Evaluation of neopterin levels in patients undergoing hemodialysis

Neopterin is a diagnostic or a prognostic biomarker for several pathologies including renal diseases. However, the association between neopterin status and causative main reasons such as diabetes and hypertension for renal disease remains unclear. The aim of the study was to evaluate neopterin levels in diabetes and hypertension patients treated with/without hemodialysis. According to primary renal disorders, the patients undergoing hemodialysis were classified into 4 groups as diabetic nephropathy, hypertensive nephropathy, reflux nephropathy or interstitial nephritis, and others. The controls consisted of healthy subjects, hypertensive subjects, and diabetic individuals without any renal disorder. In the study, both urinary and serum neopterin levels were measured using high performance liquid chromatography and enzyme‐linked immunosorbant assay in patients undergoing regular hemodialysis therapy (n=71). The effects of the duration of hemodialysis and treatment of erythropoietin and/or iron on neopterin levels were also evaluated. Neopterin levels were found to be higher in hemodialysis patients than in the healthy controls (P<0.05). A significant difference in neopterin levels was also found between diabetic control patients and diabetic nephropathy patients (P<0.05). A similar significant difference was detected in neopterin levels between hypertensive patients with/without nephropathy (P<0.05). Neopterin may be an early critical marker for progression of nephropathy in diabetic and hypertensive patients in early stages.     

Hemochromatosis gene mutations and treatment of anemia in patients on hemodialysis

Hemochromatosis causes iron overload by enhanced intestinal absorption. This study examined erythropoietin and intravenous (IV) iron requirements in hemodialysis (HD) patients with HFE mutations. Patients on HD for >90 days with no cause of anemia except chronic kidney disease were tested for HFE mutations (H63D and C282Y). Intravenous iron and erythropoietin doses were adjusted to achieve recommended targets. Monthly hemoglobin (Hb), ferritin, mean corpuscular volume, mean cell hemoglobin, erythropoietin, and IV iron doses for 3 consecutive months were averaged. Of 172 patients, 71 (41.3%) had ≥1 HFE mutation: 24 (14%) C282Y heterozygotes, 40 (23.3%) H63D heterozygotes, 5 compound heterozygotes, and 2 homozygotes. Comparing patients with ≥1 HFE mutation to those without mutations showed no significant difference in Hb or serum ferritin. There was a trend toward lower median weekly erythropoietin dose in patients with ≥1 HFE mutation (94.0 vs. 135.4 U/kg body weight; P=0.13). There was no difference in median weekly IV iron dose (1.0 vs. 0.9 mg/kg body weight; P=0.56). Comparing the 30 patients with a C282Y mutation to patients without HFE mutations produced similar results. Comparing the 47 patients with an H63D mutation, with those without HFE mutations, no discernable trend was observed. In this study, patients with HFE gene mutations on HD for established renal failure do not require less iron supplementation to achieve recommended Hb targets. We observed a trend toward lower erythropoietin requirement in patients possessing C282Y mutations. Larger studies may clarify the role of HFE mutations, regulators of iron metabolism and erythropoiesis in chronic kidney disease.     

Effects of end‐stage renal disease and dialysis modalities on blood ammonia level

Introduction: Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10‐fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Methods: Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. Findings: No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P < 0.001) which was paradoxically accompanied by a modest but significant (P < 0.05) rise in blood ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre‐ and post‐hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P < 0.01). On subgroup analysis of patients who had a rise in blood ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P < 0.01). The nadir intradialytic systolic blood pressure trended lower in the hemodialysis patients who had a rise in blood ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). Discussion: Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure.     

High prevalence of subclinical hypothyroidism and nodular thyroid disease in patients on hemodialysis

Chronic kidney disease has been known to affect thyroid hormone metabolism. Low serum levels of T3 and T4 are the most remarkable laboratorial findings. A high incidence of goiter and nodules on thyroid ultrasonography has been reported in patients with end‐stage renal disease (ESRD). Our objective is to evaluate the prevalence of laboratorial and morphologic alterations in the thyroid gland in a cohort of patients with ESRD on hemodialysis (HD). Sixty‐one patients with ESRD on HD were selected and compared with 43 healthy subjects matched by age, gender, and weight. Patients were submitted to thyroid ultrasonography. T3, free T4 (FT4), thyroid‐stimulating hormone, antithyroglobulin, and antithyroperoxidase antibodies were measured. The mean age of patients with ESRD was 47.4 ± 12.3 and 61% were women. ESRD was mainly caused by hypertensive nephrosclerosis and diabetic nephropathy. Mean thyroid volume, as determined by ultrasonography, was similar in both groups. Patients with ESRD had more hypoechoic nodules when compared with the control group (24.1% vs. 7.9%, P = 0.056). Mean serum FT4 and T3 levels were significantly lower in patients with ESRD, and subclinical hypothyroidism was more prevalent in patients with ESRD (21.82% vs. 7.14% control group, P = 0.04). Titers of antithyroid antibodies were similar in both groups. ESRD was associated with a higher prevalence of subclinical hypothyroidism and lower levels of T3 and FT4. Almost a quarter of patients showed thyroid nodules >10 mm. Periodic ultrasound evaluation and assessment of thyroid function are recommended in patients with ESRD on HD.     

Hypertension and left ventricular mass index (L.VMI) in patients on regular hemodialysis (RDT)

Background:  Because of high incidence of acquired renal cyst and renal malignancy, it is suggested that spontaneous renal rupture more frequently occurs in patients receiving long‐term hemodialysis than in the general population. This study was performed to evaluate the clinical characteristics of spontaneous renal rupture in hemodialysis patients. Methods:  This retrospective study enrolled 12 hemodialysis patients who developed spontaneous renal rupture. We investigated primary renal disease, duration of dialysis, clinical symptoms and signs, radiologic findings, treatment modalities, and histologic findings. Result:  The mean age of the patients was 54 ± 10 years old and the number of male was 9. Primary renal disease consisted of autosomal dominant polycystic kidney disease (PCKD)(n = 5), chronic glomerulonephritis (n = 2), diabetic nephropathy (n = 1), hypertensive nephropathy (n = 1), unknown cause (n = 3). Presenting symptoms and signs were sudden onset of flank pain in 9 patients and gross hematuria with mild flank pain in 3 patients. Mean duration from initiation of hemodialysis to development of spontaneous renal rupture was 53 ± 36 months. Abdominal computed tomography showed subcapsular or perinephric hematoma in all patients. Of the 7 non‐PCKD patients, 6 patients had multiple acquired renal cysts. Surgical exploration was undertaken in 9 patients. Pathologic examination demonstrated small sized renal cell carcinoma in 2 of 9 patients. Three patients were only treated with conservative management including blood transfusion. All 12 patients recovered without recurrence. Conclusion:  This study demonstrated that genetic or acquired renal cyst was an important cause of spontaneous renal rupture in hemodialysis patients and presenting manifestations were sudden onset of flank pain and gross hematuria.     

Functional iron deficiency in hemodialysis patients with high ferritin

Although functional iron deficiency (FID) may be present in hemodialysis (HD) patients with high serum ferritin levels (>800 ng/mL), current protocols often preclude the use of intravenous (IV) iron in these patients. However, it has not been demonstrated that iron supplementation during erythropoietin therapy is ineffective or unsafe in increasing hemoglobin (Hb) levels in patients with high serum ferritin. This report describes the hematologic efficacy and safety of ferric gluconate (FG) therapy in patients with serum ferritin >800 ng/mL. A retrospective analysis was performed on HD patients at a single California dialysis center from January 1 to December 31, 2003. Patients classified as having high ferritin levels (serum ferritin >800 ng/mL on at least 66% of routine monthly measurements and transferrin saturation [TSAT] <25% on at least 1 occasion) were stratified as follows: patients in Group I were suspected of having FID and received FG > or =250 mg IV over a 3-month period when Hb was <11 g/dL, and patients in Group II were thought not to have FID and received <250 mg FG over a 3-month period. Both groups received standard recombinant human erythropoietin therapy as per the unit's protocol. Of 496 patients, 95 exhibited high ferritin and of these, 39 patients had sufficient data for analysis. Group I patients (n=14) showed a significant increase in Hb levels compared with Group II (n=25). There was no increase in ferritin levels in response to iron administration. No significant differences in hospitalizations or infections were observed between groups. Hemodialysis patients with high ferritin levels may have FID, and IV iron therapy safely improves FID in some patients. A larger randomized trial examining the optimal management of iron administration in HD patients with high ferritin levels is warranted.     

Orally administrated Juzen-taiho-to/TJ-48 ameliorates erythropoietin (rHuEPO)-resistant anemia in patients on hemodialysis

Maintenance of the red blood cell volume is a fundamental aspect of ensuring oxygen supply to the tissue. Recombinant human erythropoietin (rHuEPO) was approved for marketing in Japan in 1990 for the treatment of anemia in patients on dialysis. Recombinant human erythropoietin caused a significant increase in hemoglobin (Hb) levels in patients on dialysis. However, not all have a good response to rHuEPO therapy; the causes of rHuEPO failure include iron deficiency, infection, uremia, and interaction of some drugs. Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been used traditionally to treat patients with anemia, anorexia, or fatigue. To clarify the effect of TJ-48 on erythropoietin-resistant anemia, we studied the effect of TJ-48 in patients on hemodialysis with erythropoietin-resistant anemia. We divided 42 end-stage renal disease patients on hemodialysis with erythropoietin-resistant anemia (Hb<10.0 g/dL with rHuEPO 9000 U/wk or 15 U/kg/wk treatment) into 2 groups as follows: a TJ-48-treated group (TJ-48 group, 7.5 g/d, n=22) and a TJ-48 nontreated (control group, n=20). At the beginning of this study, there was no significant difference between the groups in age, sex, serum creatinine, blood urea nitrogen, serum iron, and ferritin. After 12 weeks of treatment, the Hb level had significantly increased from 8.4 +/- 1.1 to 9.5 +/- 1.3 g/dL (P=0.0272) in the TJ-48 group. C-reactive protein (CRP) had significantly decreased from 1.4 +/- 1.7 to 0.6 +/- 0.8 mg/dL (P=0.0438). There was a significant negative correlation between Hb and CRP in the TJ-48 group (r(2)=0.121, P=0.0066). In contrast, in the control group, Hb and CRP showed no significant changes throughout this study. Nor was there a significant correlation between Hb and CRP in the control group. In conclusion, TJ-48 was effective in improving erythropoietin-resistant anemia in end-stage renal disease patients. This effect was, at least in part, due to the anti-inflammatory effect of TJ-48 in patients on hemodialysis.     

HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients

Introduction: HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. Methods: 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. Findings: Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). Discussion: Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation.     

Effect of incident nocturnal home hemodialysis versus incident continuous ambulatory peritoneal dialysis on employment rate,clinical, and laboratory outcomes: A 1‐year retrospective observation study

Introduction: While studies demonstrated favorable outcomes of nocturnal home hemodialysis (NHHD), direct comparison on employment rate, clinical and laboratory outcomes between the NHHD and continuous ambulatory peritoneal dialysis (CAPD) had not been previously performed. Methods: A 1‐year retrospective observation study was performed in 20 incidents alternate night NHHD and 81 incident CAPD patients of Chinese ethnicity, who were sex, diabetic status, and Charlson comorbidity index matched, but not age due to our center's age limit for NHHD enrollment. The primary outcome was the difference in employment rate at 1 year. Secondary outcomes included differences in clinical parameters (weight, blood pressure, number of antihypertensive medication, dosage of phosphate binders, and erythropoietin stimulating agent) and laboratory parameters (residual renal function, mineral metabolic markers, hemoglobin). Findings: NHHD subjects were 5 years younger than CAPD patients, and they had higher employment rate (80% vs. 33.3%, P < 0.01) at 1 year, with age‐adjusted odds ratio for employment was 6.10 (95% confidence interval 1.77–20.99, P = 0.04). They consumed less aluminum‐based phosphate binder (0 vs. 1800 mg, P < 0.01), but showed no significant disparities in other clinical parameters. Residual renal function in both groups declined comparably, nonetheless NHHD group had lower serum phosphate (1.37 vs. 1.71 mmol/L, P = 0.01) and calcium phosphate product (3.13 vs. 4.12 mmol²/L², P < 0.01), with similar hemoglobin levels. Discussion: NHHD appeared to offer higher employment rate, lower dosage of aluminum‐based phosphate binder and mineral metabolic markers at 1 year compared with CAPD in Hong Kong.     

The effects of hemodialysis treatment on the level of DNA strand breaks and oxidative DNA lesions measured by the comet assay

Hemodialysis patients have a higher risk for oxidative stress‐related complications, such as cardiovascular disease and cancer. The increased level of oxidative stress is due to several factors, e.g., the hemodialysis treatment itself and the uremic state. In the present study, the effects of dialysis treatment on the level of DNA breaks and oxidative DNA lesions in mononuclear cells were measured with the comet assay. Factors possibly affecting DNA damage (reported as % DNA in tail) such as the duration of dialysis, time since last dialysis session, years of dialysis treatment, nutritional status (measured as protein catabolic rate), age, and diabetes were also investigated. The levels of DNA breaks (13.6 ± 4.7 before dialysis) and oxidative DNA lesions (7.9 ± 4.8 before dialysis) were significantly higher in dialysis patients (n = 31) compared to the levels of DNA breaks (5.8 ± 1.1) and oxidative DNA lesions (3.4 ± 1.7) in 10 healthy controls (P < 0.001). A decrease of DNA breaks was observed after dialysis (P = 0.038), and the level of oxidative DNA lesions was higher when the time between two treatment sessions were 68 hours compared to 44 hours (P < 0.001). Older subjects had a higher level of DNA breaks (P = 0.003), a good nutritional status predicted a lower level of DNA breaks (P < 0.001), and the duration of the dialysis session was inversely correlated with oxidative DNA lesions (P = 0.014). Diabetes or years of dialysis treatment did not affect DNA damage. The observations in the present study suggest that accumulation of uremic toxins induce DNA damage. The hemodialysis treatment seems to change the DNA damage.     

The effect of hemodialysis session on postural strategies in older end‐stage renal disease patients

Patients suffering from end‐stage renal disease experience multiple disabilities, such as muscle wasting, weakness, higher postural sway, and fall rates compared with healthy population, which has a negative effect on physical functioning and autonomy. The vital treatment of hemodialysis is recognized to induce important post‐hemodialysis fatigue, hypotension, cramps, and headache due to the rapid fluid redistribution, among others. Nevertheless, even the well‐known negative effect of aforementioned consequences of hemodialysis treatment, its effect on physical function, especially postural balance, is unclear. Thus, this study hypothesized the adverse effect of hemodialysis treatment on postural sway in 12 end‐stage renal disease patients (mean age 63.3 ± 11 years) through the analysis of center‐of‐pressure (COP) trajectories recorded before and immediately after hemodialysis session. Evident postural alterations were observed at post‐hemodialysis balance assessment for COP position‐based (Fs < 7.7, P < 0.02) and COP velocity‐based variables (Fs > 2.33, P < 0.05), without changes in complexity of COP time series in anteroposterior and mediolateral directions. These results suggest that period after hemodialysis treatment is particularly unsafe, as evidenced by important disability in postural control, and highlight the importance of the medical support and falls‐related prevention strategies of these older frail patients after hemodialysis treatment.     

Statin use is associated with lower inflammation and erythropoietin responsiveness index in hemodialysis patients

Patients with end-stage renal disease are prone to inflammation and inflammation is related to erythropoietin-stimulating agent hyporesponsiveness and mortality in this population. Statins have been demonstrated to reduce cardiovascular mortality in selected populations of end-stage renal disease patients. These drugs have pleiotrophic effects such as anti-inflammation. In this retrospective analysis, we determined whether the use of statins improves inflammation and inflammation-related anemia in a cohort of hemodialysis patients. Data were analyzed from Fresenius Medical Care Dialysis Clinics in Turkey between 2005 and 2007. Seventy prevalent hemodialysis patients who were on statins at the start of the study and have been on statins during follow-up (statin users) and 1293 patients who were not on statin at the start of the study and had never been prescribed any lipid-modifying drugs during follow-up (statin nonusers) were included in the study. High-sensitive C-reactive protein levels were significantly decreased in statin users (1.50±1.49 vs. 1.33±1.11 mg/L, P=0.05) compared with nonusers (1.93±3.22 vs. 2.05±2.77 mg/L). Hemoglobin levels and the rate of erythropoietin-stimulating agent users were similar. However, the prescribed erythropoietin-stimulating agent dose (31.6±27.5 vs. 47.3±45.2 U/kg/week, P<0.05) and the erythropoietin response index (2.90±2.73 vs. 4.51±4.48 U/kg/week/Hb, P=0.001) were lower in statin users compared with statin nonusers. On stepwise multiple regression analysis, gender, high-sensitive C-reactive protein, duration of hemodialysis, serum ferritin, and statin use were independent determinants of the erythropoietin responsiveness index. Our results suggest that statin treatment leads to lower inflammation and improves hematopoiesis in hemodialysis patients.     

Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients

Accelerated atherosclerosis is the major cause of mortality in patients on chronic hemodialysis (HD). The aim of this study was to evaluate the relation between coenzyme Q10 (CoQ10) levels and coronary flow reserve (CFR) in HD patients as an indicator of atherosclerosis. Seventy‐one chronic HD patients and 65 age‐ and sex‐matched healthy individuals were included in the study. Plasma CoQ10 levels were performed by high‐performance liquid chromatography measurements. CFR was assessed by transthoracic Doppler echocardiography. Serum CoQ10 levels (1.36 ± 0.43 vs. 2.53 ± 0.55, P < 0.001) and CFR values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in HD patients compared with controls. There was a significant positive correlation between CFR and serum levels of CoQ10 (r = 0.669, P < 0.001). A linear regression analysis showed that serum levels of CoQ10 were still significantly and positively correlated with CFR (regression coefficient = 0.235, P < 0.001). Our data have demonstrated that HD patients exhibit decreased plasma CoQ10 levels and CFR values. The study also showed for the first time that serum CoQ10 levels independently predict CFR in HD patients.     

Effects of modality change on health-related quality of life

Patients with end‐stage renal disease (ESRD) requiring renal replacement have impaired health‐related quality of life (HRQoL), and there is general consensus that HRQoL improves with successful transplant and evidence of improvement with frequent hemodialysis. This study reports changes in HRQoL associated with changes in treatment modality to daily hemodialysis (DHD) and transplant among patients requiring renal replacement. This cohort study had assessments at baseline and 6‐month following modality change. Subjects were nondiabetic individuals receiving conventional hemodialysis who (a) remained on conventional hemodialysis (n = 13), (b) changed to daily hemodialysis (DHD) (n = 10), or (c) received a living donor transplant (n = 20). Thirty‐four healthy controls were assessed once for comparison. HRQoL was measured using the Kidney Disease Quality of Life Instrument. The Physical Functioning and Physical Composite Scale scores were primary outcomes. Transplantation resulted in significant improvements in six of eight generic scales and the physical composite scale (PCS). Those changing to DHD had significant improvements in Physical Function and PCS scales. Those remaining on dialysis remained lower than controls on all scales except for Vitality; the transplant group remained lower than controls only on the Vitality and General Health scales. Transplant resulted in significant improvements in four of the seven disease‐specific scales (symptoms, effects, and burden of kidney disease, work). DHD resulted in improvements in the effects of kidney disease. Modality change to transplant results in significant improvement in HRQoL, achieving levels similar to controls. Change to daily hemodialysis improves only select HRQoL domains and remains low in disease‐specific domains.     

Association of low vitamin D levels with metabolic syndrome in hemodialysis patients

Low vitamin D levels have been linked to metabolic syndrome in the general population. In the present study, the relationship between inadequate serum concentrations of vitamin D and metabolic syndrome in patients with end‐stage renal disease undergoing hemodialysis was explored. In a cross‐sectional setting, 145 patients undergoing maintenance hemodialysis were enrolled. Metabolic syndrome was defined using the International Diabetes Federation criteria. Serum concentration of 25(OH) vitamin D was determined by a commercially available enzyme immunosorbent assay method. The prevalence of metabolic syndrome was 53.1%. The prevalence rate of severe vitamin D deficiency (<5 ng/mL) was 3.4%, mild vitamin D deficiency (5–15 ng/mL) 31.0%, vitamin D insufficiency (16–30 ng/mL) 36.6%, and vitamin D sufficiency (>30 ng/mL) 29.0%. With the increasing number of metabolic abnormalities, vitamin D levels significantly decreased (P for trend = 0.028). Among the components of metabolic syndrome, vitamin D deficiency was significantly associated with central obesity (odds ratio [OR], 95% confident interval [CI] = 2.80, 1.11–7.04, P = 0.028). A positive, but nonsignificant association between vitamin D deficiency and raised fasting plasma glucose was noted (OR, 95% CI = 2.40, 0.94–6.11, P = 0.067). Both vitamin D deficiency and insufficiency were significantly associated with an increased likelihood of having metabolic syndrome (P < 0.05). In a final model controlling for age, sex, and parathyroid hormone levels, vitamin D deficiency increased the odds of having metabolic syndrome by more than threefold (OR, 95% CI = 3.26, 1.30–8.20, P = 0.012). Low levels of vitamin D are frequent among hemodialysis patients and are associated with the metabolic syndrome.     

Effect of a single hemodialysis session on inflammatory markers

Inflammation is a common feature of end-stage renal disease. Although there is evidence for hemodialysis (HD)-induced inflammatory process, the effect of a dialysis session on changes in inflammatory markers is still unclear. Seventeen patients of end-stage renal disease on maintenance HD along with 20 age-matched and sex-matched healthy controls were recruited after informed consent. C-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (LpPLA2) activity were measured in the study and control groups. Intradialytic in CRP and LpPLA2 were studied. Comparison of pre-HD vs. the control group and predialytic and postdialytic values was performed using the Mann-Whitney U test and Wilcoxon's test, respectively. Statistical evaluation of intradialytic changes in inflammatory markers was performed using Friedman's test. Hemodialysis patients had higher CRP levels compared with controls (P=0.001). Post-HD LpPLA2 activity (n=17) was higher (P=0.039) compared with the pre-HD activity. Intradialytic changes in inflammatory markers showed a significant increase (P=0.012) in LpPLA2 activity (n=7), while no change (P=0.133) was observed in CRP levels (n=17). Evidence on the pro-inflammatory state being initiated by dialysis is provided by increased LpPLA2 activity. This may add to the atherogenic mileu and cause endothelial dysfunction in this high-risk group. Drugs that inhibit the LpPLA2 pathway have been developed and may be effective in these patients.     

Uremic hyperhomocysteinemia: a randomized trial of folate treatment for the prevention of cardiovascular events

Homocysteine is a risk factor for atherosclerosis in the general population, and serum homocysteine levels are almost universally elevated in chronic renal failure patients. When such patients are treated with dialysis, cardiovascular disease accounts for more than 50% of their mortality, which, in some proportion, may be pathophysiologically related to the elevated serum homocysteine levels. From April 2003 to March 2005, we conducted a 2-year, double-blind, randomized, placebo-controlled trial of 186 patients with end-stage kidney disease due to any cause, who were older than 18 years and stable on hemodialysis. Patients were assigned to receive either oral folic acid 10 mg 3 times a week immediately after every dialysis session under nurse supervision or an identical-appearing placebo for the entire study. On admission, plasma total homocysteine (tHcy) levels were above 13.9 micromol/L in 96.7% of patients (median 25.0 micromol/L, range 9.3-104.0 micromol/L). In the placebo group, tHcy levels remained elevated at 6, 12, and 24 months, while oral folate significantly decreased tHcy to a median value of 10.5 (2.8-20.3) micromol/L, (p<0.01). During the study, 38 patients (folic acid group 17 vs. placebo group 21; p=0.47) died from cardiovascular disease. Kaplan-Meier life table analysis dealing with the incidence of cardiovascular events, both fatal and nonfatal (myocardial infarction, arrhythmias, angina, heart failure, cerebrovascular accident), showed that 2 years of folic acid treatment and the lowering of the homocysteine blood levels had no effect on cardiovascular events (p=0.41; hazard ratio 1.24, 95% CI 0.74-2.10). However, the carotid artery intima-media wall thickness measured in a blinded fashion decreased from 1.94 +/- 0.59 mm to 1.67 +/- 0.38 mm (p<0.01) after 2 years of folate therapy. In this short-term study of uremic patients, 2 years of folic acid supplementation normalized the tHcy blood levels in 92.3% of patients but did not change the incidence of cardiovascular events compared with the control group. However, ultrasonography of the common carotid arteries performed at entry and 24 months later showed a significant decrease in intima-media thickness with folate supplementation. This suggests that early folate supplementation may benefit patients with chronic renal failure by preventing cardiovascular deterioration.     

Effect of vitamin D supplementation on endothelial dysfunction in hemodialysis patients

Introduction: Patients with chronic kidney disease (CKD) commonly experience 25‐hydroxyvitamin D3 (25‐OH‐D3) deficiency, and these patients have a higher incidence of cardiovascular diseases (CVDs) due to endothelial dysfunction (ED). The aim of our study was to investigate the effect of 25‐OH‐D3 deficiency and its supplementation on ED in patients with CKD. Methods: Twenty‐nine uremic patients on dialysis and 20 healthy controls were evaluated for ED by high‐resolution Doppler ultrasonography of the brachial artery. In addition, 25‐OH‐D3‐deficient patients (25‐OH‐D3 < 30 nmol/L) with CKD and healthy controls were evaluated for ED before and after 8 weeks of oral vitamin D (cholecalciferol, 50,000 units) treatment. All subjects were evaluated for percent flow‐mediated dilatation (%FMD), percent endothelium‐independent nitroglycerin‐induced vasodilatation (%NID), and bilateral carotid intima‐media thickness (CIMT). Findings: Patients on dialysis had lower %FMD and %NID 6.11 [2.27–12.74] and 10.96 [5.43–16.4], respectively, than controls 15.84 [8.19–22.49] and 21.74 [12.49–29.4], respectively (P < 0.05). Patients on dialysis had higher left and right CIMT (0.79 ± 0.15 and 0.78 ± 0.14, respectively) than controls (0.60 ± 0.09 and 0.59 ± 0.09, respectively; P < 0.05). In 25‐OH‐D3‐deficient patients with CKD, after vitamin D treatment, %FMD was significantly increased in dialysis patients (10.25 [7.8–12.8]) compared to before supplementation (5.4 [2.77–6.15]; P < 0.001). Discussion: These results indicated that dialysis patients had significantly lower blood 25‐OH‐D3 levels and higher CIMT than healthy subjects. In addition, vitamin D supplementation improved ED and increased %FMD in dialysis patients. Our findings suggest that vitamin D supplementation in dialysis patients might prevent CVD.     

Genetic polymorphisms and the risk of progressive renal failure in elderly Hungarian patients

The relationship between renal disease progression and genetic polymorphism of enzymes influencing endothelial function remains incompletely understood. We genotyped three cohorts of elderly Hungarian patients: 245 patients with end‐stage renal disease (ESRD) on chronic hemodialysis (HD), 88 patients with mild chronic kidney disease (CKD), and 200 healthy controls. The underlying diagnoses of renal diseases were primary glomerulonephritis, interstitial nephritis, hypertension, diabetic nephropathy, and hereditary diseases. We examined genetic polymorphisms of eight candidate genes associated with endothelial function: endothelial constitutive nitric oxide synthase (ecNOS) T‐786C, endothelin‐1 G5727T, methylenetetrahydrofolate reductase (MTHFR) C677T, paraoxonase‐1 Q192R and M55L, angiotensinogen M235T, angiotensin‐converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C gene. Six gene polymorphisms were detected by real‐time polymerase chain reaction with melting‐point analysis, and two via allele‐specific amplification and gel electrophoresis. Control group patients were in Hardy‐Weinberg equilibrium for all tested genotypes. In ESRD patients attributed to hypertension, the endothelin gene G5727T GG genotype occurred significantly less but GT genotype more frequently (P < 0.01 for both). In ESRD patients attributed to primary glomerulonephritis, more ACE DD and less ID genotypes were found (P < 0.02 for both) than in the controls. The underlying diagnosis may modify the association of genetic polymorphism and dialysis‐dependent ESRD.