Ibrahim Akdag

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.

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.

Calcineurin inhibitors and post-transplant weight gain.

Aim:  Excessive weight gain that leads to obesity is quite common after kidney transplantation. This is often attributed to immunosuppression. The aim of this retrospective study was to assess the effect of calcineurin inhibitors on post‐transplant weight gain.

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.

Spontaneous perirenal hematoma with AA amyloidosis in a hemodialysis patient after unilateral nephrectomy

Secondary amyloidosis presents with a variety of systemic symptoms or signs. Amyloid diseases can be associated with potentially life-threatening hemorrhage. Although bleeding manifestations are common in amyloidosis, renal bleeding is rare and generally due to trauma, cyst and malignancy. For the first time we present a ureamic patient who was diagnosed with AA amyloidosis after unilateral nephrectomy because of spontaneous perirenal hematoma.

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.

MCP-1 and soluble TWEAK levels are independently associated with coronary artery disease severity in patients with chronic kidney disease

Abstract Purpose: Patients diagnosed with chronic kidney disease (CKD) have a greater rate of cardiovascular mortality when compared with the general population. The soluble form of TNF-like weak inducer of apoptosis (TWEAK) and monocyte chemoattractan protein 1 (MCP-1) play important roles in cellular proliferation, migration and apoptosis. The current study aimed to analyze whether soluble TWEAK (sTWEAK) and MCP-1 levels are associated with the severity of coronary arterial disease (CAD) in CKD patients. Methods: Ninety-seven patients diagnosed with CKD stages 2–3 according to their estimated glomerular filtration rate and the presence of kidney injury were included in the study. Plasma sTWEAK and MCP-1 concentrations were determined using commercially available ELISA kits. Coronary angiographies were performed through femoral artery access using the Judkins technique. Results: Correlation analysis of sTWEAK and Gensini scores showed significant association (p < 0.01, r2 = 0.287). Also significant correlation has been found in MCP-1 levels and Gensini scores (p < 0.01, r2 = 0.414). When patients were divided into two groups with a limit of 17 according to their Gensini score, sTWEAK levels indicated a statistically significant difference (p < 0.01). Conclusions: Our findings support a relationship between sTWEAK and MCP-1 levels and CAD in CKD stages 2–3 patients.

Bone Morphogenetic Protein-7 and disease progression in renal amyloidosis patients

Abstract Introduction: Chronic kidney disease (CKD) is an important health care problem with increasing incidence. Early diagnosis, recognition and interventions to avoid the disease progression have great value. Even some risk factors for disease progression have been described; there are still some dark spots. Transforming growth factors (TGFs), particularly bone morphogenetic protein-7 (BMP7) take place in renal fibrosis. Our study aimed to evaluate the association between serum BMP7 levels and the progression of CKD. Materials and methods: Our study has been conducted between January 2008 and December 2010. Decrease in GFR by 10%, doubling of serum creatinine and need for renal replacement therapy have been set as progression end-points. Totally 93 patients (48 female, 45 male) have been included. Baseline and end of follow-up BMP7 levels have been measured. Results: At the end of the follow-up, 46 of 93 patients have been considered as having progressive CKD. Higher levels of serum BMP7 levels have been found to be associated in progressive kidney disease. Discussion: Our results showed that BMP7 levels were higher in patients with progressive CKD, and also BMP7 to be associated with CKD progression. But this relationship was not statistically significant. In patients with progressive CKD, higher levels of proteinuria and blood pressure have been previously described. The effect of BMP7 on kidneys is not still clear, it is hypothesized that TGF-beta1 inhibition may alter renal fibrosis.

Complete Reversal of Nephrotic Syndrome Secondary to Amyloidosis with Use of Infliximab in a Patient with Inflammatory Bowel Disease and Ankylosing Spondylitis

A 30-year-old woman was diagnosed with ulcerative colitis in January 2006. One year later, she presented because of severe back pain and was diagnosed with ankylosing spondylitis (AS). In February 2008, the patient, while still under standard treatment for ulcerative colitis and AS, was admitted because of massive proteinuria and related symptoms. Nephrotic syndrome was observed and renal biopsy revealed amyloid deposits. After treatment with infliximab, nephrotic syndrome disappeared. We aim to present a case of secondary amyloidosis complicating ulcerative colitis and associated spondyloarthropathy.

Effect of indomethacin and selective cyclooxygenase-2 inhibitors on proteinuria and renal function in patients with AA type renal amyloidosis

Aims:  Because the cardiovascular system (CVS) side‐effects of cyclooxygenase‐2 (COX‐2) selective inhibitors have recently been questioned, we aimed to compare the renal and haemodynamic effects of cyclooxygenase selective (celecoxib and rofecoxib) and non‐selective non‐steroidal anti‐inflammatory drugs (NSAIDs) (indomethacin) in patients with renal amyloidosis secondary to rheumatological diseases who required anti‐inflammatory agents and are taking maximum tolerable dose of angiotensin‐converting enzyme inhibitors.