Salih Inal

Neutrophil to Lymphocyte Ratio in Evaluation of Inflammation in Patients with Chronic Kidney Disease

Aim: The current data have proven the pivotal role of inflammation in the development of atherosclerosis and cardiovascular diseases in patients with chronic kidney disease (CKD). Neutrophil to lymphocyte (N/L) ratio has increasingly been reported as a measure of systemic inflammation. This study assessed N/L ratio and investigated its associations with standard inflammatory biomarkers in different stages of CKD patients. Material and methods: This cross-sectional study included 30 predialysis, 40 hemodialysis, 35 peritoneal dialysis patients, and 30 healthy subjects. N/L ratio and important clinical and laboratory parameters were registered. Multivariate regression analyses were carried out to investigate the relations of N/L ratio. Results: N/L ratio was significantly higher in each patient group compared to the healthy subjects (for all, p < 0.001). It was positively correlated with interleukin-6 (IL-6) (r = 0.393, p < 0.001) and high-sensitivity C-reactive protein (hs-CRP) (r = 0.264, p = 0.002) levels and negatively correlated with hemoglobin (r = −0.271, p = 0.001), serum albumin (r = −0.400, p < 0.001), and high-density lipoprotein (HDL) cholesterol levels (r = −0.302, p < 0.001). In CKD patients with hypertension (HT), higher N/L ratio was detected when compared to those without HT (p = 0.006). Having CKD, the presence of HT, serum albumin, HDL-cholesterol, IL-6, and hs-CRP levels were found to be independent predictors of the ratio after adjusting for significant covariates (p < 0.001). Conclusion: An easy and inexpensive laboratory measure of N/L ratio might provide significant information regarding inflammation in CKD including predialysis and dialysis patients.

Idiopathic Hypoparathyroidism Mimicking Diffuse Idiopathic Skeletal Hyperostosis

Idiopathic hypoparathyroidism is an uncommon disease caused by insufficient secretion of parathyroid hormone. Idiopathic hypoparathyroidism may cause various musculoskeletal findings, including diffuse ligamentous and entheseal ossifications. Diffuse idiopathic skeletal hyperostosis is a disorder of the elderly characterized by ossification of the anterior longitudinal ligament of the spine and various extraspinal ligaments. We present a 50-year-old man with idiopathic hypoparathyroidism who had been diagnosed as having DISH at 40 years of age. Resistant neck, left shoulder, and left hip pain did not improve with calcium and calcitriol treatment after diagnosis of idiopathic hypoparathyroidism.

Left Ventricular Hypertrophy and Blood Pressure Control in Automated and Continuous Ambulatory Peritoneal Dialysis Patients

Hypertension, non‐dipper blood pressure (BP) pattern and decrease in daily urine output have been associated with left ventricular hypertrophy (LVH) in peritoneal dialysis (PD) patients. However, there is lack of data regarding the impact of different PD regimens on these factors. We aimed to investigate the impact of circadian rhythm of BP on LVH in end‐stage renal disease patients using automated peritoneal dialysis (APD) or continuous ambulatory peritoneal dialysis (CAPD) modalities. Twenty APD (7 men, 13 women) and 28 CAPD (16 men, 12 women) patients were included into the study. 24‐h ambulatory blood pressure monitoring (ABPM) and transthoracic echocardiography besides routine blood examinations were performed. Two groups were compared with each other for ABPM measurements, BP loads, dipping patterns, left ventricular mass index (LVMI) and daily urine output. Mean systolic and diastolic BP measurements, BP loads, LVMI, residual renal function (RRF) and percentage of non‐dippers were found to be similar for the two groups. There were positive correlations of LVMI with BP measurements and BP loads. LVMI was found to be significantly higher in diastolic non‐dippers compared to dippers (140.4 ± 35.3 vs 114.5 ± 29.7, respectively, P = 0.02). RRF and BP were found to be independent predictors of LVMI. Non‐dipping BP pattern was a frequent finding among all PD patients without an inter‐group difference. Additionally, higher BP measurements, decrease in daily urine output and non‐dipper diastolic BP pattern were associated with LVMI. In order to avoid LVH, besides correction of anemia and volume control, circadian BP variability and diastolic dipping should also be taken into consideration in PD patients.

Sunitinib- and Sorafenib-Induced Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor

Objective TO report a case of nephrotic syndrome (NS) induced by both sunitinib and sorafenib therapy. Case Summary A 61-year-old woman with metastatic gastrointestinal stromal tumor (GIST) presented with NS and hypertension following therapy with sunitinib 400 mg/day. Because of grade 3 toxicity, the drug was discontinued. After sunitinib discontinuation, NS and hypertension resolved. However, NS recurred on rechallenge. A similar picture developed following therapy with sorafenib 800 mg/day. A renal biopsy revealed a focal segmental glomerulosclerosis (FSGS). A few months after sorafenib cessation, resolution of NS and hypertension was again achieved. Discussion Several cases of NS have been reported among patients receiving sunitinib and sorafenib. However, renal histopathologic data were obtained in only a few patients. Although biopsy-proven cases of FSGS associated with sunitinib have been reported, this is, to our knowledge, the first reported case of biopsy-proven FSGS associated with sorafenib. The Naranjo probability scale indicated probable causality for NS developing with sorafenib, and definite causality with sunitinib. The clinical and histopathologic findings have led us to agree with the class effect proposal that all antiangiogenic drugs share a similar toxicity profile. Evidence supporting this hypothesis includes worsening of hypertension and proteinuria by both drugs, with full recovery occurring within a few months after cessation of the drugs, which favors the role of vascular endothelial growth factor receptor inhibition in FSGS development. Conclusions The clinical adverse spectrum of antiangiogenic drugs may be broader than initially observed because of a lack of renal biopsy data and routine screening for proteinuria. It can be speculated that proteinuria, as well as hypertension, is a class effect of all antiangiogenic drugs.

Acute Kidney Injury due to Rhabdomyolysis in H1N1 Influenza Infection

Acute kidney injury (AKI) is rarely reported in the clinical course of H1N1 infection and this condition is strongly related with increasing of mortality risk. However, there are no sufficient data about the development of AKI due to H1N1 infections. The recent reports were documented for elevation of creatinine phosphokinase levels in the course of influenza infection, but rhabdomyolysis was rarely reported. Herein, we present a 28-year-old female patient and a 19-year-old male patient with AKI in the course of H1N1 influenza infection due to rhabdomyolysis.

Novel Inflammatory Marker in Dialysis Patients: YKL-40

YKL‐40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL‐40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL‐40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine‐6 (IL‐6) and an acute phase mediator, high sensitivity C‐reactive protein (hs‐CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL‐40, IL‐6, hs‐CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL‐40, IL‐6, hs‐CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein‐cholesterol (P < 0.001). YKL‐40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL‐6 (P < 0.001, r = 0.306), hs‐CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = −0.285), serum albumin (P < 0.001, r = −0.355) and high density lipoprotein‐cholesterol (P = 0.001, r = −0.306). In multivariate regression analysis YKL‐40 was associated with creatinine, serum albumin and hs‐CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL‐40 concentrations. Associations with standard inflammatory parameters suggest that YKL‐40 might be a novel inflammatory marker in this population.

Protective effect of adrenomedullin on contrast induced nephropathy in rats

BACKGROUND AND AIMS Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. METHODS Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. RESULTS Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. CONCLUSION This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue.

Is colchicine therapy effective in all patients with secondary amyloidosis

Abstract Objective: Although colchicine is effective on prevention and regression of amyloidosis in many cases, rate of unresponsiveness to colchicine therapy is not too low. However, there is no sufficient data about which factors effect to response of colchicine therapy on regression of amyloidosis. Materials and methods: 24 patients with renal amyloidosis were enrolled into the study. The patients were divided in two groups according to urinary protein excretions: non-nephrotic stage (14/24) and nephrotic stage (10/24). The patients were also categorized according to the etiology of amyloidosis; familial Mediterranean fever (FMF)-associated amyloidosis (15/24) versus rheumatoid disorders (RD)-associated amyloidosis (9/24). The changes of amount of proteinuria and estimated glomerular filtration rates were investigated after colchicine treatment started in these groups. Results: The mean follow-up period was 27.7 ± 19.2 months. After initiating colchicine therapy, the degree of proteinuria was decreased higher than 50% in 11/14 (78%) of non-nephrotic patients and elevated only in three (22%) patients. In nephrotic group, proteinuria was increased in 5/10 (50%) of patients. Glomerular filtration rates were stable in nephrotic and non-nephrotic groups. Presenting with nephrotic syndrome was higher in RD-associated amyloidosis (RD_A) group (5/9) than FMF-associated amyloidosis (FMF_A) group (5/15) without statistical significance (p > 0.05). After colchicine treatment, proteinuria was decreased in 12/15 patients in FMF_A group, however, the significant decreasing of proteinuria was not observed in RD_A group (p = 0.05 vs. p > 0.05). Conclusion: Colchicine therapy was found more effective in low proteinuric stage of amyloidosis. The beneficial effect of colchicine therapy was not observed in patients with RD- associated amyloidosis.

Methoxy Polyethylene Glycol-Epoetin Beta (CERA) Induced Restless Legs Syndrome

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Remission of De Novo Membranous Nephropathy in a Kidney Allograft Recipient: a Case Report

Membranous nephropathy (MN), one of the most frequent causes of nephrotic syndrome in native kidneys, is also a common glomerular pathology in transplanted kidneys(Davison AM, Johnston PA. Allograft membranous nephropathy, Nephrol Dial Transplant, 1992;7(Suppl. 1):114–118. Specific treatment modalities have not been described for this population. However, renal transplanted patients presented with MN could have spontaneous remission as those with idiopathic MN. Here, we report a kidney allograft recipient diagnosed with de novo MN in early phases of posttransplantation period having a clinical remission over months.