A simple method to estimate the required dialysis time for cases of alcohol poisoning.

BACKGROUND: Conventional dialysis management of ethylene glycol and methanol poisoning includes frequent intradialytic determinations of serum toxin concentration. Dialysis is continued until a target toxin concentration is reached. Initially, the required dialysis duration is unknown, making planning difficult. We devised a simple method to estimate the duration of dialysis required and avoid quantitation of multiple toxin samples. METHODS: Using the assumption that toxic alcohols would have a dialysis clearance similar to urea, we proposed that required dialysis time (hours) to reach a 5 mmol/L toxin concentration target would be: [-V ln(5/A)]/0.06k, where V (liters) is the Watson estimate of total body water, A is the initial toxin concentration (mmol/L), and k is 80% of the manufacturer-specified dialyzer urea clearance (mL/min) at the initial observed blood flow rate. Directly measured dialysis and renal toxin clearance, and true dialysis requirement by conventional treatment protocol were compared with our estimate in two methanol and three ethylene glycol poisonings treated with Fresenius F8 dialyzers. RESULTS: There were no clinically or statistically significant differences between predicted dialysis duration (7.6 +/- 1.9 hours, +/-SD) and that actually provided using hourly toxin concentration sampling (7.4 +/- 1.9 hours). Renal toxin clearance was negligible compared to that of dialysis, and predicted dialysis clearance did not differ significantly from that observed. CONCLUSIONS: The simple estimate method is sufficiently valid to guide the prescription of dialysis for toxic alcohol poisoning. Data required at dialysis start include only the initial toxin concentration, dialyzer manufacturer's specified urea clearance at initial observed blood pump speed, and patient demographics to estimate total body water. This approach allows for planned dialysis therapy, without the need for additional toxin concentration measurements until dialysis is completed.

Progressive increases in peritoneal dialysis prescription: patient acceptance and complication rates.

Peritoneal dialysis adequacy has an impact on patient mortality. Both the CANUSA study and DOQI Guidelines outline targets for adequacy, and it has been suggested that quantitative adequacy determinations be made at regular intervals. Some groups believe these targets are not achievable because of lack of patient acceptance and high complication rate. We examined the outcome of peritoneal dialysis in a setting where prescription changes are made on clinical grounds, and determined the complication rates and patient acceptance of prescription changes. A total of 154 patients commencing peritoneal dialysis from January 1, 1994,-December 31, 1996, were studied to determine reasons for dialysis prescription changes, patient acceptance of, and complications related to these changes. Point prevalence data for dialysis prescription for our center and other Canadian centers were obtained from the Canadian Institute for Health Information. Co-morbidity - adjusted patient and technique survival for our center versus other centers in Canada was performed by Poisson regression analysis. Dialysis prescription changes were based on clinical assessment. A total of 102 patients started on either > 8 L of dialysate or had an increase in dialysis prescription during the study period. These patients were heavier, on peritoneal dialysis for longer, and fewer were transplanted compared with the patients on standard prescription (8 L or less). Only 4% of patients refused the change in dialysis prescription, and only 13 peritoneal leaks occurred, resulting in 3 transfers to hemodialysis. Our center prescribed a larger number of exchanges than other Canadian centers in 1995-1997. Adjusted mortality rate ratios for our center versus the other Canadian Centers (1990-1996) are equal. The 3 year technique survival for peritoneal dialysis patients from our center between 1990-1996 was 75% vs. 61% for other centers in Canada. At last follow-up, > 60% of patients had a Kt/V urea >2.1 and 45% had a creatinine clearance > 70 L/1.73 m2/week. This Regional Program has successfully prescribed high volume and frequency peritoneal dialysis on clinical grounds alone. This practice is associated with high patient acceptance, equivalent mortality, and higher technique survival compared with the rest of Canada.

Patients on chronic peritoneal dialysis for ten years or more in North America.

Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six North American centers were analyzed retrospectively. In the six centers, the percentage of patients surviving for more than ten years varied between 0.8% and 7.3%. The study group included 27 females and 9 males aged 38.6 +/- 14.2 years [mean +/- standard deviation (SD)] at the start of treatment. Of the 36 patients, 28 were Caucasian. The most common cause of end-stage renal disease (ESRD), present in 12 patients, was chronic glomerulonephritis. Only 4 patients had diabetes. At the beginning of the study, 19 patients had hypertension (the most common comorbid condition); 11 had no comorbid conditions at the start. Creatinine clearance at the start was 4.12 +/- 3.5 mL per minute, and the mean duration to anuria was 51 +/- 25 months. Mean initial body weight was 55 +/- 9 kg, and mean body surface area was 1.5 +/- 0.2 m2. Serum albumin levels showed an increase from 33.8 +/- 3.6 g/L at the start of the study to 38.2 +/- 3.9 g/L at the end. Hospitalization rate was low at 0.5 +/- 0.3 admissions per patient-year, and duration of hospitalization was 4.8 +/- 3.7 days per patient-year. Peritonitis was the most common cause of hospitalization. The mean peritonitis rate was 1 episode every 52 +/- 48 patient-months. There were 36 catheter changes in 18 patients; 16 patients had a single PD catheter throughout the period of study. Autonomous hyperparathyroidism was the most common long-term complication. At the end of the study period, 11 patients were still on PD, 9 had died, 5 had been transferred to hemodialysis (HD), 1 was alive with a functioning allograft, and 1 was lost to follow-up. We conclude that patients who survive longer than ten years on PD are most likely to be young Caucasian females, small in body size, who are non diabetic, with few comorbid conditions. These long-term survivors have few hospitalizations, and their peritonitis rate is low. In this group of patients, severe autonomous hyperparathyroidism is the most common long-term complication.

Comparative hospitalization of hemodialysis and peritoneal dialysis patients in Canada.

BACKGROUND: Most comparisons of hemodialysis (HD) and peritoneal dialysis (PD) have used mortality as an outcome. Relatively few studies have directly compared the hospitalization rates, an outcome of perhaps equal importance, of patients using these different dialysis modalities. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness and initial mode of dialysis collected prospectively immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994. The mean follow-up was 24 months. Admission data were used to compare hospitalization rates in HD and PD. RESULTS: Thirty-four percent of patients at baseline and 50% at three months used PD. Twenty-five percent of HD and 32% of PD patients switched dialysis modality at least once after their first treatment (P = NS). Nine percent of HD patients and 30% of PD patients switched modality after three months (P < 0. 001). Total comorbidity was higher in HD patients at baseline (P < 0. 001) and at three months (P = 0.001). The overall hospitalization rate was 40.2 days per 1000 patient days after baseline and 38.0 days per 1000 patient days after three months. When an adjustment was made for baseline comorbid conditions, patients on PD had a lower rate of hospitalization in intention-to-treat analysis according to the type of dialysis in use at baseline (RR 0.85, 95% CI, 0.82 to 0.87, P < 0.001), but a higher rate according to the type of dialysis in use three months after study entry (RR 1.31, 95% CI, 1.27 to 1.34, P < 0.001). In analyses based on the amount of time actually spent on each treatment modality, PD was associated with a higher rate of hospitalization when analyzed according to the type of dialysis in use at baseline (RR 1.10, 95% CI, 1.07 to 1.13, P < 0.001) and according to the type of dialysis in use three months after study entry (RR 1.26, 95% CI, 1.23 to 1.30, P < 0.001). CONCLUSIONS: Conclusions regarding comparative hospitalization rates are heavily dependent on the analytic starting point and on whether intention-to-treat or treatment-received analyses are used. When early treatment switches are accounted for, HD is associated with a lower rate of hospitalization than PD, but the effect is modest.

Comparative mortality of hemodialysis and peritoneal dialysis in Canada.

BACKGROUND: Comparisons of mortality rates in patients on hemodialysis versus those on peritoneal dialysis have been inconsistent. We hypothesized that comorbidity has an important effect on differential survival in these two groups of patients. METHODS: Eight hundred twenty-two consecutive patients at 11 Canadian institutions with irreversible renal failure had an extensive assessment of comorbid illness collected prospectively, immediately prior to starting dialysis therapy. The cohort was assembled between March 1993 and November 1994; vital status was ascertained as of January 1, 1998. RESULTS: The mean follow-up was 24 months. Thirty-four percent of patients at baseline, 50% at three months, and 51% at six months used peritoneal dialysis. Values for a previously validated comorbidity score were higher for patients on hemodialysis at baseline (4.0 vs. 3.1, P < 0.001), three months (3.7 vs. 3.2, P = 0.001), and six months (3.6 vs. 3.2, P = 0.005). The overall mortality was 41%. The unadjusted peritoneal dialysis/hemodialysis mortality hazard ratios were 0.65 (95% CI, 0. 51 to 0.83, P = 0.0005), 0.84 (95% CI, 0.66 to 1.06, P = NS), and 0. 83 (95% CI, 0.64 to 1.08, P = NS) based on the modality of dialysis in use at baseline, three months, and six months, respectively. When adjusted for age, sex, diabetes, cardiac failure, myocardial infarction, peripheral vascular disease, malignancy, and acuity of renal failure, the corresponding hazard ratios were 0.79 (95% CI, 0. 62 to 1.01, P = NS), 1.00 (95% CI, 0.78 to 1.28, P = NS), and 0.95 (95% CI, 0.73 to 1.24, P = NS). Adjustment for a previously validated comorbidity score resulted in hazard ratios of 0.74 (95% CI, 0.58 to 0.94, P = 0.01), 0.94 (95% CI, 0.74 to 1.19, P = NS), and 0.88 (95% CI, 0.68 to 1.13, P = NS) at baseline, three months, and six months. There was no survival advantage for either modality in any of the major subgroups defined by age, sex, or diabetic status. CONCLUSIONS: The apparent survival advantage of peritoneal dialysis in Canada is due to lower comorbidity and a lower burden of acute onset end-stage renal disease at the inception of dialysis therapy. Hemodialysis and peritoneal dialysis, as practiced in Canada in the 1990s, are associated with similar overall survival rates.

Should all Pima Indians with type 2 diabetes mellitus be prescribed routine angiotensin-converting enzyme inhibition therapy to prevent renal failure?

OBJECTIVE: To determine how effective angiotensin-converting enzyme (ACE) inhibitors must be in preventing diabetic nephropathy to warrant early and routine therapy in all Pima Indians with type 2 diabetes mellitus. DESIGN: A computerized medical decision analysis model was used to compare strategy 1, screening for microalbuminuria and treatment of incipient nephropathy as currently recommended with ACE inhibitor therapy, with strategy 2, a protocol wherein all patients were routinely administered an ACE inhibitor 1 year after diagnosis of type 2 diabetes mellitus. The model assumed that ACE inhibitors can block, at least in part, the pathogenic mechanisms responsible for early diabetic nephropathy (microalbuminuria). RESULTS: The model predicted that strategy 2 would produce more life-years at less cost than strategy 1, if routine drug therapy reduced the rate of development of microalbuminuria by 21% in all patients. Only a 9% reduction in the rate of development of microalbuminuria was cost-effective at $15,000 per additional life-year gained, and only a 2.4% reduction was cost-effective at $75,000 per additional life-year gained for strategy 2 over strategy 1. CONCLUSIONS: Routine ACE inhibitor therapy in Pima Indians with type 2 diabetes mellitus could prove more effective and even cost saving than the currently recommended approach of microalbuminuria screening. A prospective trial examining this goal should be considered.

Management of idiopathic crescentic and diffuse proliferative glomerulonephritis: evidence-based recommendations.

Idiopathic crescentic glomerulonephritis (GN) often presents with a rapid loss of renal function and pathology showing extensive crescent formation. The disease is caused by different immunopathogenetic mechanisms, pauci-immune, often antineutrophil cytoplasmic antibody (ANCA)-positive microvasculitis, antiglomerular basement membrane (GBM) antibody disease, and immune complex formation. Historical reviews reveal poor renal prognosis, even after treatment with oral steroids and cytotoxic drugs. Prognosis has improved in the last decade. In this article, evidence-based recommendations for management are presented. Because of the high risk of end-stage renal disease (ESRD), early aggressive therapy is recommended, despite weak supporting evidence. Treatment for anti-GBM antibody-induced crescentic GN should be initiated early and should include pulse methylprednisolone, a two-week course of plasmapheresis and two months of treatment with corticosteroids and cyclophosphamide (grade B and C). Treatment for pauci-immune crescentic GN should be pulse methylprednisolone, followed by oral corticosteroids and cyclophosphamide for 6 to 12 months (grade B). Recurrences can be managed similarly (grade B), along with appropriate supportive therapy. In patients who develop ESRD, successful transplantation can be performed. Diffuse endocapillary proliferative GN is classically postinfectious. It generally has a good prognosis when no crescent formation occurs. Adult patients with persistent proteinuria, hypertension, and renal function impairment need careful follow-up and management to modify progressive hemodynamic injury.

Peritoneal dialysis reduces the use of non native fistula access in dialysis programs.

Access problems remain the major difficulty associated with chronic hemodialysis. Despite recent recommendations by the Dialysis Outcomes Quality Initiative (DOQI) that native arteriovenous (AV) fistulae are the optimal form of vascular access, grafts and central catheters are used by many patients. We analyzed our large Canadian regional dialysis program, which has a high prevalence of peritoneal dialysis, to examine the effect of dialysis modality choice on vascular access utilization. Point prevalence data were collected from our program in October 1997, and technique and patient survival data for the period 1990-1996 were analyzed and compared to data for the remainder of Canada from the Canadian Organ Replacement Register. Mortality rate ratios were estimated using a Poisson regression model to correct for comorbidity, age, and end-stage renal disease etiology. Of 141 in-center hemodialysis patients, 91 had an AV fistula, 1 had a polytetrafluoroethylene (PTFE) graft, and 49 were catheter-dependent. The program also included 20 home hemodialysis patients with AV fistulae, and 156 patients on peritoneal dialysis. No mortality risk differences between hemodialysis and peritoneal dialysis are seen in our center, nor are they seen for each modality in comparison with the remainder of Canada. Technique survival for peritoneal dialysis at our center was about 80% at 2 years, significantly greater than for Canada. For the program as a whole, 49% of patients used peritoneal dialysis 35% a native AV fistula, and 15% a central catheter. For Canada and the U.S.A. respectively, the comparable data were: peritoneal dialysis, 32% and 17%; native fistula, 33% and 15%; PTFE, 19% and 41%; and central catheter 16% and 27%. These data suggest that the use of peritoneal dialysis may allow reduced use of non native AV fistula access without mortality penalty.

Routine treatment of insulin-dependent diabetic patients with ACE inhibitors to prevent renal failure: an economic evaluation.

The objective of this study was to determine how effective angiotensin-converting enzymes (ACEs) must be in preventing diabetic nephropathy to warrant routine administration to insulin-dependent diabetic patients. A Markov model was used to compare three strategies designed to prevent the development of end-stage renal disease in insulin-dependent diabetic patients. Strategy I, screening for microalbuminuria and treatment of incipient nephropathy as currently recommended, was compared with strategy II, a protocol in which patients were routinely administered an ACE inhibitor 5 years after diagnosis of diabetes, and strategy III, in which patients at high risk for nephropathy were routinely treated and low-risk patients followed a protocol in which patients were treated with an ACE inhibitor if they developed hypertension and/or macroproteinuria. The model predicted that strategy II would produce as many quality-adjusted life-years as strategy I at nearly the same cost if routine drug therapy reduced the rate of development of microalbuminuria by 26% in all patients. Strategy III produced as many quality-adjusted life-years at less cost than strategy I if a high-risk cohort could be identified with a rate of developing microalbuminuria at four times the rate of low-risk patients and if drug therapy reduced the rate of developing microalbuminuria in this high-risk group by 20%. In conclusion, routine ACE inhibitor therapy could prove to be cost-effective, especially if high-risk individuals could be identified. A prospective trial examining this goal should be considered.

Polyurethane catheters for long-term hemodialysis access.

Chronic hemodialysis patients with failed native fistulas and/or synthetic arteriovenous grafts are usually dialyzed via surgically placed silicone jugular catheters such as the PermCath (Quinton, Seattle, WA, U.S.A.). We report a successful experience with the use of double lumen polyurethane central venous catheters placed percutaneously. Catheters with poor flows were replaced over a guidewire at the bedside. Eleven long-term hemodialysis patients failed arteriovenous access, 9 of them having had multiple attempts at fistulas and/or grafts. Seven of these patients had also failed peritoneal dialysis. They were dialyzed with polyurethane catheters for a mean of 681 +/- 280 days (range 282-1150 days), requiring a mean of 3.4 +/- 0.4 new venous punctures and 8.2 +/- 1.5 catheter changes over a guidewire over that period of time. Actuarial patient survival was 50% at 2 years, and mean urea reduction during dialysis was 64.2 +/- 1.7%. The septicemia rate was only 1.2 episodes per 1,000 catheter-days, but about 20% of patients experienced central venous occlusion, attributable to the use of subclavian catheter placement in 82% of the sites. The success of this technique and its elimination of the need for urokinase, radiologic interventions, and surgical placement warrant its consideration as an acceptable form of long-term vascular access, provided jugular placement allows reduced central venous occlusion rates.

Prediction of early death in end-stage renal disease patients starting dialysis.

Demand for dialysis for patients with end-stage renal disease is growing, as is the comorbidity of dialysis patients. Accurate prediction of those destined to die quickly despite dialysis could be useful to patients, providers, and society in making decisions about starting dialysis. To determine whether age and comorbidity accurately predict death within 6 months of first dialysis for end-stage renal disease, a prospective cohort study of 822 patients starting dialysis at one of 11 Canadian centers was performed. Patient characteristics were recorded at first dialysis. Follow-up continued until death or study end (at least 6 months after enrollment). One hundred thirteen of 822 (13.7%) patients died within 6 months. Although an existing scoring system predicted prognosis, adverse scores greater than 9 were found in only 9.7% of those who died; only 52% of those who scored higher than 9 died within 6 months. No score cutoff point combined high true-positive and low false-positive rates for predicting early death. Age, severity of heart failure or peripheral vascular disease, arrhythmias, malnutrition, malignancy, or myeloma were independent prognostic factors identified in multivariate models. However, the best fit discriminant and logistic models were also unable to accurately predict death within 6 months. Clinicians were very accurate in assigning patients to prognostic groups up to a 50% risk of death by 6 months, above which they tended to overestimate risk. However, clinicians were only marginally better than the predictive models in determining whether a given high-risk patient would die. The inability of a scoring system or clinical intuition to accurately predict death soon after starting dialysis for end-stage renal disease suggests that limiting access to dialysis on the basis of likely short survival may be inappropriate in Canada.

Multicenter clinical validation of an on-line monitor of dialysis adequacy.

Quantitation of hemodialysis by measuring changes in blood solute concentration requires careful timing when taking the postdialysis blood sample to avoid errors from postdialysis rebound and from recirculation of blood through the access device. It also requires complex mathematical interpretation to account for solute disequilibrium in the patient. To circumvent these problems, hemodialysis can be quantified and its adequacy assessed by direct measurement of the urea removed in the dialysate. Because total dialysate collection is impractical, an automated method was developed for measuring dialysate urea-nitrogen concentrations at frequent intervals during treatment. A multicenter clinical trial of the dialysate monitoring device, the Biostat 1000 (Baxter Healthcare Corporation, McGaw Park, IL) was conducted to validate the measurements of urea removed, the delivered dialysis dose (Kt/V), and net protein catabolism (PCR). The results were compared with a total dialysate collection in each patient. During 29 dialyses in 29 patients from three centers, the paired analysis of urea removed, as estimated by the dialysate monitor compared with the total dialysate collection, showed no significant difference (14.7 +/- 4.7 g versus 14.8 +/- 5.1 g). Similarly, measurements of Kt/V and PCR showed no significant difference (1.30 +/- 0.18 versus 1.28 +/- 0.19, respectively, for Kt/V and 42.3 +/- 15.7 g/day versus 52.2 +/- 17.4 g/day for PCR). When blood-side measurements during the same dialyses were analyzed with a single-compartment, variable-volume model of urea kinetics, Kt/V was consistently overestimated (1.49 +/- 0.29/dialysis, P < 0.001), most likely because of failure to consider urea disequilibrium. Because urea disequilibrium is difficult to quantitate during each treatment, dialysate measurements have obvious advantages. The dialysate monitor eliminated errors from dialysate bacterial contamination, simplified dialysate measurements, and proved to be a reliable method for quantifying and assuring dialysis adequacy.

Screening to prevent renal failure in insulin dependent diabetic patients: an economic evaluation.

OBJECTIVE: To examine the conditions necessary to make screening for microalbuminuria in patients with insulin dependent diabetes mellitus cost effective. DESIGN: This economic evaluation compared two strategies designed to prevent the development of end stage renal disease in patients with insulin dependent diabetes with disease for five years. Strategy A, screening for microalbuminuria as currently recommended, was compared with strategy B, a protocol in which patients were screened for hypertension and macroproteinuria. INTERVENTION: Patients identified in both strategies were treated with an angiotensin converting enzyme inhibitor. SETTING: Computer simulation. MAIN OUTCOME MEASURES: Strategy costs and quality adjusted life years (QALYs). RESULTS: The model predicted that strategy A would produce an additional 0.00967 QALYs at a present value cost of $261.53 (1990 US$) per patient (or an incremental cost/QALY of $27,041.69) over strategy B. The incremental cost/QALY for strategy A over B was sensitive to several variables. If the positive predictive value of screening for microalbuminuria (impact of false label and unnecessary treatment) is < 0.72, the effect of treatment to delay progression from microalbuminuria to macroproteinuria is < 1.6 years, the cumulative incidence of diabetic nephropathy falls to < 20%, or > 64% of patients demonstrate hypertension at the onset of microalbuminuria, then the incremental costs/QALY will exceed $75,000. CONCLUSION: Whether microalbuminuria surveillance in this population is cost effective requires more information. Being aware of the costs, recommendation pitfalls, and gaps in our knowledge should help focus our efforts to provide cost effective care to this population.

Evidence-based recommendations for the clinical use of recombinant human erythropoietin.

In an era of increasing scrutiny regarding use of health care resources, it is critical that physicians have rational, evidence-based guidelines for treatment decisions. This review of more than 200 published papers constitutes a comprehensive approach to evaluating the current evidence regarding the clinical use of recombinant human erythropoietin therapy in renal failure patients. After this review, specific recommendations are provided regarding who should receive r-HuEPO; what the target hemoglobin should be; the best route of administration of r-HuEPO; how iron status should be evaluated and managed; and monitoring and follow-up of patients taking r-HuEPO. Throughout the article, areas for important future research are also identified.