Gut Microbiome in Chronic Kidney Disease.

With over 100 trillion microbial cells, the gut microbiome plays important roles in both the maintenance of health and the pathogenesis of disease. Gut microbiome dysbiosis, resulted from alteration of composition and function of the gut microbiome and disruption of gut barrier function, is commonly seen in patients with chronic kidney disease (CKD). The dysbiotic gut microbiome generates excessive amounts of uremic toxins, and the impaired intestinal barrier permits translocation of these toxins into the systemic circulation. Many of these uremic toxins have been implicated in the progression of CKD and increased cardiovascular risk. Various therapeutic interventions have been proposed that aim to restore gut microbiome symbiosis. If proven effective, these interventions will have a significant impact on the management of CKD patients. In this review, we discuss the consequences of gut microbiome dysbiosis in the context of CKD, discuss the consequences of gut dysbiosis, and highlight some of the recent interventions targeting the gut microbiome for therapeutic purposes.

A systems analysis of age-related changes in some cardiac aging traits.

Aging process or senescence affects the expression of a wide range of phenotypic traits throughout the life span of organisms. These traits often show modular, synergistic, and even antagonistic relationships, and are also influenced by genomic, developmental, physiological and environmental factors. The cardiovascular system (CVS) in humans represents a major modular system in which the relationships among physiological, anatomical and morphological traits undergo continuous remodeling throughout the life span of an individual. Here we extend the concept of developmental plasticity in order to study the relationships among 14 traits measured on 3,412 individuals from the Framingham Heart Study cohort, relative to age and gender, using exploratory structural equation modeling-a form of systems analysis. Our results reveal differing patterns of association among cardiac traits in younger and older persons in both sexes, indicating that physiological and developmental factors may be channeled differentially in relation to age and gender during the remodeling process. We suggest that systems approaches are necessary in order to understand the coordinated functional relationships among traits of the CVS over the life course of individuals.

Interleukin-6 modulates hepatic and muscle protein synthesis during hemodialysis.

Increased demand for amino acids to sustain acute-phase protein synthesis could be the stimulus for the increased muscle protein catabolism during hemodialysis (HD). This could be attenuated by intradialytic amino-acid infusion. To test this, we measured the fractional synthesis rates of albumin, fibrinogen, and muscle protein in eight patients with end-stage renal disease at baseline before dialysis and during HD without or with amino-acid infusion. The percentage change in the fractional synthesis rates of albumin, fibrinogen, and muscle protein from baseline was significantly higher during HD with amino-acid infusion than without amino-acid infusion. Leg muscle proteolysis was significantly increased during unsupplemented HD compared with baseline, but this was not decreased by amino-acid infusion. Arteriovenous balance studies across the leg showed a net efflux of interleukin-6 (IL-6) from the muscle into the vein during HD. The fractional synthesis rate of albumin, fibrinogen, and muscle protein correlated with each other and with the IL-6 efflux from the leg. Leg muscle protein catabolism was positively related to IL-6 release from the leg and not associated with amino-acid availability. Our results show that intradialytic cytokine activation and not amino-acid depletion is the major protein catabolic signal during HD.

Bioremediation of contaminated lake sediments and evaluation of maturity indicies as indicators of compost stability.

Land contamination is one of the widely addressed problems, which is gaining importance in many developed and developing countries. International efforts are actively envisaged to remediate contaminated sites as a response to adverse health effects. Popular conventional methodologies only transfer the phase of the contaminant involving cost intensive liabilities besides handling risk of the hazardous waste. Physico-chemical methods are effective for specific wastes, but are technically complex and lack public acceptance for land remediation. iBioremediatio nî, is one of the emerging low-cost technologies that offer the possibility to destroy various contaminants using natural biological activities. Resultant non-toxic end products due to the microbial activity and insitu applicability of this technology is gaining huge public acceptance. In the present study, composting is demonstrated as a bioremediation methodology for the stabilization of contaminated lake sediments of Hyderabad, A.P, India. Lake sediment contaminated with organics is collected from two stratums--upper (0.25 m) and lower (0.5m) to set up as Pile I (Upper) and Pile II (Lower) in the laboratory. Lime as a pretreatment to the lake sediments is carried out to ensure metal precipitation. The pretreated sediment is then mixed with organic and inorganic fertilizers like cow dung, poultry manure, urea and super phosphate as initial seeding amendments. Bulking agents like sawdust and other micronutrients are provided. Continuous monitoring of process control parameters like pH, moisture content, electrical conductivity, total volatile solids and various forms of nitrogen were carried out during the entire course of the study. The stability of the compost was evaluated by assessing maturity indices like C/N, Cw (water soluble carbon), CNw (Cw/Nw), nitrification index (NH4/NO-3), Cation Exchange Capacity (CEC), germination index, humification ratio, compost mineralization index (ash content/oxidizable carbon), sorption capacity index (CEC/oxidizable carbon). Enzyme activities of agricultural interest like urease, phosphatase, P-glucosidase, dehydrogenase and BAA-hydrolyzing protease, which are involved in the nitrogen, phosphorus and carbon cycles, were also assessed. Total content of macro and micronutrients in the final compost was also determined to assess the fertilizer value. The studies revealed that composting could be applied as a remediation technology after removing the top sediment. The maturity indices that are evaluated from the present study can be used to validate the success of the remediation technology.

Hybrid dialysis: recirculation peritoneal dialysis revisited.

In a crossover trial, eight patients were studied during one treatment each of automated peritoneal dialysis (APD) and hybrid dialysis (HyD). During HyD, a fixed quantity of peritoneal dialysis fluid (PDF) was continuously removed at a flow rate of 141.3 +/- 23. 7 mL/min, dialyzed against the secondary dialysate (250 +/- 53.5 mL/min) generated by the hemodialysis delivery system with single-needle dialysis capability, and the regenerated PDF (PDF(HyD)) was reinfused into the peritoneal cavity. Despite using a smaller volume (6,195 +/- 737 versus 13,321 +/- 1,201 mL; P < 0. 0001) of PDF(HyD) with a lower glucose concentration (729 +/- 562 versus 1,659 +/- 373 mg/dL; P < 0.0001) and osmolality (331 +/- 79 versus 387 +/- 184 mOsm/kg; P < 0.001) during HyD compared with APD (PDF(APD)), weight loss was similar with both treatments (1.4 +/- 1. 0 versus 1.6 +/- 1.2 kg). Lactate levels were lower (3.2 +/- 2.5 versus 11.4 +/- 5.4 mEq/L), but pH (7.5 +/- 1.3 versus 5.6 +/- 0.9; P < 0.001) and bicarbonate concentration (22.6 +/- 8.0 versus 11.9 +/- 7.9 mEq/L; P < 0.0001) were greater in PDF(HyD) than PDF(APD). Although the mean dialysate calcium level was lower (6.0 +/- 0.5 versus 6.9 +/- 1.1 mg/dL; P < 0.001) in PDF(HyD), it was more stable throughout the dialysis compared with PDF(APD). A steeper concentration gradient between the blood and dialysate resulted in greater clearance of urea (26.5 +/- 9.1 versus 11.0 +/- 4.7 mL/min; P = 0.04), creatinine (24.1 +/- 11.4 versus 12.0 +/- 7.9 mL/min; P = 0.03), phosphate (19.2 +/- 4.3 versus 9.8 +/- 7.2 mL/min; P = 0.01), and uric acid (15.6 +/- 6.9 versus 9.1 +/- 2.7 mL/min; P = 0.04) and a greater percentage of reduction in values for blood urea nitrogen (20.7% +/- 7.7% versus 11.6% +/- 5.5%; P = 0.02), serum creatinine (16.1% +/- 5.3% versus 6.6% +/- 3.0%; P < 0.001), phosphate (22.7% +/- 8.9% versus 9.8% +/- 4.5%; P = 0.004), and uric acid (15.8% +/- 2.9% versus 6.3% +/- 3.4%; P < 0.001) during HyD than APD. To conclude, HyD is a novel dialytic technique that uses biocompatible bicarbonate-based dialysate to achieve excellent clearance of uremic toxins and ultrafiltration with minimal glucose load.

Advanced glycation end products: a Nephrologist's perspective.

Advanced glycation end products (AGEs) are a heterogeneous group of molecules that accumulate in plasma and tissues with advancing age, diabetes, and renal failure. There is emerging evidence that AGEs are potential uremic toxins and may have a role in the pathogenesis of vascular and renal complications associated with diabetes and aging. AGEs are formed when a carbonyl of a reducing sugar condenses with a reactive amino group in target protein. These toxic molecules interact with specific receptors and elicit pleiotropic responses. AGEs accelerate atherosclerosis through cross-linking of proteins, modification of matrix components, platelet aggregation, defective vascular relaxation, and abnormal lipoprotein metabolism. In vivo and in vitro studies indicate that AGEs have a vital role in the pathogenesis of diabetic nephropathy and the progression of renal failure. The complications of normal aging, such as loss of renal function, Alzheimer's disease, skin changes, and cataracts, may also be mediated by progressive glycation of long-lived proteins. AGEs accumulate in renal failure as a result of decreased excretion and increased generation resulting from oxidative and carbonyl stress of uremia. AGE-modified beta(2)-microglobulin is the principal pathogenic component of dialysis-related amyloidosis in patients undergoing dialysis. Available dialytic modalities are not capable of normalizing AGE levels in patients with end-stage renal disease. A number of reports indicated that restoration of euglycemia with islet-cell transplantation normalized and prevented further glycosylation of proteins. Aminoguanidine (AGN), a nucleophilic compound, not only decreases the formation of AGEs but also inhibits their action. A number of studies have shown that treatment with AGN improves neuropathy and delays the onset of retinopathy and nephropathy. N-Phenacylthiazolium bromide is a prototype AGE cross-link breaker that reacts with and can cleave covalent AGE-derived protein cross-links. Thus, there is an exciting possibility that the complications of diabetes, uremia, and aging may be prevented with these novel agents.

In search of ideal hemodialysis: is prolonged frequent dialysis the answer?

Advances in technology have made it possible to deliver a high Kt/V in a shorter time. The realization that duration of dialysis may be an important predictor of survival independent of dialysis dose has resulted in the popularity of prolonged slow dialysis (PHD). The longer duration and increased frequency of dialysis achieve excellent small- and middle-molecular weight solute clearance and also attenuate the peak concentration of uremic toxins. The slow dialysis process enables the equilibration of tissue and vascular compartments, resulting in better clearance and decreased postdialysis rebound increase in solutes. Gentle, persistent ultrafiltration allows the control of hypertension with minimal antihypertensive use. The intense and more frequent dialysis improves appetite and permits liberalization of diet. This greater dietary protein intake results in a progressive increase in serum albumin level and dry weight. Nocturnal hemodialysis achieves control of hyperphosphatemia without phosphate binders and a significant reduction in serum beta(2)-microglobulin levels. Normalization of extracellular volume, better clearance of uremic toxins, and improved nutrition result in a significant improvement in survival. The flexible time schedule with home hemodialysis and improvement of sleep and neurocognitive function allow better rehabilitation. The available evidence indicates PHD may be closer to the concept of an ideal dialysis, but there is lingering uncertainty about the consequence of prolonged immune stimulation, catabolism, and loss of essential solutes with these therapies.

Is peritoneal dialysis a good option for black patients?

Blacks are less likely than whites to use peritoneal dialysis (PD) as the initial renal replacement therapy. The reason for the underusage of PD by blacks is unknown. In a cross-sectional multicenter trial, we studied peritoneal transport character, small-molecular-weight solute clearances, and nutritional status in 475 patients undergoing PD (168 whites, 192 blacks, and 115 Asians). The mean age of blacks undergoing PD was significantly younger than that of whites (47.6 +/- 14.7 v 58.2 +/- 16.7 years; P < 0.0001). Target Kt/V and weekly creatinine clearance (WCC) as defined by the Dialysis Outcome Quality Initiative Work Group was achieved by 62.5% of whites, 67.2% of blacks, and 54.8% of Asians (P = 0.05). Total protein (7.25 +/- 0.88 v 6.55 +/- 0.73 g/dL), albumin (3.72 +/- 0.57 v 3.55 +/- 0.53 g/dL), and lean body mass (LBM; 41.7 +/- 15.6 v 33.0 +/- 11.8 kg) were lower in whites compared with blacks (P < 0.001). Although the normalized protein catabolic rate (nPCR) was greater (0.82 +/- 0.24 v 0.90 +/- 0.32 g/kg/d; P = 0.04), total protein (6.24 +/- 0.85 g/dL) and serum albumin levels (3.36 +/- 0.52 g/dL) and LBM (30.1 +/- 8.0 kg) were significantly lower in Asians than blacks (P < 0.0001). The favorable anabolic response in blacks may partially be explained by a higher calorie intake in this group of patients (29.6 +/- 10.7 Cal/kg/d) compared with whites (22.4 +/- 6.8 Cal/kg/d) and Asians (23.9 +/- 9.8 Cal/kg/d; P = 0.03). Multiple regression analysis identified that black race and weight were positively associated, whereas dialysate/plasma creatinine ratio (D/P(Creat)) and age had a negative effect on serum albumin level. Follow-up data indicated that the Kt/V (2.09 +/- 0.50 v 2.39 +/- 0.56; P = 0.02) and WCC (60.8 +/- 4.3 v 70.2 +/- 7.3 L/1.73 m2; P = 0.02) increased significantly from baseline only in blacks. We conclude that PD is an ideal renal replacement therapy in at least a subset of blacks with end-stage renal disease.

Fractionation studies and bioaccumulation of sediment-bound heavy metals in Kolleru lake by edible fish.

Kolleru lake is the largest fresh water lake in the districts of East and West Godavari of Andhra Pradesh, India. Many anthropogenic sources contribute to the heavy metal pollution in the lake and the bioaccumulation of heavy metals in fish helps in assessing the aquatic pollution. Total contents and fractionation of selected heavy metals, viz., Zn, Cu, Cd, Pb, Cr, Ni and Co were measured in sediment sample and three edible fish. The investigation aimed at revealing differences in the accumulation pattern of heavy metals in fish inhabiting sediments characterized by varying metal bioavailability. The metal concentrations were found to be greater than the background concentrations of sediments indicating the anthropogenic origin of metals. Good recovery values were obtained for metal contents in sediments and fish. Large fractions of Zn, Cd and Cu were associated with mobile fraction of sediment and showed greater bioaccumulation in fish whereas Ni and Co were least mobilisable. The results clearly indicate that the fish of Kolleru lake are contaminated with metals and not advisable for human consumption.

Blood urea levels 30 minutes before the end of dialysis are equivalent to equilibrated blood urea.

The steady decline in blood urea during high efficiency hemodialysis is followed by a rebound phase after dialysis in which the level of urea rises to an equilibrium value (Ct + 30) that may be up to 20% higher than the immediate post dialysis (Ct) concentration. The artificially low urea concentration immediately after dialysis leads to an overestimate of the efficiency of the dialysis calculated by Kt/V if the true equilibrium blood concentration of urea is not used in the calculation by the single-pool urea kinetic model. The measurement of equilibrium urea concentration requires a blood sample approximately 30 min after hemodialysis, which is an encumbrance on dialysis patients. This study was undertaken to determine whether an intradialytic sample taken 30 min before the end of dialysis (Ct - 30) may be representative of the equilibrium sample, and to compare the Kt/V using the Ct - 30 and Ct + 30 samples. Thirty-six patients were studied and blood urea concentrations were measured half an hour before the end of dialysis (Ct - 30), at the end of dialysis (Ct), and half an hour after the end of dialysis (Ct + 30). Kt/V (Daugirdas method) was calculated using urea concentration 30 min before the end of dialysis (Kt/Vt - 30) and was compared with Kt/V calculated using equilibrium urea concentration (Kt/Vt + 30). There were no significant differences between the Kt/Vt - 30 and the KtVt + 30 (1.25 versus 1.22, p = 0.65). The correlation between Kt/Vt - 30 and Kt/Vt + 30 was excellent with r2 = 0.93, regression y = 1.05 x -0.033. Kt/Vt - 30 also compared favorably with the Kt/V double pool method (Kt/Vdp) described by Daugirdas (1.25 versus 1.19, p = 0.23). Using the Ct - 30 to calculate Kt/V by the percent urea reduction methods of jindal (Kt/Vpru) decreases the Kt/V value by 0.14 on average, but it remains significantly higher than the Daugirdas method. The authors conclude that calculations using urea concentration 30 min before the end of dialysis improves the accuracy of dose estimation in high efficiency dialysis, without inconveniencing the patient.

Quantitating dialysis using two dialysate samples: a simple, practical and accurate approach for evaluating urea kinetics.

Urea kinetics is now widely used to determine the adequacy of dialysis. Several simplified formulae are currently in use but only a few have been accepted into clinical practice because of their simplicity and ease of calculation. A recent analysis of these formulae showed that for the same set of blood urea values the calculated Kt/V can range from 1.0 to 1.5. We have developed a new dialysate-based method (2DSM) to estimate the urea kinetic parameters using dialysate and blood samples taken at the beginning and at the end of dialysis. The total urea removed (TUR) was calculated from the geometric mean of the two dialysate samples, dialysate flow rate and the duration of dialysis. The Watson formula was used to determine the volume of distribution of urea. A comparison of the 2DSM and the direct dialysate quantification (DDQ) method showed the following results (mean +/- sd, n = 52): for total urea removal (TUR) 697 +/- 32 vs 722 +/- 37 mmol (p = 0.6, r2 = 0.928, y = 101 + 0.83 x, mean difference 25 +/- 76 mmol, see Bland-Altman plot), dialysate urea concentration (Durea) 5.55 +/- 0.25 vs 5.75 +/- 0.29 mmol/l (p = 0.6, r2 = 0.928, y = 0.8 + 0.82 x, mean difference 0.2 +/- 0.6 mmol, see Bland-Altman plot), dialyser clearance (K) 232 +/- 4.4 vs 235 +/- 5.6 ml/min (p = 0.54), Kt/V 1.42 +/- 0.04 vs 1.51 +/- 0.04 (p = 0.21), volume of distribution of urea (Vd) 40.14 +/- 1.04 vs 38.74 +/- 1.2 L, (p = 0.38), and PCR 64.6 +/- 2.6 vs 68.1 +/- 3.1 g/day. We have developed a simple method of determining dialysate-based urea kinetics which requires two dialysate samples, one at the beginning and one at the end of dialysis and a blood sample at the midpoint of dialysis. TUR can be calculated using the dialysate flow rate and the dialysis duration and once this is known all the other kinetic parameters can be calculated.

Mass balance index: an index for adequacy of dialysis and nutrition.

Determining adequacy of dialysis has remained a problem for the nephrologist despite the results of the National Cooperative Dialysis Study published more than 20 years ago. Urea Kinetics Modelling (UKM) which requires computer data entry is time-consuming for the dialysis staff but is the only method that has been rigorously studied. Furthermore, it is unclear today what value of Kt/V represents ideal dialysis; the technique is subject to a number of errors associated with estimation of dialyser clearance (K) and volume of distribution of urea (V) but it is useful for calculating protein catabolic rate (PCR). Methods that use urea reduction ratios (URR) is widely used because it is simpler but not always accurate and suffer from an inability to calculate PCR. Direct dialysis quantification (DDQ) can overcome a number of these problems but it is too cumbersome for routine use. Simpler methods to determine dialysateside kinetics have the advantage of solving a number of these problems and also facilitate the calculation of PCR to determine the patient's nutritional state. In our study we have demonstrated that by taking two dialysate samples at the beginning and at the end of dialysis (2-DSM), it is possible to determine total urea removal (TUR) which is equivalent to DDQ. By taking blood samples after dialysis and before the next dialysis, it is possible to calculate the total urea generated (TUG). The ratio of TUR/TUG will provide an index of dialysis which places emphasis on removal of solute that has accumulated in the inter-dialytic interval thus re-establishing a state of equilibrium. We refer to this index as the Mass Balance Index (MBI). The MBI is also useful in helping to identify those patients whose PCR is inadequate since the mean MBI for patients with an nPCR <0.8 was 0.93 +/- 0.03 vs 1.08 +/- 0.02 in those with a PCR >0.8. In these two groups of patients the Kt/V was not significantly different, 1.49 +/- 0.07 vs 1.53 +/- 0.06, p -0.64. We suggest that the emphasis for adequacy of dialysis should shift away from Kt/V to maintaining a state of equilibrium by removing the solutes that accumulate between dialysis and by identifying those patients with an inadequate PCR.

Optimal cyclosporine therapy--an Indian experience.

Thirty consecutive adult patients who underwent renal transplantation were prospectively studied. The immunosuppression consisted of cyclosporine, azathioprine and prednisolone. Oral Cyclosporine CyA was initiated at a dose of 7 mg/kg/Day and reduced by 1 mg/kg/month. Blood level of CyA was monitored by monoclonal RIA (Cyclo-Trac-NS) method on 3rd, 10th, 30th, 60th, 90th and 180th days. The dose was titrated according to the blood level and the renal function. In spite of progressive reduction in the dose of CyA, the blood level did not show any significant change, probably because of increased absorption or decreased metabolism. Though the percentage change in CyA dose was significant, the CyA level and serum creatinine remained relatively stable during the follow up period. Our patients required relatively lesser dose to achieve optimum blood level. Though the blood level of CyA ranged between 387 and 2120 ng/dL. There was no evidence of rejection or irreversible nephrotoxicity.

Mitochondrial function in physically active elders with sarcopenia.

Physical activity is reported to protect against sarcopenia and preserve mitochondrial function. Healthy normal lean (NL: n=15) and sarcopenic (SS: n=9) participants were recruited based on body composition (DXA, Lunar DPX), age, and physical activity. Gastrocnemius mitochondrial function was assessed by (31)P MRS using steady-state exercise in a 4T Bruker Biospin. Total work (429.3+/-160.2J vs. 851.0+/-211.7J, p<0.001) and muscle volume (p=0.006) were lower in SS, although these variables were not correlated (NL r=-0.31, p=0.33, SS r=(0.03, p=0.93). In the SS resting ATP/ADP was lower (p=0.03) and ATP hydrolysis higher (p=0.02) at rest. Free energy ATP hydrolysis was greater at the end of exercise (p=0.02) and [ADP] relative to total work output was higher in SS (ANCOVA, p=0.005). [PCr] recovery kinetics were not different between the groups. Adjusting these parameters for differences in total work output and muscle volume did not explain these findings. These data suggest that aerobic metabolism in physically active older adults with sarcopenia is mildly impaired at rest and during modest levels of exercise where acidosis was avoided. Muscle energetics is coordinated at multiple cellular levels and further studies are needed to determine the loci/locus of energy instability in sarcopenia.

Cytokine gene polymorphism and progression of renal and cardiovascular diseases.

Cytokines are important modulators of inflammation. The balance between pro- and anti-inflammatory cytokines determines whether the intensity of inflammatory response is within physiological limits or in the pathological range. The cytokine network is highly complex, containing interactive cascades of gene activation and suppression. Both chronic kidney disease (CKD) and end-stage renal disease (ESRD) are characterized by elevated levels of proinflammatory cytokines and markers of inflammation. Cytokines may modulate the risk for progression of renal disease and the susceptibility to cardiovascular disease (CVD). Polymorphisms of cytokine genes may influence gene transcription and cytokine secretion and thereby modulate the risk of progression of renal and CVDs. The observed inconsistencies in the data regarding associations between single-nucleotide gene polymorphisms (SNPs) and their presumed phenotypic expression emphasize the need to recognize several conceptual and methodological aspects such as haplotypic rather than single SNP variations and the influence of pathway genes with synergistic or antagonistic effects that ultimately determine the phenotype. It is conceivable that when a patient with a high-risk cytokine genotype develops CKD, the risk for CVD is increased. Early interventions in CKD patients with high-risk genotypes may slow the progression of renal disease and also decrease CV mortality and morbidity.

Haemodialysis induces mitochondrial dysfunction and apoptosis.

BACKGROUND: Mitochondria play a crucial role in the regulation of the endogenous pathways of apoptosis activated by oxidant stress. Nuclear factor-kappaB (NF-kappaB) is a central integration site for pro-inflammatory signals and oxidative stress. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from eight end-stage renal disease (ESRD) patients before haemodialysis (Pre-HD) and during the last 10 min of HD (End-HD). A new polysulfone membrane (F70, Fresenius) was used for dialysis. Intracellular generation of reactive oxygen species (ROS), mitochondrial redox potential (Deltapsim) and PBMC apoptosis were determined by flow-cytometry. RESULTS: Plasma levels of interleukin-6 (IL-6) (24.9+/-7.0 vs. 17.4+/-5.5 pg dL(-1), P<0.05), IL-6 soluble receptor (52.2+/-4.9 vs. 37.6+/-3.2 ng dL(-1), P<0.02) and IL-6 gp130 (405.7+/-41.0 vs. 235.1+/-38.4 ng dL(-1), P<0.02) were higher end-HD compared to pre-HD. IL-6 secretion by the isolated PBMC (24.0+/-2.3 vs. 19.3+/-3.5 pg dL(-1), P<0.02) increased end-HD. Percentage of lymphocytes exhibiting collapse of mitochondrial membrane potential (43.4+/-4.6% vs. 32.6+/-2.9%, P<0.01), apoptosis (33.4+/-7.1% vs. 23.7+/-7.7%, P<0.01), and generation of superoxide (20.7+/-5.2% vs. 12.5+/-2.9%, P<0.02) and hydrogen peroxide (51.1+/-7.8% vs.38.2+/-5.9%, P<0.04) were higher at end-HD than pre-HD. NF-kappaB activation (3144.1+/-208.1 vs. 2033.4+/-454.6 pg well(-1), P<0.02), expression of B-cell lymphoma protein-2 (6494.6+/-1461 vs. 3501.5+/-796.5 ng mL(-1), P<0.03) and heat shock protein-70 (9.81+/-1.47 vs. 6.38+/-1.0 ng mL(-1), P<0.05) increased during HD. CONCLUSIONS: Intra-dialytic activation of cytokines, together with impaired mitochondrial function, promotes generation of ROS culminating in augmented PBMC apoptosis. There is concomitant activation of pathways aimed at attenuation of cell stress and apoptosis during HD.

Ethnic variability in peritoneal equilibration test and urea kinetics.

The influence of ethnicity on peritoneal permeability and the adequacy of peritoneal dialysis was studied in 202 end-stage renal failure patients on peritoneal dialysis. Patients were classified into whites, Orientals, blacks, and a miscellaneous group consisting of East Indians, Persians, and others whose ethnicity was unknown. The patients were on peritoneal dialysis for a mean period of 29.1 +/- 15.8 months before the study. All patients underwent a peritoneal equilibration test with 24-hour urine and dialysate collection. The kinetic parameters were calculated using commercial software (PD Adequest; Baxter Healthcare, Round Lake, IL). The mean volume of exchange, weekly Kt/V, and weekly creatinine clearance were comparable in the different ethnic groups, but the normalized protein catabolic rate was significantly higher in the Orientals (P = 0.03). The high transporters tended to be males with a large body surface area and in the older age group. The low transporters achieved a higher Kt/V than those in the other transport groups (2.3 +/- 0.4 v 2.06 +/- 0.52; P = 0.015). The women had a significantly higher Kt/V than the men (2.16 +/- 0.43 v 1.93 +/- 0.59; P < 0.01). Repeat peritoneal equilibration test was done after a mean duration of 10.5 +/- 4.9 months in 33 patients. Although the mean exchange volume (8.37 +/- 0.83 v 9.32 +/- 1.72; P = 0.003) increased significantly, weekly creatinine clearance (62.3 +/- 25.6 L/1.73 m2 to 63.1 +/- 18.3 L/1.73 m2; P < 0.05) and other kinetic parameters did not change markedly with duration. There was a tendency for the patients to move from the extreme transport groups to the average category with duration.

Plasma amino acid profile on nocturnal hemodialysis.

BACKGROUND/AIMS: The purpose of this study was to examine the effect of nocturnal hemodialysis (NHD) on serum amino acid (AA) profile. METHODS: In a cross-over trial, we studied the AA profile in 11 patients who were switched from conventional hemodialysis to NHD. Plasma levels of AA were measured at monthly intervals for a period of 1 year. RESULTS: Concentrations of AA isoleucine, threonine, phenylalanine, valine, glycine, glutamine and taurine increased on switch to NHD. Total AA (2,907.2 +/- 542.2 vs. 3,870.2 +/- 715.2 micromol/l, p = 0.03), essential AA (EAA, 842.2 +/- 259.4 vs. 1,125. 8 +/- 235.3 micromol/l, p = 0.03), nonessential AA (NEAA, 2,307.2 +/- 399.1 vs. 2,879.5 +/- 581.2 micromol/l, p = 0.03), and branched chain AA (315.5 +/- 90.8 vs. 386.0 +/- 114.3 micromol/l, p = 0.05) concentrations were significantly higher on NHD. However, abnormalities in the ratios of EAA/NEAA, valine/glycine and tyrosine/phenylalanine persisted during NHD. CONCLUSIONS: NHD alleviated some abnormalities in the aminogram of uremia, but other metabolic derangements lingered.

beta(2)-microglobulin kinetics in nocturnal haemodialysis.

BACKGROUND: beta(2)-Microglobulin (beta(2)m) is a major component of dialysis-related amyloidosis. The available therapeutic options do not permit normalization of the serum beta(2)m level. In a cross-over trial, we studied the kinetics of beta(2)m during two different dialytic techniques. METHODS: Ten stable, anuric end-stage renal disease patients were studied during two consecutive weeks of three conventional (CHD) and six nocturnal haemodialysis (NHD) sessions. CHD was performed for 4 h three times weekly using a polysulfone dialyser (F80, surface area of 1.8 m(2)) with a mean blood and dialysate flow rate of 401+/-91.6 and 514+/-10.9 ml/min, respectively. The NHD was done with a smaller dialyser (F40, surface area of 0.7 m(2)) and lower blood (281+/-17 ml/min) and dialysate flow rates (99+/-1.2 ml/min) for 8 h, six nights a week. RESULTS: Weekly removal of urea (51.6+/-24.6 vs 43.1+/-20.5 g) and creatinine (8501+/-5204 vs 6319+/-4134 mg) were comparable with the two modalities of dialysis but the mass of beta(2)m removed was significantly higher with NHD (127+/-48 vs 585+/-309 mg, P<0.001), with a percentage reduction in serum level of 20.5+/-5.8 vs 38.8+/-7. 1% (P<0.0001) and a Kt/V(beta2m) of 0.21+/-0.09 vs 0.56+/-0.17 (P<0. 0006). The mean post-dialysis beta(2)m (20.8+/-6.3 vs 14.0+/-3.8 mg/dl, P=0.02), Tac(beta2m) (26.2+/-5.2 vs 19.8+/-3.8 mg/dl, P=0.02) and pre-dialysis beta(2)m (beta(2)m(pre)) at the end of 1 week of therapy (24.4+/-7.6 vs 19.0+/-3.4 mg/dl, P=0.02) were lower with NHD. Long-term follow-up data were available in 13 and seven patients at the end of 1 and 2 years, respectively. Serum beta(2)m(pre) levels progressively declined from 27.2+/-11.7 mg/dl at initiation of NHD to 13.7+/-4.4 mg/dl by 9 months, and they remained stable thereafter. CONCLUSIONS: NHD provides a much higher clearance of beta(2)m than CHD, leading to a long-term decrease in the pre-dialysis concentration of beta(2)m.