Search

Objective: We identified factors that account for differences between lean body mass computed from creatinine kinetics (LBM(cr)) and from either body water (LBM(V)) or body mass index (LBM(BMI)) in patients on continuous peritoneal dialysis (CPD)., Design: We compared the LBM(cr) and LBM(V) or LBM(BMI) in hypothetical subjects and actual CPD patients., Patients: We studied 439 CPD patients in Albuquerque, Pittsburgh, and Toronto, with 925 clearance studies., Intervention: Creatinine production was estimated using formulas derived in CPD patients. Body water (V) was estimated from anthropometric formulas. We calculated LBM(BMI) from a formula that estimates body composition based on body mass index. In hypothetical subjects, LBM values were calculated by varying the determinants of body composition (gender, diabetic status, age, weight, and height) one at a time, while the other determinants were kept constant. In actual CPD patients, multiple linear regression and logistic regression were used to identify factors associated with differences in the estimates of LBM (LBM(cr)LBM(V). The differences in determinants of body composition between groups with high versus low LBM(cr) were similar in hypothetical and actual CPD patients. Multivariate analysis in actual CPD patients identified serum creatinine, height, age, gender, weight, and body mass index as predictors of the differences LBM(V)-LBM(cr) and LBM(BMI)-LBM(cr)., Conclusions: Overhydration is not the sole factor accounting for the differences between LBM(cr) and either LBM(V) or LBM(BMI) in CPD patients. These differences also stem from the coefficients assigned to major determinants of body composition by the formulas estimating LBM., (Published by Elsevier Inc.)

Objective: The Cockroft-Gault formula was shown to systematically overestimate the decline in creatinine excretion with age in continuous peritoneal dialysis (CPD) patients and is, therefore, not suitable for studying creatinine excretion. The purpose of the present study was to develop and test a population-specific formula predicting average creatinine excretion in CPD., Methods: Creatinine excretion in urine plus dialysate was measured in 925 CPD patients. Forty patients were excluded because of evidence of noncompliance. The remaining 885 subjects were randomly grouped into a derivation group (n = 432) and a validation group (n = 453). Stepwise multiple linear regression models were used to predict creatinine excretion in the derivation group. The candidate variables, chosen because they were previously shown to be predictors of creatinine excretion in CPD, included weight (W), age (A), gender (G), diabetes (D), and interaction terms between these four variables. Estimates of creatinine excretion from the best-fit regression formula (CrExcr1) and from the Cockroft-Gault formula (CrExcr2) were compared to creatinine excretion (CrExcr) in the validation group., Results: The best-fit regression model in the derivation group included all four candidate variables (W, A, G, D), but no interaction terms. This model was as follows: CrExcr1 = 302.150 - 4.380A + 171.234G - 39.041D + 11.730W (r2 = 0.477, p < 0.001). In the validation set, CrExcr = -15.795 + 0.988CrExcr1 (r2 = 0.447, p < 0.001), and CrExcr = -303.823 + 0.732CrExcr2 (r2 = 0.340, p < 0.001). When the differences between measured and predicted creatinine excretion did not take into account the sign of each individual difference, CrExcr - CrExcr1 = 201 +/- 156 mg/24 hours, and CrExcr - CrExcr2 = 235 +/- 174 mg/24 hr (p < 0.001) in the validation group. When the sign of the difference was taken into account, CrExcr - CrExcr1 = -28 +/- 149 mg/24 hr, and CrExcr - CrExcr2 = 63 +/- 295 mg/24 hr (p < 0.001)., Conclusions: A population-specific formula predicting creatinine excretion in CPD was derived. This formula has greater accuracy than the Cockroft-Gault formula and can be used in studies of creatinine excretion in CPD.

We investigated the hypothesis that the rate of loss of creatinine excretion with age in peritoneal dialysis (PD) patients differs from the rate predicted from the Cockroft-Gault formula (Cr(Pred)) by analyzing creatinine excretion data obtained from clearance studies of 925 patients on continuous ambulatory PD therapy with an age range of 12 to 91 years. Measured creatinine generation (Cr(Meas)) is the sum of creatinine excretion in urine plus dialysate (Cr(Excr)) plus an estimated metabolic degradation of creatinine. The effect of age on Cr(Excr) and the differences Cr(Excr) - Cr(Pred) and Cr(Meas) - Cr(Pred) were analyzed by linear regression. In 373 women, Cr(Excr) = W(16.9360 - 0.084A), r = -0.342, P < 0.001 (where W is weight in kilograms and A is age in years). The regression slope was one half of the slope in the Cockroft-Gault formula. Cr(Excr) - Cr(Pred) = -413.91 + 4.78A, r = 0.300, P < 0.001. Cr(Meas) - Cr(Pred) = -176.36 + 4.37A, r = 0.278, P < 0.001. In 552 men, Cr(Excr) = W(21.079 - 0.108A), r = -0.338, P < 0.001. The regression slope was approximately one half of the slope in the Cockroft-Gault formula. Cr(Excr) - Cr(Pred) = -493.25 + 6.28A, r = 0.267, P < 0.001. Cr(Meas) - Cr(Pred) = -66.41 + 3.63A, r = 0.143, P = 0.001. The rate of loss of creatinine excretion with age is one half of the rate predicted by the Cockroft-Gault formula in both women and men on PD therapy. Therefore, the difference between excretion (or measured generation) of creatinine and creatinine generation predicted by the Cockroft-Gault formula is not constant, but increases with age. The Cockroft-Gault formula systematically overestimates the effect of age on creatinine excretion in PD patients and is not suitable for predicting creatinine excretion in these subjects.

Lean body mass computed from creatinine kinetics (LBM) is an index of somatic nutrition and correlates with other nutrition indices in CAPD. However, LBM exceeding 90% of body weight (LBM/W > or = 0.9) may be an index of non-compliance, rather than nutrition. To test this hypothesis, we analyzed fluid and solute excretion in 40 CAPD patients with LBM/W > or = 0.9 (group A). The comparison group (group B) consisted of 885 CAPD patients with LBM/W < 0.9. Group A was younger (38.3+/-14.8 vs 54.7+/-14.7 yr) and had a lower percent of women (23.5% vs 41.1%) and diabetic subjects (17.5% vs 42.6%) than group B (at P < or = 0.019). Group A also had lower body mass index (22.7+/-2.7 vs 25.8+/-5.1 kg/m2, P <0.001) and serum albumin (33.0+/-6.7 vs 35.2+/-5.5 g/L, P = 0.014). Despite similar prescribed daily fill volumes (group A 8.3+/-2.4, group B 8.5+/-2.2 L/24 h) and similar D/P urea and creatinine values, group A had higher daily drain volume (11.0+/-3.6 vs 9.6+/-2.1 L/24 h, P < 0.001). Renal clearances were similar, while peritoneal and total clearances were apparently higher in group A. Creatinine excretion was higher in group A (27.4+/-5.1 vs 13.6+/-4.1 mg/kg x 24 h, P < 0.001), with a large part of the excess creatinine excretion in group A being accounted for by peritoneal excretion. The combination of an apparently high daily ultrafiltration volume (2.7 L/24 h on the average), unrealistically high creatinine excretion rate, and relatively poor nutrition (low body mass index and serum albumin) in group A is consistent with non-compliance. We suggest that the finding of LBM/W > or = 0.9 during a clearance study in CAPD should trigger an investigation for non-compliance.

We analyzed the effect of diabetes on the decline of residual renal function during the course of CAPD in a cross-sectional study including 105 diabetic subjects (41 women) who had 207 clearance studies and 125 non-diabetic subjects (50 women, 265 clearance studies). CAPD duration was 11.5+/-10.5 months in the diabetic group (DG) and 16.8+/-18.6 months in the non-diabetic group (NDG, P < 0.001). The DG had lower urine volume than the NDG (0.52+/-0.46 vs 0.61+/-0.50 L/24-h, P < 0.05), while urine-to-plasma concentration ratio was higher in the DG for creatinine (13.5+/-9.4 vs 11.5+/-11.0, P <0.05) and did not differ for urea. Weekly renal Kt/V urea (DG 0.51+/-0.57, NDG 0.53+/-0.49) and Ccr (DG 31.0+/-28.7 NDG 29.3+/-26.5 L/1.73 m2) did not differ. The slopes of the regressions of CAPD duration on renal clearances did not differ. These regressions allowed estimates of the time, from the onset of CAPD, at which renal clearances become negligible. These estimates differed for both urea clearance (DG 35.3, NDG 50.5 months) and creatinine clearance (DG 43.2, NDG 57.6 months). The slope of the regression of renal urea clearance on renal creatinine clearance was steeper in the DG, suggesting a higher renal creatinine clearance in the DG than in the NDG when renal urea clearance is the same in the two groups. Subtle differences in the rate of decline of renal function can be detected between diabetic and non-diabetic subjects on CAPD by detailed statistical analysis. These findings are supportive of the studies which have identified diabetes mellitus as a predictor of loss of residual renal function during the course of CAPD. In addition, the relationship between the renal urea and creatinine clearances differs between diabetic and nondiabetic subjects on CAPD. Therefore, the dose of CAPD required for adequate total clearances may differ between diabetic and non-diabetic subjects.

We studied whether anuric subjects on continuous ambulatory peritoneal dialysis (CAPD) who achieve the target Kt/V urea of 2.0 weekly will also achieve the target normalized creatinine clearance (NCCr) of 60 liter/1.73 m2 weekly, and the reasons of discrepancy between the two clearances in anuric subjects, by analyzing 476 clearance studies performed in 309 CAPD patients within 12 months of the performance of a peritoneal equilibration test (PET). On the basis of the PET, peritoneal solute transport was classified as low (37 clearance studies), low-average (199 studies), high-average (186 studies) and high (54 studies). We found that weekly values of Kt/V urea in the low transport group (LTG) was 1.74 +/- 0.51, in the low-average transport group (LATG) was 1.66 +/- 0.41, in the high-average transport group (HATG) 1.68 +/- 0.41, and in the high transport group (HTG) 1.73 +/- 0.46 (NS, variance analysis). Weekly values for NCCr, liter/1.73 m2 were: LTG, 37.8 +/- 9.0; LATG, 44.0 +/- 9.2; HATG, 49.2 +/- 10.0; HTG 56.8 +/- 13.3 (P < 0.0001). The ratios of raw (not-normalized) peritoneal creatinine clearance to peritoneal urea clearance were: LTG, 0.65 +/- 0.14; LATG, 0.76 +/- 0.09; HATG, 0.84 +/- 0.09; HTG, 0.91 +/- 0.12 (P < 0.0001). Linear regression with Kt/V urea as x and NCcr as y revealed the following results: LTG, y = 19.486 + 10.500x, r = 0.591 [if x = 2.0, y = 15.004 + confidence interval (95% CI) of y 25.3 to 55.7]; LATG, y = 15.0004 + 17.482x, r = 0.774 (if x = 2.0, y = 50.0, 95% CI of y 38.4 to 61.6); HATG, y = 15.285 + 20.162x, r = 0.829 (if x = 2.0, y = 55.6, 95% CI of y 44.4 to 66.8); HTG, y = 14.945 + 24.134x, r = 0.839 (if x = 2.0, y = 63.2, 95% CI of y 48.4 to 78.1). Peritoneal solute transport type has a major effect on peritoneal creatinine clearance, but an insignificant effect on peritoneal urea clearance. Consequently, the majority of anuric patients who achieve a weekly Kt/V urea of 2.0 will have a weekly NC cr lower than 60 liter/1.73 m2 and will require a Kt/V urea much higher than 2.0 to achieve the target NCcr of 60 liter/1.73 m2 weekly. The current targets of urea and creatinine clearance are not compatible in anuric patients on CAPD.

The effect of gender and degree of obesity on the size indicators V, used to normalize urea clearance (Kt/Vur), and body surface area (BSA), used to normalize creatinine clearance (Ccr), in peritoneal dialysis was studied by: (1) mathematical comparison of the formulae used to estimate V (Watson and Hume) with the Dubois formula used to estimate BSA in peritoneal dialysis; and (2) comparison of percent deviation of BSA (delta BSA%) and V (delta V%) from ideal weight estimates in 933 clearance studies performed in actual patients (555 in men and 378 in women on continuous ambulatory peritoneal dialysis). V was estimated by the Watson formulae and BSA by the Dubois formula in these studies. delta BSA% and delta V% were stratified in 10% increments in deviation of body weight from ideal (delta W%) in these studies. Mathematically, the relationship between V and BSA is not linear. In the same subject, as obesity develops (delta W% increases) and BSA increases in a linear manner, V increases exponentially. In addition, there are substantial differences in the relationship between V and BSA caused by gender. For the same height and BSA, men have a larger V than women. In the clearance studies performed in actual continuous ambulatory peritoneal dialysis patients, the difference between delta V% and delta BSA% increased significantly (P < 0.0001) from the wasted to the obese subjects by one-way ANOVA in both men and women. Normalization of urea and creatinine clearances by different size indicators creates two types of mathematical distortion in the relationship between the two clearances. One distortion is caused by the degree of obesity. The second distortion is caused by gender. Use of the same size indicator to normalize both urea and creatinine clearances would eliminate these distortions.

The relative contribution of urinary volume (UV) and urine-to-plasma concentration ratios for urea (U/PUr) and creatinine (U/PCr) to urinary Kt/V urea (Kt/VU) and urinary uncorrected creatinine clearance (CCrU), respectively, was studied by simple and multiple linear regression analysis in 236 urea kinetic studies and 233 creatinine kinetic studies performed in 135 patients on continuous peritoneal dialysis (CPD). The following simple regressions were obtained: Kt/VU = 0.09 + 0.72 (UV), r = 0.75; Kt/VU = -0.01 + 0.11 (U/PUr), r = 0.55; CCrU = 12.06 + 56.46 + 46.46 (UV), r = 0.62; CCrU = 3.51 + 3.40 (U/PCr), r = 0.58. All r values were significant (p < 0.001). According to these regressions, a loss of 0.2 L/24 hours in UV leads to a loss of 0.15 weekly in Kt/VU and 11.3 L/1.73 m2 weekly in corrected CCrU (approximately 8 L/1.73 m2 weekly in corrected CCrU). By multiple linear regression, (1) Kt/VU = -0.38 + 0.70 (UV) + 0.10 (U/PUr). Standardized coefficients were 0.72 for UV and 0.51 for U/PUr (2) CCrU = -33.36 + 59.83 (UV) + 3.63 (U/PCr). Standardized coefficients were 0.65 for UV and 0.61 for U/PCr. UV is the most important determinant of both urea and creatinine urinary clearances in CPD patients. The contribution of the U/P ratios to the urinary clearances is important, but less than that of UV. The primary dependence of urinary clearances on UV allows the use of UV, which can be easily monitored by patients, as a first approximation index of changing residual renal function in CPD.

Stepwise logistic regression performed in 324 clearance studies in 194 patients identified daily drain volume normalized by body water (DV/V) and peritoneal solute transport type as the predictors of peritoneal creatinine clearance (CCrp) in continuous ambulatory peritoneal dialysis (CAPD). Solution of the regression model for DV/V provided DV/V values predicted to provide a desired CCrp at different probabilities. The ability of the predicted DV/V to detect desired CCrp values was tested in a new set of 359 clearance studies in 217 CAPD patients who had a peritoneal equilibration test within 12 months of the clearance study. No patient with low transport had a CCrp exceeding 54 L/1.73 m2 weekly. The following DV/V values detected CCr > or = 54 L/1.73 m2 weekly with a probability of at least 80%: for low-average transport, 0.406 L/L per 24 hours; for high-average transport, 0.339 L/L per 24 hours; for high transport, 0.241 L/L per 24 hours. Corresponding DV/V values for a CCrp of 60 L/1.73 m2 weekly were as follows: for high-average transport, 0.351 L/L per 24 hours; for high transport, 0.271 L/L per 24 hours. For high-average transport, maximal body surface area (BSA) estimates allowing a CCrp of 60 L/1.73 m2 weekly at a CAPD schedule of four daily exchanges with 3-L exchange volume and 1.5 L/24 hour ultrafiltration volume, and with the specified DV/V values were 2.03 m2 in women and 1.77 m2 in men. Corresponding BSA estimates for high peritoneal solute transport were 2.58 m2 in women and 2.21 m2 in men. The delivered dose of CAPD, expressed as DV/V, required to achieve a target CCrp can be calculated from multivariate statistical models taking into account the peritoneal solute transport type. Multiplication of the required DV/V by V provides an estimate of the required daily exchange volume. Maximal BSA estimates allowing a target CCrp can be calculated for each gender and peritoneal solute transport type.

Objective: To study whether or not continuous peritoneal dialysis (CPD) can provide acceptable levels of normalized urea and creatinine clearance in heavyweight individuals., Design: Retrospective analysis of urea and creatinine clearance studies., Setting: CPD patients followed in four dialysis units in Albuquerque, two dialysis units in Thessaloniki, and two dialysis units in Athens., Participants: One hundred and ninety-nine patients on CPD with 266 clearance determinations between 1991 and 1995., Interventions: The heavyweight group consisted of 22 patients (24 clearance studies) weighing 100 kg or more (109 +/- 8.7 kg) at the time of the clearance study. All subjects were obese. The reference group consisted of 177 CPD subjects (242 clearance studies) of normal weight (68.7 +/- 12.2 kg). Urea fractional clearance (KT/V) and normalized creatinine clearance (Ccr) were compared between the heavyweight and the reference groups., Main Outcome Measures: The lowest acceptable weekly levels were set at 1.70 for KT/V and 54.4 L/1.73 m2 for Ccr., Results: Weekly KT/V was 1.75 +/- 0.41 in the heavyweight group and 1.94 +/- 0.52 in the reference group (p = 0.047). Corresponding weekly Ccr levels were 64.0 +/- 24.3 and 77.6 +/- 40.3 L/1.73 m2, respectively (p = 0.021). In the heavyweight group, 13 studies (54.2%) had acceptable KT/V values compared to 160 studies (66.1%) in the reference group (NS). Corresponding values for acceptable Ccr were 17 (70.8%) and 165 (68.2%), respectively (NS). Drain volume was 12.96 +/- 4.40 L/24 hours in the heavyweight group and 9.63 +/- 2.58 L/24 hours in the reference group (p = 0.001). High daily exchange volume was delivered by a combination of daily continuous ambulatory peritoneal dialysis (CAPD) and nocturnal automated peritoneal dialysis (APD) in 13/16 heavyweight studies. This combination was tolerated better than any other method of delivering a large daily exchange volume., Conclusion: Although normalized urea and creatinine clearances are lower in obese, heavyweight individuals than in lean CPD subjects with lower weight, approximately equal percentages of these two groups achieve acceptable clearance levels. However, heavyweight individuals require larger-than-usual daily exchange volumes. The preferred way to deliver these large dialysate volumes is a combination of daily CAPD and nocturnal APD.

The expression (Estimated-Predicted)/Predicted creatinine generation ¿(E-P)/P¿ has been proposed as an index of compliance in continuous peritoneal dialysis (CPD). We attempted to define an (E-P)/P value that can be used as a cut-off for non-compliance and to characterize the relation of (E-P)/P to serum albumin. In 324 clearance studies, (E-P)/P had a normal distribution with a mean of +0.094 and an SD of 0.357. In these studies, there was a weak correlation between (E-P)/P and serum albumin (r = 0.12, P < 0.05), but (E-P)/P was not a predictor of serum albumin by logistic regression. In 34 CPD patients, who had an increase in the dose of CPD resulting in an increase in measured creatinine clearance from 43.8 +/- 14.0 to 66.1 +/- 17.6 L/1.73 m2 weekly (P < 0.001), (E-P)/P increased correspondingly from +0.018 +/- 0.284 to +0.153 +/- 0.369 (P = 0.018), although all subjects should be in a steady state of creatinine excretion in the second study. The rise in (E-P)/P was statistically significant in the subgroup of 17 subjects who had a decrease in serum albumin, but not in the subgroup of 14 subjects who had an increase in serum albumin from the first to the second clearance study. The (E-P)/P cut-off for a definitive diagnosis of CPD non-compliance may be around +0.400 or +0.500. The findings of this study suggest that non-compliance, as indicated by (E-P)/P, has an adverse effect on serum albumin and that non-compliance increases after a prescribed increase in the dose of CPD.

Objectives: To identify the most advantageous formula for estimating creatinine clearance (CCr) and to establish a dose of dialysis that will ensure minimal acceptable levels of creatinine clearance in patients on continuous peritoneal dialysis (CPD)., Design: Analysis of all CCr studies performed in CPD patients over 40 months., Setting: All four dialysis units following CPD patients in one city. One dialysis unit is government-owned, one is university-affiliated, and two are community based., Participants: One hundred and ninety-four patients representing almost the entire CPD population in Albuquerque., Interventions: Creatinine and urea clearance studies were performed in 24-hour urine and drained dialysate samples. Creatinine clearance (peritoneal plus urinary) was normalized to either 1.73 m2 body surface area (CCr) or body water estimated by the Watson formulas (KT/VCr). CCr and KT/VCr were either corrected by averaging urinary creatinine and urea clearances or were not corrected. Two dialysis units were designated as the training set (92 patients, 143 clearance studies) and the other two units as the validation set (102 patients, 181 clearance studies)., Main Outcome Measures: Minimal acceptable creatinine clearance levels were determined in the training set by computing the creatinine clearance value corresponding to 1.70 weekly KT/V urea by linear regression. Logistic regression models predicting low creatinine clearance were developed in the training set and were tested in the validation set., Results: The following weekly creatinine clearance values corresponded to 1.70 KT/V urea: corrected CCr 52.0 L/1.73 m2, uncorrected CCr 54.4 L/1.73 m2, corrected KT/VCr 1.46, uncorrected KT/VCr 1.53. Logistic regression identified as predictors of low creatinine clearance low daily urine volume (UV) and low daily dialysate drain volume/body water (DV/V) for all four creatinine clearance formulas, plus low/low-average peritoneal solute transport (only for uncorrected CCr) and serum creatinine (for both KT/VCr formulas). In the validation set, the predictive models produced an area under the receiver operating characteristic (ROC) curve between 0.835 and 0.919 indicating very good predictive accuracy. For corrected CCr and anuria, the regression model produced a minimal normalized drain volume (DV/V) value consistent with minimal acceptable CCr equal to 0.305 L/L per 24 hours. This DV/V cutoff detected low corrected CCR in validation set anuric subjects (n = 55) with a sensitivity of 85% and a specificity of 71%. For uncorrected CCR and anuria, DV/V cutoffs were 0.273 L/L per 24 hours (high/high-average peritoneal solute transport) and 0.420 L/L per 24 hours (low/low-average transport). Sensitivity and specificity of these cutoffs in validation set anuric subjects were 87% and 85%, plus 86% and 33%, respectively., Conclusions: The uncorrected CCr appears to be the most advantageous creatinine clearance formula in CPD, because it allows the use of peritoneal solute transport type in the calculation of the minimal required normalized drain volume. The minimal acceptable uncorrected CCr is 54.4 L/1.73 m2 weekly. To achieve this uncorrected CCr in anuria, the required minimal normalized drain volume is 0.273 L per liter of body water daily if peritoneal solute transport is high or high-average and around 0.420 L per liter of body water daily if peritoneal solute transport is low or low-average. The required total daily drain volume is computed by multiplying the required normalized drain volume by body water.

The association between azotemic index dialyzer clearances and hematocrit was investigated in a 63-year-old dialysis-dependent man with acquired renal cysts. During 43 months of hemodialysis, hematocrit rose from 27.3 to 65.0 vol%, as a consequence of high serum erythropoietin levels. Concomitantly, dry weight also increased from 116.8 to 140.8 kg. Both hematocrit and dry weight correlated with: (a) urea reduction ratio, (b) creatinine reduction ratio (CRR), and (c) KT/V urea. All correlations were negative. Stepwise regression showed that only hematocrit was an independent correlate of the CRR (CRR = 0.662 - 007* Hct, R2 = 0.770); whereas, both hematocrit (Hct) and weight (W) were independent correlates of KT/V urea (KT/V = 2.070 - 0.005*Hct - 0.009*W,R2 = 0.721). In addition to creatinine clearance, urea clearance through the dialyzer is reduced by a rising hematocrit. The effect of hematocrit on urea clearance is relatively small. Therefore, it requires large changes in hematocrit in order to be detected.