Ilia Beberashvili

Serum uric acid as a clinically useful nutritional marker and predictor of outcome in maintenance hemodialysis patients

OBJECTIVE The importance of serum uric acid (SUA) for the maintenance of a hemodialysis (MHD) population has not been well established. The aim of this study was to determine if SUA levels are associated with nutritional risk and consequently with adverse clinical outcomes in MHD patients. METHODS This was a 2-y prospective observational study, performed on 261 MHD outpatients (38.7% women) with a mean age of 68.6 ± 13.6 y. We measured prospective all-cause and cardiovascular (CV) hospitalization and mortality, nutritional scores (malnutrition-inflammation score [MIS) and geriatric nutritional risk index (GNRI), handgrip strength (HGS), and short-form 36 (SF36) quality-of-life (QoL) scores. RESULTS SUA positively correlated with laboratory nutritional markers (albumin, creatinine), body composition parameters, HGS (r = 0.26; P < 0.001) and GNRI (r = 0.34; P < 0.001). SUA negatively correlated with MIS (r = -0.33; P < 0.001) and interleukin-6 (r = -0.13; P = 0.04). Patients in the highest SUA tertile had higher total SF-36 scores (P = 0.04), higher physical functioning (P = 0.003), and role-physical (P = 0.006) SF-36 scales. For each 1 mg/dL increase in baseline SUA levels, the first hospitalization hazard ratio (HR) was 0.79 (95% confidence interval [CI], 0.68-0.91) and first CV event HR was 0.60 (95% CI, 0.44-0.82); all-cause death HR was 0.55 (95% CI, 0.43-0.72) and CV death HR was 0.55 (95% CI, 0.35-0.80). Associations between SUA and mortality risk continued to be significant after adjustments for various confounders including MIS and interleukin-6. Cubic spline survival models confirmed the linear trends. CONCLUSIONS In MHD patients, SUA is a good nutritional marker and associates with body composition, muscle function, inflammation, and health-related QoL, upcoming hospitalizations, as well as independently predicting all-cause and CV death risk.

IL-6 Levels, Nutritional Status, and Mortality in Prevalent Hemodialysis Patients

BACKGROUND AND OBJECTIVES The influence of serum IL-6 levels on nutritional status in chronic hemodialysis (HD) patients remains to be elucidated. The present report describes a prospective longitudinal study of IL-6 levels and nutritional parameters to determine whether high IL-6 levels are independently associated with nutritional status over time in a cohort of prevalent hemodialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 85 clinically stable hemodialysis patients (37.6% women), with a mean age of 66.5 ± 10.6 years, were studied after exclusion of patients with BMI < 20 kg/m(2) and/or serum albumin <35 g/L. IL-6, dietary energy and protein intake, and biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18, and 24 months following enrollment. Observation of this cohort was continued over 2 additional years. RESULTS IL-6 levels increased with time in both unadjusted (linear estimate: 2.57 ± 0.44 pg/ml per 2 yrs; P = 0.001) and adjusted models (linear estimate: 2.35 ± 0.57 pg/ml per 2 yrs; P = 0.049). Significant reductions of daily energy intake, laboratory markers (albumin, transferrin, cholesterol, creatinine), and body composition (fat mass) with higher IL-6 levels were observed over the duration of the longitudinal observation period. However, none of the studied parameters were associated with changes in IL-6 levels over time (IL-6-by-time interactions were NS). Furthermore, cumulative incidences of survival were correlated with the baseline serum IL-6 levels (P = 0.004 by log-rank test). Finally, for each pg/ml increase in IL-6 level, the hazard ratio for death from all causes was 1.06 (95% CI 1.01 to 1.10) after adjustment for demographic and clinical parameters. CONCLUSIONS Our results suggest that higher serum IL-6 levels are associated with all-cause mortality without additional changes in clinical and laboratory markers of nutritional status in clinically stable HD patients.

Longitudinal study of leptin levels in chronic hemodialysis patients

BackgroundThe influence of serum leptin levels on nutritional status and survival in chronic hemodialysis patients remained to be elucidated. We conducted a prospective longitudinal study of leptin levels and nutritional parameters to determine whether changes of serum leptin levels modify nutritional status and survival in a cohort of prevalent hemodialysis patients.MethodsLeptin, dietary energy and protein intake, biochemical markers of nutrition and body composition (anthropometry and bioimpedance analysis) were measured at baseline and at 6, 12, 18 and 24 months following enrollment, in 101 prevalent hemodialysis patients (37% women) with a mean age of 64.6 ± 11.5 years. Observation of this cohort was continued over 2 additional years. Changes in repeated measures were evaluated, with adjustment for baseline differences in demographic and clinical parameters.ResultsSignificant reduction of leptin levels with time were observed (linear estimate: -2.5010 ± 0.57 ng/ml/2y; p < 0.001) with a more rapid decline in leptin levels in the highest leptin tertile in both unadjusted (p = 0.007) and fully adjusted (p = 0.047) models. A significant reduction in body composition parameters over time was observed, but was not influenced by leptin (leptin-by-time interactions were not significant). No significant associations were noted between leptin levels and changes in dietary protein or energy intake, or laboratory nutritional markers. Finally, cumulative incidences of survival were unaffected by the baseline serum leptin levels.ConclusionsThus leptin levels reflect fat mass depots, rather than independently contributing to uremic anorexia or modifying nutritional status and/or survival in chronic hemodialysis patients. The importance of such information is high if leptin is contemplated as a potential therapeutic target in hemodialysis patients.

Role of IL-10 in the progression of kidney disease.

Interleukin-10 (IL-10), a cytokine with anti-inflammatory and immunomodulatory functions, regulates the biology of B and T cells. The present review describes the role of IL-10 in normal renal physiology, during acute kidney injury and in the development of chronic renal failure. We further discuss IL-10-induced cellular and molecular pathways and their link to the progression of kidney injury.

Nutritional and Inflammatory Status of Hemodialysis Patients in Relation to Their Body Mass Index

OBJECTIVE The study tested whether obese hemodialysis (HD) patients have a better nutritional and inflammatory state than those with overweight or normal body mass index (BMI). DESIGN This was a single-center, cross-sectional study. SETTING AND PATIENTS Ninety-six stable HD patients from a local HD unit were divided into 3 groups according to BMI (normal, overweight, and obese). MAIN OUTCOME MEASURES Anthropometry, body composition by multifrequency bioelectrical impedance analysis, biochemical nutritional markers, as well as interleukins (IL-1, IL-6, and IL-10), tumor necrosis factor, leptin, and soluble leptin receptor (sOB-R) were measured. RESULTS Serum creatinine was significantly elevated in the highest BMI category. Albumin and transferrin were significantly elevated in higher BMI groups after adjustment for age, sex, and diabetes status. The higher BMI group had greater lean body mass (P = .001) and fat mass (P = .0001), higher phase angle (PA), and lower extracellular mass-to-body-cell-mass ratio (ECM/BCM) (P < .05). Inflammatory cytokine levels were not different in the 3 BMI groups. In parallel with increasing BMI, a gradual increase in serum leptin and a trend for decreasing sOB-R were detected (P = .0001 and P = .055, respectively). Both PA (r = 0.295, P = .008) and ECM/BCM (r = -0.345, P = .002) significantly correlated with serum leptin concentration. According to a multiple linear regression analysis, with PA as the dependent variable, age (beta = 0.274, P = .008), creatinine (beta = 0.355, P = .001), and log sOB-R/leptin ratio (beta = -0.465, P = .008) were significant independent predictors of PA. CONCLUSION HD patients with elevated BMI demonstrate better nutritional status compared to normal BMI or overweight patients, whereas the severity of inflammation is not related to BMI in HD patients.

Mesangial cells initiate compensatory tubular cell hypertrophy.

Unilateral nephrectomy results in compensatory renal growth, in which both the size and the functional capacity of the remaining kidney are increased. The functional adaptation to the removal of the contralateral kidney consists mostly of an increase in the glomerular filtration rate of the remaining kidney, and hypertrophy of cells comprising the nephron, mainly of the proximal tubular cells. Although the phenomenon of single kidney hypertrophy has been known for the past thousand years and despite intensive research over the past century, the mechanism of this process still remains unclear. The present article reviews the role of mesangial cells in compensatory renal hypertrophy.

N-Acetylcysteine Improves Residual Renal Function in Peritoneal Dialysis Patients: A Pilot Study

♦ Background: Preservation of peritoneal membrane function and residual renal function is important for the optimal care of peritoneal dialysis patients. N-Acetylcysteine may ameliorate oxidative stress, which is thought to be involved in peritoneal membrane dysfunction. In addition, N-acetylcysteine may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. The aim of this study was to investigate the effect of N-acetylcysteine on peritoneal and residual renal function in peritoneal dialysis patients. ♦ Methods: Ten prevalent peritoneal dialysis patients were administered oral N-acetylcysteine 1200 mg twice daily for 4 weeks. At baseline and at the end of treatment, peritoneal membrane function and residual renal function were assessed using a 4.25% dextrose peritoneal equilibration test and 24-hour dialysate and urine collection for calculation of peritoneal and residual renal Kt/V and mean urea and creatinine residual renal clearance. ♦ Results: No significant changes were demonstrated in peritoneal membrane function, including dialysate-to-plasma creatinine ratio, sodium sieving, and net ultrafiltration. Residual renal function improved significantly: urine volume increased from 633 ± 426 to 925 ± 552 mL/24 hours (p = 0.022), residual renal Kt/V increased from 0.56 ± 0.41 to 0.75 ± 0.47 (p = 0.037), and mean residual urea and creatinine clearance increased from 4.96 ± 3.96 to 5.95 ± 4.08 mL/min/1.73 m2 (p = 0.059). ♦ Conclusions: N-acetylcysteine may improve residual renal function in patients treated with peritoneal dialysis.

The cyclin kinase inhibitor p57kip2 regulates TGF-β-induced compensatory tubular hypertrophy: effect of the immunomodulator AS101

BACKGROUND Compensatory tubular cell hypertrophy following unilateral nephrectomy is a cell cycle-dependent process. Our previous study showed that treatment of unilaterally nephrectomized rats with the immunomodulator AS101 partially inhibits compensatory hypertrophy of the remaining kidneys through the inhibition of IL-10-induced TGF-beta secretion by mesangial cells. The present study is focused on understanding the intracellular mechanism(s) of this phenomenon. METHODS A total of 120 male Sprague-Dawley rats were unilaterally nephrectomized or sham-operated and treated with AS101 or PBS. Kidney weight and protein/DNA ratio were assessed for each experimental animal. The expression of TGF-beta, PCNA, CDK 2, pRb, ppRb, p21(Waf1), p27(kip1) and p57(kip2) proteins in renal tissues was determined by western blot analysis and immunohistochemistry, and the immunoprecipitation of cyclin E complexes was performed. RESULTS Compensatory renal growth is initiated by proliferation of resident renal cells that precedes hypertrophy. Changes in TGF-beta expression were positively correlated with the amounts of p57(kip2), but not with p21(Waf1) and p27(kip1) expression in the remaining kidneys. Moreover, there was a marked abundance of p57(kip2) but not p21(Waf1) and p27(kip1) binding to the cyclin E complex in PBS-treated unilaterally nephrectomized rats compared to sham-operated animals. Treatment of uninephrectomized rats with AS101 reduced kidney weight and protein/DNA ratio, inhibited TGF-beta and p57(kip2) expression in the remaining kidneys, and decreased the level of p57(kip2) binding to cyclin E complexes. CONCLUSION These results demonstrate that TGF-beta-induced compensatory tubular cell hypertrophy is regulated in vivo by p57(kip2) but not by the p21(Waf1) and p27(kip1) cyclin kinase inhibitor proteins.

N‐acetylcysteine may improve residual renal function in hemodialysis patients: A pilot study

Clinical outcomes in chronic dialysis patients are highly dependent on preservation of residual renal function (RRF). N‐acetylcysteine (NAC) may have a positive effect on renal function in the setting of nephrotoxic contrast media administration. In our recent study, we showed that NAC may improve RRF in peritoneal dialysis patients. The aim of the present study was to investigate the effect of NAC on RRF in patients treated with chronic hemodialysis. Prevalent chronic hemodialysis patients with a residual urine output of at least 100 mL/24 hours were included. The patients were administered oral NAC 1200 mg twice daily for 2 weeks. Residual renal function was assessed at baseline and at the end of treatment using a midweek interdialytic urine collection for measurement of urine output and calculation of residual renal Kt/V and glomerular filtration rate (GFR). Residual GFR was measured as the mean of urea and creatinine residual renal clearance. Each patient served as his own control. Twenty patients were prospectively enrolled in the study. Administration of NAC 1200 mg twice daily for 2 weeks resulted in significant improvement in RRF: urine volume increased from 320 ± 199 to 430 ± 232 mL/24 hours (P < 0.01), residual renal Kt/V increased from 0.19 ± 0.12 to 0.29 ± 0.14 (P < 0.01), and residual GFR increased from 1.6 ± 1.6 to 2.4 ± 2.3 mL/minute/1.73 m2 (P < 0.01). N‐acetylcysteine may improve RRF in patients treated with chronic hemodialysis.

Effect of Timing of Thrombectomy on Survival of Thrombosed Arteriovenous Hemodialysis Grafts

Background: The use of an arteriovenous (AV) graft for hemodialysis is associated with a relatively high rate of thrombosis. Unfortunately, the urgent thrombectomy is not always readily available. Our aim was to investigate a possible association between the timing of thrombectomy and the patency rates of AV grafts. Methods: A retrospective single-center study on patients who underwent thrombectomy of clotted AV grafts was conducted. According to the time of thrombectomy, all patients were divided into 4 groups. Results: Primary graft patency at 6 months after thrombectomy was 28.3%, with no significant difference between the study groups (P = .161). Secondary graft patency at 6 months was significantly worse in the group that underwent thrombectomy between the third and fifth days than in the whole cohort: 15.4% versus 45.6% (P = .038). Conclusions: Timing of thrombectomy of a clotted AV graft may have a significant impact on the graft survival.