Nitrogen Appearance Research Articles

Addendum Regarding “Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements” (Am J Kidney Dis. 76[1]:22-31)

Addendum Regarding “Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements” (Am J Kidney Dis. 76[1]:22-31)

EFFECT OF RENAL SPECIFIC ORAL NUTRITION (ONCE RENAL) ON DIETARY INTAKE AND SERUM ELECTROLYTES IN CHRONIC KIDNEY DISEASE STAGE IV

Background and Objectives: Low nutritional intake is common in advanced chronic kidney disease (CKD) and poses a direct risk for malnutrition. Our study evaluated the effects of a renal specific oral nutrition (ONCE Renal) supplement concerning nutritional status, minerals and electrolytes among patients with stage IV CKD.
 Methods and Study Design: A total of 32 CKD patients with an estimated glomerular filtration rate 16-29 mL/min/1.73 m2, well nourished subjects and anticipated good compliance with the diet received the ONCE Renal diet instead of 1 meal daily for 30 days. Dietary protein and energy intake, body compositions, and serum concentrations of urea, creatinine, calcium, magnesium, phosphate and albumin were assessed at baseline, and at 30 days. A dietary intake by three-day food record were also evaluated by a registered dietitian.
 Results: At the end of 30 days, significant improvements in energy, fat, fiber and magnesium intake by dietary interview were noted. In addition, the patients also increased body weight and body mass index after supplement. No significant changes in renal function, serum electrolytes, calcium, phosphorus, magnesium concentration and other nutritional markers including serum albumin, body compositions and protein equivalence of total nitrogen appearance were observedduring study. The compliance with the ONCE Renal diet was good among enrolled patients and no adverse reactions were found.
 Conclusions: Renal specific oral diet supplement can improve energy intake, body weight and maintain serum electrolytes concentrations among patients with stage IV CKD.

Production of added-value microbial metabolites during growth of yeast strains on media composed of biodiesel-derived crude glycerol and glycerol/xylose blends.

A total of 11 yeast strains of Yarrowia lipolytica, Metschnikowia sp., Rhodotorula sp. and Rhodosporidium toruloides were grown under nitrogen-limited conditions with crude glycerol employed as substrate in shake flasks, presenting interesting dry cell weight (DCW) production. Three of these strains belonging to Metschnikowia sp. accumulated significant quantities of endopolysaccharides (i.e. the strain V.V.-D4 produced 11.0g/L of endopolysaccharides, with polysaccharides in DCW≈63% w/w). A total of six Y. lipolytica strains produced either citric acid or mannitol. Most of the screened yeasts presented somehow elevated lipid and polysaccharides in DCW values at the early steps of growth despite nitrogen appearance in the fermentation medium. Lipid in DCW values decreased as growth proceeded. R. toruloides DSM 4444 cultivated on media presenting higher glycerol concentrations presented interesting lipid-accumulating capacities (maximum lipid=12.5g/L, maximum lipid in DCW=43.0-46.0% w/w, conversion yield on glycerol=0.16g/g). Replacement of crude glycerol by xylose resulted in somehow decreased lipid accumulation. In xylose/glycerol mixtures, xylose was more rapidly assimilated from glycerol. R. toruloides total lipids were mainly composed of triacylglycerols. Total cellular fatty acid composition on xylose presented some differences compared with that on glycerol. Cellular lipids contained mainly oleic and palmitic acid.

Integrating the Surprise Question, Palliative Care Screening Tool, and Clinical Risk Models to Identify Peritoneal Dialysis Patients With High One-Year Mortality

ContextUniversal screening to identify vulnerable patients who may receive limited benefits from life-sustaining treatments can facilitate palliative care in dialysis populations. ObjectivesWe aimed to develop prediction models for one-year mortality in peritoneal dialysis (PD) patients. MethodsThis prospective cohort study included 401 adult Taiwanese prevalent PD patients (average age 56.2 ± 14 years). In addition to obtaining clinical characteristics and laboratory data, the primary care nurses evaluated the surprise question (SQ) and palliative care screening tool (PCST) for each patient in March 2015. Multivariate logistic regression models were conducted to predict the primary outcome of one-year all-cause mortality. ResultsThere were 34 (8.5%) patients who died during the first year of follow-up. Patients allocated to the not surprised group according to the SQ and those who received a score of ≥4 on the PCST had increased odds of death (odds ratio 24.68 [95% CI 10.66–57.13] and 12.18 [95% CI 5.66–26.21], respectively). We also developed a clinical risk model for one-year mortality that included sex, dialysis vintage, coronary artery disease, malignancy, normalized protein nitrogen appearance, white blood cell count, and serum albumin and sodium levels. Integrating the SQ, PCST, and clinical risk model exhibited good discrimination with an area under the receiver operating characteristic curve of 0.95. Kaplan-Meier analysis showed worse survival in high-risk patients predicted by the integrated model (log-rank P < 0.001). ConclusionScreening with the use of the integrated measurement can identify high-risk PD patients. This approach may facilitate palliative care interventions for at-risk subpopulations.

Routine Kt/V and Normalized Protein Nitrogen Appearance Rate Determined From Conductivity Access Clearance With Infrequent Postdialysis Serum Urea Nitrogen Measurements

Conventional monitoring of hemodialysis dose is implemented using urea kinetic modeling based on single-pool Kt/V, which requires both pre- and postdialysis serum urea nitrogen (SUN) measurements. We compared this conventional approach to one in which Kt/V is calculated using conductivity clearance, thereby reducing the need for regular postdialysis SUN measurements. Comparative study of 2 diagnostic tests. Prevalent patients receiving maintenance hemodialysis for at least 2 years for whom both urea reduction ratio (URR) and average conductivity clearance (Kecn) were measured. During the initial 8 months (baseline interval), average Kecn and URR were used to calculate a median patient-specific, modeled, calibration solute distribution volume (Vcal). During months 9 to 16 (period 1) and 17 to 24 (period 2), Kt/V was conventionally computed using URR and also by a new method using Vcal and Kecn without postdialysis SUN values. We examined the percentage error between these 2 methods of calculating Kt/V. Concordance between the 2 methods of calculating Kt/V. Among 1,093 patients, mean individual-level median single-pool Kt/V values derived using the conventional method during the baseline interval, period 1, and period 2 were 1.62±0.24 (SD), 1.66±0.24, and 1.67±0.24, respectively. During periods 1 and 2, patient-level median Kt/V values derived using Kecn were 1.64±0.24 and 1.65±0.24, respectively. Percent differences between patient-level median values of Kt/V (conductivity minus conventional URR methods) were-0.63%±7.7% and-0.75%±8.4% for periods 1 and 2. Normalized protein nitrogen appearance were comparable between the 2 methods. Data were collected over 2 years. Study was limited to in-center hemodialysis patients dialyzed 3 times per week. Dialysis session length was not adjusted for treatment interruptions. A new method of calculating Kt/V based on Kecn that requires fewer postdialysis SUN measurements provided diagnostic data comparable to those from conventional use of URR and has the potential to avoid errors related to postdialysis blood sampling and measurement.

High Serum Adipocyte Fatty Acid-Binding Protein Is Associated With Peripheral Artery Disease in Peritoneal Dialysis Patients

BACKGROUND: Peripheral arterial disease (PAD) is a vascular disorder wherein peripheral ischemia is caused by arterial obstruction and results in increased events of cardiovascular disease (CVD). Peritoneal dialysis (PD) is an independent predictor of subclinical PAD and the subsequent mortality in patients with end-stage renal disease. Adipocyte fatty acid-binding protein (A-FABP) is a potential biomarker for CVD risk, especially in patients with overt atherosclerosis. This study was conducted to determine the relationship between PAD and fasting serum levels of A-FABP in patients undergoing PD. METHODS: Fasting blood samples were obtained from 66 PD patients. A-FABP levels were measured using a commercially available enzyme immunoassay kit. Ankle-brachial index (ABI) values were measured using the automated oscillometric method. Serum left or right ABI values of ＜ 0.9 were included in the low ABI group. RESULTS: There were 14 patients (21.2%) in the low ABI group. Compared with patients in the control group, those in the low ABI group had a higher prevalence of diabetes (P = 0.045) and higher serum C-reactive protein (P ＜ 0.001) and A-FABP (P ＜ 0.001) levels but lower weekly Kt/V (P = 0.014) and lower normalized protein equivalent of nitrogen appearance (P = 0.034) values. Multivariate logistic regression analysis of the factors that were significantly associated with PAD revealed that A-FABP (odds ratio, 1.038; 95% confidence interval [CI], 1.004-1.074; P = 0.030) was an independent predictor of PAD in PD patients. The area under the curve plotted to estimate the optimal level of A-FABP predicting PAD in PD patients by the receiver operating characteristic curve analysis was 0.757 (95% CI, 0.636-0.854; P = 0.0004). CONCLUSION: This study demonstrated that a higher serum A-FABP level is an independent predictor of PAD in patients undergoing PD.

Dietary intake of tyrosine and phenylalanine, and p-cresyl sulfate plasma levels in non-dialyzed patients with chronic kidney disease.

ABSTRACTBackground: Patients with chronic kidney disease (CKD) present an imbalance of the gut microbiota composition, leading to increased production of uremic toxins like p-cresyl sulfate (PCS), product from bacterial fermentation of the amino acids tyrosine (Tyr) and phenylalanine (Phe) from the diet. Thus, diet may be a determinant in the uremic toxins levels produced by the gut microbiota. The aim of this study was to evaluate the possible relationship between Tyr and Phe intake and PCS plasma levels in non-dialysis CKD patients.Methods: Twenty-seven non-dialysis CKD patients (stages 3 and 4) without previous nutritional intervention were evaluated. The dietary intake was evaluated using a 24-hour recall, 3-day food record and protein intake was also estimated by Protein Nitrogen Appearance (PNA). The plasma levels of PCS were measured using reverse phase high performance liquid chromatography.Results: The evaluated patients (GRF, 34.8 ± 12.4 mL/min, 54.2 ± 14.3 years, BMI, 29.3 ± 6.1 kg/m2) presented mean protein intake of 1.1 ± 0.5 g/kg/day), Tyr of 4.5 ± 2.4 g/day and Phe of 4.6 ± 2.5 g/day. PCS plasma levels (20.4 ± 15.5 mg/L) were elevated and positively associated with both, Tyr (r = 0.58, p = 0.002) and Phe intake (r = 0.53, p = 0.005), even after adjustments for eGFR and age.Conclusion: This study suggests that the diet is an important modulator of the uremic toxins plasma levels produced by the gut microbiota, in non-dialysis CKD patients.

Dietary pattern analysis among stone formers: resemblance to a DASH-style diet.

Recent epidemiological studies have shown that dietary patterns may have a more persistent impact on the risk of stone formation than single nutrients of the diet. Dietary Approaches to Stop Hypertension (DASH), a low-sodium and fruits/vegetables-rich diet, has been associated with a lower risk of nephrolithiasis, due to altered urinary biochemistry. This observational study aimed to investigate whether the dietary pattern of stone formers (SF) resembled a DASH-diet and its influence on urinary lithogenic parameters. Anthropometric data, fasting serum sample, 24-h urine samples, and a 3-day food intake record under an unrestricted diet were obtained from 222 SF and compared with 136 non-SF subjects (controls). The DASH-diet food portions were determined from the food records whereas intakes of sodium chloride (NaCl) and protein (protein equivalent of nitrogen appearance, PNA) were estimated from 24-hr urinary sodium and urea. A dietary profile close to a DASH-diet was not observed in any of the groups. NaCl intake and PNA were significantly higher in SF versus non-SF (12.0 ± 5.2 v.s. 10.1 ± 3.4 g/day, p = 0.01 and 1.8 ± 0.1 v.s. 1.4 ± 0.1 g/kg/day, p = 0.03). SF exhibited a positive correlation of NaCl intake and PNA with urinary calcium, oxalate and uric acid, and of PNA with urinary sodium. SF consumed more vegetables and legumes, but less fruits and low-fat dairy items than non-SF. The present series presented a dietary profile characterized by low calcium and high salt and protein contents, not reflecting an ideal DASH-style diet pattern.

Fatigue in Peritoneal Dialysis Patients and an Exploration of Contributing Factors: A Cross-Sectional Study

ContextFatigue is a common and detrimental symptom in dialysis patients; however, our understanding of it and investigation of its contributing factors is still very limited, especially in peritoneal dialysis (PD) patients. ObjectivesTo assess fatigue in PD patients and identify contributing factors. MethodsOne hundred eight PD patients in a comprehensive hospital in China were recruited. The fatigue severity of the participants was assessed using the Chalder Fatigue Scale 11. Demographic factors and results of physiological tests were collected. Quality of sleep, mental health, and social support were assessed with the Pittsburgh Sleep Quality Index, Symptom Checklist 90, and Social Support Rating Scale, respectively. Multiple linear regression models were conducted with candidate variables with a P-value of less than 0.1 on univariate analysis and variables that were clinically relevant to identify contributing factors for fatigue. ResultsThe fatigue level in PD patients was significantly higher than the community population, and 78.7% of them were suffering from fatigue. The factors that were significantly associated with fatigue were quality of sleep, normalized protein nitrogen appearance, transferrin, alkaline phosphatase, and total cholesterol (adjusted R squared 0.86). Among them, quality of sleep, transferrin, alkaline phosphatase, and total cholesterol were significant contributors for physical fatigue, whereas the quality of sleep and normalized protein nitrogen appearance were contributing factors for mental fatigue. ConclusionFatigue is a common symptom in PD patients, suggesting that increased awareness of this symptom is required. The identification of correlates by extensive exploration of multidimensional factors in this study may help practitioners to identify patients at higher risk and to develop a multidimensional and targeted intervention plan.

Sodium loss, extracellular volume overload and hypertension in peritoneal dialysis patients treated by automated peritoneal dialysis cyclers.

Achieving sodium balance is important for peritoneal dialysis patients, as sodium excess may lead to hypertension and extracellular water expansion. We wished to determine whether greater sodium removal had adverse consequences. We calculated 24-h urinary and peritoneal sodium losses in peritoneal dialysis patients treated by automated cyclers, when attending for peritoneal membrane and bioimpedance assessments. We reviewed 439 peritoneal dialysis patients, 56.7% male, average age 54.6 years, median sodium loss 110 (68-155) mmol/day. Sodium loss was strongly associated with urine volume, r = 0.37, protein nitrogen appearance rate, r = 0.29, and body cell mass, r = 0.21, all p < 0.001. We found no association with blood pressure or anti-hypertensive medication prescription, or extracellular water. On multivariable logistic regression analysis, sodium loss was associated with greater urine output, odds ratio 1.001, 95% confidence interval 1.00-1.001, p < 0.001, and protein nitrogen appearance (odds ratio 1.023, confidence interval 1.006-1.04), p = 0.008. Adjusting for body weight, sodium loss was associated with urine output (odds ratio 1.001, confidence interval 1.001-1.002, p < 0.001), and negatively with body fat index (odds ratio 0.96, confidence interval 0.93-0.99, p = 0.008) and co-morbidity grade (odds ratio 0.58, confidence interval 0.36-0.39, p = 0.023). Heavier peritoneal dialysis patients with greater estimated dietary protein intake (protein nitrogen appearance), those with greater residual renal function and peritoneal clearances, along with lower co-morbidity, had greater daily sodium losses. Adjusting for body weight, then sodium losses were greater with higher daily urine output, and lower in patients with proportionately more body fat and co-morbidity. Sodium losses would appear to primarily determined by body size and not associated with hypertension or extracellular water expansion.

High rates of protein intake are associated with an accelerated rate of decline of residual kidney function in incident peritoneal dialysis patients.

Preservation of residual kidney function (RKF) is a relevant objective in peritoneal dialysis (PD) patients. The influence of dietary protein intake (PI) on this variable has not been adequately investigated. Following an observational design, we studied 336 patients incident on PD, with a minimum follow-up of 6 months. The main study variable was the mean PI [normalized rate of protein nitrogen appearance (nPNA)] during the first 4 months on PD. The main outcome variables were the absolute rate of decline of RKF and the proportion of patients presenting a >50% decay of their RKF during the first year of follow-up. We applied univariate and multivariate strategies of analysis, taking into consideration the main control variables bearing a correlation with nPNA and/or RKF. Mean nPNA (first 4 months) was 1.23 ± 0.33 g/kg/day, while the overall rate of decline of RKF was -0.13 ± 0.29 mL/min/month; 69 patients (25.1%) had lost >50% of their initial RKF by the end of the first year. Univariate analysis disclosed consistent associations between the main study variable on one hand and baseline RKF (r = 0.32, P < 0.0005) and its rate of decline (r = -0.23, P < 0.0005) on the other. The latter two variables were also significantly correlated (r = -0.36, P < 0.0005). Multivariate analysis identified mean nPNA as an independent predictor of the rate of decline of RKF [odds ratio 1.09 per 0.10 g/kg/day, 95% confidence interval (CI) 0.99-1.19, P = 0.058] and, in particular, of the probability of losing >50% of the baseline RKF during the first year of treatment (odds ratio 1.15 per 0.10 g/kg/day, 95% CI 1.04-1.27, P = 0.006). Higher rates of PI during the first months of therapy are associated with a faster decline of RKF among patients incident on PD. Our results underline the convenience of keeping an adequate balance between sufficient protein ingestion, to prevent malnutrition and wasting, and sensible restriction in stable, adequately nourished individuals with rates of intake in the higher range or above-recommended allowances.

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3–5: A cross-sectional study

IntroductionA controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3–5. MethodCross-sectional study in 134 CKD patients in stages 3–5 (mean e-GFR: 19.4±8.7ml/min/1.73m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: <0.8g/kg/day; G2: 0.8–1g/kg/day and, G3: ≥1g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS v.20. ResultsOverall mean nPNA values were 0.91±0.23g of protein/kg BW/day and only 32.1% had a dietary protein intake <0.8g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein–energy–wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥1g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R=0.51; R2=0.29; R2 adjusted=0.23; p<0.001). ConclusionControlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4–5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression.

Differences between Measured Total Nitrogen Losses in Spent Peritoneal Dialysate Effluent and Estimated Nitrogen Losses

Patients treated by peritoneal dialysis (PD) are at increased risk of muscle wasting, and clinical guidelines recommend assessing dietary intake, by calculating protein equivalent of nitrogen appearance (PNA) to assure protein sufficiency. The PNA equations were developed many years ago, and we wished to re-evaluate them by comparing estimated and measured peritoneal nitrogen losses. This is a cross-sectional observational cohort study. The study setting was an outpatient PD center of a university hospital and the study subjects included 67 patients undergoing PD, in which 61.2% were males, and the median age was 67.3 (53.2-79.4) years. The nitrogen content of 24-hour spent peritoneal dialysate by automated chemiluminescence analyzer was measured and compared with estimates of nitrogen losses based on dialysate urea loss using the Bergstrom, Randerson, and Blumenkrantz equations. Measured total dialysate nitrogen was more than urea nitrogen equivalent, 5.79 ± 4.07 versus 2.66 ± 1.67 g/day (P<.001). Each equation has an inflation factor to compensate for nonurea protein losses; however, measured nitrogen loss was 27.7 (15.5-59.6) g/day versus Bergstrom, 16.5 (9.8-27.1); Randerson, 16.4 (9.8-27.3); and Blumenkrantz, 12.9 (7.9-25.4) g/day, P< .001. The BlandAltman analysis demonstrated systematic bias with increasing underestimation by these equations with increasing measured nitrogen losses (r = 0.74, P < .001). Our findings demonstrate that at higher protein losses, the currently used predictive equations underestimate the amount lost. It is important to attempt to compensate the iatrogenic protein loss by recommending the appropriate intake of dietary protein to patients, in an attempt to minimize muscle wasting. This discrepancy may have arisen because of the characteristics of newer PD prescriptions and change in patient demographics. We propose a new equation PNA g/day = 0.31 × (urea loss mmol) + 7.17, whichwill require prospective validation in additional studies.

Influence of dietary protein intake on body composition in chronic kidney disease patients in stages 3–5: A cross-sectional study

IntroductionA controlled protein intake has shown beneficial effects to preserve renal function and nutritional status in chronic kidney disease (CKD) patients. This study aimed to analyze usual dietary protein intake and its potential contribution to body composition in CKD patients in stages 3–5. MethodCross-sectional study in 134 CKD patients in stages 3–5 (mean e-GFR: 19.4±8.7ml/min/1.73m2; males 68.7% and primary CKD etiology was diabetes mellitus, 35.8%). Demographic, clinical and nutritional parameters were evaluated. Normalized protein nitrogen appearance (nPNA), was used as a surrogate marker of dietary protein intake. The sample was classified into three nPNA groups (Gn): G1: <0.8g/kg/day; G2: 0.8–1g/kg/day and, G3: ≥1g/kg/day. Assessment of nutritional status using the malnutrition-inflammation score (MIS), anthropometric measures and laboratory parameters. Analysis of body composition and hydration status by bioelectrical impedance analysis (BIVA-101-RJL system). Statistical analysis by SPSS v.20. ResultsOverall mean nPNA values were 0.91±0.23g of protein/kg BW/day and only 32.1% had a dietary protein intake <0.8g of protein/kg BW/day. Most of the CKD patients (65.5%) were in stages 4 or 5. Prevalence of protein–energy–wasting (PEW) syndrome measured by MIS was 15%. By analyzing differences between nPNA groups, body weight (BW), BMI and triceps-skinfold (TSF) thickness were significantly higher in the group with nPNA ≥1g/kg BW/day (G3), whereas a significant inverse relationship was found with the percentages of body cell mass (BCM%), fat-free mass (FFM%), muscle mass (MM%) and phase angle (PA) in the group with the lowest nPNA (G1). Analysis of gender among subjects showed significant differences with BW, FFM%, TSF and mid-arm muscle circumference (MAMC%). Linear regression analysis showed that resistance, BCM%, MM%, and serum albumin were significant predictors of nPNA as a surrogate marker of daily protein intake (R=0.51; R2=0.29; R2 adjusted=0.23; p<0.001). ConclusionControlled protein intake is one of the cornerstones of treatment in CKD patients. A low protein intake in patients with CKD stages 3 and 4–5 was associated with loss of muscle mass in the advanced-CKD unit. The loss of muscle mass appears as an early indicator of nutritional comprised. Factors such, elderly age and loss of eGFR, showed lower protein intake and were associated with muscle loss, especially in women. Further longitudinal studies are required to evaluate the contribution of different protein intakes to uremic symptoms, nutritional status, body composition and CKD progression.

A16521 Serum Advanced glycation end-products are associated with nutrition status but not aortic stiffness in end-stage renal disease

Objectives: Advanced glycation end-products (AGEs) are a heterogeneous group of uremic toxins, which are acquired via endogenous pathways and through absorption of AGE-modified peptides found in food. Through modification of extracellular structural proteins of the arterial wall, AGEs can lead to vascular stiffness. In this study, we aimed to examine the association of serum fluorescent AGEs with aortic stiffness (AS), tissue AGEs and protein intake in a cohort of subjects undergoing chronic hemodialysis. Methods: In 166 subjects with a mean age of 65 ± 15, 55% male, 48% diabetic and 59% with established cardiovascular disease, serum AGEs was determined by total serum and molecular weight based serum autofluorescence (HPLC), tissue levels of AGEs was measured by skin autofluorescence (AF), AS was measured by determination of carotid-femoral pulse wave velocity (cfPWV). Results: Despite higher levels of HbA1C in diabetic patients (0.063 ± 0.011 vs 0.052 ± 0.004, p = 0.001) and higher cfPWV (14.9 ± 3.7 vs 12.4 ± 3.8, p < 0.001), total serum AGEs was lower in diabetic subjects (3.47 ± 0.77 vs 2.97 ± 0.76, p < 0.001). There was a positive association between total serum AGEs and normalized protein nitrogen appearance rate in both diabetics (r = 0.337, p = 0.004) and non-diabetics (r = 0.362, p < 0.001). There were no correlations between skin AF and total serum AGEs or any of the fractions of molecular weight using various cut-offs (2, 5, 10 and 30 kd). In non-diabetics, there was a consistent negative association between serum AGEs and AS (even after adjustments for confounding factors), but there was not any associations between serum AGEs and AS in diabetics. Conclusion: Serum measurements of AGEs based on serum auto-fluorescence is better correlated to protein intake and is not associated with tissue levels of AGEs or AS.

Estimating Dietary Protein Intake in Peritoneal Dialysis Patients: The Effect of Ethnicity.

Kidney dialysis patients with sarcopenia have increased mortality. Clinical guidelines recommend peritoneal dialysis (PD) patients have a target daily protein intake to prevent sarcopenia. Protein intake is estimated from total daily urea losses in urine and peritoneal dialysate to assess the protein equivalent of nitrogen appearance rate adjusted for body weight (nPNA). Dietary habits differ among ethnic groups, so we reviewed nPNA and body composition in a multi-ethnic PD population. Body composition was measured with multifrequency bioimpedance in 598 patients (301 white, 136 black, 123 South-Asian, and 38 Asian-Pacific). South-Asians had a lower nPNA compared with white and black individuals (Randerson 0.80 ± 0.21 vs 0.88 ± 0.24 and 0.85 ± 0.24 g/kg/day, Blumenkrantz 0.97 ± 0.14 vs 1.04 ± 0.22 and 0.99 ± 0.22 g/kg/day, Bergström 0.87 ± 0.4 vs 0.95 ± 0.24 and 0.92 ± 0.24 g/kg/day all p < 0.001). South-Asians had lower weights (68.9 ± 14.9 vs 74.4 ± 16.6 and 73.5 ± 16.3 kg, p < 0.001), and although of similar body mass index (25.9 ± 4.9 vs 28.5 ± 4.9 and 26.5 ± 5.2 kg/m2), had both lower skeletal muscle and appendicular muscle mass indexed for height (9.08 ± 1.45 vs 9.89 ± 1.62 and 10.1 ± 1.85, p < 0.001; and 6.95 ± 1.39 vs 7.68 ± 1.48 and 7.67 ± 1.58 kg/m2p < 0.01). South-Asian patients had a lower calculated basal metabolic rate (BMR) (1,358 ± 218 vs 1,487 ± 257 and 1,489 ± 271 kcal/day, p < 0.001).Asian PD patients, particularly South-Asians, have lower dietary protein intakes when calculated by nPNA. However, South-Asians had lower measured muscle mass and calculated BMR. As such, dietary protein intake targets derived from studies in 1 ethnic group are not necessarily applicable for all patients, as those with less muscle mass and lower BMR may well need less daily protein intake to maintain homeostasis.

Percorsi pratici per intraprendere un programma di dialisi monosettimanale combinato con una nutrizione ipoproteica personalizzata

The aim of this article is to provide detailed information to nephrologists on how to apply the combined diet dialysis program (CDDP) in selected patients. Patients are evaluated by urea nitrogen appearance, which allows the sustainability and compliance of patients on 0.6 g/kg per day low-protein diet to be verified by calculating the protein catabolic rate at a metabolic steady state. The combined action of nutrition and less frequent hemodialysis may preserve residual renal function with a further chance of achieving greater excretion of the protein-bound uremic toxins, thereby obtaining a positive phosphate balance. This paper describes all fundamental steps and calculations, although a greater clinical commitment is required to achieve a tailored therapeutic protocol such as Combined Diet Dialysis Program (CDDP).

Does Low-Protein Diet Influence the Uremic Toxin Serum Levels From the Gut Microbiota in Nondialysis Chronic Kidney Disease Patients?

To evaluate the effects of low-protein diet (LPD) on uremic toxins and the gut microbiota profile in nondialysis chronic kidney disease (CKD) patients. Longitudinal study with 30 nondialysis CKD patients (stage 3-4) undergoing LPD for 6months. Adherence to the diet was evaluated based on the calculation of protein equivalent of nitrogen appearance from the 24-hour urine analysis. Good adherence to LPD was considered when protein intake was from 90% to 110% of the prescribed amount (0.6g/kg/day). Food intake was analyzed by the 24-hour recall method. The anthropometric, biochemical and lipid profile parameters were measured according to standard methods. Uremic toxin serum levels (indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid) were obtained by reversed-phase high-performance liquid chromatography (RP-HPLC). Fecal samples were collected to evaluate the gut microbiota profile through polymerase chain reaction and denaturing gradient gel electrophoresis. Statistical analysis was performed by the SPSS 23.0 program software. Patients who adhered to the diet (n=14) (0.7±0.2g/kg/day) presented an improvement in renal function (nonsignificant) and reduction in total and low-density lipoprotein cholesterol (183.9±48.5-155.7±37.2mg/dL, P=.01; 99.4±41.3-76.4±33.2mg/dL, P=.01, respectively). After 6months of nutricional intervention, p-cresyl sulfate serum levels were reduced significantly in patients who adhered to the LPD (19.3 [9.6-24.7] to 15.5 [9.8-24.1] mg/L, P=.03), and in contrast, the levels were increased in patients who did not adhere (13.9 [8.0-24.8] to 24.3 [8.1-39.2] mg/L, P=.004). In addition, using the denaturing gradient gel electrophoresis technique, it was observed change in the intestinal microbiota profile after LPD intervention in both groups, and the number of bands was positively associated with protein intake (r=0.44, P=.04). LPD seems be a good strategy to reduce the uremic toxins production by the gut microbiota in nondialysis CKD patients.

Existing creatinine-based equations overestimate glomerular filtration rate in Indians

BackgroundAccurate estimation of glomerular filtration rate (GFR) is important for diagnosis and risk stratification in chronic kidney disease and for selection of living donors. Ethnic differences have required correction factors in the originally developed creatinine-based GFR estimation equations for populations around the world. Existing equations have not been validated in the vegetarian Indian population. We examined the performance of creatinine and cystatin-based GFR estimating equations in Indians.MethodsGFR was measured by urinary clearance of inulin. Serum creatinine was measured using IDMS-traceable Jaffe’s and enzymatic assays, and cystatin C by colloidal gold immunoassay. Dietary protein intake was calculated by measuring urinary nitrogen appearance. Bias, precision and accuracy were calculated for the eGFR equations.ResultsA total of 130 participants (63 healthy kidney donors and 67 with CKD) were studied. About 50% were vegetarians, and the remainder ate meat 3.8 times every month. The average creatinine excretion were 14.7 mg/kg/day (95% CI: 13.5 to 15.9 mg/kg/day) and 12.4 mg/kg/day (95% CI: 11.2 to 13.6 mg/kg/day) in males and females, respectively. The average daily protein intake was 46.1 g/day (95% CI: 43.2 to 48.8 g/day). The mean mGFR in the study population was 51.66 ± 31.68 ml/min/1.73m2. All creatinine-based eGFR equations overestimated GFR (p < 0.01 for each creatinine based eGFR equation). However, eGFR by CKD-EPICys was not significantly different from mGFR (p = 0.38). The CKD-EPICys exhibited lowest bias [mean bias: −3.53 ± 14.70 ml/min/1.73m2 (95% CI: -0.608 to −0.98)] and highest accuracy (P30: 74.6%). The GFR in the healthy population was 79.44 ± 20.19 (range: 41.90–134.50) ml/min/1.73m2.ConclusionExisting creatinine-based GFR estimating equations overestimate GFR in Indians. An appropriately powered study is needed to develop either a correction factor or a new equation for accurate assessment of kidney function in the Indian population.

Peritoneal Protein Losses Depend on More Than Just Peritoneal Dialysis Modality and Peritoneal Membrane Transporter Status.

Peritoneal protein clearance (PPCl) depends upon vascular supply and size selective permeability. Some previous reports suggested PPCl can distinguish fast peritoneal membrane transport due to local or systemic inflammation. However, as studies have been discordant, we wished to determine factors associated with an increased PPCl. Consecutive patients starting peritoneal dialysis (PD) who were peritonitis-free were studied. Data included a baseline peritoneal equilibration test (PET), measurement of dialysis adequacy, 24-h dialysate PPCl and body composition measured by multifrequency bioimpedance. 411 patients, mean age 57.2 ± 16.6 years, 60.8% male, 39.4% diabetic, 20.2% treated by continuous ambulatory peritoneal dialysis (CAPD) were studied. Mean PET 4-h Dialysate/Serum creatinine was 0.73 ± 0.13, with daily peritoneal protein loss 4.6 (3.3-6.4) g, and median PPCl 69.6 (49.1-99.6) mL/day. On multivariate analysis, PPCl was most strongly associated with CAPD (β 0.25, P < 0.001), extracellular water (ECW)/total body water (TBW) ratio (β 0.21, P < 0.001), skeletal muscle mass index (β 0.21, P < 0.001), log N-terminal brain natriuretic peptide (NT-proBNP) (β 0.17, P = 0.001), faster PET transport (β 0.15, P = 0.005), and normalized nitrogen appearance rate (β 0.13, P = 0.008). In addition to the longer dwell times of CAPD, greater peritoneal creatinine clearance and faster PET transporter status, we observed an association between increased PPCl and ECW expansion, increased NT-proBNP, estimated dietary protein intake and muscle mass, suggesting a link to sodium intake and sodium balance, increasing both ECW and conduit artery hydrostatic pressure resulting in greater vascular protein permeability. This latter association may explain reports linking PPCl to patient mortality.