Kinetic modelling and underdialysis in CAPD patients

Kinetic analysis was performed in all 58 patients undergoingstandard CAPD. The urea distribution volume was estimated fromanthropomorphic measurements (Watson formulae). Normalized proteincatabolic rate (NPCR), daily protein leak (PL), urea and creatinineKt/Vs, clearances and peritoneal mass transfer coefficients(Kp) were calculated from measurements on serum, 24-h urineand PD fluid effluent. The mean total (renal+PD) daily creatinine and urea Kt/Vs (KT/V)were 0.31 (range 0.15–0.79) and 0.31 (0.18/0.65). Therewas no relationship between KT/V and serum urea or Kp. The strongestdeterminant of the urea KT/V was the residual renal urea clearance(KrU)(R=079, P<0.001) which decreased with time on dialysis(R=–0.38, P<0.005). There was a significant correlationbetween the hospital admissions per year and both the urea andcreatinine KT/V and KrU (R=–0.30, –0.32, P<0.05).Patients with urea KT/V<0.25 (n=22) had more hospital admissions/yearthan those with KT/V>0.25 (mean of 2.6 versus 1.5, P<0.05).NPCR correlated with urea KT/V (R=0.62, P<0.001) but notwith serum albumin or the PL. Patients identified by UKM to be less well dialysed have a lowerresidual renal function and are more likely to be hospitalized.Undernutrition in CAPD patients appears to be related to underdialysisrather than protein loss.     

Use of a modified peritoneal equilibration test to optimize solute and water clearance

The standard peritoneal equilibration test (PET) characterizes the peritoneal transport of fluid, creatinine and urea. However, the applicability of the standard PET may be limited in patients on cycling peritoneal dialysis due to the choice of 2- and 4-h sampling times which exceed the usual dwell time of most patients on cycling peritoneal dialysis. We have performed a modified PET on seven pediatric dialysis patients in an effort to optimize dwell time to achieve maximal clearance of solutes and fluid. When compared with the standard PET, values obtained for dialysate/plasma urea and dialysate/plasma creatinine with the modified PET are significantly different. This resulted in an increased estimated creatinine clearance in five of seven and increased estimated urea clearance in six of seven patients. The modified PET is a more appropriate method for evaluation of peritoneal clearances in children as well as older patients who may require cycling peritoneal dialysis.     

Elimination of gadolinium-DTPA by peritoneal dialysis

Magnetic resonance urography (MRU) after i.v. injection of gadolinium-DTPA(0.1 mmol/kg bodyweight) was performed in a patient with transplantdysfunction after renal allograft transplantation. Renal replacementtherapy was accomplished by means of peritoneal dialysis. Gadolinium–DTPAconcentrations in urine and dialysate were measured repeatedlyduring a 48-h period with inductively coupled plasma atomicemission spectrometry. The total 24-h creatinine clearance was10.8 ml/min on day 1 and 13.7 ml/min on day 2. The correspondingtotal gadolinium clearance was 12.8 ml/min and 15.8 ml/min respectively.Gadolinium–DTPA was removed from the body through peritonealdialysis at a mean clearance rate of 5.13 ml/min. Plasma half-lifeof gadolinium–DTPA was prolonged to 9 h. No side-effectsdue to gadolinium–DTPA were noted. MRU provided a bettervisualization of the morphology of the urinary tract than scintigraphicstudies. By measuring the changes of signal intensity, the gadoliniumexcretion could be calculated.     

The equivalent renal urea clearance: a new parameter to assess dialysis dose

BACKGROUND.: Currently the total (dialytic plus renal) urea clearance (KT)is computed as Kt/V plus the equivalent Kt/V (KT/V_KR) providedby the renal urea clearance (KR). However, KT/V_KR is computedwith two different formulae, by Gotch and Keshaviah respectively.Moreover Teschan suggested a weekly KT, that is a multiple ofKeshaviah's KT. We suggest the equivalent renal urea clearance(EKR), that kinetically quantifies the ‘time-averagedKT’ and is independent of treatment type and schedule. METHODS.: Computer simulation has been used to analyse the relationshipbetween EKR, as corrected for urea volume (EKRc), and Kt/V.Data from 66 HD patients, of whom eight were on once-weeklyand 11 on twice-weekly HD, had been used to compare EKR withcurrent KTs. RESULTS.: For each individual schedule, the relationship between EKRcand Kt/V is linear and each ml/min of KR increases EKR by thesame amount. For instance, for thrice-weekly HD patients, EKRc=1+10xKt/V:so that, the critical Kt/V values of 0.8 and 1.0 correspondto EKRc values of 9.0 and 11 ml/min respectively, independentlyfrom treatment type and schedule. As to the clinical data, allonce- and twice-weekly patients had a significant KR and excellentclinical status, but most of them had 9EKRc<11 ml/min. Afterappropriate reconciliation of units, it has been found thatkinetic KT was overestimated by about 10–12% (range, 2–23%)by Keshaviah and Teschan's KT, and by about 2–7% (range,0.3–15%) by Gotch's KT. CONCLUSIONS.: EKRc can account for KR and provide guidelines for all typesof dialysis treatments: as far as urea is concerned, dialysisadequacy should require EKRc11 ml/min. However, it is likelythat EKRc9 ml/min could suffice for patients with a substantialresidual renal function.     

Creatinine kinetic modelling: a simple and reliable tool for the assessment of protein nutritional status in haemodialysis patients

While the mathematical modelling of urea kinetics is in wideuse for evaluating treatment adequacy and protein nutritionin dialysis patients, the kinetics of creatinine generationin dialysis patients has been relatively unexplored. In thisstudy creatinine kinetic modelling as a clinical tool was investigatedin a group of 90 patients treated by haemodialysis (n=20), haemodiafiltration(60), haemofiltration (7), or biofiltration (3) over a 6–36-monthperiod. A single pool model of creatinine kinetics was employedto obtain monthly values of creatinine distribution space andcreatinine appearance rate. Extrarenal creatinine degradationrate, estimated using a clearance of 0.038 l/kg/24 h as suggestedby Mitch and co-workers, was added to creatinine appearancerate in urine and dialysate to calculate a corrected creatinineindex (CI). Extrarenal degradation accounted for 12 ±2% of CI. CI was higher in males (22.4 ± 4.5 mg/kg/24h) than females (19.8 ± 4.8) and decreased with age,falling off more sharply for the female group (CI=29.9–0.185.age,R=0.72) than the males (CI=24.1–0.030.age, R=0.31). CIwas found to correlate strongly with protein catabolic ratedetermined by urea kinetic modelling (CI=8.84+10.91.PCR). Lowor reduced CI was associated in this study group with severemalnutrition status and high mortality rate. CI is suggestedas a strong predictor of patient morbidity and mortality.     

A hypothesis: the protein catabolic rate is dependent upon the type and amount of treatment in dialyzed uremic patients

Urea kinetic modelling was performed serially, over 24 months, on 55 patients undergoing hemodialysis and eight patients receiving peritoneal dialysis. The data obtained, together with changes in therapy aimed at increasing or decreasing the normalized dose of dialysis [KT/V (urea)], suggested the dependence of dietary protein intake and protein catabolic rate (PCR; g/kg/d) on the KT/V (urea). The studies also indicated that the nature of this relationship may be dependent upon the dialysis treatment used; dialysis by AN69S membrane hemodialyzers required less KT/V (urea) than hemodialysis by cellulosic membranes to obtain a given PCR. This difference may be explained by the beneficial effect of removal of "middle molecular weight" uremic toxins by the AN69S membrane, which has a different solute clearance profile than the cellulosic membrane. The studies also indicated a similar relationship between PCR and KT/V (urea) for peritoneal dialysis. With this form of therapy, however, it is difficult to obtain a PCR greater than 1 g/kg/d without first achieving very high values for KT/V (urea). It is postulated that this is due to an independent adverse effect of peritoneal dialysate in suppressing appetite. The data presented suggest that the conclusions of the National Cooperative Dialysis Study may be reinterpreted by assigning a major role to the nutritional status of patients in morbidity, with satisfactory nutritional status attained only in patients receiving adequate dialysis which, in turn, ensures control of plasma urea levels. Studies to prove this hypothesis are indicated.     

Ionic dialysance as a method for the on-line monitoring of delivered dialysis without blood sampling

BACKGROUND: It is well known that the difference between prescribed anddelivered dialysis doses greatly affects the morbidity and mortalityof dialysed patients. The on-line monitoring of delivered dialysisis therefore of paramount importance. Recently, a conductivity-based method for determining Kt/V on a routine basis has beenproposed. METHODS: The study was performed using a specially designed module (BiofeedbackModule, COT, Hospal) which, when connected to a dialysis monitor,automatically determines effective ionic dialysance (ID). Duringthree consecutive dialysis sessions, administered to each ofeight patients at the same depurative efficiency, we determinedKt/V by using mean effective ionic dialysance and by assuming,as suggested, that urea distribution volume corresponded to55% of body weight. This method was compared with the gold standardof the direct quantification method. The Kt/V was also calculatedby using mean effective ionic dialysance and the volume of ureadistribution derived from anthropometric parameters. RESULT: The Kt/V determined by using mean effective ionic dialysanceand by assuming that urea distribution volume corresponded to55% of body weight was heavily underestimated (–22%).This difference was due to both the overestimate of urea distributionvolume (+l7%) and underestimate of effective urea clearance(Kueff) (–11%). The mean Kt/V calculated on the basisof ionic dialysance and anthropometric volume was also underestimated(–23%) since this volume was overestimated (+17%). Nevertheless,ionic dialysance and urea clearance proved to be closely correlated(r²=0.89) so that effective urea clearance can be derived accordingto: Kueff=IDx0.865+39.89. CONCLUSIONS: In steady-state patients, once urea distribution volume hasbeen correctly determined by means of direct quantification,effective urea clearance can be easily derived from ionic dialysanceand Kt/V calculated on-line at each session, without blood samplingor any additional costs.     

KT/V and protein catabolic rate determination from serial urea measurement in the dialysate effluent stream

A bloodless technique of evaluating protein catabolic rate (PCR) and KT/V (K, clearance; T, dialysis time; V, urea distribution volume) in hemodialysis patients is presented based on serial measurement of urea in the dialysate effluent stream. PCR follows from equating urea generation and urea removal over a 7 day cycle, changes in body stores being comparatively negligible: PCR = 0.026 [U1 + U2 + U3]/BWdry + 0.17, where U1 is the amount of urea in mmol appearing in the dialysate for each session in the 7 day period. KT/V is obtained from the slope of the natural logarithm of spent dialysate urea concentration-time plot: KT/V = [- slope.T + 3.delta BW/BWdry]/[1 - 0.01786.T(hr], where delta BW = amount ultrafiltered in liters. The dialysate-based approach was validated and compared with conventional urea kinetic modeling (UKM) for 17 patients studied for three consecutive dialyses. The dialysate-based and UKM values of PCR agreed well when in vivo clearance values based on total dialysate collection were used for UKM. KT/V values agreed poorly on a session-by-session basis but were nearly equivalent when averaged for the three dialyses of the week. These findings lay the foundation for UKM automation with a urea sensor in the effluent dialysate stream.     

Clinical outcome of continuous ambulatory peritoneal dialysis predicted by urea and creatinine kinetics.

The effectiveness of urea kinetics (Kt/V, where K is urea clearance, t is treatment time, and V is the volume of distribution for urea) to assess the adequacy of continuous ambulatory peritoneal dialysis (CAPD) and clinical outcome has not been established prospectively, and cross-sectional clinical studies have been inconclusive. A minimum weekly creatinine clearance of 40 to 50 L is recommended, but the adequacy of this dose is unproven. We introduced a simpler approach to creatinine kinetics in the form of an efficacy number (EN) calculated from data obtained in a standardized 4-h dwell exchange. To determine the most effective model for predicting CAPD adequacy, residual renal function, weekly Kt/V urea, weekly creatinine clearance standardized to body surface area, and EN (liters per gram of creatinine per day) were measured in 18 stable CAPD patients followed prospectively for at least 12 months. Patients were divided into three groups, good (G), intermediate (I), and poor (P), on the basis of uremic symptoms, mortality, hospital days, biochemical indices, and the need for transfer to hemodialysis. When comparing groups G (N = 6) and P (N = 8), weekly Kt/V were 2.3 +/- 0.2 versus 1.5 +/- 0.1 (P less than 0.005), weekly creatinine clearances were 71.5 +/- 8.6 versus 35.1 +/- 1.3 L (P less than 0.001), and EN were 7.4 +/- 0.8 versus 3.6 +/- 0.2 L/g of creatinine/day (P less than 0.005). Creatinine kinetics (weekly clearance and EN) but not urea kinetics could differentiate group I (N = 4) from groups G or P. Both urea and creatinine kinetics predict clinical outcome in CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adequacy Indices for Dialysis in Acute Renal Failure: Kinetic Modeling

Many aspects of the management of renal replacement therapy in acute renal failure (ARF), including the appropriate assessment of dialysis adequacy, remain unresolved, because ARF patients often are not in a metabolic steady state. The aim of this study was to evaluate a system of adequacy indices for dialysis in ARF patients using urea and creatinine kinetic modeling. Kinetic modeling was performed for two different fictitious patients (A and B) with characteristics described by the average parameters for two patient groups and for two blood purification treatments: sustained low efficiency daily dialysis (SLEDD) in Patient A and continuous venovenous hemofiltration (CVVH) in Patient B, based on data from a clinical report. Urea and creatinine generation rates were estimated according to the clinical data on the solute concentrations in blood. Then, using estimated generation rates, two hypothetical treatments were simulated, CVVH in Patient A and SLEDD in Patient B. KT/V, fractional solute removal (FSR) and equivalent renal clearance (EKR) were calculated according to the definitions developed for metabolically unstable patients. CVVH appeared as being more effective than SLEDD because KT/V, FSR, and EKR were higher for CVVH than SLEDD in Patients A and B. Creatinine KT/V, FSR, and EKR were lower and well correlated to the respective indices for urea. Urea and creatinine generation rates were overestimated more than twice in Patient A and by 30–40% in Patient B if calculated assuming the metabolically stable state than if estimated by kinetic modeling. Adequacy indices and solute generation rates for ARF patients should be estimated using the definition for unsteady metabolic state. EKR and FSR were higher for urea and creatinine with CVVH than with SLEDD, because of higher K·T and minimized compartmental effects for CVVH.     

Effect of diet on creatinine clearance and excretion in young and elderly healthy subjects and in patients with renal disease.

Thirty-seven young healthy subjects with normal renal function were studied to assess the quantitative effect of protein intake on creatinine clearance. A standard 24-h urine collection and blood sample at the end of the collection were obtained for creatinine and urea concentrations. Correlations between creatinine clearance and urinary urea nitrogen excretion (r = 0.8; P less than 0.0001) and calculated protein intake (r = 0.8; P less than 0.0001) were observed. A significant relationship between creatinine clearance and urea nitrogen excretion was also demonstrated in 28 elderly healthy subjects and 33 patients with renal disease. To demonstrate a cause and effect between urea nitrogen excretion and creatinine clearance in healthy subjects, 18 of the 37 healthy subjects repeated the 24-h urine collection and blood sample after ingesting 5 g of urea in addition to their usual diet. Mean urinary urea nitrogen excretion increased from a mean value of 9.8 +/- 4.0 to 11.8 +/- 4.0 g/day. There was a strong correlation between the changes in urea nitrogen excretion and the changes in creatinine clearance. In acute studies with oral protein loading, there was a significant correlation between creatinine clearance and urinary urea nitrogen excretion. It was concluded that protein intake has a direct and quantitative effect on creatinine clearance in healthy subjects. In normal humans, it is likely that GFR is not a fixed function. Thus, a low creatinine clearance is not a categorical sign of renal disease. A low creatinine clearance adjusted for urea nitrogen excretion may be a useful clinical tool to assess renal function.     

Measurement of peritoneal dialysis delivery in children

We measured urea [weekly urea clearance/total body water (KT/V_urea)] and creatinine (C _Cr) clearances on 35 occasions in 15 stable chronic peritoneal dialysis patients to determine the feasibility and reproducibility of such measurements in children. In addition, we performed peritoneal equilibration tests (PETs) to characterize our patients' peritoneal membranes and to estimate weekly clearances. We demonstrated that dialysis delivery can be quantified by these standard measurements in children of widely varying size. Further, we found that clearances predicted from PET data were similar to measured values in all patients. However, predicted and measured values were most significantly correlated in patients with high and high-average peritoneal membrane permeability. KT/V_urea andC _Cr were correlated overall, but differences in scaling affected the validity of the relationship. When both clearances were scaled to weight, the correlation was closer, but still differed between PET-determined peritoneal membrane types.     

Peritoneal dialysis adequacy and risk of death

BACKGROUND: The purpose of this study was to evaluate the relationship between dialysis dose, patient characteristics, and medical comorbidities on mortality in chronic peritoneal dialysis patients. METHODS: This work comprised a study cohort of 1446 patients obtained from a random sample of chronic peritoneal dialysis patients from each dialysis center in three southeastern states. Data collected on a standardized form were used to calculate weekly Kt/V urea and creatinine clearance. Data were linked to Network files containing data on patient demographic and medical comorbidities. RESULTS: Both weekly Kt/V urea and creatinine clearance were measured at least once in only 60.5% of continuous ambulatory peritoneal dialysis (CAPD) patients and 63.7% of cycler patients. Among the 873 patients who had at least one calculable adequacy measure, the mean (+/-SD) weekly Kt/V urea was 2.13 +/- 0.55, and the normalized mean weekly creatinine clearance was 62.9 +/- 20.4 L/week/m2. During the seven month period of follow-up, there were 140 deaths. In separate logistic regression models that included all of the studied risk factors, using separate variables for the urinary and peritoneal components of dialysis adequacy, each 10 L/week/1.73 m2 increase in the urinary component of weekly creatinine clearance was associated with a 40% decreased risk of death, and each 0.1 unit increase in the urinary component of weekly Kt/V urea was associated with a 12% decreased risk of death. In contrast, the dialysate components of neither weekly creatinine clearance nor weekly Kt/V urea were predictive of death. Other factors that were associated with an increased risk of death included increasing age, diabetes mellitus as the cause of end-stage renal disease (ESRD), and a history of myocardial infarction. CONCLUSIONS: Residual renal function, as expressed by weekly creatinine clearance or Kt/V urea, is an important predictor of death in chronic peritoneal dialysis patients. The nonsignificant findings regarding peritoneal clearances and mortality may possibly be secondary to the narrow range of peritoneal clearances in this study cohort.     

Influence of hyperfiltration on the measurement of urinary N-acetyl-β-D-glucosaminidase

The measurement of urinary enzymes in patients with diabetes mellitus has become a useful additional test for the early detection of nephropathy. Controversy persists concerning methods of measurement since during early stages of insulin-dependent diabetes mellitus children develop the so-called hyperfiltration syndrome. This study was performed to determine whether elevated levels of excreted creatinine influence the determination of the enzyme N-acetyl-β-D-glucosaminidase (NAG). Reference values for NAG in single-spot urines (units NAG/mmol creatinine) and in 24-h collections (units NAG/l urine) were established in two different groups of 105 and 111 healthy children. NAG was then measured in single-spot urines (as NAG/mmol creatinine) and in collection urines of 30 diabetic children within the same 24-h period and compared with the reference population. These results were compared with hemoglobin (Hb)A1_a–c and fructosamine values as well as creatinine clearance of the diabetic patients. There was a direct correlation between the NAG levels in single-spot and 24-h urine collections of diabetic patients. However, the NAG/creatinine ratio in the single-spot urines did not correlate with the HbA1_a–c or fructosamine level. When 24 h collections (expressed as NAG/l) were used, the results correlated well with HbA1_a–c and fructosamine. There was an inverse correlation between the creatinine clearance and the NAG/creatinine ratio, i.e., a high creatinine clearance correlated with a low NAG/creatinine ratio. This was not the case for 24 h collections (expressed as units/l). Hence, in children with insulin-dependent diabetes mellitus 24-h urine collections should be used for urinanalysis. Parameters should not be related to creatinine, since the ratio of urinary protein and creatinine is unreliable because of the high urinary creatinine during the hyperfiltration state. Received: 16 July 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Effect of dietary protein restriction on the progression of renal failure: a prospective randomized trial

One hundred twenty-eight patients with different renal diseasesand chronic renal failure, stratified according to the underlyingdisease, were enrolled in a randomized controlled trial to investigatethe effects on the rate of decline of renal function of twodiets, a controlled protein diet (CPD) of 1 g protein/kg idealbody-weight (i.b.w.)/day, and a low-protein diet (LPD) of 0.6g protein/kg i.b.w./day, given for 27.1±21.8 months.Dietary compliance was assessed by a dietary questionnaire,dietary interviews and measurement of 24-h urinary urea excretion.At the end of 6 months, actual mean protein intake was higherthan expected (1.06±0.25 g/kg i.b.w./day) in CPD patients,and (0.80±0.21 g/kg i.b.w./day) in LPD patients: valueswere similar at 12 and 18 months after the time of enrollment.The end-point, defined as halving of creatinine clearance, wasreached in 40% of patients on CPD, and in 28.6% of those onLPD (P= 0.038 by comparative life-table analysis). Multivariateregression analysis confirmed that CPD was associated with ahigher risk of progression than LPD, and that two additionalparameters (creatinine clearance at the time of randomizationand average proteinuria during the follow-up) were significantindependent risk factors, even more important than protein intake.     

Automated peritoneal dialysis: a Spanish multicentre study

Background: A prospective sequential study on continuous ambulatory peritoneal dialysis (CAPD) and three techniques of automated peritoneal dialysis (APD) was conducted to assess peritoneal clearances, the influence of peritoneal permeability on nocturnal APD clearances and the suitability of the peritoneal equilibration test (PET) for predicting clearances on APD. Methods: After performing a PET, a series of clinical, biochemical and dialysis adequacy markers were evaluated after 2 months on CAPD, continuous cycling peritoneal dialysis (CCPD) and tidal volume peritoneal dialysis (TPD) with 50% and 25% tidal volumes. Forty five patients participated and 33 completed the study. Results: Serum urea and creatinine decreased significantly whereas haemoglobin and glucose increased. Mean peritoneal urea clearance (1/week) was 55.40±8.76 on CAPD, 74.82±12.62 on CCPD, 69.20±14.63 on TPD (tidal 50%) and 66.89±13.23 on TPD (tidal 25%); mean creatinine clearance (1/week/1.73 m²) was 42.80±9.95, 52.19±11.11, 51.31±13.3 and 49.17±11.83 respectively. Both clearances were significantly lower on CAPD than on APD (<0.001). CCPD was the automated technique that provided the best nocturnal urea clearance (P<0.01). Nocturnal creatinine clearance did not show significant differences between CCPD and TPD (tidal 50%), being better with both techniques than with TPD (tidal 25%). There were statistically significant differences between nocturnal dialysate to plasma (D/P) ratios and those corresponding to the nearest times in the PET. The urea D/P ratio at 180 min and the creatinine D/P ratio at 240 min of the PET were the parameters that better estimated nocturnal clearances on APD. Conclusions: This study confirms that TPD does not improve the results of CCPD. Significant differences between D/P ratios during actual nocturnal cycles and PETs were observed. Key words: automated peritoneal dialysis; CAPD; clearances; PET      

Two by two hour creatinine clearance--repeatable and valid.

AIM: The purpose of this study was to determine the repeatability and validity of 2 x 2 hour creatinine clearance, and the validity of creatinine clearances estimated by equations. PATIENTS AND METHODS: In 30 patients two 2 x 2 h and two 24-h creatinine clearances were performed on consecutive days. In addition, creatinine clearances estimated by 4 different equations were calculated. Two by two hour creatinine clearance provided a measurement of GFR as valid as 24-h creatinine clearance. RESULTS: We found, that 2 x 2 h creatinine clearance was well repeatable with a mean difference between 2 repeated measurements of 0.8 ml/min and low coefficients of repeatability of 14.5 ml/min. The validity of 2 x 2 h creatinine clearance, assessed by the mean difference between 2 x 2 and 24-h creatinine clearances, was 1.2 ml/min with tight 95% limits of agreement with a range from -8.1 to 10.5 ml/min. This high degree of repeatability and validity was present over the entire range of renal function (6-141 ml/min). As 2 x 2 h creatinine clearance is more simple and rapid than 24-h creatinine clearance, results are obtained on the same day and easy, but repeatable and valid day-to-day monitoring of renal function is possible. In addition, the two times two hour clearances allow for quality control. In contrast, estimated creatinine clearances show only poor validity. CONCLUSION: Because of the high degree of repeatability and validity, 2 x 2 h creatinine clearance may replace 24-h creatinine clearance as the standard method to determine renal function in clinical practice.