Asymmetric dimethylarginine: a novel cardiovascular risk factor in end-stage renal disease.

OBJECTIVE: This cross-sectional study explored the association between carotid intima-media thickness (CIMT) and the oxidative stress markers asymmetric dimethylarginine (ADMA) and homo cysteine in patients with end-stage renal disease who were on haemodialysis. METHODS: A total of 30 patients undergoing chronic haemodialysis treatment were recruited to this study. Homocysteine and ADMA levels were determined using a fluorescence polarization immunoassay and an enzyme-linked immunosorbent assay, respectively. CIMT was measured as a marker of atherosclerosis using high-resolution ultrasonography and was performed after haemodialysis. RESULTS: Significant positive correlations were found between CIMT and ADMA, and CIMT and duration of haemodialysis. Linear regression analysis showed that ADMA level and age were significant independent determinants of CIMT, whereas homo cysteine was not. CONCLUSIONS: The relationship demonstrated between plasma ADMA and carotid artery thickening suggests that ADMA may be a novel marker of atherosclerosis in patients on haemodialysis.

Acute renal failure in a patient with severe malaria and dengue shock syndrome.

Malaria is an infectious disease caused by plasmodium, which lives and breeds in human blood cells, and is transmitted through the bites of Anopheles mosquitoes. Renal impairment, often caused by malaria, is acute renal failure (ARF) due to acute tubular necrosis (ATN). Dengue virus is transmitted from human to human through Aedes aegypti mosquito bites. Dengue hemorrhagic fever (DHF), the most severe stage of infection, is characterized by bleeding and shock tendencies (dengue shock syndrome, DSS). ARF is a less common complication in patients with DHF, with an incidence of less than 10%. Mixed infections of two infectious agents may cause overlapping symptoms and have been reported in Africa and India. We report here a patient with ARF due to mixed infection of severe malaria and DSS. The patient presented with fever and had a history of repeated malaria infection. Physical examination revealed stable vital signs and hepatosplenomegaly. Laboratory data showed hemoconcentration, thrombocytopenia and increased serum aminotransferase. Chest X-ray showed pleural effusion. A malarial antigen and thick smear examination showed the trophozoite stage of P. falciparum. On Day 3, blood pressure dropped to 80/60 mmHg, pulse was 120 beats/minute, weak, and body temperature 36.8 C, with icterus. Other tests revealed an increase of serum urea nitrogen and creatinine levels, and serologically anti-dengue IgG antibody (+) and anti-dengue IgM antibody (-). Based on these findings, we diagnosed the patient as having both malaria and DDS. We treated the patient with the parenteral anti-malarial agent, artemisinin. Supportive treatment and treatment of complications were also performed simultaneously for DSS. The patient experienced an oliguria episode but responded well to a diuretic. The patient was discharged after clinical and laboratory examinations showed positive progress.

Association of endothelial nitric oxide synthase Glu298Asp polymorphism with end-stage renal disease.

BACKGROUND: Impairment of nitric oxide generation caused by gene polymorphism is considered as a major factor in the deterioration of progressive renal disease, including diabetic nephropathy and hypertension. The aim of the present study was to examine the Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) in patients with end-stage renal disease (ESRD). METHODS: The Glu298Asp polymorphism in exon 7 was determined in 100 ESRD patients who were maintained on hemodialysis at Dr. Soetomo Hospital, Surabaya, Indonesia, and in a control group of 100 unrelated healthy individuals. In the patient group, 39 patients had Type 2 diabetes mellitus (DM), 44 hypertension (HT) and 17 miscellaneous conditions. The mean length of time from onset of ESRD to the start of this study was 24.37 +/- 32.37 months (Mean +/- SD). RESULTS: The positivity of Glu298Asp in the ESRD group was significantly higher than that in the control group (p < 0.0001). The odds ratio for this group was 4.57 (95% confidence interval 2.52 - 8.31). The positivity of 298Asp in Type 2 DM ESRD with subgroup was significantly higher than that in healthy controls (p < 0.0001). The positivity of 298Asp in the subgroup of patients with HT-derived ESRD was also significantly higher (males p < 0.036, females p < 0.005) than that in healthy control group. Homozygotes with glutamate to aspartate substitution at nucleotide position 7702 showed a single band at 457 bp. CONCLUSION: It appears that Glu298Asp may be a predisposing factor in DM-derived and HT-derived ESRD.

Intravenous N-acetylcysteine during hemodialysis reduces asymmetric dimethylarginine level in end-stage renal disease patients.

AIM: Cardiovascular disease is the main cause of mortality in chronic kidney disease patients. Moreover, uremic patients are in a pro-oxidant state and show an increase in asymmetric dimethylarginine (ADMA) levels due to inhibition of the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Asymmetric dimethylarginine per se seems responsible for a 52% increase in the risk of death and for a 34% increase in the risk of cardiovascular events in dialysis patients. N-acetylcysteine (NAC) is a thiol molecule that has direct and indirect antioxidant effects which decrease reactive oxidant species and increase the bioavailability of the DDAH enzyme. The aim of the current study was to determine the effect of intravenous NAC on plasma ADMA level when administered during hemodialysis in end-stage renal disease (ESRD) patients. MATERIALS AND METHODS: 40 patients with ESRD were randomized to receive a 4-hour intravenous infusion of NAC or placebo during a 4-hour hemodialysis session. There were 3 diabetic patients (15%) in the treatment group and 6 patients in the control group. Plasma ADMA levels were measured before and immediately after hemodialysis. Hemodynamic parameters, including pulse pressure, were also measured. The paired t-test was used to compare the difference of ADMA levels before and after hemodialysis in each group, while the independent t-test was used to compare the difference of ADMA levels between the groups. RESULTS: Compared with the pre-dialysis condition, there was a decrease of ADMA level in the control group (1.1253 +/- 0.1797 microM to 0.8676 +/- 0.1449 microM) (p < 0.001), and in the NAC group (1.1522 +/- 0.1737 microM to 0.7844 +/- 0.1586 microM) (p < 0.001). Compared with hemodialysis alone, NAC had a greater lowering effect on the ADMA level (21.3 vs. 31.9%, p < 0.05). CONCLUSION: N-acetylcysteine (NAC) administered intravenously during hemodialysis reduced asymmetric dimethylarginine (ADMA) levels more significantly than hemodialysis alone.

Correlation between intradialytic hypotension in patients undergoing routine hemodialysis and use of acetate compared in bicarbonate dialysate.

AIM: To determine the incidence of intradialytic hypertension (IDH) during hemodialysis (HD) in end-stage renal disease (ESRD) patients using acetate dialysate compared to those using bicarbonate dialysate. METHODS: This study was a double-blind cross-over randomized clinical trial. The effect of acetate and bicarbonate dialysate on blood pressure was analyzed in two consecutive HD sessions. The selected subjects were 41 stable ESRD patients scheduled for dialysis 2 times/week/from the HD unit of Dr.Soetom Hospital Surabaya, aged between 21-65 years old, with a hemoglobin level > or = 7 g/dL, serum albumin > or = 3 mg/dL and interdialytic weight gain < 4 Kg, and an average Qb 150-250 ml/minute. The dialysate sodium level was 138 mEq/L/ The study subjects were divided into tow groups: 21 patients in the group who received Acetate on the first session and Bicarbonate on the next (AB) and 20 patients in the group receiving Bicarbonate first (BA). Comparison of IDH during use of each dialysate was analyzed by Chi-Square and Mc Nemar Chi-Square test. RESULTS: No characteristic differences were found in both groups: HD duration (for AB) was 28.83 +/- 13.89 vs. 34.95 +/- 24.80 months (for BA) (p = 0.333); Age (for AB) was 47.61 +/- 9.49 vs. 47.75 +/- 11.80 years (for BA) (p = 0.969); Hemoglobin (Hb) level (for AB) 8.19 +/- 0.84 vs. 7.94 +/- 0.41 mg/dL (for BA) (p = 0.238); serum Albumin (for AB) was 3.79 +/- 0.26 vs. 3.82 +/- 0.30 g/dl (for BA) (p = 0.652). The number of patients with IDH during acetate dialysate with IDH during bicarbonate dialysate was 1 (2.4%). Overall, there were 11 patients with Diabetic Kidney Disease (26.8%). Six out of them (54.5%) had IDH during acetate dialysate and only and 1 patient (9.1%) had IDH during acetate and bicarbonate. CONCLUSION: The incidence of IDH in hemodialysis using acetate is significantly greater than that when bicarbonate is used (p = 0.000).

A discussion of 61 cases of optic nerve coloboma.

Colobomata of the optic disc result from failure of closure of the most anterior portion of the optic stalk. Therefore the great majority of these defects are found at the six o'clock position in the region of the embryonic defect. The authors examined 61 patients with optic nerve coloboma from 1972 to 1983. The clinical data of these patients are given. It was remarkable that the optic nerve colobomata occurred in combination with the same systemic and 'midline'-defects that are often seen in combination with optic nerve hypoplasia.