Abdulmecit Yildiz

Colchicine in Renal Medicine: New Virtues of an Ancient Friend

Colchicine is a plant-derived alkaloid that disrupts the cell microtubule system and accumulates in neutrophils, inhibiting neutrophil adhesion and recruitment. Colchicine has been used extensively in the prevention and treatment of gouty arthritis attacks, familial Mediterranean fever attacks and resultant AA amyloidosis, and recurrent pericarditis. Colchicine also disrupts the intracellular traffic of additional inflammatory and fibrosis mediators. Renal fibrosis is the final common pathway of chronic renal disease. Colchicine had anti-fibrotic effects in experimental diabetic nephropathy, renal mass reduction, and cyclosporine nephrotoxicity among others and is undergoing clinical trials for non-diabetic metabolic syndrome and diabetic nephropathy. In this review, we summarize the anti-inflammatory and anti-fibrotic properties of colchicine in experimental and clinical studies in renal diseases or other fibrotic disease processes with renal consequences. We also discuss the potential future uses of colchicine in renal medicine and challenges faced with its use in patients with impaired kidney function.

Association of monocyte to HDL cholesterol level with contrast induced nephropathy in STEMI patients treated with primary PCI.

Abstract Background: Contrast induced nephropathy (CIN) has been proven to be a clinical condition related to adverse cardiovascular outcomes. In recent studies, the monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with CIN in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods: Consecutive STEMI patients treated with primary PCI were prospectively recruited. Subjects were categorized into two groups; as patients who developed CIN (CIN+) and patients who did not develop CIN (CIN–) during hospitalization. CIN was defined as either a 25% increase in serum creatinine from baseline or 44.20 µmol/L increase in absolute value, within 72 h of intravenous contrast administration. Results: A total number of 209 patients were included in the study. Thirty-two patients developed CIN (15.3%). In the CIN (+) patients, monocytes were higher [1.02 (0.83–1.39) vs. 0.69 (0.53–0.90) 109/L, p<0.01] and HDL cholesterol levels were lower [0.88 (0.78–1.01) vs. 0.98 (0.88–1.14) mmol/L, p<0.01]. In addition, MHR was significantly higher in the CIN (+) group [1.16 (0.89–2.16) vs. 0.72 (0.53–0.95) 109/mmol, p<0.01]. In multivariate logistic regression analysis, MHR, Mehran score, AGEF score and CV/eGFR were independently correlated with CIN. Conclusions: Higher MHR levels may predict CIN development after primary PCI in STEMI patients.

Urea to creatinine ratio: a forgotten marker of poor nutritional state in patients undergoing hemodialysis treatment

Abstract Background: Malnutrition is common in subjects undergoing hemodialysis and is associated with increased morbidity and mortality. Studies investigating factors associated with malnutrition and effect of various interventions to treat these patients are needed. We aimed to screen older and young patients undergoing chronic hemodialysis, for malnutrition, and seek its association with clinical factors including anxiety and depression and laboratory variables including urea/creatinine ratio (UCR). Methods: Duration of hemodialysis treatment, medications taken, anthropometric measurements and routine laboratory results were recorded. Mini nutritional assessment and Beck anxiety and Beck depression inventories were applied. Study variables between subjects with malnutrition, malnutrition risk and normal nutritional states were compared. Older and younger patients were also compared regarding malnutrition and laboratory results. Linear regression analysis was performed to seek independent factors associated with malnutrition score. Results: Clinical and laboratory data except for UCR were found to be similar among young and older patients. UCR increased, while albumin, body mass index and weight circumference decreased along with worse nutritional state. Low albumin level, body mass index and UCR and higher hemoglobin level and depression score were independent factors associated with malnutrition. Conclusion: In addition to routinely used markers of malnutrition UCR may provide additional information regarding malnutrition in this population.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever

AIM Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. METHODS One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. RESULTS As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p<0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p>0.05). CONCLUSIONS To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Obesity: a possible risk factor for restless legs syndrome

Abstract Aim/Background: Restless legs syndrome (RLS) is a frequent neurological and sleep disorder. Metabolic disorders are known to be related to sleep disorders. We prospectively evaluated whether obesity and its possible cofactors were related to the presence of RLS. Materials and Methods: The study included 143 obese and 94 non-obese individuals. Obese patients had a BMI of 30 and over, while non-obese patients had a BMI lower than 30. Patients with arthritis and pregnancy were excluded but not those with diabetes mellitus. Participants who met diagnostic criteria recommended by the International RLS Study Group were diagnosed as having RLS. Depression, anxiety, daytime sleepiness, insomnia and sleep quality were evaluated in detail. Results: The mean age of obese patients was 40.52 years and that of non-obese patients was 39.76 years. The mean body mass index was 36.77 in the obese group and 25.71 in the non-obese group. The occurrence of depression, anxiety, sleep quality, and insomnia scores were significantly higher in obese individuals. The evaluations of daytime sleepiness, sleep efficiency and sleep latency were not significantly different between the groups. Discussion: Although the presence of RLS was correlated with obesity and vascular risk factors at a significant level, it was also shown that depression, anxiety and insomnia were significantly frequent in obese patients (although not daytime sleepiness). Further studies are needed.

Fluvastatin Decreases Oxidative Stress in Kidney Transplant Patients.

OBJECTIVE Oxidative stress has been suggested to have a pivotal role in the development of cardiovascular disease in kidney transplant patients (KTPs). The effects of fluvastatin on oxidative status in KTPs have not been well evaluated. The aim of the present study was to evaluate the effects of fluvastatin on oxidative status by investigating erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx), serum paraoxonase (PON1), and serum arylesterase (ARE), along with lipid peroxidation products, serum malonldialdehyde, and apolipoprotein B malondialdehyde (ApoB MDA). METHODS Eighteen KTPs were included in the present study. Blood samples were obtained after 1 nights fast. Erythrocyte SOD, erythrocyte GPx, serum PON1, serum ARE, serum MDA, and ApoB MDA were measured using methods described previously. Paired-sample t test was used for comparing the changes from week 0 to week 4 of parameters that might be associated with fluvastatin treatment. RESULTS The present study has shown that erythrocyte SOD and GPx, and serum PON1 and ARE activities increased at the fourth week of the statin treatment. Furthermore an increase in the antioxidant enzymes following fluvastatin may be a clue for the antioxidant effects of this drug. Four weeks of fluvastatin long-acting tablets 80 mg/day led to a decrease in plasma Apo-MDA and MDA levels. CONCLUSION The findings of the present study demonstrate that fluvastatin 80 mg long-acting tablets may be used safely for 4 weeks and decrease atherogenic lipoproteins in KTPs. Furthermore, after 4 weeks of fluvastatin treatment, the levels of antioxidant parameters increased and oxidative parameters decreased. Further placebo-controlled treatment studies would be helpful to evaluate the effects of fluvastatin on oxidant and antioxidant parameters including PON1 in patients with KT.

Assessment of Cognitive Dysfunction in Hemodialysis Patients By the Mini Mental Test and the Clock Drawing Test

OBJECTIVE: Our aim was to assess cognitive dysfunction, which is common in hemodialysis patients and difficult to diagnose, by an easily applicable test, the Mini Mental State Examination and Clock Drawing Test. MATERIAL and METHODS: Two hundred and sixty six (266, 88.37%) dialysis patients that were followed-up at the Nephrology Clinic of Bursa Specialty Training and Research Hospital and private dialysis centers, and 35 (11.63%) healthy control individuals were involved in our study. Mini Mental State Examination and Clock Drawing Test were applied by a neurologist to the subjects. MMSE and CDT scores of the patients were compared with the control group. RESULTS: Patient and control groups were similar in terms of age, gender, diabetes, and smoking. The rate of hypertension was significantly higher in the dialysis group. Mini Mental State Examination and Clock Drawing Test success rates were significantly higher in the control group. Orientation, attention and language modalities evaluated in the MMSE were observed to be significantly lower in the hemodialysis group. A statistically significant inverse correlation was found between registration memory and recall scores in MMSE, and urea. CONCLUSION: Cognitive performances of hemodialysis patients must be monitored closely. The relationship between record memory and recall scores and urea suggests that uremic toxins may affect memory functions negatively. In addition, cognitive performance can be monitored by Clock Drawing Test in these patients.

Sexual Dysfunction and Risk Factors in Females Patients on Renal Replacement Therapy

Introduction Women with chronic kidney disease have a higher risk of sexual dysfunction (SD). The etiology is often multifactorial and may include psychological problems. A successful kidney transplantation can improve SD. This study aimed to investigate SD frequency, and risk factors in the females under renal replacement therapy (RRT) and in the healthy ones. Materials and Methods A total of 62 kidney transplant recipients (Tx), 43 hemodialysis (HD) and 35 predialysis (PreD) patients and 52 healthy females were included. Sociodemographic and risk factor survey forms, the hospital anxiety depression scale and the 36-Item Short Form Health Survey were used. Sexual function was assessed according to the Female Sexual Function Index (FSFI). Women with a score ⩽22.7 were classified as presenting sexual dysfunction. Results Control and Tx patients groups were significantly younger than HD and PreD patients. There were differences in the ratios of asthenia and fatigue, pelvic surgery, urinary incontinence, cystitis history, dyspareunia, smoking, use of antidepressant and beta blockers between the groups. The depression and anxiety ratios of the groups were similar. The physiological health scores of the control group were significantly higher than those of the PreD and Tx groups and also scores of the Tx group than those of the HD and PreD groups. Mental health scores of the control group were significantly higher than those of the PreD and HD groups. The SD ratio of Tx group with FSFI (n:10, 16.1%) was significantly lower than HD group (n:18, 41.9%, p=0.006). The SD ratio of PreD group was 31.4% (n:11). The SD ratio of control group was 23.1% (n:12). Desire scores of the Tx and control groups were higher than those of HD and PreD groups. Arousal scores of HD and PreD group were significantly lower than those of control (p=0.013 vs. HD, p=0.047 vs. PreD) and Tx (p=0.004 vs. HD, p=0.015 vs. PreD) groups. Lubrication score of HD group was lower than those of Tx (p=0.006) and control (p=0.014) groups. Orgasm score of HD group was lower than those of Tx (p=0.012) and control (p=0.009) groups, and PreD group score was lower than that of control group (p=0.046). The overall scores of the HD and PreD groups were significantly lower than those of Tx (p=0.001 vs. HD, p=0.002 vs. PreD) and control (p=0.003 vs. HD, p=0.005 vs. PreD) groups (Table 1). Logistic regression analysis showed that inadequate sexual information (OR:3.333, 95%CI: 1.426-7.790, p=0.005), presence of anxiety (OR:2.978, 95%CI: 1.093-8.117, p=0.033) and depression (OR:4.514, 95%CI: 1.676-12.156, p=0.003) increased SD risk. Kidney transplantation significantly reduced SD risk (OR:0.236, 95%CI: 0.073-0.766, p=0.016). Conclusion SD improve after successful transplant. Our results do not support the impact of the sociocultural and economic factors in sexual function of women on renal replacement treatment. However, psychological factors negatively affect sexual function in dialysis patients. Table. No title available.

Clinical outcomes and survival in AA amyloidosis patients

AIM Amyloid A amyloidosis is a rare complication of chronic inflammatory conditions. Most patients with amyloid A amyloidosis present with nephropathy and it leads to renal failure and death. We studied clinical characteristics and survival in patients with amyloid A amyloidosis. METHODS A total of 81 patients (51 males, 30 females) with renal biopsy proven amyloid A amyloidosis were analyzed retrospectively. The patients were divided into good and poor outcomes groups according to survival results. RESULTS Most of the patients (55.6%) had nephrotic range proteinuria at diagnosis. Most frequent underlying disorders were familial Mediterranean fever (21.2%) and rheumatoid arthritis (10.6%) in the good outcome group and malignancy (20%) in the poor outcome group. Only diastolic blood pressure in the good outcome group and phosphorus level in the poor outcome group was higher. Serum creatinine levels increased after treatment in both groups, while proteinuria in the good outcome group decreased. Increase in serum creatinine and decrease in estimated glomerular filtration rate of the poor outcome group were more significant in the good outcome group. At the time of diagnosis 18.5% and 27.2% of all patients had advanced chronic kidney disease (stage 4 and 5, respectively). Median duration of renal survival was 65±3.54 months. Among all patients, 27.1% were started dialysis treatment during the follow-up period and 7.4% of all patients underwent kidney transplantation. Higher levels of systolic blood pressure [hazard ratios 1.03, 95% confidence interval: 1-1.06, p=0.036], serum creatinine (hazard ratios 1.25, 95% confidence interval: 1.07-1.46, p=0.006) and urinary protein excretion (hazard ratios 1.08, 95% confidence interval: 1.01-1.16, p=0.027) were predictors of end-stage renal disease. Median survival of patients with organ involvement was 50.3±16 months. CONCLUSION Our study indicated that familial Mediterranean fever constituted a large proportion of cases and increased number of patients with idiopathic amyloid A amyloidosis. Additionally, it was observed that patient survival was not affected by different etiological causes in amyloid A amyloidosis.

Use of tolvaptan in patients hospitalized for worsening chronic heart failure with severe hyponatremia: The initial experience at a single-center in Turkey

OBJECTIVE The aim of the present study was to assess the efficacy and safety of tolvaptan for severe hyponatremia (SH) in hypervolemic heart failure (HF) patients within daily clinical practice. METHODS We restrospectively reviewed our database on tolvaptan as an add-on treatment in hypervolemic patients admitted to our clinic due to deterioration of HF and having hyponatremia resistant to standard therapy. Severe hyponatremia was defined as serum sodium concentration ≤125 mEq/L. The database included demographic, clinical, laboratory, and echocardiographic findings on admission, and numerous outcome measures for oral tolvaptan treatment were used to assess its efficacy and safety. RESULTS The study group consisted of 56 hypervolemic HF patients with severe hyponatremia (25 female and 31 male) with mean age of 66 years. All patients received a single dose of tolvaptan 15 mg daily for an average of 3.2 days due to severe hyponatremia. Sodium and potassium concentrations, fluid intake, and urine volume increased (p<0.0001, p=0.037, p<0.0001, and p<0.0001, respectively), whereas furosemide dosage, body weight, heart rate, systolic and diastolic blood pressure, and New York Heart Association class decreased significantly in response to tolvaptan treatment, without a rise in serum creatinine or urea concentrations (p<0.0001, p<0.0001, p=0.001, p<0.049, p<0.009 ve p=0.001, respectively). CONCLUSION In this retrospective, single-centered study conducted in a small group of Turkish patients, short-term treatment with low-dose tolvaptan added to standard therapy of hypervolemic HF patients with severe hyponatremia was well tolerated with a low rate of major side effects and was effective in correcting severe hyponatremia.