Protein Equivalent Of Nitrogen Appearance Research Articles

High creatinine excretion ratio predicts a good outcome in peritoneal dialysis patients

The creatinine excretion (CrEx) ratio was first described as a method for detecting noncompliance in peritoneal dialysis (PD) patients. However, a high CrEx ratio is not specific for noncompliance and may also be found in compliant patients with a relatively greater lean body mass (LBM). A cohort of 44 PD patients was followed up for a mean of 13 ± 8 months after measurement of baseline CrEx ratio to investigate whether greater values were predictive of good or poor clinical outcomes. During this follow-up, 11 patients died, 12 patients transferred to hemodialysis, 4 patients underwent transplantation, 1 patient recovered renal function, and 16 patients continued on PD. The mean CrEx ratio in all patients was 1.14 ± 0.32. It did not differ between men and women (1.15 versus 1.13, respectively; P = 0.76) but showed a trend toward being less in patients with diabetes (1.03 versus 1.19; P = 0.19). The mean weekly Kt/V, weekly creatinine clearance, normalized protein equivalent of nitrogen appearance, and serum albumin values were 2.18 ± 0.57, 73.57 ± 33.75 L/1.73 m2, 0.80 ± 0.22 g/kg/d, and 3.22 ± 0.59 g/dL, respectively. Technique failure (P < 0.001) and death (P < 0.05) were significantly more common in patients with a CrEx ratio less than 1 compared with those with a CrEx ratio greater than 1. On Cox regression analysis, the CrEx ratio was the only significant predictor of technique failure and was also an independent predictor of death. High CrEx ratio is a predictor of good, rather than poor, outcome in PD patients, perhaps because it is primarily an index of nutrition. This further weakens the argument that it is a reliable or useful marker of noncompliance.

Randomized prospective study of the effect of increased dialytic dose on nutritional and clinical outcome in continuous ambulatory peritoneal dialysis patients

Cohort studies have shown that greater urea (Kt/V) and creatinine clearances (CCr) were associated with better survival in patients on continuous ambulatory peritoneal dialysis (CAPD). The possibility of improved patient outcome with increased dialytic dose remains unknown. We prospectively studied over 1 year the effects of an extra 2-L bag on the outcome of 82 patients undergoing three daily 2-L exchanges for at least 12 months. At 1 year, 36 patients were undergoing 6-L exchanges, whereas 30 patients underwent 8-L exchanges. The increased dialytic dose resulted in increased total weekly Kt/V (TKt/V; 1.82 to 2.02), whereas total weekly CCr (TCCr) was maintained (63.2 to 61.9 L/1.73 m2). Control patients had reduced solute clearances (TKt/V, 1.87 to 1.67; TCCr, 64.8 to 54.6 L/1.73 m2). The fourth bag exchange resulted in a significant increase in net ultrafiltration (0.83 to 1.51 L/d), whereas the control group also had greater ultrafiltration (0.68 to 1.01 L/d) after 1 year. Although the normalized protein equivalent of nitrogen appearance (nPNA) was stable in the controls, the patients using 8-L exchanges achieved a greater nPNA (1.10 to 1.24 g/kg/d). There was no associated change in serum albumin levels (3.79 to 3.48 g/dL). The hospitalization rate increased in the controls (0.9 to 1.8 admissions/12 mon), whereas it was unchanged in the patients using 8-L exchanges. In conclusion, a 33% increase in dialytic prescription led to increased peritoneal and total clearances. Despite achieving increased nPNA (13%), the serum albumin level was unchanged. However, the increased hospitalization rate observed in the controls was avoided in the group using 8-L exchanges.

Incremental Initiation of Dialysis: One Center's Experience over a Two-Year Period

This pilot study describes our center's experience with peritoneal dialysis (PD) over the past 2 years using a "healthy start" dialysis protocol with an incremental approach to prescription management. Nonrandomized, prospective pilot study. Single PD unit of a university teaching hospital. Thirteen PD patients who initiated dialysis at our center from April 1997 to June 1999. Patients initiating PD with residual renal Kt/V of 1.0 - 2.0/week were invited to participate. They were given an initial dialysis prescription so that total (residual renal + dialysis) weekly Kt/V exceeded 2.0. The dialysis prescription was "incrementally" increased as residual renal function (RRF) declined. Data collected for all patients included monthly serum chemistries, residual renal weekly Kt/V and creatinine clearance (CCr) at 1- to 2-month intervals, and peritoneal weekly Kt/V and CCr at 3-month intervals and 1 month after each prescription change. To date, we have followed 13 patients on our incremental PD protocol for a total of 159.3 patient-months. Mean serum albumin concentration and mean normalized protein equivalent of nitrogen appearance (nPNA) were stable throughout the study. Mean total Kt/V and CCr remained above the recommended targets of 2.0/wk and 60 L/wk, respectively. Residual renal function declined rather slowly in our PD patients. One patient died from complications of aortic valve surgery and a second died from pneumonia. A third patient died from peritonitis. One patient required a new Tenckhoff catheter after catheter migration. Three patients were temporarily switched to hemodialysis after a hernia repair, a pleural leak, and elective native/transplant nephrectomies, respectively. Two patients were permanently switched to hemodialysis: one after an episode of peritonitis, the second after accidentally damaging his PD catheter. Providing incremental dialysis to maintain adequate total small solute clearance has been technically feasible in our patient population. However, a larger than expected number of complications was seen in our study. Fortunately, complications were easier to manage due to the presence of RRF. Because this study was not designed to compare outcome with that observed after traditional initiation of dialysis, further large-scale studies are needed.

Hyperhomocysteinemia, nutritional status, and cardiovascular disease in hemodialysis patients

Hyperhomocysteinemia, cardiovascular disease (CVD), and malnutrition are common in patients with end-stage renal disease (ESRD). This study was designed to assess possible relationships between total plasma homocysteine (tHcy), nutritional status, and ischemic CVD. We performed a cross-sectional study in 117 unselected patients on maintenance hemodialysis (HD) treatment, among whom there was a high prevalence of malnutrition (56%), as assessed by the subjective global nutritional assessment (SGNA), and a high prevalence of CVD (60%), and prospectively, we followed-up the overall mortality for four years. The level of tHcy was elevated in 95% of the HD patients, and that of total plasma cysteine (tCys) was also significantly elevated, while the plasma concentrations of methionine (Met), serine (Ser), and taurine (Tau) were significantly lower than those in healthy controls. The 65 patients who were malnourished according to the SGNA score had significantly lower levels of serum albumin (SAlb), plasma IFG-1 (p-IGF-1), tHcy, tCys, and Met than the 52 patients with normal nutritional status, whereas the levels of Ser, Tau, plasma folate, and vitamin B12 were similar in the two groups. The prevalence of malnutrition was 30% in the 47 patients without CVD and was significantly higher (70%, P < 0.001) in the 70 patients with CVD, who also had lower tHcy, SAlb, plasma IGF-1, serum creatinine (SCr), and blood hemoglobin. The tHcy levels were positively correlated with SAlb, Met, tCys, and SCr. Stepwise, multiple-regression analysis showed that tCys, SAlb, and normalized protein equivalent of nitrogen appearance (nPNA), an indicator of protein intake, were independent predictors of tHcy. The patients with tHcy <24 micromol/L (median value) had a significantly worse four-year survival than those with a higher tHcy (> or =24 micromol/L). Our results demonstrate that most of HD patients have grossly elevated tHcy levels, but that the absolute level appears to be dependent on nutritional status, protein intake, and SAlb. The results also suggest that the lower tHcy levels in patients with CVD than in those without CVD may be related to the higher prevalence of malnutrition and hypoalbuminemia in the CVD patients. This is also in accordance with our observation that the patients with lower tHcy had a worse survival rate than those with higher tHcy, considering that malnutrition is a strong risk factor for mortality and that CVD is the most common cause of death in ESRD patients.

1997 Peritoneal Dialysis-Core Indicators Study: Dialysis Adequacy and Nutritional Indicators Report.

The 1997 Peritoneal Dialysis-Core Indicators Study: Dialysis Adequacy and Nutritional Indicators Report documents the current status of peritoneal dialysis within the United States. A national random sample of adult peritoneal dialysis (PD) patients participating in the United States End Stage Renal Disease (ESRD) program was surveyed. PD subjects were large, with a mean body weight of 76 +/- 18.9 kg (mean +/- 1 SD) and a body mass index (BMI) of 27 +/- 6.4. The dialysis prescriptions documented achieved a mean weekly Kt/Vurea (wKt/V) and weekly creatinine clearance (wCrCl) of 2. 45 +/- 2.29 and 65.5 +/- 35.2 L/wk/1.73m2, respectively. The serum albumin of these patients was 3.5 +/- 0.48 g/dL, their normalized protein equivalent of nitrogen appearance (nPNA) 1.0 +/- 0.63 g/kg/d, and their normalized creatinine appearance rate (nCAR) 14 +/- 6.0 mg/kg/d. Serum albumin correlated meagerly but in a positive fashion with BMI, nPNA, and nCAR, and negatively with wCrCl. Among adult US PD patients, serum albumin values appear to correlate poorly with alternative measures of nutritional status and are inversely related to the intensity of renal replacement therapy. The presumptive dietary protein intake (nPNA) and creatinine appearance rate (nCAR) derived for PD patients do correlate in a positive fashion with dialysis delivery, at least up to a wCrCl of 60 to 80 L/wk/1.73 m2 and wKt/V = 2.1, but their values suggest that 30% to 50% of PD patients have marginal nutritional status.

1996 Peritoneal Dialysis Core Indicators Study: Report on Nutritional Indicators

The 1996 Peritoneal Dialysis Core Indicators Study illustrates the conduct of peritoneal dialysis in the United States during 1996. DESIGN AND PATIENT POPULATION: The survey is a medical records audit of 1317 randomly selected adult U.S.A. Medicare patients using peritoneal dialysis during 1996. Abstracted data included basic demographic characteristics, dialysis prescription, delivered dialysis dose, residual renal function, serum albumin, hematocrit, anemia management, and patient status. The survey included 785 patients using continuous ambulatory peritoneal dialysis (CAPD) and 423 using automated peritoneal dialysis (APD) primarily in the form of continuous cycling peritoneal dialysis (CCPD). Except for the prescription mechanics and a greater likelihood that African-Americans would use CAPD, the groups did not differ substantially from one another. Evaluation of patient weight (W), body mass index (BMI), residual renal function, average serum albumin, protein equivalent of nitrogen appearance (nPNA), and dialysis efficiency as weekly fractional urea nitrogen removal (wKt/Vurea) and weekly creatinine clearance (wCrCl) revealed a picture of reasonable dialysis delivery and marginal protein nutrition. Additionally, there was little evidence that "dialysis efficiency," over the range assessed, had a major influence on nutritional status. Despite a tendency toward obesity (body weight = 76.6+/-20.0 kg and BMI = 27+/-7), 47% of patients had an average serum albumin below"normal" (3.5 g/dL by bromcresol green) and 70% had a nPNA below 1.0 g/kg/day. Peritoneal dialysis patients appear to have marginal protein reserves despite surfeit energy stores.

Toward Targets for Initiation of Chronic Dialysis

To better define the targets for initiation of chronic dialysis, we compared the relationship between the normalized protein equivalent of nitrogen appearance (nPNA, g/kg standard weight/day) and weekly urea clearance (Kt) normalized to total body water (V) in predialysis chronic renal failure (CRF) patients and in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). We also studied the relationships of other nutritional parameters to weekly Kt/Vurea in CRF patients. This cross-sectional study was a prospective observational design meant to study each patient once. The University Hospital and Clinics and Harry S. Truman VA Medical Center, Columbia, Missouri. Forty-five consecutive predialysis CRF patients were enrolled and the results compared with patients on CAPD and HD. In CRF, the nPNA calculated from urea appearance correlated with the weekly Kt/Vurea (r = 0.57, p < 0.0001) and, using exponential best-fit, nPNA = 1.217 x (1-e-0.769Kt/V). This exponential relationship was similar to that for CAPD and both were different from that in patients on HD. Likewise, nPNAs, calculated from Kjeldahl nitrogen output, and weekly Kt/Vurea were correlated (r = 0.37, p = 0.014) and, using exponential best-fit, nPNA = 1.102(1-e-0.867Kt/V), similar to the relationship in patients on CAPD. Evidence is presented that these relationships are not explained only by mathematical coupling. There was a significant correlation between the weekly Kt/Vurea and 24-hour urinary creatinine excretion. The findings suggest that in CRF, as in CAPD, a weekly Kt/Vurea less than 2.0 is likely to be associated with a nPNA less than 0.9 g/kg standard weight. In CRF patients, initiation of chronic dialysis should be considered if weekly renal Kt/Vurea falls below 2.0 and a nPNA greater than 0.8 is desired.

EVIDENCE THAT UREA IS A BETTER SURROGATE MARKER OF UREMIC TOXICITY THAN CREATININE

The protein equivalent of nitrogen appearance normalized to standard weight was determined from urea nitrogen appearance (nPNA U) and from total Kjeldahl nitrogen appearance (nPNA K) in dialysate and/or urine in 45 predialysis patients (pre D) and in 95 patients on continuous ambulatory peritoneal dialysis (CAPD). Correlations with weekly Kt/Vurea and creatinine clearance (Ccr, L/wk/1.73 m2) were determined; renal contributions of CCr in both populations were calculated both as total CCr (A) and as CCr by GFR (CCr [B], mean of renal CCr and Curea). Correlations with weekly Kt/Vurea were significant in individual (pre D:nPNA U 0.57, p < 0.01, and nPNA K 0.37, p < 0.01; CAPD:nPNA U 0.50, p < 0.01, and nPNA K 0.43, p < 0.01) and pooled populations (nPNA U 0.54, p < 0.01 and nPNA K 0.37, p < 0.01). Correlations with neither Ccr (A) nor Ccr (B) were significant. The data also allowed comment on mathematical coupling. Ccr vs nPNA K correlations share even more mathematical couplers than does the nPNA K vs Kt/Vurea correlation, yet the correlation of nPNA K with Ccr is quite low. The authors conclude that urea is a better surrogate marker of small molecular weight toxins that inhibit protein intake in uremia, and correlations of nPNA with Kt/Vurea represent more than simple mathematical coupling.

Protein nitrogen appearance in CAPD patients: what is the best formula?

The protein equivalent of nitrogen appearance is an indirect index commonly used to assess dietary protein intake in patients on CAPD. Moreover it has been suggested that the ratio between nitrogen appearance and dietary nitrogen intake (fractional urea synthesis) can predict nitrogen balance in uraemic patients. Several formulae to directly calculate the protein equivalent of nitrogen appearance have been published. It has not been established, however, what formulae give the most appropriate estimate of protein intake and nitrogen appearance. Nitrogen balance studies were carried out in seven stable patients on CAPD. All of the patients were receiving a diet whose protein content (1.2 g/kg/body wt/day) and calorie content (35 kcal/kg/body wt/day) were rigorously controlled. Six formulae for calculating protein equivalent of nitrogen appearance and nitrogen appearance were tested and the agreement of the estimating formulae was evaluated by means of the Bland and Altman method. Net nitrogen balance was 1.68 +/- 0.9 g/N day, protein intake (g/day) 81 +/- 19, protein intake (g/kg) 1.05 +/- 0.17. Differences in protein equivalent of nitrogen appearance of up to about 20% were found. The smallest differences between protein equivalent of nitrogen appearance and protein intake were obtained by the formulae of Bergstrom (1 +/- 7 g, limits of agreement -12 and +15 g) and Blumenkrantz (-2 +/- 5 g, limits of agreement -11 and +7 g). The formula of Bergstrom most closely estimated nitrogen appearance (-0.35 +/- 0.89 g). Using such formula, the fractional urea synthesis was 54 +/- 12%, giving evidence of positive nitrogen balances. For the routine monitoring of protein equivalent of nitrogen appearance in CAPD patients, we recommend Bergstrom's formula with the determination of dialysate protein losses.

An Elevated Ratio of Measured to Predicted Creatinine Production in Capd Patients is Not a Sensitive Predictor of Noncompliance with the Dialysis Prescription

To determine the effect a period of "intentional noncompliance" in stable continuous ambulatory peritoneal dialysis (CAPD) patients has on the ratio of measured to predicted creatinine generation. Prospective study that compares baseline to noncompliant periods in individual CAPD patients. Nine chronic, stable CAPD patients. At baseline, measured creatinine production and adequacy parameters (KT/V, creatinine clearance, lean body mass, and protein equivalent of nitrogen appearance) were calculated from 24-hour collections of dialysate and urine while patients were performing their routine dialysis prescriptions. After three days of intentional noncompliance (one less exchange/day) the patients repeated their 24-hour collections, again performing their routine number of exchanges. Measured creatinine production and adequacy parameters were again calculated. Predicted creatinine production for each patient was calculated from standard equations. All parameters at baseline were compared to corresponding parameters after intentional noncompliance. In all patients, except one where there was no change, there was a statistically significant increase in not only the ratio of measured to predicted creatinine production but also all other parameters. As suspected by previous investigators, this study suggests that one cause of an elevated ratio of measured to predicted creatinine production may be a recent period of noncompliance with the patient's dialysis prescription. However, these data suggest that an isolated ratio of measured to predicted creatinine generation is not a sensitive predictor of noncompliance with the peritoneal dialysis prescription.

Normalization of Protein Equivalent of Nitrogen Appearance and Dialytic Adequacy in Capd

Caloric-proteic malnutrition is frequently encountered in peritoneal dialysis and is associated with an increased risk of morbidity and mortality. Our paper aims to assess any greater reliability of protein equivalent of nitrogen appearance (PNA) normalization to desirable body weight (dBW) compared to actual body weight (aBW) and resulting implications for the relationship between dialytic adequacy and protein intake in continuous ambulatory peritoneal dialysis (CAPD). We studied 36 patients on CAPD, 24 male and 12 female (aged 66.6 +/- 10.2 years, 24 +/- 29 months on dialysis), collecting dialysate and urine over 24 hours (126 samples) to calculate the PNA according to Randerson and the total weekly KT/V. The total body muscle mass (TBMM) was calculated by anthropometry and the dBW according to Metropolitan Life Insurance tables. Finally, PNA was normalized to aBW (aPNA, g/kg/day) and to dBW (dPNA, g/kg/day). Average aBW proved to be higher than dBW (66.0 +/- 11.1 vs 59.8 +/- 6.9 kg, p < 0.0001) and aPNA lower than dPNA (0.96 +/- 0.31 vs 1.08 +/- 0.3 g/kg/day, p < 0.005). Compared to aPNA, dPNA correlates better with both blood urea nitrogen (BUN) (R2 = 0.702 vs 0.614) and KT/V (R2 = 0.348 vs 0.306). The TBMM is higher in the group with dPNA > or = 1.0 vs < 1.0 g/kg/day (25.5 +/- 0.6 vs 23.1 +/- 0.7 kg, p < 0.02) while, paradoxically, it is lower in patients with aPNA > or = 1.0 vs < 1.0 g/kg/day (22.8 +/- 0.8 vs 25.4 +/- 0.6 kg, p < 0.01). The KT/V of the patients with dPNA < 0.8, 0.8-1.2 and > 1.2 g/kg/day proved to be different (1.52 +/- 0.06 vs 1.80 +/- 0.03 vs 2.04 +/- 0.04, p < 0.005). On analysis of the linear regression, dPNA = 1.0 and 1.2 g/kg/day corresponds to KT/V values of 1.7 and 2.05, respectively. We consider dPNA to be more suitable then aPNA for the correct assessment of protein intake, and a weekly KT/V of 1.7-2.05 as being sufficient to guarantee satisfactory dPNA.

Nursing Forum: Urea Kinetics and Nitrogen Appearance Rates in Diabetic Patients on Peritoneal Dialysis

ObjectiveWe compared the relationship of protein intake (as measured by protein nitrogen appearance) and dialysis delivery in insulin-dependent diabetic (IDDM) and nondiabetic patients.DesignOne to two 24-hour dialysate and urine collections were obtained in 20 diabetic patients and 42 nondiabetic patients. The protein equivalent of nitrogen appearance (PNA) was calculated by the Randerson formula. KTN was determined using V obtained by the Watson formula. PNA was normalized using three different methods to determine body weight: first, by normal or ideal body weight according to the Metropolitan Table (nPNA); second, by standard body weight according to the NHANES Table (sPNA); and third, by V/0.58 (vPNA).ResultsThe mean PNA was not different in diabetics and nondiabetics (53±21 g/day vs 60±14 g/day), nor was weekly KTN (2.1 ±0.6 vs 2.1 ±0.6). Mean normalized PNA was not different in IDDM versus non-DM regardless of the method. KTN correlated with nPNA in IDDM (r = 0.54, p = 0.002 and non-DM, r = 0.31, p = 0.03), and with vPNA in IDDM (r = 0.73, p &lt; 0.00001, and non-DM, r = 0.45, p = 0.0009). KTN also correlated with sPNA in IDDM (r = 0.57, p = 0.001), but not in non-DM (r = 0.25, p = 0.08). The slope for normalized PNA versus KTN was steeper for IDDM than for non-DM.ConclusionKTN and PNA are more closely correlated in IDDM patients than in non-DM patients. Thus it is extremely important that IDDM patients receive an adequate level of dialysis.

Urea Kinetics and Nitrogen Appearance Rates in Diabetic Patients on Peritoneal Dialysis

We compared the relationship of protein intake (as measured by protein nitrogen appearance) and dialysis delivery in insulin-dependent diabetic (IDDM) and nondiabetic patients. One to two 24-hour dialysate and urine collections were obtained in 20 diabetic patients and 42 nondiabetic patients. The protein equivalent of nitrogen appearance (PNA) was calculated by the Randerson formula. KT/V was determined using V obtained by the Watson formula. PNA was normalized using three different methods to determine body weight: first, by normal or ideal body weight according to the Metropolitan Table (nPNA); second, by standard body weight according to the NHANES Table (sPNA); and third, by V/0.58 (vPNA). The mean PNA was not different in diabetics and nondiabetics (53 +/- 21 g/day vs 60 +/- 14 g/day), nor was weekly KT/V (2.1 +/- 0.6 vs 2.1 +/- 0.6). Mean normalized PNA was not different in IDDM versus non-DM regardless of the method. KT/V correlated with nPNA in IDDM (r = 0.54, p = 0.002 and non-DM, r = 0.31, p = 0.03), and with vPNA in IDDM (r = 0.73, p < 0.00001, and non-DM, r = 0.45, p = 0.0009). KT/V also correlated with sPNA in IDDM (r = 0.57, p = 0.001), but not in non-DM (r = 0.25, p = 0.08). The slope for normalized PNA versus KT/V was steeper for IDDM than for non-DM. KT/V and PNA are more closely correlated in IDDM patients than in non-DM patients. Thus it is extremely important that IDDM patients receive an adequate level of dialysis.

Predicted and Measured Daily Creatinine Production in CAPD: Identifying Noncompliance

To evaluate the ratio of measured creatinine (Cr) production to predicted creatinine production as an index of noncompliance in patients on continuous ambulatory peritoneal dialysis (CAPD). A cross-sectional analysis. One hundred and twenty-one patients on CAPD. We have calculated Cr production from measured Cr outputs in 24-hour collections of urine and dialysate. Predicted Cr productions were calculated from standard tables. Weekly KT/V urea and weekly Cr clearances were determined from the same 24-hour urine and dialysate collections. Lean body mass (LBM) was calculated from the Cr production. Serum albumin concentration was measured. The ratio of measured/predicted Cr production correlated positively and significantly with weekly KT/V urea, the protein equivalent of nitrogen appearance (PNA), weekly Cr clearance, and LBM. There was a decline in serum albumin concentration at ratios greater than 1.24, supporting the opinions of previous authors who have suggested that ratios greater than 1.24 are highly suggestive of noncompliance with the dialysis prescription. Defining noncompliance as a ratio greater than 1.24 implied that at least 5% of the female and 17% of the male patients were noncompliant. Declining serum albumin concentrations at higher ratios of measured/predicted Cr production support the opinion that this is an index of noncompliance. However, not all noncompliant patients necessarily have a ratio greater than 1.24. Weekly KT/V urea, weekly Ccr and LBM are all artifactually increased by "washout effects" if all exchanges are done only or mainly on the collection day.