Mustafa Gullulu

Clinical Value of the Malnutrition-Inflammation- Atherosclerosis Syndrome for Long-Term Prediction of Cardiovascular Mortality in Patients with End- Stage Renal Disease: A 5-Year Prospective Study

Background/Aim: Mortality resulting from cardiovascular disease in patients with end-stage renal disease (ESRD) is high. In this study we sought to investigate the clinical value of the malnutrition-inflammation-atherosclerosis (MIA) syndrome for long-term prediction of cardiovascular mortality in patients treated with ESRD. Methods: A total of 42 ESRD patients on hemodialysis were enrolled. Inflammatory markers and nutritional parameters were determined. Carotid atherosclerosis was investigated by ultrasonographically evaluated carotid intima-media thickness (cIMT). Mortality was evaluated at a 5-year follow-up. Results: No correlation was evident between nutritional markers and inflammatory indexes. cIMT was inversely correlated with predialysis serum albumin. In the overall population of 42 patients, 11 (26.2%) died of cardiovascular causes during follow-up. Kaplan-Meier survival curves indicate that cIMT (≧0.9 mm), C-reactive protein (CRP) (>1 mg/dl), and serum albumin (<3.5 g/dl) predict cardiovascular death in patients with ESRD. Conclusions: We have demonstrated that cIMT, CRP and serum albumin predict long-term mortality in ERSD patients. Our study suggests that further investigation of the MIA syndrome will provide insights into the susceptibility to CVD in this patient group.

Urinary IL-18: a marker of contrast-induced nephropathy following percutaneous coronary intervention?

OBJECTIVES Contrast-induced nephropathy (CIN) is a complication that is underestimated in clinical practice after cardiac catheterization. Recently, the value of interleukin (IL)-18 as a novel biomarker for the detection of acute renal failure has been highlighted. In the present study, we sought to investigate whether urine IL-18 may be an early diagnostic marker of CIN. DESIGN AND METHODS We performed a nested case-control study using a hospital based cohort of all patients (n=157) admitted for elective PCI for stable angina to the Uludag University School of Medicine between February 2007 and June 2007. We identified 15 patients (9.5%) with CIN. Controls were matched with cases at an attempted 2.5:1 ratio by age and gender. Urinary IL-18 values were measured before as well as 24 and 72 h after the PCI. RESULTS No statistically significant differences in urine IL-18 were detected between cases (n=15) and controls (n=36) or between the patient samples obtained before PCI and after the invasive procedure in both study groups. CONCLUSIONS These findings argue against the hypothesis that urine IL-18 may be clinically useful as a biomarker of CIN after radiological procedures requiring intravascular administration of iodinated contrast media. Further studies with larger sample sizes are needed to validate our findings.

Angiotensin-II receptor antagonist losartan reduces microalbuminuria in hypertensive renal transplant recipients

In recent years, it has been demonstrated that losartan lowers macroproteinuria in diabetic or non‐diabetic renal transplant recipients (RTx) similar to angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may reflect subclinical hyperfiltration damage of the glomerulus. It could be a marker of kidney dysfunction in renal transplantation. The aim of the study was to assess the efficacy of losartan in hypertensive RTx with MAU. This study was conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical treatment of the patients. All cases received 50 mg/day losartan therapy for 12 wk. Renal functions and MAU were determined 12 and 6 wk and just before the treatment as well as sixth and twelfth week of the treatment in all patients. Losartan satisfactorily lowered systemic blood pressure. A significant reduction in MAU was observed from 103 ± 53 μg/min at the beginning to 59 ± 25 μg/min in the sixth week and 47 ± 24 μg/min in the twelfth week (p=0.0007 and 0.0005, respectively). From the sixth week of the treatment, the therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but did not change mean leukocyte and platelet counts, urea, creatinine levels and creatinine clearances. No serious side‐effect was observed during the study.

Effect of fluvastatin on serum prohepcidin levels in patients with end-stage renal disease

OBJECTIVES Anemia, low-grade inflammation and/or alterations in lipid metabolism are common findings in individuals with end-stage renal disease (ESRD) despite advances in dialysis treatment. Hepcidin, a key regulator of iron metabolism, may play an important role in the interdependence of inflammation and anemia in ESRD patients. Statins may reduce cardiovascular events in dialysis patients and have pleiotropic effects in addition to lowering total and low-density lipoprotein (LDL)-cholesterol. DESIGN AND METHODS Because there is a paucity of data on the effect of statins on serum prohepcidin levels in dialysis patients, this 8-week study was conducted to test the effect of fluvastatin (80 mg/day, n=22) compared with placebo (n=18) on circulating serum prohepcidin, a prohormone of hepcidin, and high-sensitive C-reactive protein (hs-CRP) in dyslipidemic ESRD patients with renal anemia. RESULTS Fluvastatin treatment decreased total cholesterol (P<0.05), LDL-cholesterol (P<0.01), hs-CRP (P<0.05) and serum prohepcidin levels (P<0.05) significantly. CONCLUSION Our pilot data suggest that short-term statin treatment may exert a beneficial effect on serum prohepcidin levels in ESRD patients. The potential clinical benefits of statins on renal anemia need to be confirmed and expanded with an appropriately powered long-term study.

Efficacy of losartan in patients with primary focal segmental glomerulosclerosis resistant to immunosuppressive treatment

Abstract. Usta M, Ersoy A, Dilek K, Özdemir B, Yavuz M, Güllülü M, Yurtkuran M (Uludağ University Medical School, Bursa, Turkey). Efficacy of losartan in patients with primary focal segmental glomerulosclerosis resistant to immunosuppressive treatment. J Intern Med 2003; 253: 329–334.

Prevalence of hepatitis C virus antibody in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease of unknown aetiology characterised by impaired immune regulation and production of polyclonal autoantibodies. It is reported in the medical literature that in patients with chronic hepatitis resulting from hepatitis C virus (HCV) more autoantibodies such as antinuclear antibodies, anti-ds DNA, antiphospholipid antibody, antithyroglobulin antibody, rheumatoid factor, cryoglobulinaemia, and anti-GOR (an HCV induced, host derived epitope) are seen than in patients with other causes of hepatitis virus.1-3 There have also been reports on HCV associated with several immunological …

Aldosterone Blockage in Proliferative Glomerulonephritis Prevents Not Only Fibrosis, but Proliferation as Well

Studies performed recently have determined that aldosterone has not only a major role in electrolyte and water balance and K excretion, but it also modulates myofibroblast growth in the heart and blood vessels and causes fibrosis. This study investigated the effects of aldosterone blockers in rats with anti-thy 1.1 nephritis, both on proliferation and fibrosis, by comparing it to an angiotensin receptor inhibitor valsartan. Rats with anti-thy 1.1 nephritis were randomly allocated to one of the three following groups of treatment: the control group (group 1); those treated with the aldosterone receptor blocker spironolactone (group 2); and those treated with the ATRB valsartan (group 3). On day 7, the parameters of glomerular fibrosis [transforming growth factor beta, TGF staining areas %], proliferation (Ki-67), and renal damage scores were determined. The TGF-β and Ki-67 levels of control group were significantly more than the other two groups (p<0.01). The TGF staining areas percentages were significantly decreased compared to control group. The artery, glomerular, and renal injury scores evaluated between the groups were found to be significantly decreased compared to control group. In line with previous studies, this study found that in anti–thy 1.1 mesangioproliferative glomerulonephritis, aldosterone blockage affected proliferation and fibrosis.

Long-term Effects of Losartan on Proteinuria and Renal Function in Patients with Renal Amyloidosis

Objective : To investigate the effect of the angiotensin II receptor antagonist losartan on proteinuria in secondary amyloidosis cases. Material and Methods : Sixteen patients with renal biopsy-proven AA amyloidosis with proteinuria were included in the study. All the patients had received colchicine treatment for at least 18 months. The patients were divided into two groups with similar age and gender distributions. Eight patients were given losartan at a dose of 50 mg/day for 12 months and the other 8 patients served as controls. Mean arterial blood pressure, proteinuria, serum albumin level and renal function were determined at the initiation of the study and after 1 and 12 months. Results : There were no significant differences in proteinuria, serum albumin level, renal function or mean arterial blood pressure at the initiation of the study. In the losartan group daily proteinuria decreased significantly from 5.2 - 0.7 g at the initiation of the study to 3.9 - 1.2 g at 1 month and 3.6 - 0.8 g at 12 months, while in the control group it changed from 4.6 - 1.0 g to 4.7 - 1.0 g and 6.1 - 1.2 g, respectively. The increment at 12 months was significant. After 12 months of treatment with losartan, proteinuria was significantly lower in comparison to the degree of proteinuria in the control group. Serum albumin level increased significantly in the losartan group but was unchanged in the control group. In the control group, creatinine clearance showed a significant decrease. There was no significant difference in mean arterial blood pressure measurements, serum creatinine levels, total protein, albumin and creatinine clearance levels between the two groups. Conclusions : Losartan seemed to prevent an increase in proteinuria without altering the creatinine clearance level in patients with amyloidosis type AA during a 12-month period. This indicates that losartan may be used to decrease proteinuria in this patient group. However, our results are only preliminary and need to be confirmed by larger studies.

Prevalence of Transfusion Transmitted Virus Infection and its Effect on Renal Graft Survival in Renal Transplant Recipients

Objective : Little is known about the prevalence of transfusion transmitted virus (TTV) infection in renal transplant recipients (RTxs) and its effects on allograft survival. We investigated the prevalence of TTV and its effects on liver injury and graft survival in RTxs. Material and Methods : The study was performed in 33 consecutive RTxs (8 females, 25 males) and 100 blood donors (35 females, 65 males). A nested polymerase chain reaction was used to detect TTV DNA in serum. Serum creatinine and alanine aminotransferase (ALT) levels and 24-h protein excretion were determined in both TTV-positive and -negative patients. The total number of blood transfusions, the duration of hemodialysis and the total duration after transplantation were recorded in RTxs. In addition, hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and hepatitis G virus DNA antibodies were determined in all patients. Results : TTV DNA was detected in 51.5% of RTxs and in 7% of the control group and this difference was statistically significant ( p < 0.01). In the RTx group, 64.7% of TTV-positive and 56.2% of TTV-negative patients had undergone a previous blood transfusion. However, the blood transfusion replacement rate, total duration of dialysis therapy and posttransplant period did not differ between these two groups. Five (15.1%) patients in the RTx group had abnormal liver function tests (ALT >40 IU/l). Of these patients, 2 were anti-HCV-positive, 1 was HBsAg-positive and anti-HCV- plus TTV DNA-positive and the serologic tests of the remaining 2 patients were all negative. Among the TTV-positive patients, 2 (11.7%) were anti-HCV-positive, 1 (5.8%) was HBsAg-positive and 3 (17.6%) were HGV DNA-positive. The baseline serum creatinine levels did not differ significantly between the TTV-positive and -negative patients, being 1.5 - 0.6 and 1.4 - 0.6 mg/dl, respectively (p > 0.05). Two of the TTV-positive patients and 1 of the TTV-negative patients had proteinuria. A 1-year follow-up of TTV-positive and -negative patients demonstrated neither acute nor chronic graft rejection. Conclusion : In RTxs, TTV infection was more prevalent than in the normal population. In our patients the virus did not have an important effect on renal graft rejection and did not cause liver injury. However, the question of whether TTV infection may affect graft survival requires further long-term investigation in larger groups.

Paraoxonase Activity in Glomerulonephritic Patients

Background. Cardiovascular disease is the most common cause of morbidity and mortality in patients with chronic renal failure. Glomerulonephritic patients have an increased risk for cardiovascular disease, but its etiology is unclear. It is known that an increase in oxidizability of apolipoprotein B-containing lipoproteins has a key role in the initiation of atherosclerosis, and paraoxonase enzyme activity particularly has a preventive role against atherosclerosis. The aim of the present study was to evaluate the oxidizability of apolipoprotein B-containing lipoproteins, serum, and urinary paraoxonase/arylesterase activities in glomerulonephritis patients who had normal lipid parameters and creatinine levels. Methods. Thirty-two patients with glomerulonephritis and 22 healthy controls were included in this study. A total of 32 patients (including nine with membranous GN, eight with immunoglobulin A nephropathy, eight with mesangial proliferative GN, five with focal-segmental glomerulosclerosis, one with diffuse proliferative GN, and one with minimal chance disease having biopsy proven GN) were enrolled into the study. We compared serum and urinary paraoxonase, arylesterase, serum lipids, urea, creatinine, hemoglobin, total protein and albumin values between groups. Results. Serum urea, creatinine, total protein, albumin, uric acid, hemoglobin, and lipid parameters were similar in the glomerulonephritis and control groups (p > 0.05). PON1 activity was significantly lower in GN group than controls, but there was no statistically significant difference on arylesterase activity between groups. Oxidizability of apolipoprotein B-containing lipoproteins was significantly higher in GN group than controls. Conclusion. Our study shows that the findings of normal serum levels of creatinine, lipids, and proteins increased the oxidizability of apolipoprotein B-containing lipoproteins, and any decrease in PON1 activity in patients diagnosed with GN should be considered important. Hence, the immediate commencement of preventive as well as curative treatment in other to avoid the risk of cardiovascular and renal problems would be a correct approach.