Evaluation of low-dose glucocorticoid regimen in association with cyclophosphamide in patients with glomerulonephritis.

BACKGROUND: The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis. METHODS: This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria < 0.3 g per 24 h (urinary protein-creatinine rate < 300 mg/g [< 30 mg/mmol]]; partial remission (proteinuria > 0.3 but < 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events. RESULTS: At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance. CONCLUSION: Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

The impact of periodontal disease on physical and psychological domains in long-term hemodialysis patients: a cross-sectional study.

PURPOSE: Periodontal disease is a chronic infectious disease. Individuals with end-stage kidney disease (ESKD) experience impaired quality of life (QoL) and low oral health. This is the first comprehensive study which aimed to explore the link between periodontal disease and quality of life, assessed with the Short Form 36-Item Health Survey in hemodialysis patients. METHODS: In total, 101 patients (57 females) with ESKD were recruited from two Romanian dialysis centers. Periodontal disease assessment included the measurement of periodontal disease index, with its three components: the gingival and periodontal index (GP), the bacterial plaque index (PI) and the calculus index (CI). For assessing QoL, we used the Short Form 36-Item Health Survey (SF-36), with its two components: physical component (PCS) and mental component (MCS). RESULTS: The mean age was 52.5 ± 14.3 years. The dialysis vintage was 6.7 ± 5.6 years. According to periodontal status, the mean value of GP was 4.0 ± 1.3, mean PI was 1.8 ± 0.9, and mean CI was 1.3 ± 0.7. Regarding the QoL, the means for PCS and MCS were 38.0 ± 17.3 and 45.0 ± 16.3, respectively. In univariate analysis, the physical and mental components of QoL were significantly associated with the gingival and periodontal index, the bacterial plaque index and the calculus index. In the multivariable linear regression, only the gingival and periodontal index remained significantly associated with physical component (ß = -3.26, p = 0.04, 95% CI -6.39 to -0.13) and mental component (ß = -5.57, p = 0.001, 95% CI -8.74 to -2.41) of QoL. CONCLUSION: Our study shows a high prevalence and severity of periodontal disease. The gingival and periodontal index was associated with low QoL, both on physical and on mental components.

Increased arterial stiffness predicts cognitive impairment in hemodialysis patients.

Introduction Cognitive impairment is a major, but underdiagnosed, risk factor for negative outcomes in patients with chronic kidney disease (CKD). The main goal of this study was to evaluate, for the first time, the relationship between arterial stiffness and cognitive impairment in a cohort of hemodialysis patients. Methods We prospectively analyzed the cognitive function and pulse wave velocity (PWV) of 72 hemodialysis patients, mean age 56.54 ± 13.96 y, from two Romanian dialysis centers. We administered to all patients the Mini Mental State Examination (MMSE), Trail Making Test Part-A (TMTA) and Part-B (TMTB), and Mini-Cog Test. Radial arterial waveforms during 40 cardiac cycles were recorded in each patient. Findings Mean MMSE score was 25.13 ± 3.47, mean MiniCog score was 3.51 ± 1.18, mean TMTA (sec) was 103.77 ± 53.13 and mean TMTB (sec) was 214.93 ± 112.25. In linear unadjusted regression, PWV values were associated with worse MMSE scores (ß = -0.36, P = 0.001, 95% CI: -0.68 to -0.17), and MiniCog scores (ß = -0.26, P = 0.02, 95% CI: -0.19 to -0.01). Also, PWV value was significant associated with TMTA test, but not with TMTB. After further adjustments, PWV remained a strong predictor for cognitive impairment measured by MMSE, TMTA, MiniCog, but not for TMTB. Discussion Cognitive impairment was associated with higher PWV values in our cohort. Further evidence is needed in order to support arterial stiffness as a long-term predictor for cognitive decline in ESRD patients.

Overhydration, Cardiac Function and Survival in Hemodialysis Patients.

BACKGROUND AND OBJECTIVES: Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). RESULTS: In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30-3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72-4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12-3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60-4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56-3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29-5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42-3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48-7.02 for RFO >17.4%) Cox regression analysis. CONCLUSIONS: The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

Association of Serum Uric Acid Level With Blood Pressure Variability in Newly Diagnosed Essential Hypertension.

Serum uric acid (UA) is independently associated with hypertension and blood pressure (BP) variability (BPV) is associated with cardiovascular events and mortality in hypertensive patients. The aim of the present study was to assess the association of serum UA with BPV in 300 untreated essential hypertension patients (mean age 57.3±13.6 years). BPV was quantified as the standard deviation (SD) of the 24-hour, daytime, and nighttime mean values obtained by using ambulatory BP monitoring. In correlation analysis, log UA values were found to be positively correlated with 24-hour systolic BPV and nighttime systolic and diastolic BPV (Pearson coefficients of 0.246, 0.280, and 0.353, respectively; P<.001 for all). In multivariate analysis, log UA had an independent association with 24-hour systolic BPV and nighttime systolic and diastolic BPV. This study show for the first time that increased serum UA is independently associated with BPV in untreated essential hypertension patients.

Tissue advanced glycation end products (AGEs), measured by skin autofluorescence, predict mortality in peritoneal dialysis.

PURPOSE: The relation between tissue AGEs and mortality in end-stage renal disease (ESRD) is documented, but only in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGEs levels in patients receiving either HD or peritoneal dialysis (PD) and to study the effect of these products on all-cause, cardiovascular or sepsis-related mortality. METHODS: Tissue AGEs were noninvasively assessed in 304 dialysis patients (202 on chronic HD and 102 on continuous ambulatory PD) by measuring skin autofluorescence using a validated Autofluorescence Reader (AGE Reader, DiagnOptics b.v., Groningen, The Netherlands). RESULTS: There was no difference in regard to AGEs levels between the HD (3.6 ± 0.8 AU)- and PD (3.5 ± 0.7 AU, p = 0.2)-treated patients. Diabetic patients had higher AGEs values in the HD group (3.97 ± 0.81 vs. 3.52 ± 0.77, p = 0.002), but not in the PD group (3.68 ± 0.6 vs. 3.45 ± 0.70, p = 0.26). In PD patients, increasing AGEs levels were associated with an elevated risk of all-cause mortality (a 2.09-fold increase for each increment of 1 AU in AGEs values) and sepsis (a 3.44-fold increase for each increment of 1 AU in AGEs values)-related mortality. Performing a similar analysis in diabetic patients, AGEs was associated only with sepsis-related mortality (a 3.08-fold increase for each increment of 1 AU in AGEs values). CONCLUSIONS: This is the first study that demonstrates a relationship between tissue AGEs levels and sepsis-related mortality in PD-treated or diabetic ESRD patients. Future studies are necessary to evaluate the non-cardiovascular effects of tissue AGEs in ESRD patients.

Prognostic significance of 25-hydroxivitamin D entirely explained by a higher comorbidity burden: experience from a South-Eastern European Dialysis Cohort.

Vitamin D deficiency is still a common problem particularly in the elderly and in individuals with various degrees of renal impairment. The present study aimed to evaluate the association between plasma concentrations of 25(OH)D and death in a large cohort of prevalent patients on hemodialysis (HD) from south-east Romania, a typical Balkan region. This is an observational prospective study that included a total of 570 patients on maintenance HD. Study patients were classified into three groups by baseline 25(OH)D levels: (1) sufficient 25(OH)D--i.e., >30 ng/mL; (2) insufficient 25(OH)D--i.e., between 10 and 29 ng/mL; and (3) deficient 25(OH)D--i.e., <10 ng/mL. During the follow-up period of 14 months, 68 patients (11.9%) died, the Kaplan-Meier analysis showing significant differences in all-cause mortality for chronic kidney disease patients in different 25(OH)D groups (P = 0.002). Unadjusted Cox regression analysis also showed significant differences in survival. The multivariate Cox regression model showed no significant differences in survival according to vitamin D levels. Hazard ratio for death in the "<10 ng/mL" group was 1.619 (P = 0.190) and in the "10-30 ng/mL" group was 0.837 (P = 0.609). In our dialysis population with a high comorbidity burden, low 25(OH)D concentration was not associated with mortality in the adjusted Cox model, suggesting that vitamin D deficiency could represent only a non-specific marker for a poor health status, with less impact on mortality.

Serum sclerostin and adverse outcomes in nondialyzed chronic kidney disease patients.

BACKGROUND: The chronic kidney disease (CKD)-mineral and bone disorder (MBD) syndrome is an important contributor to the CKD-associated cardiovascular disease and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a potent downregulator of bone metabolism and a novel candidate for the bone-vascular axis in CKD patients. We tested whether serum sclerostin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. METHODS: Serum sclerostin was obtained from 173 CKD (stage 3-5) and 47 control patients, and its concentration was correlated with estimated glomerular filtration rate and to mineral and vascular abnormalities that are present in the CKD evolution. All-cause mortality and CVEs were also analyzed in relation to serum sclerostin values. RESULTS: Patients with CKD showed higher sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P < .001) than controls, with values progressively higher across the CKD stages. In univariate analysis, serum sclerostin concentrations were correlated with gender, estimated glomerular filtration rate, flow-mediated dilatation, and endothelium-independent vasodilatation as markers of endothelial dysfunction and with different serum CKD-MBD-associated parameters. However, in multivariate analysis, only gender, fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol remained significantly associated with sclerostin levels. During the observational period, there were 19 deaths and 50 CVEs. In survival analysis, different sclerostin levels were associated with all-cause mortality and CVEs in these patients. CONCLUSIONS: This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.

Protein-energy wasting, as well as overweight and obesity, is a long-term risk factor for mortality in chronic hemodialysis patients.

INTRODUCTION: In patients with end-stage renal disease on chronic hemodialysis (HD), protein-energy wasting (PEW) is very common and is associated with increased morbidity and mortality. Evaluation of nutritional status should be performed regularly in all such patients, using multiple methods. In this study, we analyzed the influence of several nutritional markers on long-term (5 years) survival of HD patients in one center. This is the first study on the long-term influence of nutritional status on mortality in dialysis patients ever conducted in Romania. MATERIALS AND METHODS: We included all prevalent HD patients in our center. Those with ongoing acute illnesses and with inflammation (C-reactive protein ≥ 6.0 mg/l) were excluded. In the remaining subjects (N = 149, 82 males, mean age 55 years old), we performed the following measurements of nutritional status: estimation of dietary protein intake by normalized protein equivalent of nitrogen appearance (nPNA), subjective global assessment (SGA), body mass index (BMI), tricipital skinfold thickness, mid-arm circumference, assessment of body composition by bioelectrical impedance analysis (BIA), and pre-dialysis serum creatinine, albumin, and total cholesterol. We used receiver operating characteristic curves to determine the cutoff points for most of the variables, and we applied the Kaplan-Meier estimator and the Cox's proportional hazards model (stepwise method) to analyze the influence of these variables on survival. RESULTS: In univariate analysis, general factors including age ≥ 65 years, male gender, dialysis vintage ≥ 2 years, and the presence of diabetes and heart failure were all significant predictors of mortality. Among nutritional parameters, BMI ≥ 25 kg/m(2), SGA-B (mild PEW), nPNA < 1.15 g/kg per day, and the BIA-derived phase angle (PhA) <5.58° were also significantly associated with reduced survival. All of these factors maintained statistical significance in multivariate analysis, except for male gender and heart failure. CONCLUSION: We showed that low values of SGA, nPNA, and PhA independently predict mortality in HD patients. In conjunction with an earlier study, we demonstrated that the relative risk of death associated with these markers is highest during the first year of monitoring and it decreases in the following 4 years, although it still remains significantly increased. On the other hand, overweight and obesity were also associated with lower survival after 5 years, whereas this association was not apparent after 1 year.

[Risk of sudden death in patients with chronic renal failure and hemodialysis]. / Riscul mortii subite la pacientii cu insuficienta renala cronica hemodializati.

Cardiovascular mortality in uremic patients treated by hemodialysis overrates ten times cardiovascular mortality in general population. Approximatively 40% of patients on iterative hemodialysis die from cardiac diseases, half of cases by sudden death. Several risk factors for sudden death are well known: QTc interval prolongation, decrease of RR interval <750 msec, decrease of heart rate variability, presence of late ventricular potentials (LVP), presence of high risk ventricular extrasystoles, decrease of ejection fraction (EF) <40 %, presence of left ventricular hypertrophy. Our study evaluated the above-mentioned risk factors for sudden death in patients with chronic renal failure on hemodialysis. We studied 37 patients, 22 males and 15 females, with mean age of 42 years old, without diabetes, heart failure and arrhythmias, without myocardial ischemia on ECG, being on hemodialysis (HD) programme for minimum 1 year (HD parameters are: 4 h x 3/week, qB = 300 ml/min, buffer = bicarbonate, Ca dialysate = 1.75 mmol/l, K dialysate = 2.1 mmol/l, conductivity = 135 mS). The patients were evaluated by echocardiography, standard and Holter ECG. Statistics evaluation was performed in SPSS v.9.0. Program. The results proved that 80% of patients on HD have risk factors for sudden death, which are closely related with age and hyperhydration. Statistics proved that presence of high-risk arrhythmias is connected with heart rate variability and prolongation of QTc interval (favored by HD). 50% of our patients have 2 to 4 risk factors for sudden death, which increase incidence of sudden death in patients on HD.