Alexander Biro

Comparison of hemostatic factors and serum malondialdehyde as predictive factors for cardiovascular disease in hemodialysis patients

Hemodialysis (HD) patients have accelerated cardiovascular morbidity and mortality rates compared with the general population. Identifying the factors that predict major coronary events in this population can direct the focus on prevention. This cross-sectional study compares known and suspected cardiovascular risk factors in HD patients with and without prevalent cardiovascular disease (CVD). In 76 HD patients (prevalent CVD, 44 of 76 patients), serum lipid, lipoprotein, apolipoprotein (Apo), plasma fibrinogen, tissue plasminogen activator (TPA), plasminogen activator inhibitor (PAI-1), and factor VII levels were measured using standard kits. Serum malondialdehyde (MDA; a marker of oxidative stress) was measured using spectrophotometry. Predictor variables were compared using analysis of variance and chi-squared tests, as appropriate. CVD prevalence was modeled using multiple logistic regression analysis, and odds ratios (OR) were calculated. Serum lipid, lipoprotein, Apo, plasma TPA, PAI-1, and factor VII values did not differ significantly from laboratory norms or discriminate for prevalent CVD in HD patients. Plasma fibrinogen levels were significantly elevated in HD patients compared with laboratory norms (369.4 +/- 130.02 v 276.7 +/- 77.7 mg/dL; P < 0.0001) but were not significantly different in HD patients with and without prevalent CVD. Serum MDA levels, both before and after the midweek HD treatment, were significantly elevated in all HD patients compared with laboratory norms (pretreatment, 2.6 +/- 0.8 nmol/mL; posttreatment, 2.1 +/- 0.3 v 0.91 +/- 0.09 nmol/mL; P < 0.01) and were significantly elevated in HD patients with prevalent CVD versus those without (pretreatment, 2.8 +/- 0.6 v 2.4 +/- 0.4 nmol/mL; P < 0.01; posttreatment, 2.3 +/- 0.4 v 1.94 +/- 0.2 nmol/mL; P < 0.01). Only serum MDA levels, both before and after the midweek treatment, contributed to the explanation of variation in CVD prevalence. OR for CVD in the highest versus lowest tertile of pretreatment MDA level was 2.71 (95% confidence interval [CI], 1.42 to 5.19). ORs for CVD in the highest versus lowest tertile of posttreatment MDA level was 3.65 (95% CI, 1.6 to 8.32).

Pamidronate-induced nephrotoxic tubular necrosis--a case report.

Few cases of pamidronate (bisphosphonate class of drugs) nephrotoxicity in humans have been previously reported in the literature. In 7 patients, the pamidronate-related nephrotoxicity was attributed to focal collapsing glomerulosclerosis [Markowitz et al. 2001], and in 1 patient was related to tubulo-interstitial inflammatory nephritis [Van Doom et al. 2001]. We report herein on a 65-year-old Caucasian female patient who presented with acute chronic renal failure due to pamidronate-induced toxic proximal tubular necrosis without immunologic or inflammatory tubulo-interstitial involvement. The acute pattern of renal failure resolved following cessation of pamidronate administration in this patient for osteoporosis; the patient also had a monoclonal gammopathy of unspecific origin (MGUS).

Baseline Oxysterols and Other Markers of Oxidative Stress, Inflammation and Malnutrition in the Vitamin E and Intima Media Thickness Progression in End-Stage Renal Disease (VIPER) Cohort

Background and Objectives: Oxysterols are markers of oxidative stress, levels of which have not yet been reported in hemodialysis (HD) patients. This study was designed to compare levels of the oxysterols 7-ketocholesterol (7KC) and 7β-hydroxycholesterol (7βOH) between a cohort of HD patients and healthy controls. Methods: This nested cross-sectional study reflects baseline (pre-intervention) values for markers of oxidative stress, inflammation and nutrition status in the 160-member vitamin E and carotid intima media thickness progression in end-stage renal disease (VIPER) cohort (age 64.1 ± 8.8, 33.5% female). Age- and sex-matched healthy volunteers served as controls. Plasma oxysterols 7KC and 7βOH were determined by isotope dilution gas chromatography/mass spectrometry. Results: Despite higher plasma α-tocopherol levels in HD patients than controls (36.0 ± 9.3 vs. 31.8 ± 8.4 µmol/l, p = 0.007), 7KC levels (9.8 ± 6.9 vs. 5.9 ± 2.8 nmol/mmol cholesterol, p < 0.0001) and 7βOH levels (8.7 ± 4.3 vs. 2.7 ± 1.6 nmol/mmol cholesterol, p < 0.0001) were higher in HD patients. The oxysterol 7βOH was significantly, inversely associated with prealbumin (r = –0.18, p = 0.03), though neither oxysterol was significantly associated with any other marker of oxidative stress, inflammation or nutrition status and did not discriminate for CVD in HD patients. Conclusions: Elevated levels of the oxysterols 7KC and 7βOH indicate that HD patients are in a state of oxidative stress compared to healthy controls. However, oxysterols 7KC and 7βOH did not appear to contribute additional information about oxidative stress among HD patients.

Medication Apprehension and Compliance among Dialysis Patients – A Comprehensive Guidance Attitude

Background: Compliance with treatment regimens is a continuing challenge for chronic dialysis patients and their medical caregivers. Poor patient adherence to prescribed medications can adversely affect treatment outcome. Study Design: In this pre- versus post-intervention study, 89 chronic dialysis patients [75 hemodialysis (HD), 14 continuous ambulatory peritoneal dialysis (CAPD); mean age 62.7 ± 12.39 years, 34 females] responded to a written questionnaire designed to assess knowledge about and compliance with 5 groups of prescribed medications: metabolic drugs, antihypertensives, cardiac-supporting agents, peptic disease therapy and hematological replacement therapy. Mode of intake, storage, means of supply and source of information for each class of drug were also assessed. Patients then received both oral and written instructions regarding their prescribed medications (intervention). This information was repeated 3 months later. Six months after the intervention, patients were re-administered the questionnaires. Response to the questionnaires and laboratory data were compared prior to and following the intervention. Results: Overall, compliance with prescribed medications significantly improved following the intervention, from 89 to 95.7%, p = 0.0007. This relative improvement was greater in HD than CAPD patients (27 vs. 2%, p < 0.0001). Improvement in compliance was associated with lower initial scores, fewer years of education, and longer dialysis vintage. Compared to baseline values, post-intervention blood hemoglobin, hematocrit, mean corpuscular volume, ferritin and Ca levels were significantly improved. Conclusions: Dialysis patients appear to benefit from receiving comprehensive guidance about medications, in terms of compliance with medications and blood chemistry and hematology measures.

Effect of atorvastatin on IgA nephropathy in the rat.

BACKGROUND IgA nephropathy (IgAN) is the most common chronic glomerulonephritis in humans and is a major cause of end-stage kidney disease worldwide. There is no agreement on the exact underlying mechanism or therapeutic intervention for this disorder. Mesangial proliferation typifies the renal histopathology in IgAN. Statin drugs, as prenylationinhibitors, have been shown to have an antiproliferative effect on renal mesangial cells and to reduce IgAN-associated glomerulusclerosis and proteinuria. The aim of this study is to examine the effect of atorvastatin on kidney function, proteinuria and kidney histology changes in IgANinduced rats. METHODS IgAN was induced in Wistar-Kyoto rats by bovine γ-globulin (BGG). Four groups of rats were treated in metabolic cages: 1) control; 2) atorvastatin (2 mg/kg body weight/day through nasogastric tube) - treated rats; 3) IgAN-rats; 4) IgAN-rats treated with atorvastatin. Urine volume, urine protein excretion, blood urea and creatinine concentrations in addition to creatinine clearance were examined every 14 days, throughout the duration of the study (56 days). All kidneys from sacrificed rats were examined for histology including glomerular cell nuclei count and immunofluorescence. RESULTS There were no differences in blood creatinine concentrations between the groups. Creatinine clearance was lower on the 42nd day and proteinuria was higher on Days 14, 42 and 56, in rats in Group 3 compared to all others; additionally, histology examination revealed a higher glomerular cell nuclei count in this group. Immunofluorescence was equally positive for IgA in mesangial cells in the kidneys from rats of Groups 2, 3 and 4. CONCLUSIONS Atorvastatin attenuates kidney-function impairment, proteinuria and mesangial cell proliferation in BGG model of IgANinduced rats.

Effect of sevelamer hydrochloride exposure on carotid intima media thickness in hemodialysis patients.

Background: Elevated phosphorus (P) and calcium (Ca)-P product (Ca × P) are associated with vascular calcification and cardiovascular disease (CVD) morbidity and CVD and all-cause mortality. Objectives: This study examined the effect of sevelamer hydrochloride exposure (regardless of calcium carbonate exposure) on carotid and femoral intima media thickness (IMT), reliable surrogate measures of prospective intimal thickening, in end-stage renal disease patients on maintenance hemodialysis. Methods: The present cross-sectional study is nested in the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima media thickness progression in end-stage renal disease (SUMMER) clinical trial. Carotid and femoral arteries were visualized in B-mode ultrasonography. Log-transformed IMT was compared by sevelamer hydrochloride exposure and modeled using multiple linear regression. Results: Forty-five subjects were exposed to sevelamer hydrochloride and 130 were not. Exposed subjects had significantly lower carotid IMT, an association which persisted in the multiple linear regression model even after controlling for potentially confounding variables including serum Ca, history of CVD and body weight. Exposed subjects had lower low-density lipoprotein cholesterol levels and significantly higher parathyroid hormone, but no differences in P, Ca and Ca × P. Conclusions: Sevelamer hydrochloride was associated with lower carotid IMT. This association may be mediated through reduction in Ca load, low-density lipoprotein cholesterol lowering or some other pleiotropic effect.

A Randomized Controlled Clinical Trial Comparing the Efficacy of Dead Sea Mineral-Enriched Body Lotion versus Two Types of Placebo in the Treatment of Cutaneous Dryness, Itching, Peeling and Tightness in Hemodialysis Patients (EDIT)

Background/Aims: The present study was designed to investigate the short-term safety and efficacy of topical application with body lotion enriched with minerals from the Dead Sea versus 2 different placebo treatments in reducing symptoms of uremic pruritus. Methods: In this single-center, randomized, double placebo-controlled clinical trial, 78 hemodialysis patients with self-reported uremic pruritus were randomized to twice-daily topical treatment with body lotion enriched with minerals from the Dead Sea (DS) or to each of 2 types of placebo: (1) lotion with no Dead Sea minerals but otherwise identical to DS (P1) or (2) lotion with no active ingredients (P2). Symptoms of uremic pruritus (itching, dryness, peeling, tightness) were evaluated at baseline and 2 weeks (14 days) after treatment intervention using a 5-point Likert scale. Results: Following treatment, significant differences in symptom severity scores between DS and P1 and, separately, between group DS and P2, were not detected. Additionally, when DS was compared to the combined placebo groups (P1 and P2 together), significant post-treatment differences in symptom severity scores were not observed. Symptoms were less severe post-treatment regardless of treatment assignment. Conclusions: DS was not superior to either of the placebo treatments in the symptomatic relief of uremic pruritus.

Noninvasive skin measurements to monitor chronic renal failure pathogenesis.

BACKGROUND/AIMS Cutaneous manifestations are common in hemodialysis (HD) patients with chronic renal failure (CRF). Associated with uremia, pruritus is a frequently observed symptom in CRF patients and increases with deteriorating renal function. Skin hydrophilic biomarkers (SHB) may be altered in CRF compared to healthy controls. METHODS A noninvasive skin wash sampling technique to detect the expression of SHB, by measuring their secretion on skin surface, was used on HD patients and healthy controls. Hydrophilic antioxidants such as total antioxidant scavenging capacity (TSC) and uric acid (UA) content, and cytokine inflammatory biomarkers such as TNFα and IL-10 levels were estimated. RESULTS Our findings demonstrate significant alterations of the SHB level between HD patients and healthy volunteers. Furthermore, such alterations of secreted SHB correlated markedly with detected changes in blood biochemistry and dermatology severity score. CONCLUSION Skin wash sampling of SHB is a noninvasive technique that distinguishes between HD patients and healthy controls. In HD patients, SHB is associated with biochemical markers in blood and dermatologic symptom severity. This technique is also suggested, as a monitoring tool for diagnosis and treatments of various diseases, in which skin dysfunction is involved.

Pregnancy in membranous glomerulonephritis: course, treatment and outcome

BACKGROUND The effect and outcome of pregnancy in women with preexisting glomerulonephritis is a controversial issue. CASE We report the clinical course and treatment of a 23-year-old pregnant woman with biopsy-proven membranous glomerulonephritis. When she conceived, the patient had been in stable remission for 1 year. In the 14th week of pregnancy, the patient developed uncontrolled hypertension and nephrotic syndrome. Daily 1 g methylprednisolone intravenous pulses were administered for 3 days, followed by a 4-week course of oral prednisone, 50 mg/day. Clinical improvement and normalization of arterial blood pressure were achieved. Oral prednisone 60 mg was administered on alternate days for another 4 weeks following 3 days of pulse therapy. At the end of treatment (26th gestational week), we observed a decrease of proteinuria (from 10.6-4.8 g/24 h) and rise in serum albumin (from 2.1-2.9 g/100 ml). At this time, blood pressure was 130/85. In the 34th week, a normal healthy male newborn was delivered by cesarean section. One year later she felt well, her blood pressure was 140/90, serum albumin was 3.4 g/100 ml, urine protein was 1.65 g/24 h and renal function was normal. The patients child was healthy and well developed. CONCLUSION Judicious use of a specific therapy to the underlying renal disease during pregnancy, together with a continuous supervision, can improve outcomes of these particular high-risk conditions.

The effect of poly (ADP-ribose) polymerase inhibition on aminoglycoside-induced acute tubular necrosis in rats.

INTRODUCTION Aminoglycosides (AG) cause nephrotoxicity in 10 - 20% of patients. One of the mechanisms is by generating reactive oxygen species (ROS), leading to DNA destruction and activation of poly(ADPribose) polymerase (PARP) causing necrotic tubular cell death. PARP inhibition on gentamicin-induced nephrotoxicity was studied. METHODS 19 female Wistar-Kyoto rats divided into 3 groups: control (3 rats receiving no treatment); gentamicin-treated group (8 rats); and 8 rats treated with gentamicin combined with 3-aminobenzamide (3 AB). Kidney functions, protein, and gentamicin levels as well as urinary trypsin inhibitory activity (TIA) were measured. Tissue microscopic examination and immunohistochemical study for proliferative cell nuclear antigen (PCNA) were determined. The effect of PARP inhibitor on the bactericidal activity of gentamicin was also assessed. RESULTS The following results were statistically significant: urea (mg/dL) 39.9 ± 5.86, 88.3 ± 50.3, and 48.5 ± 12.7 (p = 0.048); serum creatinine (mg/dL): 0.6 ± 0.26, 1.05 ± 0.7, 0.6 ± 0.06 (p = 0.043); proteinuria (mg/24-hours): 7.27 ± 3.65, 41.2 ± 18.1, and 17.6 ± 13.9 (p = 0.050); the number of tubular macronuclei (per 10 mm2): 18.33 ± 16.07, 218 ± 101.8, 41.7 ± 36.2 (p = 0.012); the number of dilated tubes (per 10 mm2): 61.67 ± 12.58, 276.3 ± 112.7, 140.0 ± 90.9 (p = 0.04); and the number of PCNA positive nuclei (per 10 mm2): 223.3 ± 95.69, 3,585 ± 2,215.3, 626.7 ± 236.9 (p = 0.034) in the control, gentamicin, and gentamicin+3AB-treated groups, respectively. The following biochemical and histologic parameters were also examined, however, they showed no statistically significant difference: TIA (p = 0.055), mitoses (p = 0.14), mononuclear infiltrate (p = 0.188), and intratubular cast formation (p = 0.084). No effect on bactericidal activity was observed. CONCLUSION This study illustrates that PARP inhibitor significantly attenuates gentamicin-induced nephrotoxicity in rats with no effect on the bactericidal activity.