.

BACKGROUND: The feasibility of anticoagulating the extracorporeal circuit during haemodialysis using a simple citrate-enriched dialysate was evaluated in a prospective, randomised, cross-over study of 24 patients who were at high risk for bleeding. METHODS: A dialysate, with a citrate level of 3 mEq/L (1 mmol/L), was generated by adding citrate to the conventional liquid 'bicarbonate concentrate' of a regular, dual-concentrate, bicarbonate-buffered dialysate delivery system. Each of the 24 patients received two dialysis treatments. For anticoagulation of the extracorporeal circuit, one treatment used the citrate-enriched dialysate (Citrate Group), while the other treatment used conventional saline flushing (Saline Group). The order of the two treatments was randomised. With either method, a heparinized, saline-rinsed dialyser was used, and no heparin was administered during dialysis. RESULTS: Ninety-two per cent (22 out of 24) and 100% of patients tolerated the procedure well in the Citrate Group and the Saline Group, respectively. Eight per cent (two out of 24) of the treatments in each group had to be abandoned because of clotting in the extracorporeal circuit. Significantly less thrombus formation in the venous air traps was detected in the Citrate Group. No patients from either group suffered from hypocalcaemic or bleeding complications, but the immediate post-dialysis and 0.5-h post-dialysis plasma levels of ionised calcium and of magnesium were slightly lower in the Citrate Group than in the Saline Group. CONCLUSIONS: Our findings suggest that it is feasible to use the present simple citrate-enriched dialysate to dialyse patients safely and effectively. Furthermore, the approach is much simpler than a conventional, intermittent, saline-flushing method.

Forced euvolemic diuresis with mannitol and furosemide for prevention of contrast-induced nephropathy in patients with CKD undergoing coronary angiography: a randomized controlled trial.

BACKGROUND: Contrast-induced nephropathy is common in patients with coronary angiography. Mechanistically, forced euvolemic diuresis with mannitol and furosemide ought to prevent contrast-induced nephropathy. Our objectives are to: (1) undertake a randomized trial testing this hypothesis, and (2) conduct a meta-analysis of our findings with 2 earlier studies. STUDY DESIGN: (1) Randomized allocation-concealed controlled trial with blinded ascertainment of outcomes, and (2) random-effects meta-analysis of 3 trials. SETTING & PARTICIPANTS: Single-center study of consenting adults with serum creatinine level greater than 1.7 mg/dL undergoing coronary angiography; patients unable to tolerate fluid challenge or receiving dialysis were excluded. Two previous trials had randomly assigned 159 patients. INTERVENTION: Forced euvolemic diuresis with saline, mannitol, and furosemide compared with saline hydration controls. All patients were pretreated with at least 500 mL of half-normal saline before angiography; during and 8 hours after, urine output was replaced milliliter per milliliter with half-normal saline. OUTCOMES & MEASUREMENTS: The primary outcome was contrast-induced nephropathy within 48 hours of the procedure, defined as a 0.5-mg/dL absolute or 25% relative increase in creatinine level. RESULTS: Overall, 92 patients were allocated to intervention (n = 46) or control (n = 46). Mean age was 64 +/- 14 (SD) years, 23% were women, 37% had diabetes, 47% used oral furosemide, mean creatinine level was 2.8 +/- 1.6 mg/dL, and most patients (72%) underwent diagnostic catheterization. Patients had a net positive fluid balance (389 +/- 958 mL for intervention versus 655 +/- 982 mL for controls; P = 0.2). Contrast-induced nephropathy occurred in 23 (50%) intervention patients versus 13 (28%) controls (relative risk, 1.77; 95% confidence interval, 1.03 to 3.05; P = 0.03; adjusted odds ratio, 3.73; P = 0.03). Within 48 hours, creatinine level had increased by 0.8 +/- 1.1 mg/dL with intervention versus 0.2 +/- 0.6 mg/dL for controls (P = 0.002). Overall, 11 (12%) patients died or required dialysis, with no difference according to allocation status (P = 0.5). Random-effects meta-analysis of published data (3 trials; 251 patients) suggests furosemide-based interventions lead to significant harm compared with hydration: pooled relative risk, 2.15; 95% confidence interval, 1.37 to 3.37; I(2) = 0%. LIMITATIONS: Small single-center study that cannot determine whether harms were related to furosemide, mannitol, or a combination. CONCLUSIONS: Forced euvolemic diuresis led to a significantly increased risk of contrast-induced nephropathy. This strategy should be abandoned, and our results suggest that oral furosemide therapy perhaps should be held before angiography.

Short daily haemodialysis: survival in 415 patients treated for 1006 patient-years.

BACKGROUND: Survival statistics for daily haemodialysis are lacking as most centres providing this have treated only a small number of patients for short observation times. We pooled our 23-year, 1006-patient-year, five-centre experience of 415 patients treated by short daily haemodialysis. METHODS: One hundred and fifty patients were treated in-centre, most because of medical complications and 265 by home or self-care haemodialysis. Patients were on daily haemodialysis for 29 +/- 31 (0-272) months. Forty-two percent had primary and 31% had secondary renal failure. Treatment time was 136 +/- 35 min, frequency 5.8 +/- 0.5 times/week and weekly stdKt/V 2.7 +/- 0.55. RESULTS: Eighty-five patients (20%) died; 5-year cumulative survival was 68 +/- 4.1% and 10-year survival was 42 +/- 9%. Age, secondary renal failure and in-centre dialysis were associated with mortality, while gender, frequency of dialysis (5, 6 or 7 per week), continent, country and blood access were not. Survival was compared with matched patients from the USRDS 2005 Data Report using the standardized mortality ratio and cumulative survival curves. Both comparisons showed that the survival of the daily haemodialysis patients was 2-3 times higher and the predicted 50% survival time 2.3-10.9 years longer than that of the matched US haemodialysis patients. Survival of patients dialyzing daily at home was similar to that of age-matched recipients of deceased donor renal transplants. CONCLUSIONS: Survival of patients on short daily haemodialysis was 2-3 times better than that of matched three times weekly haemodialysis patients reported by the USRDS.

The ideal home hemodialysis machine.

Daily home hemodialysis (HD) patients have a much superior survival rate than patients on regular, 3 times a week in-center HD or on peritoneal dialysis. Present-day HD machines are unsuitable for use at home by patients. We present our concept of the ideal home HD machine that allows daily short and long HD, does all the work preparing for and cleaning up after dialysis, has an intravenous infusion system controlled by the patient, needs no systemic anticoagulation, and teaches and interacts with the patient during dialysis. To fulfill these functionalities, the dialyzer and blood tubing must be integrated with the machine and replaced less often than monthly, the machine must be capable of at least 200 L/week of hemodiafiltration, prepare all fluids necessary between and during dialyses, and all the components and fluids must be much beyond ultrapure.

Comparison of survival between short-daily hemodialysis and conventional hemodialysis using the standardized mortality ratio.

More frequent hemodialysis (5 or more times weekly, both short during the day and long overnight) has been shown to improve patient well-being, reduce symptoms during and between treatments, and have beneficial effects on clinical outcomes. Because of the relatively small patient sample sizes, there are little or no data on mortality from any single study at this time. This study compares survival in 117 U.S. patients treated by short-daily hemodialysis in 2003 and 2004, with patients reported in the 2003 data from the United States Renal Data System (USRDS). Expected mortality was calculated from the USRDS and compared with observed actual mortality. The standardized mortality ratio (SMR) was used to adjust for differences in patient age, sex, race, and cause of renal failure. The SMR for the short-daily hemodialysis patients was 0.39, statistically significantly better (p < 0.005) than data from the overall U.S. population of hemodialysis patients and indicating that daily hemodialysis patients had a 61% better survival. Patients treated by short-daily hemodialysis have a better survival rate than comparable populations treated by conventional hemodialysis.

Composition and clinical use of hemodialysates.

A thorough knowledge and understanding of the principles underlying the preparation and the clinical application of hemodialysates can help us provide exemplary patient care to individuals having end-stage renal disease. It is prudent to be conversant with the following: (a) how each ingredient in a dialysate works, (b) the clinical circumstances under which the concentration of an ingredient can be altered, and (c) the special situations in which unconventional ingredients can be introduced into a dialysate. The potential to enrich dialysates with appropriate ingredients (such as iron compounds) is limited only by the boundaries of our imagination.

Daily dialyses decrease plasma levels of brain natriuretic peptide (BNP), a biomarker of left ventricular dysfunction.

Brain natriuretic peptide or B-type natriuretic peptide (BNP) is a sensitive marker of heart disease. Plasma levels of BNP increase in left ventricular failure and determination of plasma BNP has become a useful tool in the diagnosis of heart failure. Hemodialysis (HD) patients may have elevated plasma levels of BNP, particularly predialysis, that correlate with echocardiographic signs of left ventricular dysfunction. High BNP levels are also a strong predictor of mortality in both nonrenal and HD patients. We studied plasma BNP levels in patients who changed from conventional thrice-weekly dialysis to daily dialysis 6 times a week while maintaining a total weekly time on dialysis of 12 hr. Twelve HD patients, mean age 55 years, had 4 hr of conventional thrice-weekly treatment for 4 weeks. Predialysis and postdialysis blood samples were obtained at the last dialysis. Patients were then dialyzed for 2 hr, 6 times weekly, for 4 weeks (daily dialysis). Again, predialysis and postdialysis blood samples were collected at the last HD. Brain natriuretic peptide plasma concentrations were determined by immunoradiometric assay. Predialysis BNP levels decreased from 194+/-51 ng/L (68+/-19 pmol/L; mean+SE) during thrice-weekly HD to 113+/-45 ng/L (41+/-18 pmol/L; p = 0.001) after 4 weeks on daily dialysis. With thrice-weekly HD, predialysis BNP levels were higher than postdialysis levels: 120+/-26 ng/L (39+/-8 pmol/L; p = 0.059). With daily dialysis, predialysis BNP levels did not differ significantly from postdialysis levels. Elevated predialysis plasma levels of BNP, considered sensitive and early markers of left ventricular dysfunction, decreased when patients were changed from conventional thrice-weekly HD to daily dialysis maintaining total hours of dialysis per week constant. Given the accumulated evidence that BNP is a biomarker of left ventricular dysfunction and can be used for risk stratification and guidance in pharmacotherapy of heart failure, daily dialysis appears to lead to less cardiac distress.

Early clinical, quality-of-life, and biochemical changes of "daily hemodialysis" (6 dialyses per week).

BACKGROUND: Advantages associated with an increased frequency of hemodialysis have been reported previously. However, previous studies were either small or not controlled and did not detail early clinical, biochemical, quality-of-life, urea kinetic, and dynamic changes when patients switched from a conventional (3 times/wk) dialysis regimen to "daily" (6 times/wk) dialysis therapy when total weekly dialysis time was unchanged. METHODS: A prospective sequential study with 21 patients as their own controls was performed. A 4-week period of conventional thrice-weekly dialysis (N = 240 treatments) was followed immediately by a 4-week period of daily (ie, 6 times/wk) dialysis (N = 480 treatments), in which each treatment was half the length of a conventional dialysis treatment session. Clinical parameters and symptoms during and between dialysis treatments were graded, and urea-related parameters, blood chemistry results, and nutritional data were determined. RESULTS: Within 4 weeks of switching to this daily dialysis regimen, there were improvements in blood pressure, dialysis "unphysiology," intradialytic and interdialytic symptoms, and urea kinetics and dynamics. There were fewer machine alarms and less need for nursing interventions during dialysis. Nutrition and quality of life began to improve. There was no increase in blood access complications and no significant changes in blood chemistry results, hematologic parameters, or use of medications. CONCLUSION: In this short-term study, daily dialysis appears to be a safe, better, and more physiological method to deliver dialysis care to patients with end-stage renal disease.

Neuropeptide-Y and atrial natriuretic peptide as prognostic markers in patients on hemodialysis.

We conducted a study of the influence of the vasoactive peptides atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) on survival of patients on hemodialysis and their association and relative importance with cardiac and clinical variables. Thirty-three hemodialysis patients were characterized by age, sex, diagnosis, blood pressure, serum (S)-albumin, serum (S)-urea, hemoglobin, dialysis dose, weight gain, duration of dialysis, cardiac hypertrophy, volume, failure, and ischemia and plasma levels of ANP and NPY. The outcomes were analyzed for early deaths (< 1 year) and for all deaths. The association of the variables to early deaths and all deaths, respectively, was studied in Cox proportional hazard analyses. The variables were also studied in three hierarchical steps: clinical variables only, clinical and cardiac variables, and all variables. For all deaths, the independent variables were plasma NPY (pmol/L) (hazard ratio [HR] = 1.035, p = 0.004), heart volume (ml/m2) (HR = 1.009, p = 0.001), and S-albumin (g/L) (HR = 0.750, p = 0.034). For early deaths, the independent variables were predialysis ANP (pmol/L) (HR = 1.008, p = 0.034) and NPY (pmol/L) (HR = 1.031, p = 0.026). In the hierarchical study, excluding the vasoactive peptides, heart volume, heart failure and S-albumin were independently associated with all deaths, and mean arterial blood pressure was associated with early death. When also excluding the cardiac parameters, S-albumin was associated with all deaths and mean arterial blood pressure with early death. In conclusion, plasma levels of the vasoactive peptides ANP and NPY are the most important group in a hierarchy of variables that predict imminent death in hemodialysis patients, and NPY is associated with late death. ANP and NPY apparently sum up the detrimental influence of many factors in hemodialysis patients.

Differences in dialysis practice are the main reasons for the high mortality rate in the United States compared to Japan.

The cumulative survival of Japanese hemodialysis patients is more than 2.5 times better than that of dialysis patients in the United States (U.S.). The difference is particularly pronounced in older patients, being 4 times better in patients over the age of 50 years. The mortality in U.S. patients has increased from 10 to 25% over the last three decades, but has remained stable at around 10% in Japan. There is no obvious difference in patient selection. The Japanese accept almost as high a proportion of diabetic patients as does the United States, and the mean age of incident patients is higher in Japan. Renal transplantation, virtually absent in Japan, should increase mortality in U.S. dialysis patients by removing patients with the highest probability of survival, but even if one adds surviving transplant patients and studies prevalent populations, the survival rate is much better in Japan. Genetic factors are unlikely to explain differences in mortality, as older Americans live much longer than older Japanese. We speculate that the difference lies in the practice of dialysis. Patients in the United States are generally treated by much faster and shorter dialysis than in Japan. This puts a severe burden on the cardiovascular system of older patients, leading to the poorer survival rate. Japanese physicians also appear to be better trained in dialysis and to spend more time with their patients. The nursing shortage in the United States may also contribute to the increased mortality. Whatever the explanations, the U.S. dialysis community must work to equal and, hopefully, surpass the now superior survival of Japanese dialysis patients.

Phosphorus-enriched hemodialysates: formulations and clinical use.

Although hyperphosphatemia is a cardinal feature of renal failure, the occasional patient suffering from end-stage renal disease (ESRD) may present with hypophosphatemia. For example, hypophosphatemia can develop in ESRD patients if they suffer from malnutrition or if they are aggressively dialyzed. Hypophosphatemia is commonly prevented or treated with the oral or the intravenous administration of soluble phosphate salts; however, determination of the required oral or intravenous dose is difficult. Under appropriate circumstances, phosphorus-enriched dialysates can also be employed for the purpose of phosphorus administration. Various preparations of soluble phosphate salts can be used to enrich hemodialysates.

Phosphorus, phosphorous, and phosphate.

This article distinguishes the terms "phosphorus, phosphorous, and phosphate" which are frequently used interchangeably. We point out the difference between phosphorus and phosphate, with an emphasis on the unit of measure. Expressing a value without the proper name or unit of measure may lead to misunderstanding and erroneous conclusions. We indicate why phosphate must be expressed as milligrams per deciliter or millimoles per liter and not as milliequivalents per liter. Therefore, we elucidate the distinction among the terms "phosphorus, phosphorous, and phosphate" and the importance of saying precisely what one really means.

Acidosis and coma in adult diabetic maintenance dialysis patients with extreme hyperglycemia.

BACKGROUND: Extreme hyperglycemia (serum glucose ≥ 800 mg/dL or 44.4 mmol/L) is infrequently associated with impaired consciousness in patients on maintenance dialysis. The purpose of this study was to determine features of extreme hyperglycemia that bring about coma in dialysis patients who do not have any of the potential conditions, other than hyperglycemia, that can affect the sensorium. METHODS: We analyzed 24 episodes of extreme dialysis-associated hyperglycemia in men who did not have neurological disease or sepsis. We compared serum parameters related to hyperglycemia between a group of 12 patients (8 on peritoneal dialysis, 4 on hemodialysis) who were alert and oriented (group A) and another group of 12 patients (5 on peritoneal dialysis, 7 on hemodialysis) who displayed varying degrees of impairment of sensorium, ranging from drowsiness to coma (group B). RESULTS: Group B had, in the serum, lower total carbon dioxide (TCO2, 8 ± 4 vs. 20 ± 3 mmol/L, P < 0.01) and higher anion gap (AG, 32 ± 8 vs. 15 ± 4 mEq/L, P < 0.01) and potassium (6.3 ± 1.5 vs. 4.6 ± 1.0 mEq/L, P < 0.05) than group A. Serum levels of glucose, chloride, urea nitrogen, calculated osmolarity and tonicity did not differ between the two groups. The test for serum ketone bodies was positive only in group B (all patients). Stepwise multiple linear regression identified serum TCO2 and AG as the only predictors of impaired sensorium (r (2) = 0.74. P < 0.01). CONCLUSION: There is a strong statistical association between the severity of diabetic ketoacidosis (DKA) and the level of impairment of consciousness in patients on dialysis with extreme hyperglycemia and no neurological or infectious disease. This association suggests that the presence or absence of DKA is usually the primary etiologic factor in the development of impaired sensorium in these patients.

Superior patient and technique survival with very high standard Kt/V in quotidian home hemodialysis.

We studied the association of patient and dialysis factors with patient and technique survival in a cohort of all of our 191 of patients surviving >3 months on quotidian home hemodialysis (QHHD). Eighty-one patients were on nocturnal QHHD and 110 on short -daily QHHD. Weekly dialysis time was 7.5-48 hours, single pool Kt/V was 0.38-4.5 per treatment, and weekly standardKt/V was 2.1-7.5. The association of 18 patient and dialysis variables with patient and technique survival was analyzed by Kaplan-Meier and Cox analyses. Ninety-nine patients (52%) remained on QHHD, 34 (18%) were transplanted, 31 (16%) returned to 3/week HD, and 27 (14%) died. The 5-year patient survival was 71% ± 6% (night: 79% ± 7%, day: 69% ± 9%, P = 0.002). The 5-year technique survival was 80% ± 4% (night: 93% ± 3%, day: 46% ± 17%, P = 0.001). In Cox analyses, patient survival was independently associated with standard Kt/V (hazard ratio [HR] = 0.29, P < 0.0001), graduating from high school (HS) (HR = 0.11, P = 0.0002), and use of graft/fistula (HR = 0.22, P = 0.007). Technique survival was independently associated with standard Kt/V (HR = 0.50, P = 0.0003) and start of QHHD after 2003 (HR = 0.18, P = 0.007). Every increase in standard Kt/V was associated with improved survival. The highest survival occurred when standard Kt/V exceeded 5.1, only possible when weekly dialysis hours exceed 35 hours. In QHHD, higher standard Kt/V, education, and subcutaneous access are associated with better patient survival and higher standard Kt/V and longer experience of center with better technique survival. There was no upper limit of standard Kt/V, where survival plateaus. The amount of minimally "adequate" dialysis should be much increased.

Nightly home hemodialysis: outcome and factors associated with survival.

Nightly home hemodialysis (NHHD) has been reported to have a much better survival than the excessive mortality of thrice-weekly in-center dialysis, but the factors influencing survival of NHHD have not been investigated in detail. We studied the association of survival in a 12-year study of 87 NHHD patients from a single center evaluating demographic, sociologic, and anthropomorphic factors, diagnosis, comorbidity, vintage, and dialysis performance and efficiency. Secondly, we compared the survival of the 87 NHHD patients with that reported by the United States Renal Data System (USRDS) using standardized mortality rate (SMR). The average patient age was 52 ± 15 years, and 59% were males, 51% African Americans, and 25% had diabetes. The patients dialyzed 40 ± 6 hours weekly with a stdKt/V of 5.25 ± 0.84. Thirteen patients died. The cumulative survival was 79% at 5 years and 64% at 10 years. Using Cox proportional hazards univariate analysis, 7 of 26 factors studied were associated with mortality: less than high school education, hour of each dialysis, comorbidities, secondary renal disease, congestive heart failure, Leypoldt's eKt/V, and Daugirdas Kt/V. In backward stepwise Cox analysis, education and hour of dialysis were the only factors independently associated with survival. The standardized mortality rate was only 0.30 of that reported by the United States Renal Data System for patients on thrice-weekly hemodialysis adjusted for age, gender, race, and diagnosis. The influence of education was the most significantly associated with survival, and the duration of each dialysis treatment was important. The survival rate of NHHD patients appeared to be superior to intermittent hemodialysis.