Effect of cause and time of dropout on the residual GFR: a comparative analysis of the decline of GFR on dialysis.

BACKGROUND: The decline of residual renal function (RRF) on dialysis has been reported to be slower in peritoneal dialysis (PD) then hemodialysis (HD). However, some clinicians have questioned whether this reported difference might not be caused by selection bias. In particular, if continuous ambulatory PD (CAPD) delivers only marginally adequate therapy as some clinicians speculate, then perhaps those patients on CAPD with low glomerular filtration rate (GFR) are purposefully switched to HD. If true, transferring CAPD patients with low GFR to HD could create a selection bias that very well may account for the differences in GFR between PD and HD. This is particularly problematic if one then censors patients at the time of transfer from PD to HD from analysis (that is, patients are no longer followed in the study once they have switched treatment modalities). When this occurs, the data are said to be informatively censored, a term used by statisticians to describe any kind of systematic bias associated with censored or incomplete data. In particular, informative censoring occurs when patients who die or transfer to another modality very early have an associated lower starting GFR or higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship differs between PD and HD but is ignored in the analysis, then the results of such analysis may be biased. METHODS: This article analyzes the decline in GFR among 141 incident dialysis patients (39 HD and 102 PD) undergoing either HD or PD at the University of Missouri-Columbia. The decline in GFR was modeled as a nonlinear function of time, taking into account the possibility that missing values of GFR may be associated with patient dropout (death, transfer to another modality, or transplantation). To safeguard against this possibility, we utilized a conditional nonlinear mixed-effects model. The model was used to fit and compare each patient's GFR data to time adjusting for the patient's treatment modality (HD vs. PD), cause of dropout (death, transfer, transplant, lost to follow-up/study ended), and time to dropout. The model allowed a comparison of the starting GFR and the rate of decline in GFR between PD and HD adjusting for these three factors. RESULTS AND CONCLUSIONS: The results of our analysis suggest that such informative censoring is independent of treatment modality and that even after correcting for dropout caused by death or transfer to another modality, patients starting on PD have a lower rate of decline in GFR (that is, better preservation of GFR) than patients starting on HD.

Preservation of glomerular filtration rate on dialysis when adjusted for patient dropout.

BACKGROUND: Residual renal function (RRF) plays an important role in dialysis patients. Studies in patients on maintenance dialysis suggest that RRF is better preserved in patients receiving peritoneal dialysis (PD) vis-à-vis those receiving hemodialysis (HD). We speculated that regardless of the patient's type of therapy, the estimate obtained for the rate of decline in glomerular filtration rate (GFR) may be biased because of informative censoring associated with patient dropout. Informative censoring occurs when patients who die or transfer to another modality very early have associated with them a lower starting GFR or a higher rate of decline of GFR than patients who either complete the study or who die or transfer much later. If patient dropout is indeed related to the rate of decline in GFR and if this relationship is ignored in the analysis, then the estimate obtained of the rate of decline in GFR may be biased. METHODS: In an attempt to determine if there is a relationship between patient dropout and the decline in GFR, we reanalyzed the CANUSA data by modeling GFR as a nonlinear function of time with the rate of decline being exponential. RESULTS: This article highlights the significance of "informative censoring" when studying the decline of RRF on dialysis. The results show that for the CANUSA cohort, the mean initial GFR was significantly lower, and the rate of decline was significantly higher for patients who died or transferred to HD than for patients who were randomly censored or received a transplant. It is important to emphasize that the impact of informative censoring on previous analyses of the decline of RRF between PD versus HD is presently unclear. If bias caused by informative censoring is the same regardless of what therapy a patient is on, then conclusions from previous studies comparing the decline in GFR between PD and HD would still be valid. However, if the magnitude of the bias differs according to therapy, then additional adjustments would be needed to fairly compare the decline in GFR between PD and HD. Because this analysis is restricted to patients on PD, it would be scientifically incorrect to interpret previous studies solely on the basis of the results from this analysis. CONCLUSION: In any longitudinal study designed to estimate trends in an outcome measured over time, it is important that the analysis of the data takes into account any effect patient dropout may have on the estimated trend. This analysis demonstrates that among PD patients, both the starting GFR and the rate of decline in GFR are associated with patient dropout. Consequently, future studies aimed at estimating the rate of decline in GFR among PD patients should also account for any dependencies between dropout and GFR. Similarly, data analyzing for apparent differences in the rate of decline of GFR between PD and HD should also adjust for possible informative censoring.

Hematocrit stability following intravenous versus subcutaneous administration of epoetin alfa to dialysis patients: a post hoc analysis.

UNLABELLED: BACKGROUND, SUBJECTS AND METHODS: A previous study of epoetin alfa dose requirements [Paganini et al. 1995] among hemodialysis patients who were switched from thrice weekly intravenous (i.v.) to thrice weekly subcutaneous (s.c.) administration showed that the weekly epoetin alfa dose requirement decreased by 18.5% after 13 to 16 weeks s.c. treatment and 26.5% after 21 to 24 weeks, without significant change in hematocrit. There was patient-to-patient variation in response, however, and 39% of the patients required the same or greater doses of epoetin alfa after the change from i.v. to s.c. administration. The present study reexamines the database to compare hematocrit stability between the two routes of administration. RESULTS: During 4 weeks of i.v. epoetin alfa administration, the pooled standard deviation (SD) for the patients' (n = 72) weekly hematocrit measurements was 1.40, compared with weeks 13 to 16 of s.c. epoetin alfa administration when the SD was 1.66 (p < 0.01). Among 41 patients who completed 24 weeks of s.c. therapy, the pooled SD for the 4 weeks of i.v. treatment was 1.37 compared with 2.02 during weeks 21-24 of s.c. treatment (p < 0.01). Sixty-eight percent of patients had lower hematocrit SD during 4 weeks of i.v. therapy than during the 4 weeks of s.c. therapy (p = 0.03). CONCLUSION: These data suggest that hematocrits may be more stable when epoetin alfa is administered i.v. rather than s.c. to patients on dialysis. These results would be expected since 100% of i.v.-administered epoetin alfa reaches the systemic circulation compared with 18% to 80% bioavailability of s.c.-administered epoetin alfa. Within-patient variation in s.c. epoetin alfa absorption may be related to non-uniformity of adipose tissue, blood supply, lymphatic drainage, and other factors at sequential injection sites, and may explain the variability in hematocrit after s.c. administration.

All currently used measurements of recirculation in blood access by chemical methods are flawed due to intradialytic disequilibrium or recirculation at low flow.

Blood flows and recirculations with standard and reversed direction of lines were measured by chemical (urea and creatinine) and ultrasound dilution (saline) methods in 47 chronic hemodialysis patients. Thirty-seven patients had 47 dual-lumen, central vein (CV) catheters: 32 were PermCath (Quinton Instruments Company, Seattle, WA), 6 were Access Cath (MEDCOMP, Harleysville, PA), 3 were Soft Cell PC (Vas Cath, Mississauga, Ontario, Canada) and 6 were SNIJ (experimental catheters). Three of these last catheters had the tip staggered 7 mm, and three had flush tips; PermCath, Access Cath, and Soft Cell PC catheters have the tips staggered 23 to 25 mm. Forty-six catheters were implanted into the superior vena cava/right atrium, and one catheter was implanted through the left saphenous vein into the left iliac vein. The catheters were studied 1 to 31 months after implantation (median, 3.0 months). Ten patients with arteriovenous (AV) graft access were also studied. The stop-flow method was used in catheter dialysis, and the slow-flow method was used to calculate recirculations in AV access dialysis with samples for systemic blood concentrations taken from arterial line both before and after samples from the arterial and venous lines. At 500 mL/min pump speed, actual blood flow was 436+/-18 mL/min (mean+/-SD; range, 407 to 464 mL/min) with standard direction of catheter lines. At 500 mL/min pump speed, the arterial chamber pressure was -330+/-48 mm Hg (mean+/-SD; range, -380 to -225 mm Hg, and the venous chamber pressure was 259+/-48 mm Hg (mean+/-SD; range, 140 to 310 mm Hg). Arterial chamber pressure was less negative, and venous chamber pressure was less positive with SNIJ catheters, which had larger internal diameter (2.1 mm) compared with the other catheters (2.0 mm). Recirculation varied with the catheter design and the location of the catheter tip. In the catheters with tip staggered more than 20 mm and with standard line connection at pump speeds of 50 mL/min and 500 mL/min, recirculations were approximately 1 % and 5%, respectively, when measured by the chemical method. In the same catheters with reversed lines, the recirculations were approximately 5% and 27%, respectively. Inflow failure catheters with reversed lines had similar recirculation values to those of well-functioning catheters with reversed lines. In catheters with tips staggered 7 mm, and with standard connection of lines, recirculations were approximately 3% and 8%, respectively, at pump speeds of 50 and 500 mL/min. With reversed lines, at the same pump speeds, the values were 7% and 12%, respectively. In flush-tip catheters, the recirculation was higher at a 50 mL/min pump speed (approximately 17%) than at a pump speed of 500 mL/min (approximately 13%). The ultrasound dilution method usually gave lower values than the chemical methods, most likely because of overestimation of recirculation by chemical methods. At least triplicate measurements are needed because single measurements by the ultrasound dilution method are associated with substantial variation. We conclude that both currently used methods (stop flow and slow flow) of taking systemic samples for measurements of recirculation by chemical methods are flawed because of disequilibrium and recirculation at low flow.

Dialysis equipment and dialysate, past, present and the future.

From the beginning of the first described hemodialysis in 1889, history has shown an exponential evolvement of systems that have resulted in greater safety, efficiency, and broader utilization. It took 60 years, 1947, for the technology to be used in a clinical setting in North America, treating acute renal failure. Commercial interests became involved in the mid 1950s, resulting in the "twin coil" dialyzer, costing five times the current cost of similar membranes. The entry of commercial entities created a rapidly escalating technology in dialysis delivery systems to be used in the chronic recurring dialytic procedure: blood pumps, pressure monitors, needles, dialysate delivery, ultrafiltrate control, membrane design and configuration, dialysate composition. All of these have, for the most part, required trained staff and increasingly comfortable facilities to accommodate the rather static thrice-weekly hemodialysis procedure. The future will likely see more home dialysis, more frequent dialysis, better on-line monitoring, with attention to those factors which have allowed the greatest cause of morbidity, cardiovascular disease, to be controlled.

Peripheral venous blood is not the appropriate specimen to determine the amount of recirculation during hemodialysis.

When recirculation is determined by the classic method of comparing the blood urea concentrations in the dialysis inflow and outflow lines with blood obtained from a peripheral vein, any difference in peripheral venous and systemic arterial blood urea concentration will result in an error in recirculation calculation. The purposes of these studies are threefold: 1. To determine the arterial to venous urea, creatinine, albumin, and hematocrit gradients during hemodialysis treatments. 2. To compare recirculation calculated by the standard technique with that calculated by obtaining the systemic sample from the dialysis inflow line after slowing the blood pump to 50 ml/min. 3. To calculate the recirculation values obtained by the two methods when intra-access recirculation is prevented by drawing the inflow blood from the arterial venous access and returning the dialyzed blood directly into the vena cava. During hemodialysis, an arterial venous urea nitrogen gradient of 9.6 +/- 7.0% (standard deviation) was found. The arterial venous creatinine gradient was 10.8 +/- 5.5%, and there were no significant gradients for albumin or hematocrit. In 161 patients at 6 outpatient dialysis centers, the mean recirculation was 6.4% with the systemic sample obtained from the dialysis inflow line compared with 11.9% with the sample obtained from a peripheral vein. When recirculation was determined by the standard technique in 13 patients in whom the possibility of recirculation was prevented by returning the dialyzer outflow blood directly into the central venous system, an average recirculation of 9.8% was found. The blood urea concentration in the dialysis inflow blood line was found to increase for at least 15 min after slowing the blood pump. The author concludes that drawing blood from a peripheral vein for the systemic sample induces a significant error and should be abandoned. An alternate source is the dialysis inflow line after slowing the blood pump to a low value. The blood should be obtained as soon as the previous blood has been cleared from the line.

Peritoneal dialysis kinetics.

Traditionally, for patients maintained with peritoneal dialysis (PD), the level of blood urea nitrogen (BUN), creatinine, and other clinical and laboratory data have been used to judge the adequacy of treatment. Because of the relatively high mortality rates in patients maintained with continuous PD, in the United States and the high failure rate of PD itself, concern has been raised about both the adequacy of PD and its measurement. Underdialysis could be a cause of morbidity and mortality that may be masked by a reduction in protein intake that also lowers the BUN, giving a false sense of security. The peritoneal equilibration test (PET) is widely applied to classify an individual patient's peritoneal membrane permeability but when used alone, the PET is not a measure of adequacy. Currently, for both hemodialysis and PD, the near universally accepted method of quantification is Kt/Vurea, an index of small molecule clearance also known as the fractional urea clearance per dialysis. The continuous or near continuous nature of PD requires a different interpretation of Kt/V, which is usually expressed on a weekly basis using a different set of standards. The currently accepted minimum is 1.7 per week for continuous dialysis (CAPD) with somewhat higher values for intermittent PD. Measurement of Kt/V for PD patients is more direct than for hemodialyzed patients but also more tedious and subject to some pitfalls. A representative clearance must be obtained from dialysate collected preferably over a 24-hour period, and an independent measure of the patient's urea volume or total body water is required. The latter is usually estimated from anthropometric data. The average rate of net protein catabolism, an index of protein nutrition, can be calculated from the urea generation rate obtained from the same 24-hour dialysate collection and normalized to the patient's urea volume, similar to PCRn measured in hemodialyzed patients. An allowance for loss of protein in the dialysate is accomplished by application of the Randerson equation, which is similar to the Borah equation used for hemodialysis. Prospective controlled trials are necessary to examine the relationship between nutrition and dialysis dosage. The hope of the future is that prospective studies of dialysis adequacy, including a full clinical assessment of each patient, will help to establish the optimal dose of PD that will eliminate both the short-term and the long-term complications of uremia and allow a proper focus on other common causes of morbidity and mortality that are associated with the loss of kidney function.

Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients.

Hemodialysis patients were studied to determine whether the dose of recombinant human erythropoietin (Epoetin alfa; Amgen Inc, Thousand Oaks, CA) required to maintain a therapeutic hematocrit level changed when the route of administration was switched from intravenously (IV) three times per week to subcutaneously (SC) three times per week. Thirteen to 16 weeks after patients were changed from IV three times per week to SC three times per week treatment, the Epoetin alfa requirement was reduced by 18.5% +/- 3.8% (P < 0.001; n = 72), and after 21 to 24 weeks of SC treatment the mean dosage had decreased from the IV dose by 26.5% +/- 4.2% (P < 0.001; n = 41). Sixty-one percent (44 of 72) of patients experienced maintenance-dose reductions over 13 to 16 weeks of treatment and 80% (33 of 41) were maintained on lower weekly doses after 21 to 24 weeks of treatment than at baseline (IV). There was interpatient variability, however: 26% of the patients required greater doses SC than IV following 13 to 16 weeks of SC treatment, and 15% required greater doses SC than IV following 21 to 24 weeks. On completing the initial SC three-times-per-week stage of the study, patients were randomized to one of three SC dosing strategies for an additional 12 weeks: (1) once per week, (2) three times per week Epoetin alfa diluted 1:2 with bacteriostatic saline to mitigate stinging at the injection site, or (3) continued three times per week with undiluted Epoetin alfa. Patients who were switched to administration of SC once per week undiluted Epoetin alfa (n = 20) had their total weekly dose lowered by 18.0% +/- 9.4% (P > 0.05), but the mean hematocrit for this cohort also decreased, from 34.3% +/- 3.0% to 32.4% +/- 3.9% (P > 0.05), rendering dose comparison between the two schedules ambiguous. The maintenance dose for patients who received Epoetin alfa diluted 1:2 with bacteriostatic saline (n = 23) did not differ from the undiluted three times per week dose at the end of stage 1. The third cohort of patients (n = 24), who continued to receive undiluted Epoetin alfa on the same SC three-times-per-week schedule, did not require a significant change in dosage over the ensuing 12 weeks. Comparison of SC three times per week mean dosage after an average of 32 weeks following the switch from IV three times per week for this latter cohort revealed a decrease of 23.5% +/- 6.5% (P < 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)

A new approach to optimizing urea clearances in hemodialysis and continuous ambulatory peritoneal dialysis.

Recent studies suggest that the relationship of the net normalized protein catabolic rate (which is the normalized protein equivalent of nitrogen appearance [nPNA]) to the weekly clearance of urea normalized to total body water (Kt/V urea) in patients on continuous ambulatory peritoneal dialysis (CAPD) is curvilinear, rather than linear, as has been thought. The authors have reexamined the relationship of nPNA to weekly Kt/V urea in a CAPD population by cross-sectional analysis to see if the curvilinear definition of the relationship is as good as or better than the usual linear description. They also examined this relationship in the hemodialysis populations at the Dialysis Clinics Inc. in Columbia, Missouri, and in the Renal Kidney Disease Program in Minneapolis, Minnesota. It seems obvious that there should be a plateau of nPNA in each therapy because extension of linear regressions would predict protein intakes of normal individuals exceeding 8 g/kg/body weight/day. The authors compared their findings to other published results. Intuitively and analytically, the curvilinear relationships seem likely. The authors observed that the nPNA plateau is achieved at lower Kt/V in patients on CAPD than in those on hemodialysis, which is compatible with the peak concentration hypothesis. Asymptotes for CAPD and hemodialysis are similar. Weekly Kt/V urea requirements to achieve nPNA values at 95% of the asymptote are greater than those usually delivered. However, such nearly complete elimination of uremic appetite suppression may not be practical or necessary for achieving acceptable nutritional status and long-term survival in most patients. Optimum therapy may be well above adequate therapy relative to minimizing appetite suppression by uremia.

Does cholestyramine interfere with cyclosporine absorption? A prospective study in renal transplant patients.

Increased cardiovascular deaths have been reported in long-term survivors after renal transplantation. In the primary and secondary coronary prevention trials, reduction of elevated cholesterol has been demonstrated to decrease the incidence of cardiovascular events. The authors previously reported that only 33% of renal transplant patients achieved the National Cholesterol Education Program Expert Panel target values of total and low density lipoprotein cholesterol with niacin > or = 2 g/day or lovastatin 40 mg/day. Indeed, combination therapy with the bile acid sequestrant, cholestyramine appears to be a logical choice. Hence, the pharmacokinetics of cyclosporine were studies before (baseline, on day 1) and after starting cholestyramine 4 g/day, given as a single dose at noon (study repeated on day 4) in six nondiabetic renal transplant patients. Included were 1 woman and 5 men; their mean age (+/- SEM) was 45 +/- 6 years, and they were all > 1 year post transplantation. These patients were receiving cyclosporine, azathioprine, and prednisone based maintenance immunosuppression. Compared to day 1 (baseline period), the peak (644 +/- 142 ng/ml versus 625 +/- 168 ng/ml; ns) and trough (196 +/- 17 ng/ml versus 214 +/- 32 ng/ml; ns) cyclosporine levels and the time to peak (2 hr versus 2 hr) were not significantly different on day 4 (post cholestyramine period) of the study. Furthermore, the area under the curve (3721 +/- 586 ng/hour/ml versus 4143 +/- 778 ng/hour/ml; ns) was not significantly different. Our data suggest that cholestyramine 4 g, given once a day at noon, did not interfere with the absorption of oral cyclosporine. Hence, combination therapy with cholestyramine appears to be a reasonable choice in renal transplant patients with resistant hypercholesterolemia.

The effect of dialyzer membrane and etiology of kidney disease on the preservation of residual renal function in chronic hemodialysis patients.

It is commonly believed that renal function rapidly decreases in the vast majority of chronic hemodialysis patients. Three hundred thirty-four patients starting chronic hemodialysis between 1/1/88 and 12/31/92 at six hemodialysis units were prospectively studied. Renal function was determined every 3 months by 68 hr urine collection expressed as weekly fraction urea clearance (L/L total body water/wk). glomerular filtration rate was calculated from the mean of the urea and creatinine clearance. After 3 years, glomerular filtration rate exceeded 4 ml/min in 14% of patients. For a thrice weekly dialysis schedule, it was assumed that a weekly fractional urea clearance of 3 L/L/wk is equal to a dialysis KT/V of 1 and patients need a minimum KT/V of 1.2 per treatment. After 3 years of chronic hemodialysis therapy, residual renal function was found to provide 15% of the dialysis requirement in 19% of patients and 30% of the dialysis requirements in 9% of patients. The occasional patient maintains sufficient residual renal function to provide over 40% of the dialysis requirement for over 4 years. In a retrospective analysis, patients treated only with Cupraphan membrane had a more rapid loss of renal function compared to those never treated with Cupraphan (Besnberg Corp., Germany). The majority of patients with polycystic kidney disease maintained a glomerular filtration rate greater than 2 ml/min for 4 years or longer.

Effects of nicotinic acid and lovastatin in renal transplant patients: a prospective, randomized, open-labeled crossover trial.

Lipid abnormalities are seen frequently in renal transplant patients. Cardiovascular disease is an important cause of morbidity and mortality in these patients. We assessed the efficacy and safety of the lipid-lowering drugs, nicotinic acid (short acting) and lovastatin, the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Twelve renal transplant patients who had persistent hyperlipidemia despite 6 weeks of dietary treatment participated in this prospective, randomized, open-labeled crossover trial. At 16 weeks, when compared with control values, nicotinic acid (> or = 1.5 g twice a day) significantly reduced the total cholesterol (from 312 +/- 18 [+/- SEM] mg/dL to 229 +/- 19 mg/dL; P = 0.03) and the low-density lipoprotein cholesterol (from 218 +/- 15 mg/dL to 142 +/- 13 mg/dL; P = 0.03) and significantly increased the high-density lipoprotein cholesterol (from 44 +/- 3 mg/dL to 58 +/- 5 mg/dL; P = 0.03). The triglyceride level was reduced from 255 +/- 40 mg/dL to 150 +/- 23 mg/dL (P = 0.09). At 16 weeks, lovastatin therapy (40 mg/d) significantly reduced the total cholesterol (from 285 +/- 13 mg/dL to 233 +/- 10 mg/dL; P = 0.005) and the low-density lipoprotein cholesterol (from 201 +/- 11 mg/dL to 147 +/- 7 mg/dL; P = 0.001). There were no significant changes in the triglyceride and high-density lipoprotein cholesterol levels. Although flushing developed in 67% of patients treated with nicotinic acid, this was not a reason for any of the study dropouts. During this short-term study period no adverse biochemical effects were noted with either of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of dietary therapy on post renal transplant hyperlipidemia. A prospective study.

Hyperlipidemia often occurs after renal transplantation and may contribute to increased cardiovascular morbidity. The National cholesterol education program guidelines (NCEP) recommend dietary modification as the initial therapeutic intervention. We evaluated the effects of the AHA Step I and Step II diets on the serum total cholesterol (TC) and the triglyceride (TG) levels in nondiabetic renal transplant patients. Both the AHA Step I (TC 296 +/- 7 vs 294 +/- 9 mg/dL, p = ns) and Step II diets (TC 282 +/- 8 vs 292 +/- 16 mg/dL, p = ns) failed to significantly lower the serum total cholesterol and the triglycerides levels. During this dietary intervention, the patients' body weight and serum creatinine level remained stable. Our data suggest that neither the AHA Step 1 nor the Step II diet are effective in significantly lowering elevated serum lipids in nondiabetic renal transplant recipients.

Detection of hemodialysis access outlet stenosis by measuring outlet resistance.

Stenosis of the outflow segment of hemodialysis access grafts frequently leads to thrombosis and loss of the access. Previous studies have shown that early detection and correction of the stenosis can prevent graft failure. The purpose of the present study was to compare four methods of detecting outflow segment stenosis: measurement of the pressure in the venous line during dialysis, measurement of the pressure in the distal portion of the access graft, measurement of the relative resistance of the outflow segment of the graft relative to the total resistance of the graft, and measurement of recirculation of venous dialysis blood into the dialysis arterial line. The graft pressure was determined by measuring the pressure in the dialysis venous line with the blood pump turned off. The relative resistance of the outflow segment was determined by dividing the graft blood flow-induced pressure decrease across this segment by the difference between mean systemic arterial and venous pressures. Sixty-eight chronic hemodialysis patients were followed prospectively for 11 months. Sixty-nine complications occurred in 31 accesses in 24 patients. Outlet obstruction was present in 21 of the 31 accesses. Relative graft resistance and recirculation rate measurement were found to be most useful in detecting hemodialysis access outlet obstruction.

A regional blood circulation alternative to in-series two compartment urea kinetic modeling.

Assuming that the clearance of urea from total body water (TBW) is flow limited, the authors developed a parallel flow model using physiologic data. Organ systems with a blood flow to water volume ratio of greater than 0.2 min-1 were allocated to the high flow system. Remaining organs were represented in the low flow system. In end-stage renal disease patients with minimal renal blood flow, the high flow system contained 20% TBW and received 70% of the systemic blood flow. The authors used this flow heterogeneity to predict the post-dialysis urea rebound (R) in 12 patients after 1 hr of hemodialysis. Dialyzer clearance was 248 +/- 14.5 ml/min (mean +/- SEM) Access recirculation was obviated by returning cleared blood into a central vein. In these patients, R at 1, 3, 5, 7, 10, and 15 minutes. after slowing dialyzer blood flow (Qb) from 383 +/- 18 to 50 ml/min was 3.8 +/- 2.9, 6.2 +/- 3.4, 7.6 +/- 3.1, 8.8 +/- 3.9, 9.0 +/- 4.1, and 9.9 +/- 4.4%, respectively. CO and QAc were modeled with values of 5.5 and 0.5 L/min, respectively. The modeled TBW was 35 L. Total body water derived by nomogram was 38.1 +/- 2.0 L. Our results suggest that the parallel-flow model for urea transport can be used to explain the amount and time course of post dialysis R on a physiologic basis.

Blood recirculation in intravenous catheters for hemodialysis.

Long-term i.v. catheters for hemodialysis have the outflow tip extending approximately 2 to 3 cm beyond the inflow tip to prevent blood recirculation during dialysis; however, the lumens are frequently reversed because of inflow failure (i.e., inadequate flow when the inflow lumen is used for blood inflow into the dialyzer). Blood recirculation with reversed lumens (outflow lumen used for blood inflow) in inflow failure catheters and with standard and reversed lumens in well-functioning catheters was measured. Recirculation was measured at a blood flow of 300 mL/min. Systemic blood samples were taken after blood flow was slowed to 50 mL/min. Blood recirculation was calculated as a percentage of the difference between systemic and inflow lumen solute concentrations divided by the difference between systemic and outflow lumen solute concentrations. For each catheter, the recirculation values were calculated separately for urea and creatinine. Average recirculation as measured by both solutes was also calculated. Blood recirculations with standard lumens of well-functioning catheters, reversed lumens of well-functioning catheters, and reversed lumens of inflow failure catheters were 2.09 +/- 1.95, 13.58 +/- 9.87, and 7.10 +/- 5.12 (mean +/- SD), respectively. Whereas recirculation with standard lumens of well-functioning catheters is negligible, reversal of lumens causes considerable recirculation. Recirculation in inflow failure catheters with reversed lumens is significantly less than that with reversed lumens of well-functioning catheters. It was proposed that a blood clot attached at and/or immediately distal to the inflow lumen may disperse outflowing blood and diminish recirculation in inflow failure catheters.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences between KT/V measured during dialysis and KT/V predicted from manufacturer clearance data.

We retrospectively analyzed data from 3,863 dialysis treatments in 329 end-stage renal disease patients over a period of 33 months to evaluate the accuracy of in vitro KT/V estimated by manufacturer's urea clearance data in relation to in vivo measured KT/V. In 1,087 urea clearances measured, mean actual clearance was 87% of predicted. At all blood flows, actual clearances were significantly lower than predicted (8-16% lower than predicted). In 2,807 KT/V measurements, predicted KT/V was 1.238 +/- 0.005 whereas the mean of actual measured KT/V was 16% lower or 1.024 +/- 0.005 (P less than 0.0001). At different blood flows and with different dialyzers, predicted KT/V overestimated actual values. With increasing numbers of reuse, actual/predicted clearance ratios and actual/predicted KT/V ratios progressively dropped. Prescribing dialysis treatments using manufacturer's in vitro generated clearance data can lead to marked underdialysis of patients.

Arterial-venous determinations of the "immunoreactive" angiotensin peptides in human subjects.

Simultaneous measurements of arterial and venous plasma "immunoreactive" angiotensin II and angiotensin II peptide fragments (octapeptide, heptapeptide, hexapeptide, and pentapeptide), done with high performance liquid chromatography and radioimmunoassay, were obtained in nine human subjects. Results indicate that the angiotensin II octapeptide is the major peptide fragment in both arterial and venous plasma. Approximately 80% of the "immunoreactive" angiotensin II measured in both arterial and venous plasma is the angiotensin II octapeptide fragment. The concentration of angiotensin II octapeptide in venous blood approximated the concentration of angiotensin II octapeptide measured in arterial blood. These data suggest that venous concentrations of angiotensin II octapeptide probably reflect the activity of the tissue renin angiotensin system, because its concentration was much higher than would be predicted from inactivation of arterial blood angiotensin II octapeptide in peripheral tissues.

Who should receive recombinant human erythropoietin?

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.

The peak concentration hypothesis: a urea kinetic approach to comparing the adequacy of continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis.

The KT/V urea index (K, clearance; T, treatment time; V, volume of urea distribution) has become an established index of hemodialysis (HD) adequacy, values of KT/V less than 0.8 being associated with overt uremic toxicity. For the typical continuous ambulatory peritoneal dialysis (CAPD) regimen of 4 X 2 L exchanges/day, the equivalent KT/V approximately 0.6. Paradoxically, overt uremic toxicity is not commonly observed in CAPD patients with this typical therapy prescription. Application of the urea kinetic model demonstrates that HD and CAPD have the same time-averaged urea concentration at the same KT/V. However, as HD is an intermittent therapy, the urea concentration in HD exceeds the time-averaged concentration for about half the hours in the week. If uremic toxicity is related to the peak rather than the time-averaged urea concentration, a higher KT/V would be required in HD to achieve a peak concentration at or below the steady-state CAPD concentration. This peak concentration hypothesis predicts, based on the results of the National Cooperative Dialysis Study, that underdialysis with CAPD would occur at KT/V less than 0.4 for a protein intake of 1.1 gm/kg/day.