Cardiovascular risk profile in individuals initiating treatment for overactive bladder - Challenges and learnings for comparative analysis using linked claims and electronic medical record databases.

For managing overactive bladder (OAB), mirabegron, a ß3 adrenergic receptor agonist, is typically used as second-line pharmacotherapy after antimuscarinics. Therefore, patients initiating treatment with mirabegron and antimuscarinics may differ, potentially impacting associated clinical outcomes. When using observational data to evaluate real-world safety and effectiveness of OAB treatments, residual bias due to unmeasured confounding and/or confounding by indication are important considerations. Falsification analysis, in which clinically irrelevant endpoints are tested as a reference, can be used to assess residual bias. The objective in this study was to compare baseline cardiovascular risk among OAB patients by treatment, and assess the presence of residual bias via falsification analysis of OAB patients treated with mirabegron or antimuscarinics, to determine whether clinically relevant comparisons across groups would be feasible. Linked electronic health record and claims data (Optum/Humedica) for OAB patients in the United States from 2011-2015 were available, with index defined as first date of OAB treatment during this period. Unadjusted characteristics were compared across groups at index and propensity-matching conducted. Falsification endpoints (hepatitis C, shingles, community-acquired pneumonia) were compared between groups using odds ratios (ORs) and 95% confidence intervals (CI). The study identified 10,311 antimuscarinic- and 408 mirabegron-treated patients. Mirabegron patients were predominantly older males, with more comorbidities. The analytic sample included 1,188 antimuscarinic patients propensity-matched to 396 mirabegron patients; after matching, no significant baseline differences remained. Estimates of falsification ORs were 0.7 (CI:0.3-1.7) for shingles, 1.5 (CI:0.3-8.2) for hepatitis C, 0.8 (CI:0.4-1.8) and 0.9 (CI:0.6-1.4) for pneumonia. While propensity matching successfully balanced observed covariates, wide CIs prevented definitive conclusions regarding residual bias. Accordingly, further observational comparisons by treatment group were not pursued. In real-world analysis, bias-detection methods could not confirm that differences in cardiovascular risk in patients receiving mirabegron versus antimuscarinics were fully adjusted for, precluding clinically relevant comparisons across treatment groups.

Mortality studies comparing peritoneal dialysis and hemodialysis: what do they tell us?

Several recent large-scale epidemiological studies comparing mortality among end-stage renal disease (ESRD) patients receiving hemodialysis (HD) versus peritoneal dialysis (PD) show conflicting results. In this paper, we undertake a critical review of these studies. Our goal is to determine if there are any consistent trends in outcomes between HD and PD within select subgroups of patients once methodological differences have been accounted for. A total of six large-scale registry studies and three prospective cohort studies conducted in the United States (US), Canada, Denmark, and the Netherlands were reviewed. Summary findings from these studies are presented for comparative purposes. Additional summary analyses based on previously reported data on 398 940 incident US Medicare patients are included for the purpose of comparing results from this population of patients to those of the other select studies when similar methods of analysis are applied. Results are summarized in terms of the relative risk of death for PD versus HD (RR[PD:HD]). Differences in results between the nine studies can be attributed to the degree of case-mix adjustment carried out and to the use of different subgroups when comparing mortality between HD and PD. When these differences are accounted for, we found a remarkable degree of synergism in results between the registry studies and, to a lesser degree, the prospective cohort studies. PD was generally found to be associated with equal or better survival among non-diabetic patients and younger diabetic patients in all four countries. However, among older diabetic patients, results varied by country. The Canadian and Danish registries showed no difference in survival between PD and HD among older diabetics while in the US, HD was associated with better survival for diabetics aged 45 and older. All studies show a time-dependent trend in the RR of death with PD generally associated with equivalent or better survival during the first year or two of dialysis. However, results on longer-term survival varied according to study and to different subgroups within studies. Subgroup analyses in the prospective cohort studies were limited by small numbers of patients resulting in highly varied and somewhat controversial results when compared to the larger registry-based studies. Based on our review of recent publications and additional analyses of US Medicare data, we conclude that overall patient survival is similar for PD and HD but that important differences do exist within select subgroups of patients, particularly those subgroups defined by age and the presence or absence of diabetes.

Validation of PD Adequest 2.0 for pediatric dialysis patients.

Kinetic modeling has proven to be a valuable tool for peritoneal dialysis (PD) prescription in adult PD patients. The clinical application of this procedure has rarely been studied in children. We therefore evaluated the PD Adequest 2.0 for Windows program (Baxter Healthcare Co., Deerfield, IL) as a prescription aid for the management of pediatric PD patients by comparing the measured and predicted PD clearances, total drain volumes, and net ultrafiltration in 34 children (15 males) (mean age 10.9 +/- 6.0 years) receiving long-term PD. In each case, a 4-h peritoneal equilibration test was conducted with a standardized test exchange volume of 1,100 ml/m2 BSA. A total of 43 24-h dialysate (plus urine in 12) collections were analyzed. The levels of agreement between measured and predicted values for weekly peritoneal and total urea Kt/V, weekly peritoneal and total creatinine clearance, daily drain volume, net ultrafiltration and daily peritoneal urea and creatinine mass removal were assessed with correlation coefficients (re) and Bland-Altman limits of agreement. The study revealed that there is a basic level of agreement between measured and modeled values for solute removal and total drain volume, with correlation coefficients ranging from 0.75 to 0.98. In contrast, the rc for net ultrafiltration was only 0.34. The majority (75%) of patients had modeled urea and creatinine clearances that were within 20% of their measured values. These data suggest that the PD Adequest 2.0 for Windows program can predict urea and creatinine clearances with reasonable accuracy in pediatric PD patients, making it a valuable resource in prescription management.

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.

Patient survival among incident peritoneal dialysis and hemodialysis patients in an urban setting.

We retrospectively evaluated 432 patients (336 black; 78%; and 96 white; 22%) incident to our peritoneal dialysis (PD; 195 patients; 45%) and hemodialysis (HD; 237 patients; 55%) programs from January 1987 to December 1997 who survived their first 90 days of dialysis therapy. Black patients comprised 70% of the PD and 84% of the HD patients (P: < 0.01). PD patients were more often men and younger than HD patients and less often had diabetes (40% versus 56% of HD patients; P: < 0.01) and cardiac disease (44% versus 58% of HD patients; P: < 0.01) than HD patients. Adjusting for baseline clinical and comorbid features, patient survival was determined by Cox regression analysis. Survival was better on PD therapy overall (relative risk [RR] for PD versus HD, 0.80; 1-, 2-, and 5-year survival rates, 90%, 77%, and 43% on PD versus 88%, 72%, and 35% on HD, respectively; P: = 0.21) and among black patients (RR for PD versus HD, 0.69; 1-, 2-, and 5-year survival rates, 92%, 80%, and 52% on PD versus 88%, 74%, and 40% on HD, respectively; P: = 0.09), but these were not statistically significant. The RR for PD versus HD was 1.08 for white patients (1-, 2-, and 5-year survival rates, 82%, 61%, and 23% for PD versus 82%, 62%, and 24% for HD; P: = 0.79). Significant predictors of mortality were race (RR for whites versus blacks, 1.51), age (RR, 1.03), cardiac disease (RR, 1.57), baseline albumin level (RR, 0.60), baseline serum creatinine level (RR, 0.91), baseline blood urea nitrogen level (RR, 1.01), and baseline weight (RR, 0.98). In conclusion, patient survival on dialysis therapy is significantly better for black patients and for patients entering dialysis with signs of adequate nutrition (increased weight and creatinine and albumin levels) and without evidence of cardiac disease. In an urban dialysis program, we find that adjusted patient survival on PD equals or is better than that on HD therapy, particularly among black patients, making PD a viable alternative to HD in our patient population.

Correlation between peritoneal equilibration test and dialysis adequacy and transport test, for peritoneal transport type characterization. Mexican Nephrology Collaborative Study Group.

OBJECTIVE: The aim of this study was to analyze the correlation between the peritoneal equilibration test (PET) and the dialysis adequacy and transport test (DATT) for peritoneal transport type characterization, and the degree of patients' acceptance for each test. DESIGN: Cross-sectional, observational multicenter study. SETTING: Five referral (tertiary) dialysis centers of institutional practice. PATIENTS: The study included 107 adult continuous ambulatory peritoneal dialysis (CAPD) patients with a prescription of four exchanges of 2 L per day, irrespective of age, gender, cause of end-stage renal disease, time on dialysis, nutritional status, or residual renal function. Patients on immunosuppressive therapy and those with cancer, hepatitis B, or HIV, and those having a peritonitis episode within the previous 30 days, or three or more episodes during the previous 12 months, were excluded. MAIN MEASURES: Peritoneal transport type as classified by creatinine and urea dialysis-to-plasma (D/P) ratios by PET and DATT. RESULTS: Correlation coefficients between D/P ratios for creatinine and urea, obtained for the PET and the DATT, were 0.73 for D/P creatinine and 0.96 for D/P urea. Patients were classified into high, high-average, low-average, and low transport categories according to the mean and standard deviation of D/P creatinine values obtained from the PET at 4 hours. These values showed excellent concordance with those generated from the DATT data (alpha = 0.82, 95% confidence interval 0.67 - 0.93). Nineteen percent of patients showed discordance in their category when classified according to the PET versus the DATT. Patients' acceptance was better for the DATT than for the PET, as evaluated with a questionnaire. CONCLUSION: The DATT is an easy, inexpensive, and reliable test to assess peritoneal transport type, and it also provides information about peritoneal clearance of solutes and ultrafiltration. The DATT has better patient acceptance than the PET. Since the DATT has only been validated for patients on a fixed CAPD daily schedule of 4 x 2 L, the results should be confined only to patients receiving such a prescription.

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.

Racial differences in survival in an urban peritoneal dialysis program.

We retrospectively evaluated 233 incident patients (61% black, 27% white, and 12% Hispanic/Asian) to our peritoneal dialysis (PD) program from January 1987 to September 1997 to identify any possible racial differences in patient survival. Information collected included clinical features, comorbid conditions, nutritional status, and dialysis dose at initiation of dialysis. The average age was 52 +/- 16 (SD) years, and 49% were men. Diabetes mellitus was present in 41% of patients. Overall follow-up was 31 +/- 24 (median 26) months during which time 21% of patients underwent transplant, 29% of patients transferred to hemodialysis (HD), and 42% of patients died. The Cox proportional hazards analysis, based on intent-to-treat, identified age (RR: 1.03), race (RR: 2.35, white versus black), cardiac disease (RR: 1.97), and serum albumin (RR: 0. 44) to independently predict mortality. Further analysis was performed based on diabetic status, and the analysis identified age (RR: 1.06), race (RR: 2.45, white versus black), and peripheral vascular disease (RR: 2.88) as predictors of mortality in diabetic patients. In nondiabetic patients, age (RR: 1.03), race (RR: 2.24, white versus black), cardiac disease (RR: 2.48), cerebrovascular disease (RR: 3.17), and serum albumin (RR: 0.39) were significant predictors of mortality. The significance of race persisted even after adjusting patients transferring to hemodialysis. The adjusted patient survival at 1, 2, and 5 years was 94%, 87% and 53% for black patients, and 86%, 72%, and 23% for white patients. The adjusted patient survival in diabetics at 1, 2, and 5 years was 92%, 79%, and 37% for black patients, and 82%, 56%, and 9% for white patients. The adjusted patient survival in nondiabetics at 1, 2, and 5 years was 94%, 91%, and 63% for black patients, and 88%, 82%, and 35% for white patients. In conclusion, long-term patient survival is better for black patients than white patients in our peritoneal dialysis program. Peritoneal dialysis should be considered a viable dialytic option for black patients entering an end-stage renal disease program.

Mortality in end-stage renal disease: a reassessment of differences between patients treated with hemodialysis and peritoneal dialysis.

Recent registry studies comparing mortality between peritoneal dialysis (PD) and hemodialysis (HD) patients show conflicting results. The purpose of this study is to determine whether previously published results showing higher mortality for patients treated with PD versus HD in the United States continue to hold true over the period 1987-1993. National mortality rates for PD and HD were extracted from the U.S. Renal Data System (USRDS) annual reports for the cohort periods: 1987-1989, 1988-1990, 1989-1991, 1990-1992, and 1991-1993. Using Poisson regression, death rates per 100 patient years were compared between PD and HD for each cohort period controlling for age, gender, race, and cause of end-stage renal disease (diabetes versus nondiabetes). When incident patients and patients with a prior transplant were included in the analysis, starting with the 1989-1991 cohort, we found little or no difference in the relative risk (RR PD:HD) of death between PD and HD (1987-1989: RR = 1.17, P < 0.001; 1988-1990: RR = 1.12, P < 0.001; 1989-1991: RR = 1.06, P = NS; 1990-1992: RR = 1.06, P = NS; 1991-1993: RR = 1.08, P = 0.043). After a test for goodness-of-fit, separate analyses for diabetic patients and nondiabetic patients were done to examine unexplained variation in death rates. For nondiabetic patients, there was less than a 1% difference in the adjusted 1-yr survival between PD and HD from 1989-1993 (1989-1991: RR = 1.05, P = NS; 1990-1992: RR = 1.04, P = NS; 1991-1993: RR = 1.07, P < 0.01). Among diabetic patients, the PD:HD death rate ratio varied significantly according to gender and age. For the average male diabetic patient, there was little or no difference in risk between PD and HD from 1989-1993 (1989-1991: RR = 1.02, P = NS; 1990-1992: RR = 1.05, P = NS; 1991-1993: RR = 1.08, P < 0.01). For diabetic patients under the age of 50, those treated with PD had a significantly lower risk of death than those treated with HD (1989-1993: 0.84 < or = RR < or = 0.89, P < 0.005). Over the same period, female diabetic patients treated with PD had a higher risk, on average, than HD (1.18 < or = RR < or = 1.19, P < 0.001) as did diabetic patients over the age 50 (1.28 < or = RR < or = 1.30, P < 0.001). Unlike previously published results that were restricted to prevalent-only patients, this national study of both prevalent and incident patients found little or no difference in overall mortality between PD and HD. The recent trends in mortality likely reflect the inclusion of incident patients, but they may also reflect changes in case-mix differences and/or improved PD practice. Additional incident-based studies that allow for additional case-mix adjustments are needed to better compare outcomes between HD and PD.

Quantifying the effect of changes in the hemodialysis prescription on effective solute removal with a mathematical model.

One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins. This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and beta2-microglobulin (beta2M). The regimens assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, QB = 350, QD = 600; B (daily/short-time): F = 7, T = 100, QB = 350, QD = 600; C/D/E (low-flow/long-time): F = 3/5/7, T = 480, QB = 300, QD = 100. HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and beta2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM) G values. Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and beta2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and beta2M, respectively. For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; beta2M: 1.00, 1.27, 1.73, and 2.19. The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (beta2M). The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal. (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and beta2M removal. A daily low-flow/long-time regimen substantially increases the effective removal of all solutes.

A multinational clinical validation study of PD ADEQUEST 2.0. PD ADEQUEST International Study Group.

OBJECTIVE: To clinically validate the use of the newly released kinetic modeling program, PD ADEQUEST 2.0 for Windows (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), by assessing the level of agreement between measured and modeled values of urea and creatinine clearances (CCr), glucose absorption, total drain volumes, and net ultrafiltration for all forms of peritoneal dialysis. DESIGN: A nonrandomized, multinational, prospective longitudinal study. PATIENTS: The study involved 104 adult patients [41 on continuous ambulatory peritoneal dialysis (CAPD), 63 on automated peritoneal dialysis (APD)] from 16 centers in 7 countries. All patients underwent a 4-hour peritoneal equilibration test (PET) but with varying percentage dextrose concentrations (1.5% or 2.5% dextrose) and varying fill volumes (range 1.5 - 2.5 L). Patients with a residual renal function greater than 10 mL/min were excluded, as were patients who had peritonitis within 6 weeks prior to baseline. MAIN OUTCOME MEASURES: Correlation coefficients and Bland-Altman limits of agreement were used to assess the level of agreement between measured and modeled values of weekly peritoneal urea Kt/V (pKt/V) and total Kt/V, weekly peritoneal creatinine clearance (pCCr, L/week/1.73 m2) and total CCr (L/week/1.73 m2), daily drain volume (L/day), net ultrafiltration (UF, L/day), daily peritoneal urea and creatinine mass removal (g/day), and daily peritoneal glucose absorption (g/day). Measured values were obtained from three repeat 24-hour urine and dialysate collections per patient, while modeled values were calculated using the Baxter PD ADEQUEST 2.0 program in conjunction with kinetic parameters estimated from a 4-hour PET and long-dwell exchange independent of the 24-hour collections. RESULTS: The results show there is excellent agreement between measured and modeled urea Kt/V and CCr with concordance correlation coefficients ranging from 0.83 to 0.97 among CAPD and APD patients. There was also excellent agreement between measured and modeled values of glucose absorption and total drain volumes (concordance correlations of 0.90 and 0.98, respectively). This level of agreement was further supported by a Bland-Altman analysis of individual differences, including differences between measured and modeled net UF (coefficient of clinical agreement ranged from 0.66 to 0.92). CONCLUSIONS: Data from a carefully performed PET and overnight exchange can, in combination with a scientifically and clinically validated kinetic model, provide clinicians with a powerful mathematical tool for use in CAPD and APD prescription management. Although not intended to replace actual measurements, kinetic modeling can prove useful as a means for quickly estimating approximate levels of clearance for a wide variety of alternative prescriptions. This, in turn, should speed up the process by which a physician can optimize the dose of dialysis suitable for a given patient and his/her lifestyle.

Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study.

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.

Lower probability of patient survival with continuous peritoneal dialysis in the United States compared with Canada. Canada-USA (CANUSA) Peritoneal Dialysis Study Group.

In a prospective cohort study of 680 incident continuous peritoneal dialysis (PD) patients in North America, dialysis in the United States compared with Canada was associated with a relative risk (RR) of death of 1.93 (95% confidence interval [CI], 1.14 to 3.28). The 2-yr survival probability was 79.7% in Canada and 63.2% in the United States. This difference was not explained by race, age, gender, functional status, insulin-dependent diabetes mellitus, history of cardiovascular disease (CVD), nutritional status, or adequacy of dialysis. Other potential explanatory variables were further evaluated. These included severity of CVD, residual renal function, race, differential transfer to hemodialysis or transplantation, patient compliance, modality selection bias, and incidence of endstage renal disease requiring dialysis. Cardiovascular morbidity and peritonitis probabilities were compared. The CVD severity index was not different between countries; the RR risk associated with dialysis in the United States remained high at 1.87 (95% CI, 1.09 to 3.19). Residual renal function at initiation of dialysis was not different between countries. The 2-yr survival for Caucasians was 77% in Canada and 55% in the United States. There was no difference in the probability of transfer to hemodialysis or transplantation. The RR of a nonfatal cardiovascular event in the United States compared with Canada was 1.80 (95% CI, 1.21 to 2.67). There was no difference in time to first peritonitis. The observed to predicted creatinine ratio, as an estimate of compliance, was 1.13 in Canada and 1.00 in the United States. The prevalence of PD in the study centers was 48% in Canada and 22% in the United States. The incidence of new dialysis patients in 1992 was 100/million population in Canada compared with 211/ million in the United States. The survival difference is not explained by age, gender, insulin-dependent diabetes mellitus, nutritional status, or adequacy of dialysis. Neither is it explained by race, severity of CVD, transfer to hemodialysis, transplantation, or an estimate of compliance. The lower proportion of patients receiving PD in the United States may represent a selection bias of uncertain direction. The higher acceptance rate for dialysis in the United States may explain, in part, the greater cardiovascular morbidity and the decreased survival observed.

Peritoneal membrane transport function in children receiving long-term dialysis.

Accurate characterization of peritoneal solute transport capacity in children has been hampered by a lack of standardized test mechanics and small patient numbers. A standardized peritoneal equilibration test was used to study 95 pediatric patients (mean age, 9.9 +/- 5.6 yr) receiving chronic peritoneal dialysis at 14 centers. Patients were divided into four age groups (< 1, 1 to 3, 4 to 11, 12 to 19 yr) for analysis. Each patient received a 4-h peritoneal equilibration test with an exchange volume of 1100 mL/m2 per body surface area. Dialysate to plasma (D/P) ratios for creatinine (C) and urea (U) and the ratio of dialysate glucose (G) to initial dialysate glucose concentration (D/D0) were determined. Mass transfer area coefficients (MTAC) were calculated for the three solutes and potassium (P). The mean (+/- SD) 4-h D/P ratios for C and U were 0.64 +/- 0.13 and 0.82 +/- 0.09, respectively. The mean 4-h D/D0 for G was 0.33 +/- 0.10. D/P and D/D0 ratio results were similar across age groups. Normalized (for body surface area) mean MTAC (+/- SD) values were as follows: C, 10.66 +/- 3.74; G, 12.93 +/- 5.02; U, 18.43 +/- 4.02; and P, 14.02 +/- 3.94. Whereas a comparison of the normalized MTAC values across age groups with an analysis of variance showed significant age group differences only for glucose (P = 0.001) and potassium (P = 0.036), analysis by quadratic regression demonstrated a nonlinear decrease with age for C (P = 0.016), G (P < 0.001), and P (P = 0.034). In summary, evaluation of D/P and D/D0 ratios obtained from a large group of children in a standardized manner reveals values that are similar across the pediatric age range and not unlike the results obtained in adults. In contrast, normalized MTAC values of young children are greater than the values of older children, possibly as a result of maturational changes in the peritoneal membrane or differences in the effective peritoneal membrane surface area.

Peritoneal dialysis kinetic modeling: validation in a multicenter clinical study.

OBJECTIVE: To clinically validate the use of a computer-based kinetic model for peritoneal dialysis (PD) by assessing the level of agreement between measured and modeled values of urea and creatinine clearances and ultrafiltration (UF). DESIGN: An open multicenter observational study. PATIENTS: There were 111 adult continuous ambulatory peritoneal dialysis (CAPD) patients (47 female, 64 male) in four centers. All patients underwent a four-hour peritoneal equilibration test (PET) using 2.5% dextrose but with variable fill volumes (range: 1-3 L). Patients with a residual renal function greater than 10 mL/min were excluded. MAIN OUTCOME MEASURES: Correlations and limits of agreement between measured and modeled values of total weekly urea KT/V, total weekly normalized creatinine clearance (L/week/1.73 m2), daily drain volume (L), net ultrafiltration (L), daily peritoneal urea clearance (L/day), and daily peritoneal creatinine clearance (L/day). Measured values were obtained from 24-hour urine and dialysate collections while modeled values were based on results from the PET in combination with the PD ADEQUEST kinetic program. RESULTS: The results show there is excellent agreement between measured and modeled urea KT/V and creatinine clearances, with concordance correlations of 0.94 and 0.92, respectively. Given the excessive variation and limited range in ultrafiltration values, the concordance correlation between measured and modeled UF was only 0.50. In terms of daily peritoneal clearances and ultrafiltration, the level of precision (i.e., standard deviation) in the differences between modeled and measured values is +/- 1.05 L/day for urea clearance +/- 1.03 L/day for creatinine clearance, and +/- 0.919 L/day for ultrafiltration. By contrast, the level of precision (i.e., standard deviation) in the differences between two measured values is estimated to be +/- 0.979 L/day for urea clearance, +/- 0.802 L/day for creatinine clearance, and +/- 0.707 L/day for ultrafiltration. Defining the limits of clinical agreement to be +/- 2 standard deviations of the differences between two clinically measured 24-hour clearances (or ultrafiltration), we find that 94% of the modeled urea clearances, 87% of the modeled creatinine clearances, and 86% of the modeled ultrafiltration values fall within the limits of clinical agreement. CONCLUSION: Data for a carefully performed PET and overnight exchange can, in combination with a scientifically validated kinetic model, provide clinicians with a powerful mathematical tool for use in CAPD dialysis prescription management. Although not intended to replace actual measurements, kinetic modeling can prove useful as a means for predicting clearances for various alternative prescriptions and perhaps also as a means for checking certain types of noncompliance.

Goodness-of-fit in generalized nonlinear mixed-effects models.

In recent years, generalized linear and nonlinear mixed-effects models have proved to be powerful tools for the analysis of unbalanced longitudinal data. To date, much of the work has focused on various methods for estimating and comparing the parameters of mixed-effects models. Very little work has been done in the area of model selection and goodness-of-fit, particularly with respect to the assumed variance-covariance structure. In this paper, we present a goodness-of-fit statistic which can be used in a manner similar to the R2 criterion in linear regression for assessing the adequacy of an assumed mean and variance-covariance structure. In addition, we introduce an approximate pseudo-likelihood ratio test for testing the adequacy of the hypothesized convariance structure. These methods are illustrated and compared to the usual normal theory likelihood methods (Akaike's information criterion and the likelihood ratio test) using three examples. Simulation results indicate the pseudo-likelihood ratio test compares favorably with the standard normal theory likelihood ratio test, but both procedures are sensitive to departures from normality.

Peritonitis in an urban peritoneal dialysis program: an analysis of infecting pathogens.

We have previously found that race, level of education, and peritoneal dialysis system are factors that significantly and independently influence peritonitis rates in our patient population. We now extend these observations by assessing the pathogens responsible for peritonitis in these subgroups. Between January 1, 1981, and May 15, 1993, 248 peritoneal dialysis patients underwent dialysis at our facility. The rate of peritonitis by pathogen was determined in these patients using the fixed effects Poisson model. Total peritonitis rates in black patients (1.89 episodes/patient-year) were significantly greater compared with white patients (1.11 episodes/patient-year; P < 0.0001). Increased infection rates in black patients were significant for Staphylococcus epidermidis, Staphylococcus aureus, and gram-negative pathogens. The level of education had a negative correlation with peritonitis rates (< or = 8 years, 2.00 episodes/patient-year; 9 to 12 years, 1.64 episodes/patient-year; and > or = 13 years, 1.24 episodes/patient-year) with patients having > or = 13 years of education at the start of dialysis demonstrating a significantly lower total peritonitis rate compared with patients with 9 to 12 years (P = 0.001) or < or = 8 years (P < 0.001) of education. This was accounted for by a significant decrease in infection rates for S epidermidis, polymicrobial, and gram-negative organisms. Finally, patients on automated peritoneal dialysis had significantly lower total peritonitis rates (0.59 episodes/patient-year) compared with patients on either a connect (2.11 episodes/patient-year) or disconnect (1.46 episodes/patient-year) system.(ABSTRACT TRUNCATED AT 250 WORDS)