Residual Renal Urea Clearance Research Articles

The urate-lowering efficacy of febuxostat and its relationship with residual renal function in peritoneal dialysis patients with hyperuricemia

Objective: To investigate the urate-lowering efficacy of febuxostat in peritoneal dialysis (PD) patients with hyperuricemia (HUA) and its relationship with residual renal function. Methods: Patients with HUA who underwent PD in Ningbo First Hospital from January 2018 to October 2021 were enrolled and divided into experimental group and control group according to whether to use febuxostat. The clinical baseline data before treatment and clinical indicators during 1-12 months after treatment were collected in two groups, and the adverse reactions during the use of febuxostat were also recorded. The changes of serum uric acid, standard-reaching rate and residual renal function were compared between the two groups during the follow-up. Results: A total of 105 patients were included in the study. There were 55 patients in the experimental group [27 males and 28 females, with a mean age of (54.5±14.8) years] and 50 patients in the control group [32 males and 18 females, with a mean age of (53.8±15.2) years]. No statistically significant difference was detected in clinical baseline data between the two groups (all P>0.05). The serum uric acid of the experimental group [(479±77), (311±69), (286±61), (307±65), (312±57) μmol/L] and control group [(486±59), (454±71), (453±76), (463±70), (459±76) μmol/L] were lower than baseline values at 1, 3, 6 and 12 months after treatment and the differences of two groups were statistically significant (all P<0.05). The serum uric acid in experimental group was significantly lower than that of control group (P<0.05). At 1, 3, 6 and 12 months after treatment, the standard-reaching rate of serum uric acid in the experimental group was significantly higher than that of the control group (all P<0.05). The decrease of residual estimated glomerular filtration rate (eGFR) and residual renal urea clearance index (Kt/V) in the experimental group were significantly lower than those in the control group at 12 months after treatment (all P<0.05). During the follow-up, the incidence of adverse reactions in the experimental group was 9.09% (5/55). Conclusions: Febuxostat can effectively treat PD patients with hyperuricemia and has a high safety profile. Moreover, it may delay the loss of residual renal function.

Residual Renal Phosphate Clearance in Patients Receiving Hemodialysis or Hemodiafiltration

Substantial levels of residual renal clearance and urine output may occur in patients treated with hemodialysis or hemodiafiltration. However, the relationships among residual renal urea, creatinine, and phosphate clearances, respectively, and between clearances and urine volume have not been well described. We performed a prospective, cross-sectional study which enrolled hemodialysis and hemodiafiltration patients with a urine volume of >100mL/day, in whom at least 2 residual renal clearances were obtained over a 6-month observation period. Urine was collected for 24hours prior to the midweek treatment session and concentrations of urea, creatinine, and phosphate were measured. Thirty-eight patients (24 men, 14 women) with a mean age of 70.4±12.4 (SD) years were included in this analysis. All patients were dialyzed 3 times per week with mean treatment duration of 243±7.89minutes. Twenty patients were undergoing hemodiafiltration and 18 patients high-flux hemodialysis. In total, 102 dialysis sessions, of which 52 were hemodiafiltration, and urine collections were analyzed. Mean urine volume was 457±254mL per 24hours. Residual renal clearance rates of urea (Kr Urea), creatinine (Kr Cr), and phosphate (Kr Phos) were 1.60±0.979, 4.69±3.79, and 1.98±1.36mL/minute, respectively. Mean ratios of Kr Cr/Kr Urea, Kr Phos/Kr Urea, and Kr Phos/Kr Cr were 2.83±1.21, 1.23±0.387, and 0.477±0.185, respectively. There was a modest correlation between Kr Phos and daily urine volume (r=0.605, P=.001). In maintenance hemodialysis and hemodiafiltration patients, residual renal phosphate clearance is approximately 23% higher than residual renal urea clearance. Urine volume is a modestly accurate surrogate for estimating residual renal phosphate clearance, but only when urine volume is <300mL/day.

Predicting Decline in Residual Renal Urea Clearance via Random Forest Regression

Predicting Decline in Residual Renal Urea Clearance via Random Forest Regression

37 Predicting Decline in Residual Renal Urea Clearance via Machine Learning

37 Predicting Decline in Residual Renal Urea Clearance via Machine Learning

The lacking equation that estimates the protein catabolic rate in patients on once-weekly haemodialysis.

The normalized protein catabolic rate (PCRn) is one of the key indices derived from the urea kinetic model (UKM) in haemodialysis (HD) patients. Ideally, it should be assessed using the double pool UKM (KDOQI clinical practice guidelines, AIKD, 2015), as the web-based software Solute-Solver (SS) does (Daugirdas et al., AJKD, 2009). Simple formulae exist to compute PCRn for patients on thrice- or twice-weekly HD schedule, but not for patients on once-weekly HD schedule (1HD/wk). Aim of the present technical note was to introduce the lacking equation that estimates PCRn in the 1HD/wk regimen. Data of a single HD session associated to monthly UKM studies were retrieved from the electronic database of our dialysis unit for 80 historical patients on 1HD/wk regimen. The UKM parameters, as calculated with SS, were used in a subgroup of 40 randomly selected patients (group 1) to build-up a multiple regression model of PCRn. The latter was used to predict PCRn (PCRnPred) values in the cohort of the remaining 40 patients (group 2). The Bland-Altman plot was used to analyse the agreement between PCRnPred and the paired "observed" (PCRnObs) values, as measured with SS. The following equation was established by means of the multiple regression analysis: PCRn =-0.46 + 0.01 × C0 + 0.09 × eKt/V + 3.94 × Kru/V, where C0 is pre-dialysis blood urea nitrogen concentration, eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. The PCRnPred values were 0.99 ± 0.24g/kg/day; the PCRnObs values were 0.96 ± 0.23g/kg/day (mean difference 0.03 ± 0.05g/kg/day). Their difference at the Bland-Altman analysis ranged from -0.08 to + 0.13g/kg/day. Finally, a nomogram was drawn: it can be used to estimate not only PCRn from Kru/V and C0, but also C0 as a function of Kru/V and PCRn. The equation here introduced allows a simple and accurate estimate of PCRn in patients on once-weekly HD regimen. The availability of the nomogram relating C0 to PCRn and Kru/V could be a further step to make safer and safer the once-weekly HD regimen. The following equation was established by means of the multiple regression analysis [Formula: see text] where PCRn is the normalized protein catabolic rate (PCRn), C0 is pre-dialysis blood urea nitrogen concentration (BUN), eKt/V is the equilibrated Kt/V, Kru is the residual renal urea clearance and V is the post-dialysis urea distribution volume. A nomogram relating pre-dialysis BUN to PCRn and Kru/V could be drawn: it can be used to estimate not only PCRn from Kru/V and pre-dialysis BUN, but also pre-dialysis BUN as a function of Kru/V and PCRn.

A faster decline of residual kidney function and erythropoietin stimulating agent hyporesponsiveness in incident hemodialysis patients.

Erythropoietin stimulating agents (ESA) hyporesposiveness has been associated with increased mortality in hemodialysis (HD) patients. However, the impact of decline of residual kidney function (RKF) on ESA hyporesposiveness has not been adequately elucidated among patients receiving HD. The associations of RKF decline with erythropoietin resistance index (ERI; average weekly ESA dose [units])/post-dialysis body weight [kg]/hemoglobin [g/dL]) were retrospectively examined across four strata of annual change in RKF (residual renal urea clearance [KRU] < -3.0, -3.0 to <-1.5, -1.5 to <0, ≥0 mL/min/1.73 m2 per year; urinary volume < -600, -600 to<-300, -300 to <0, ≥0 mL/day per year) using logistic regression models adjusted for clinical characteristics and laboratory variables in 5239 incident HD patients in a large US dialysis organization between 1 January 2007 and 31 December 2011. The median values of the annual change in KRU and urinary volume were -1.2 (interquartile range [IQR]: -2.8 to 0.1) mL/min/1.73 m2 per year and -250 (IQR: -600 to 100) mL/day per year. A faster KRU decline in the first year of HD was associated with higher odds for ESA hyporesponsiveness: KRU decline of <-3.0, -3.0 to <-1.5, and -1.5 to <0/min/1.73 m2 per year were associated with adjusted odds ratios (OR) of 2.07 (95% confidence interval [CI]: 1.66-2.58), 1.54 (95%CI: 1.28-1.85), and 1.26 (95%CI: 1.07-1.49), respectively (reference: ≥0 mL/min/1.73 m2 per year). These associations were consistent across strata of baseline KRU, age, sex, race, diabetes, congestive heart failure, hemoglobin, and serum albumin. Sensitivity analyses using urinary volume as another index of RKF showed consistent associations. A faster RKF decline during the first year of dialysis was associated with ESA hyporesponsiveness and low hemoglobin levels among incident HD patients.

P1248DOES INCREMENTAL HAEMODIALYSIS PRESERVE NATIVE KIDNEY FUNCTION? A MULTI-CENTRE FEASIBILITY RANDOMISED CONTROL TRIAL

Abstract Background and Aims Incremental HD is a method of individualising haemodialysis (HD) dose according to level of residual renal function(RRF) such that as RRF reduces, HD dose is upwardly adjusted. Retrospective data suggest potential benefit of this approach in preserving RRF, a key predictor of survival for dialysis patients. Method A randomised, intention-to-treat, multi-centre trial was designed to determine the feasibility of a future definitive trial of incremental HD to establish if this approach preserves RRF. The trial was designed to estimate effect size of potential benefit in terms of RRF. 55 patients with RRF urea clearance≥3ml/min/1.73m2 BSA and within 3 months of starting HD were randomised across 4 UK dialysis centres to either conventional 3x weekly HD for 3.5-4 hours or incremental HD. The incremental HD protocol involved initiation of HD 2x weekly after randomization and upward adjustment of HD frequency and time as RRF was lost. In the conventional HD arm, patients were dialysed to ensure Standard Kt/VDialysis&amp;gt;2.0. In the incremental HD arm, patients were dialysed to ensure Standard Kt/VDialysis+Standard Kt/VResidual Renal Function&amp;gt;2.0 so both groups were dialysed to the same urea clearance target, except that urea clearance incorporated RRF in the incremental HD arm. Follow up was for 6 months (primary outcome data) but secondary outcome data will be for 12m. Patients were withdrawn for transplant, dialysis modality change or for patient choice. The primary outcome was rate of change of RRF in the first 6 months after randomization (effect size of intervention). Recruitability, retainability, protocol adherence and rate of adverse events were also measured as a primary objective. As a secondary outcome, we determined proportion of patients with urea clearance≥2 and ≥3ml/min /1.73m2 BSA at the 6 month time point. Impact of dialysis treatment was measured using questionnaire-based assessments at baseline and 6 months. Results 26 patients were randomised to standard HD and 29 to incremental HD. Baseline demographics including age, weight, haemoglobin, blood pressure, Charleson Comorbidity Index, were not significantly different between study arms. Baseline residual renal urea clearance was 5.1 ± SD 1.8 ml/min/1.73m2 BSA in the standard HD arm and 5.72 ± SD 2.49 in the incremental HD arm. 6 months, residual renal urea clearance reduced to 2.68±SD 1.73 in the standard HD arm and 3.80±SD 1.85 in the incremental arm. In the first 6 months, 3 patients recovered to dialysis independence (standard arm=1, incremental arm=2). Slope of RRF was not significantly different between two arms (p=0.39). The proportion of patients with significant urea clearance&amp;gt;2ml/min/1.73m2 BSA at 6 months was significantly higher in the incremental HD arm (92%) compared to the standard HD arm (65%), p=0.032. Rate of major adverse cardiac events, fluid overload, hyperkalaemia, vascular access events, deaths and infections did not differ significantly between groups. There were 2 deaths in the standard HD arm (in 4025 patient days) versus 1 in the incremental HD arm in the first 6 months(4666 patient days). There was no significant difference in Clinical Frailty Score, Montreal Cognitive Assessment score, depression score (PHQ-9), Quality of Life (EQ-5D-5L) and Illness Intrusiveness Rating Scale between groups at baseline and 6m time points. Conclusion Rate of loss of RRF (slope) was not significantly different between incremental HD and standard HD arms but incremental HD was associated with significantly higher probability of retaining urea clearance&amp;gt;2ml/min/1.73m2. There was no evidence of any clinical detrimental effect of incremental HD in terms of mortality, fluid overload or hyperkalaemic events. Incremental HD does not appear to be harmful and may confer a small benefit to preservation of residual renal function. A definitive study is required to define clinical benefits further.

Effect of hemodiafiltration on renal function in elderly patients with uremia

Objective To investigate the effect of hemodiafiltration (HDF) on renal function in elderly patients with uremia. Methods From February 2015 to February 2017, 94 cases of elderly patients with uremia in our hospital were selected, among them, 45 cases were treated with HDF (HDF group), and 49 cases were received conventional hemodialysis (HD) (HD group), the levels of toxin and residual renal function were observed before and after dialysis in the two groups. Results Homocysteine (Hcy), parathyroid hormone (iPTH), urea nitrogen (BUN) and creatinine (Scr) of HDF group after dialysis 1 month were lower than pre dialysis (P<0.05). Hcy, BUN and Scr of HD group after dialysis 1 month were lower than pre-dialysis (P<0.05). Hcy, and iPTH of HDF group after dialysis 1 month were (24.08±4.52) mol/L and (1.63±0.70) g/L, significantly lower than that of HD group (P<0.05). After dialysis 1 month, residual renal urea clearance (KRU) of HDF group was (1.22±0.30) mL/min, significantly higher than the HD group (P<0.05). The complication rate of HDF group was 2.22%(1/45), which was significantly lower than that of HD group (P<0.05). Conclusions Compared with HD treatment, HDF can effectively remove the harmful substances in serum, and has little influence on the residual renal function of patients, less complications, it is worthy of clinical application. Key words: Uremia; Hemodiafiltration; Aged

Vascular calcification and cardiac function according to residual renal function in patients on hemodialysis with urination

BackgroundVascular calcification is common and may affect cardiac function in patients with end-stage renal disease (ESRD). However, little is known about the effect of residual renal function on vascular calcification and cardiac function in patients on hemodialysis.MethodsThis study was conducted between January 2014 and January 2017. One hundred six patients with residual renal function on maintenance hemodialysis for 3 months were recruited. We used residual renal urea clearance (KRU) to measure residual renal function. First, abdominal aortic calcification score (AACS) and brachial-ankle pulse wave velocity (baPWV) were measured in patients on hemodialysis. Second, we performed echocardiography and investigated new cardiovascular events after study enrollment.ResultsThe median KRU was 0.9 (0.3–2.5) mL/min/1.73m2. AACS (4.0 [1.0–10.0] vs. 3.0 [0.0–8.0], p = 0.05) and baPWV (1836.1 ± 250.4 vs. 1676.8 ± 311.0 cm/s, p = 0.01) were significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than a KRU ≥ 0.9 mL/min/1.73m2. Log-KRU significantly negatively correlated with log-AACS (ß = -0.29, p = 0.002) and baPWV (ß = -0.19, P = 0.05) after factor adjustment. The proportion of left ventricular diastolic dysfunction was significantly higher in patients with a KRU < 0.9 mL/min/1.73m2 than with a KRU ≥ 0.9 mL/min/1.73m2 (67.9% vs. 49.1%, p = 0.05). Patients with a KRU < 0.9 mL/min/1.73m2 showed a higher tendency of cumulative cardiovascular events compared to those with a KRU ≥ 0.9 ml/min/1.73m2 (P = 0.08).ConclusionsResidual renal function was significantly associated with vascular calcification and left ventricular diastolic dysfunction in patients on hemodialysis.

Longitudinal Associations among Renal Urea Clearance-Corrected Normalized Protein Catabolic Rate, Serum Albumin, and Mortality in Patients on Hemodialysis.

There are inconsistent reports on the association of dietary protein intake with serum albumin and outcomes among patients on hemodialysis. Using a new normalized protein catabolic rate (nPCR) variable accounting for residual renal urea clearance, we hypothesized that higher baseline nPCR and rise in nPCR would be associated with higher serum albumin and better survival among incident hemodialysis patients. Among 36,757 incident hemodialysis patients in a large United States dialysis organization, we examined baseline and change in renal urea clearance-corrected nPCR as a protein intake surrogate and modeled their associations with serum albumin and mortality over 5 years (1/2007-12/2011). Median nPCRs with and without accounting for renal urea clearance at baseline were 0.94 and 0.78 g/kg per day, respectively (median within-patient difference, 0.14 [interquartile range, 0.07-0.23] g/kg per day). During a median follow-up period of 1.4 years, 8481 deaths were observed. Baseline renal urea clearance-corrected nPCR was associated with higher serum albumin and lower mortality in the fully adjusted model (Ptrend<0.001). Among 13,895 patients with available data, greater rise in renal urea clearance-corrected nPCR during the first 6 months was also associated with attaining high serum albumin (≥3.8 g/dl) and lower mortality (Ptrend<0.001); compared with the reference group (a change of 0.1-0.2 g/kg per day), odds and hazard ratios were 0.53 (95% confidence interval, 0.44 to 0.63) and 1.32 (95% confidence interval, 1.14 to 1.54), respectively, among patients with a change of <-0.2 g/kg per day and 1.62 (95% confidence interval, 1.35 to 1.96) and 0.76 (95% confidence interval, 0.64 to 0.90), respectively, among those with a change of ≥0.5 g/kg per day. Within a given category of nPCR without accounting for renal urea clearance, higher levels of renal urea clearance-corrected nPCR consistently showed lower mortality risk. Among incident hemodialysis patients, higher dietary protein intake represented by nPCR and its changes over time appear to be associated with increased serum albumin levels and greater survival. nPCR may be underestimated when not accounting for renal urea clearance. Compared with the conventional nPCR, renal urea clearance-corrected nPCR may be a better marker of mortality.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m2) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance (Pinteraction=0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance (i.e., <1.5 ml/min per 1.73 m2), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance (i.e., ≥1.5 ml/min per 1.73 m2; Pinteraction<0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk (Ptrend<0.001 for both) irrespective of residual renal urea clearance strata (Pinteraction=0.34 and Pinteraction=0.53, respectively). Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population.

The variable target model: a paradigm shift in the incremental haemodialysis prescription.

The recent interest in incremental haemodialysis (HD) is hindered by the current prescription based on a fixed target model (FTM) for the total (dialytic + renal) equivalent continuous clearance (ECC). The latter is expressed either as standard Kt/V (stdKt/V), i.e. the pre-dialysis averaged concentration of urea-based ECC, or EKRc, i.e. the time averaged concentration-based ECC, corrected for volume (V) = 40 L. Accordingly, there are two different targets: stdKt/V = 2.3 volumes per week (v/wk) and EKRc = 13 mL/min/40 L. However, fixing the total ECC necessarily implies perfect equivalence of its components-the residual renal urea clearance (Kru) and dialysis clearance (Kd). This assumption is wrong because Kru has much greater clinical weight than Kd. Here we propose that the ECC target varies as an inverse function of Kru, from a maximum value in anuria to a minimum value at Kru levels not yet requiring dialysis. The aim of the present study was to compare the current FTM with the proposed variable target model (VTM). The double pool urea kinetic model was used to model dialysis sessions for 360 virtual patients and establish equations predicting the ECC as a function of Kd, Kru and the number of sessions per week. An end-dialysis urea distribution V of 35 L (corresponding to a body surface area of 1.73 m 2 ) was used, so that the current EKRc target of 13 mL/min/40 L could be recalculated at an EKRc 35 value of 12 mL/min/35 L equal to 12 mL/min/1.73 m 2 . The latter also coincides with the maximum value of the EKRc 35 variable target in anuria. The minimum target value of EKRc 35 was assumed to coincide with Kru corrected for V = 35 L (i.e. Krc 35 = 6 mL/min/1.73 m 2 ). The corresponding target for stdKt/V was assumed to vary from 2.3 v/wk at Krc 35 = 0 to 1.7 v/wk at Krc 35 = 6 mL/min/1.73 m 2 . On this basis, the variable target values can be obtained from the following linear equations: target EKRc 35 = 12 - Krc 35 ; target stdKt/V = 2.3 - 0.1 × Krc 35 . Two versions of stdKt/V were considered: the classic version (stdKt/V Gotch ) with Kru at 70%, and the current version (stdKt/V Daug ) with Kru at 100%. The VTM with stdKt/V Gotch produces results very close to those using the FTM with stdKt/V Daug . Once-weekly HD is virtually not allowed by the FTM. In contrast, the VTM allows dialysis to start at Krc 35 ∼5 mL/min/1.73 m 2 on a once-weekly HD schedule, at least in relatively healthy patients; this schedule can be maintained until Krc 35 falls below 4 mL/min/1.73 m 2 , at which point the schedule should be changed to a twice-weekly HD schedule, that, in turn, could be maintained until Krc 35 falls below 2 mL/min/1.73 m 2 . A paradigm shift from the FTM to the VTM in the prescription of incremental HD is proposed, whereby the VTM would allow less frequent treatments at lower Kru, with important clinical and economic implications. This approach is likely to be safe but needs to be confirmed by randomized controlled trials.

Measuring residual renal function in dialysis patients: can we dispense with 24-hour urine collections?

Residual renal function is associated with improved survival and quality of life for dialysis patients. Whereas residual renal function is monitored in peritoneal dialysis patients, many hemodialysis centers simply concentrate on achieving dialyzer urea clearance targets. Accurately quantifying residual renal function from urine collections is arduous. Thus, there is a clinical need to develop alternative methods of assessing residual renal function based on serum testing, especially for patients receiving less than thrice weekly dialysis.

Insight: Effects of Reduced Intradialytic Urea Generation Rate and Residual Renal Clearance on Modeled Urea Distribution Volume and Kt/V in Conventional, Daily, and Nocturnal Dialysis

Classic urea modeling assumes that both urea generation rate (G) and residual renal urea clearance (Kru) are constant throughout the week, but this may not be true. Reductions in intradialysis G could be caused by lower plasma amino acid levels due to predialysis/intradialysis fasting and also to losses of amino acids into the dialysate. Intradialytic reductions in Kru could be due to lower intravascular volume, blood pressure, or osmotic load. To determine the possible effects of reduced G or Kru during dialysis on the calculation of the volume of distribution (V) and Kt/Vurea, we modeled 3 and 6/week nocturnal, 6/week short daily, and 3/week conventional hemodialysis. A modified 2-pool mathematical model of urea mass balance with a constant time-averaged G was used, but the model was altered to allow adjustment of the ratio of dialytic/interdialytic G (Gd/Gid) and dialytic/total Kru (Krud/Kru) to vary from 1.0 down to near zero. In patients dialyzed six times per week for 400 minutes per session, when Gd/Gid was decreased from 1.0 to 0.05, the predicted urea reduction ratio (URR) increased from 68.9% to 80.2%. To achieve an increased URR of this magnitude under conditions of constant G (Gd/Gid=1.0) required a decrease in modeled urea volume (V) of 36%. At Gd/Gid ratios of 0.8 or 0.6 (corresponding to 20% or 40% reductions in intradialysis G), the modeled URR was increased to 71.0% or 73.3%, causing a 7% or 15% factitious decrease in V. The error was intermediate for the 3/week nocturnal schedule, and was much less pronounced for the 6/week daily and 3/week conventional treatments. Reductions in intradialytic Kru had the opposite effect, lowering the predicted URR and increasing the apparent V, but here the errors were of much lesser amplitude. The results suggest that, particularly for nocturnal dialysis, the standard "constant G" urea kinetic model may need to be modified.

Simple and accurate quantification of dialysis in acute renal failure patients during either urea non-steady state or treatment with irregular or continuous schedules.

The quantification of dialysis in critically ill acute renal failure (ARF) patients requires a unifying expression that can establish kinetic equivalence amongst patients treated with irregular or frequent intermittent haemodialysis (IHD) schedules or with differing renal replacement therapies. EKRjc is a generalized form of the equivalent urea renal clearance (EKRc), and represents the equivalent continuous urea clearance that will result in the given time-averaged concentration of urea, for the given amount of urea removal. The suitability of EKRjc for the measurement of dialysis dose in this setting is examined. 420 weeks of renal replacement therapy (IHD and continuous renal replacement therapy) were simulated in 15 virtual 'patients' using a variable volume double pool urea kinetic model. Additional data from eight ARF patients were used to exemplify calculations. 1260 EKRjc values were calculated using both formal urea kinetic modelling, as well as a simplified method that requires input of changes in patient fluid state and blood urea nitrogen concentrations over a period of observation, in addition to an initial estimate of patient post-dialysis urea distribution volume (V(T)). EKRjc is shown to provide a unifying expression of dialysis dose irrespective of IHD schedule or renal replacement therapy. EKRjc is shown to be independent from the assumption of the urea steady state, and intrinsically normalized to patient urea distribution volume to allow dose comparisons between patients of different size. Residual renal urea clearance is easily incorporated where present. EKRjc is easily calculated using the simplified method without the need for iterative urea kinetic modelling. The accuracy of this simplified method is maintained when the initial estimation of V(T) is both 25% greater or smaller than the true value. Calculation of EKRjc is exemplified using the clinical data. EKRjc is the most suitable urea kinetic expression for the quantification of dialysis in critically ill ARF patients.

Adjustment of hemodialysis dose for residual renal urea clearance: a two year study of impact on dialysis time.

Urea kinetic modeling suggests that significant time reductions may be realized in hemodialysis patients with residual renal urea clearance (K(r)t/V urea). However, the actual impact of a strategy that integrates such function into the dialysis prescription is not clear, because of both uncertainty regarding the rate of decay of K(r)t/V urea, as well as potential clinical constraints upon dose reduction. To examine this issue, we retrospectively reviewed data from 51 patients with K(r)t/N urea after initiation of maintenance hemodialysis. In 31 cases, there were no clinical barriers to adjustment of the dialysis prescriptions. Regression analysis revealed that each 0.10 increment in K(r)t/V urea yielded an actual dialysis time reduction of 12 minutes per week with average cumulative reduction of 80 minutes per week per patient. At approximately 1 year after initiation of dialysis, there were still 10 patients whose dialysis prescriptions were being adjusted on the basis of K(r)t/V urea. In conclusion, our results suggest that the incorporation of K(r)t/V urea in the hemodialysis prescription allows for substantial and enduring reductions in dialysis time in a significant minority of patients. Larger prospective studies are needed to evaluate the long-term safety of this strategy in modifying the dose of hemodialysis.

Impact of residual renal function in children on hemodialysis.

Residual renal function (RRF) contributes to dialysis adequacy as well as lower mortality and morbidity in dialysis patients. Even very small changes in glomerular filtration rate (GFR) account for considerable improvements in complications of dialysis. The purpose of this cross-sectional study is to determine the possible contribution of RRF to hemodialysis clearance and to compare the biochemical markers of this patient group with anuric patients. Ten patients with RRF on chronic hemodialysis for more than 6 months were enrolled in the study. Duration of dialysis was not different between the two patient populations. Average GFR was 3.4+/-2.6 ml/min in the group with RRF. Cholesterol, albumin, and triglyceride levels were not different between the groups. Residual renal urea clearance enhanced mean Kt/V of patients from 1.29 to 1.52. However erythropoietin and renin levels were higher in the group with RRF (P=0.019, P=0.044, respectively). There was a positive correlation between erythropoietin, renin levels, and average GFR of all patients (r=0.69, P=0.002, r=0.60, P=0.014). We conclude that RRF plays a greater role in pediatric patients on hemodialysis than previously recognized, and knowledge about patients' RRF should assist in improved overall management.

Reproducibility of studies of peritoneal dialysis adequacy

To assess the variability and reproducibility of dialysis adequacy clearance measurements (weekly Kt/V and weekly creatinine clearance/1.73 m2 BSA) in a given patient, 42 patients underwent three clearance studies in a one week period. The dialysis prescription was kept constant. There were 21 males with a group mean age of 49 +/- 15 years; 37 patients performed CAPD and 5 DAPD; the dialysis prescription was 6 to 12 liters/day; and 17 patients were anuric. To assess test variability within each patient, the coefficient of variation (CV) and the range were determined for each patient's three clearance values, and for the factors that determine those values. These were averaged to determine the mean patient variability (CV and range) of those measurements. The mean patient CV of the weekly Kt/V was 8.1%. The mean patient range of the weekly Kt/V was 0.30. Of the determinants of total Kt/V, the greatest variability (GV) existed in residual renal urea clearance at 35.4%, with moderate variability seen for peritoneal dialysis urea clearance at 7.0%, which was more a function of variability in D/P urea (CV = 6.3%) than variability in drain volume (CV = 4.1%). There was little variability in V (CV = 0.6%). Similar results were seen for the variability in weekly creatinine clearance measurements. We found that the day-to-day reproducibility of Kt/V measurements is limited, especially in patients with residual renal function, although day-to-day variability in D/P urea also affects Kt/V reproducibility in all patients. Values that fall into the borderline "adequate" range may need to be repeated when considering a patient's dialysis prescription. In addition, research that involves the measurement of Kt/V should utilize more than one collection to increase the reliability of those measurements.

Kinetic modelling and underdialysis in CAPD patients

Kinetic analysis was performed in all 58 patients undergoing standard CAPD. The urea distribution volume was estimated from anthropomorphic measurements (Watson formulae). Normalized protein catabolic rate (NPCR), daily protein leak (PL), urea and creatinine Kt/Vs, clearances and peritoneal mass transfer coefficients (Kp) were calculated from measurements on serum, 24-h urine and 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). There was no relationship between KT/V and serum urea or Kp. The strongest determinant of the urea KT/V was the residual renal urea clearance (KrU)(R = 0.79, P < 0.001) which decreased with time on dialysis (R = -0.38, P < 0.005). There was a significant correlation between the hospital admissions per year and both the urea and creatinine 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/year than 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 not with serum albumin or the PL. Patients identified by UKM to be less well dialysed have a lower residual renal function and are more likely to be hospitalized. Undernutrition in CAPD patients appears to be related to underdialysis rather than protein loss.

Measurement of Residual Renal Function in Hemodialysis Patients

The residual renal urea clearance (KrU) plays an important role in determining the patient's kinetically modeled dialysis prescription and in calculating the protein catabolic rate to assess dietary protein intake. Measurement of renal function, which requires an interdialytic urine collection and blood samples taken during two different dialyses, may be prone to collection and blood sampling omissions. This study compared the accuracy of residual KrU calculations using two different methods to determine the mean blood urea nitrogen (BUN) level during the urine collection interval. A comparison of residual renal creatinine clearance (KrCr) calculations was simultaneously evaluated. Interdialytic urine collections including measurements of urine urea nitrogen, creatinine, and total urine volume, were obtained from 30 patients during a 10-month period. The collection time was shortened from an entire interdialytic interval to 24 to 36 hours. Calculation of the mean blood levels using the first method required measurements of BUN and serum creatinine (Cr) at the end of the first dialysis and at the start of the second dialysis. The second method measured pre- and post-BUN and serum Cr during the second dialysis. A renal function program for the 41 CX programmable calculator (Hewlett Packard, Palo Alto, CA) was used to calculate 110 KrU and 88 KrCr measurements. The mean residual renal clearance values were identical using both methods (KrU = 2.8 ± 1.6 mL/min; KrCr = 5.5 ± 3.1 mL/min; P = NS). These results show that the residual KrU and KrCr can be accurately calculated from the measurement of a single dialysis pre- and post-BUN and serum Cr in conjunction with a urine collection. The residual renal urea clearance (KrU) plays an important role in determining the patient's kinetically modeled dialysis prescription and in calculating the protein catabolic rate to assess dietary protein intake. Measurement of renal function, which requires an interdialytic urine collection and blood samples taken during two different dialyses, may be prone to collection and blood sampling omissions. This study compared the accuracy of residual KrU calculations using two different methods to determine the mean blood urea nitrogen (BUN) level during the urine collection interval. A comparison of residual renal creatinine clearance (KrCr) calculations was simultaneously evaluated. Interdialytic urine collections including measurements of urine urea nitrogen, creatinine, and total urine volume, were obtained from 30 patients during a 10-month period. The collection time was shortened from an entire interdialytic interval to 24 to 36 hours. Calculation of the mean blood levels using the first method required measurements of BUN and serum creatinine (Cr) at the end of the first dialysis and at the start of the second dialysis. The second method measured pre- and post-BUN and serum Cr during the second dialysis. A renal function program for the 41 CX programmable calculator (Hewlett Packard, Palo Alto, CA) was used to calculate 110 KrU and 88 KrCr measurements. The mean residual renal clearance values were identical using both methods (KrU = 2.8 ± 1.6 mL/min; KrCr = 5.5 ± 3.1 mL/min; P = NS). These results show that the residual KrU and KrCr can be accurately calculated from the measurement of a single dialysis pre- and post-BUN and serum Cr in conjunction with a urine collection.