THYROID DISORDERS PREVALENCE IN A COHORT OF KIDNEY TRANSPLANT RECIPIENTS.

CONTEXT: As the life expectancy prolongs, malignancy has become an important issue in renal transplant recipients (RTRs). Thyroid cancer is the most common endocrine malignancy with ongoing increase in incidence all over the world. OBJECTIVE AND DESIGN: This is a cross-sectional study that investigates the thyroid disorders and the prevalence of thyroid nodule and cancer in RTRs. SUBJECTS AND METHODS: 204 RTRs were evaluated for the thyroid diseases with ultrasonography, serum thyroid stimulating hormone, free T4, free T3 levels, anti-thyroglobulin antibody and anti-thyroid peroxidase antibody levels; FNAB was carried if required. RESULTS: 191 patients (94.1%) had normal thyroid function. Subclinical hypothyroidism was diagnosed in 11 patients, subclinical hyperthyroidism in 1 patient and low T3 syndrome in 4 patients. The FNAB was performed in 17 (27.9%) from 61 patients with thyroid nodule. The cytological examination of biopsy materials revealed that 2 (11.8%) nodules were suspicious for malignancy, 13 (76.5%) were benign, and 2 (11.8%) with non diagnostic cytology. Thyroid cancer prevalence was 0.2% in Turkey but we detected that 0.98% of RTRs had thyroid cancer. CONCLUSIONS: Screening the RTRs for thyroid disorders is necessary, so that early diagnosis and appropriate treatment of thyroid disease and cancer may improve the quality of life.

The LDL/HDL ratio and atherosclerosis in ankylosing spondylitis.

OBJECTIVES: In ankylosing spondylitis (AS) patients, cardiac and vascular involvement may manifest as atherosclerosis and coronary artery disease. Systemic inflammation, oxidative stress, increased low-density lipoprotein (LDL) cholesterol and decreased high-density lipoprotein (HDL) cholesterol constitute a significant risk for atherosclerosis. This study investigated the relationship between carotid intima-media thickness (CIMT), LDL/HDL ratio, total oxidant status (TOS; an indicator of oxidative stress) and ischemic modified albumin (IMA; an ischemic marker in AS patients). PATIENTS AND METHODS: Sixty AS patients were diagnosed using the Modified New York Criteria; 54 age- and gender-matched participants were included as controls. CIMT, LDL/HDL ratio, TOS and IMA were measured using the most appropriate methods. RESULTS: IMA was higher in AS patients compared to controls (p < 0.0001). TOS was also increased in AS patients (p = 0.005); as was CIMT (p < 0.0001). The LDL/HDL ratio was also greater in AS patients compared to controls (p = 0.047). A positive correlation was found between CIMT and LDL/HDL ratio among AS patients. CONCLUSION: Elevated CIMT, IMA and TOS levels suggest an increased risk of atherosclerotic heart disease in AS patients. The LDL/HDL ratio was higher in AS patients compared to controls, and there was a correlation between LDL/HDL ratio and CIMT, albeit statistically weak. Therefore, the LDL/HDL ratio is not a reliable marker to predict atherosclerotic heart disease in AS patients.

Could immune cells be associated with nephropathy in Fabry disease patients?

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT. MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration. RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3-CD16+CD56+ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3+4+T-cells infiltration remained the same, whereas CD8+T cells, CD16+ and 56+NK-cells infiltration were significantly decreased. In contrast, CD20+B cells and CD138+plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20+B and CD138+ plasma cells and IF were positively correlated with proteinuria. CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

Insulin resistance and coronary flow velocity reserve in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). AIM: The aim of this study was to investigate coronary flow velocity reserve (CFVR) as a marker of endothelial dysfunction, carotid intima media thickness (CIMT) as a marker of subclinical organ damage and insulin resistance (IR) as a cardiovascular risk factor in patients with ADPKD. METHODS: Twenty-two normotensive ADPKD patients with well-preserved renal function and 19 healthy subjects were included in the study. Creatinine clearances were calculated by the Cockcroft-Gault formula. The homeostasis model of IR (HOMA-IR) was used to measure IR. CIMT was measured by high-resolution vascular ultrasound. CFVR was calculated as the ratio of hyperaemic to baseline diastolic peak velocities by echocardiography. RESULTS: There was no significant difference between the two groups regarding age, gender, body mass index, systolic and diastolic blood pressures, cholesterol and triglyceride levels. However, CIMT and HOMA-IR were significantly increased and CFVR was significantly decreased in patients with ADPKD compared with healthy subjects. CONCLUSIONS: The findings of decreased CFVR, increased CIMT and increased IR suggest that cardiovascular risk is elevated even in the early stages of ADPKD.

Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis.

Fungal pathogens are increasingly encountered after renal transplantation. Aspergillus causes significant morbidity and mortality in transplant patients. Fungal thyroiditis is a rare occurrence owing to unique features of the thyroid gland. Most cases are caused by Aspergillus species and have been described in immunocompromised patients. Presentation may be identical with that of subacute thyroiditis, in which hyperthyroidism features and painful thyroid are the prominent findings. Diagnosis can be ascertained by fine-needle aspiration of thyroid showing branching hyphae of Aspergillus. We describe a renal transplant patient who developed Aspergillus thyroiditis as part of a disseminated infection successfully treated with voriconazole.

Community-acquired carbapenem-resistant Acinetobacter baumannii urinary tract infection just after marriage in a renal transplant recipient.

Urinary tract infection (UTI) is common in renal transplant recipients and may worsen allograft and patient survival. Many risk factors such as age, female gender, immunosuppression, comorbidity, deceased-donor kidney transplantation, and uretheral catheterization are involved in development of UTI. Acinetobacter baumannii has rarely been reported as a causative agent for development of UTI. Here, we present an unusual case of a renal transplant recipient who developed community-acquired carbapenem-resistent A. baumannii UTI.

Fabry disease: where are we now?

Fabry disease (FD) is a multisystemic X-linked disorder characterized by the accumulation of lysosomal globotriaosylceramide (Gb3) secondary to decreased activity of α-galactosidase in cells. Generally, males are more severely affected due to the X-linked inheritance pattern of the disease. However, females are asymptomatic or have a less severe pattern of disease. Enzyme replacement therapy (ERT) is the cornerstone of the treatment of FD. At present, there are two forms of ERT that can be applied to FD patients. Novel therapeutic approaches including chaperone therapy, substrate reduction therapy, and gene therapy have been introduced in the era of treatment of FD. In this review, we aimed to discuss the prevalence, clinical and genetic features, pathophysiology, diagnosis, and therapeutic options in FD patients with nephropathy.

The Emerging Role of Sirtuin 1 in Cellular Metabolism, Diabetes Mellitus, Diabetic Kidney Disease and Hypertension.

Despite diagnostic and therapeutic approaches, diabetic kidney disease (DKD) is the most common cause of end-stage renal disease worldwide. Sirtuins, a group of nicotinamid adenine dinucleotide (NAD) dependent enzymes, can deacetylase target enzymes that regulate a wide variety of cellular processes regarding protein, carbohydrate and lipid metabolism, mitochondrial homeostasis and programmed cell death mechanisms including autophagy and apoptosis. Among sirtuins, sirtuin 1 (SIRT1) has been the most studied one in the pathogenesis and progression of DKD. In recent years, the relation between SIRT1 and hypertension was also evaluated.In the present review, we aimed to represent the mechanisms of SIRT1 in glucose and lipid metabolism and in the pathogenesis of diabetes mellitus. We also sought to highlight the emerging role of SIRT1 in the pathogenesis and treatment of DKD and hypertension.

The relationship between colonization of Oxalobacter formigenes serum oxalic acid and endothelial dysfunction in hemodialysis patients: from impaired colon to impaired endothelium.

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in chronic kidney disease (CKD) patients receiving hemodialysis (HD). Oxalic acid is a uremic retention molecule that has been extensively studied in the pathogenesis of calcium-oxalate stones. Oxalobacter formigenes (O. formigenes), a component of the colonic microbiota, plays an important role in oxalate homeostasis. Little is known regarding the colonization of HD patients by O. formigenes and the exact role of this bacterial species in oxalic acid metabolism in these patients. We hypothesized that oxalic acid may be insufficiently degraded in HD patients due to under colonization of the colon by O. formigenes in these patients. To test this hypothesis, we sought to quantitatively measure fecal O. formigenes levels and serum oxalic acid levels in HD patients. We also suggest that increased oxalic acid levels may be associated with endothelial dysfunction and aortic stiffness, both of which are commonly observed in HD patients. Increased colonization with O. formigenes via the ingestion of prebiotics and probiotics could potentially decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients.

Benefical effects of lycopene against contrast medium-induced oxidative stress, inflammation, autophagy, and apoptosis in rat kidney.

Currently, the number of imaging and interventional procedures that use contrast agents (CAs) is gradually increasing. Contrast-induced nephropathy (CIN) is the most important CA-related complication. Oxidative stress plays a significant role in its pathophysiology. Lycopene (LPN) is a natural substance with strong antioxidant capacity. The present study aimed to investigate the potential preventive effects of LPN against CIN. In total, 28 male Wistar albino rats were divided into 4 groups with 7 rats in each group; the groups include normal control group, LPN only group at a dose of 4 mg/kg/day for 10 days, CIN group by administering 10 mg/kg furosemide IM + 10 mg/kg indomethacin IP + 10 ml/kg iomeprol IV following 24-h dehydration, and CIN + LPN group. There were statistically significant increase in urea, creatinine, and malondialdehyde levels (p < 0.001, for all) but a significant decrease in glutathione, superoxide dismutase, catalase, and glutathione peroxidase levels (p < 0.001, for all) in the CIN group compared with the control group. On histological examination, a significant increase of infiltrated inflammatory cells and necrotic degenerative changes were observed in the CIN group and the immunohistochemical examination revealed a significant increase in inflammation (inducible nitric oxide synthase), autophagy (LC3/B), and apoptosis (cleaved caspase 3) in the CIN group compared with the control group (p < 0.05, for all). Significant improvements in these unfavorable parameters were observed with CIN + LPN group compared with the CIN only group. In conclusion, the favorable effects of LPN as an anti-inflammatory, antiautophagic, and antiapoptotic agent in an experimental model of CIN have been demonstrated.

Neutrophil-to-lymphocyte ratio, insulin resistance, and endothelial dysfunction in patients with autosomal dominant polycystic kidney disease.

Endothelial dysfunction (ED), insulin resistance (IR), and inflammation are risk factors for increased cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD). ADPKD patients may have increased carotid intima-media thickness (CIMT) and decreased coronary flow velocity reserve (CFVR). The neutrophil-to-lymphocyte ratio (NLR) was introduced as a marker to determine inflammation in various disorders. We aimed to investigate the relationship between NLR and IR, CFVR, CIMT, and the left ventricular mass index (LVMI) in normotensive ADPKD patients. Twentynine ADPKD patients (age 38.8 ± 10.2 years; 8 men and 21 women) and 19 healthy controls (age 33.8 ± 7.4 years; 8 men and 11 women) were included in this cross-sectional study. CFVR was calculated with echocardiography as the ratio of hyperemic to baseline diastolic peak coronary flow velocities. CIMT was measured in the distal common carotid artery by using a 10-MHz linear echocardiography probe. HOMA-IR was calculated NLR was calculated as the ratio of the neutrophil and lymphocyte counts. Age, sex, body mass index, and levels of glucose, creatinine, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, C-reactive protein (CRP), microalbuminuria, and creatinine clearance were similar between ADPKD patients and healthy subjects. NLR, CIMT, LVMI, and HOMA-IR were significantly higher and CFVR values were significantly lower in patients with ADPKD compared to that in healthy subjects. NLR showed positive correlation with CIMT, HOMA, insulin, glucose, and HDL cholesterol levels, while it was inversely correlated with CFVR and albumin level in all subjects. In patients with ADPKD, NLR showed positive correlation with HDL cholesterol level and inverse correlation with LVMI and albumin level. NLR that was found to be increased in patients with ADPKD may be a readily available marker of inflammation and ED.

Peri-aortic fat tissue and malnutrition-inflammation-atherosclerosis/calcification syndrome in end-stage renal disease patients.

PURPOSE: Thoracic peri-aortic fat tissue (PFT) is considered as a metabolically active organ in atherosclerosis. Malnutrition, inflammation and atherosclerosis/calcification (MIAC) are the most commonly encountered risk factors of cardiovascular disease in end-stage renal disease (ESRD) patients. Calcification of the aorta was found to be an important cardiovascular risk marker predicting future events, morbidity and mortality in this population. We aimed to investigate the relationship between PFT, MIAC syndrome and thoracic aortic calcification (TAC) in ESRD patients. METHODS: Seventy-nine ESRD patients receiving hemodialysis (HD) or peritoneal dialysis (PD) and 20 control subjects were enrolled in this cross-sectional study. PFT and TAC were assessed using a 64-MDCT scanner. Patients with serum albumin <3.5 g/dL were defined as patients with malnutrition; those with serum C-reactive protein level >10 mg/L had inflammation, and those with coronary artery calcification score (CACS) >10 had atherosclerosis/calcification. RESULTS: TAC and PFT were significantly higher in ESRD patients compared with control subjects. There was a statistically significant relationship between PFT and TAC in ESRD patients (r = 0.458, p < 0.0001). PFT was found to be significantly increased when the MIAC components increased. PFT was positively associated with age, BMI, uric acid, hemoglobin and CAC. The multivariate analysis revealed that age and uric acid were independent predictors of increased PFT. Twenty-four (30.4 %) patients had none, 30 (37.9 %) had one component, 17 (21.5 %) had two components, and 8 (10.2 %) had all MIAC components. PFT was highest among patients having all three components (28.6 cm(3)) and lowest among those who do not have the MIAC syndrome (8.54 cm(3)). TAC was highest among patients having all three components (179.2 HU) and lowest among those who do not have the MIAC syndrome (0 HU). CONCLUSIONS: We found a relationship between PFT and MIAC syndrome in ESRD patients.

Falls in elderly hemodialysis patients.

The elderly, (age ≥ 65 years) hemodialysis (HD) patient population is growing rapidly across the world. The risk of accidental falls is very high in this patient population due to multiple factors which include aging, underlying renal disease and adverse events associated with HD treatments. Falls, the most common cause of fatal injury among elderly, not only increase morbidity and mortality, but also increase costs to the health system. Prediction of falls and interventions to prevent or minimize fall risk and associated complications will be a major step in helping these patients as well as decreasing financial and social burdens. Thus, it is vital to learn how to approach this important problem. In this review, we will summarize the epidemiology, risk factors, pathophysiology and complications of falls in elderly HD patients. We will also focus on available methods to assess and predict the patients at higher risk of falling and will provide recommendations for interventions to reduce the occurrence of falls in this population.

Fetuin-A, inflammation, and coronary artery calcification in hemodialysis patients.

Hemodialysis patients have extremely increased cardiovascular mortality. Vascular calcification, inflammation, and low serum fetuin-A levels are implicated for increased mortality. In this study, relationship between coronary artery calcification, inflammation, and serum fetuin-A levels were investigated. Seventy-eight hemodialysis patients (38 male, 40 female, mean age: 52±14.5 years) were included. All patients were on dialysis for more than 6 months. Coronary artery calcium scores (CACS) are determined by electron-beam computed tomography. Serum CRP, IL-1ß, IL-6, TNF-α, and serum fetuin-A levels were measured. Mean CACS value was 488.5±94.5. Serum fetuin-A levels were negatively correlated with CACS (r:-0.30, P=0.009). Patients are divided into two groups according to total CACS value; group 1 (CACS<10), group 2 (CACS≥10). There was a statistically significance difference in fetuin-A levels between CACS group 1 and group 2 (P=0.001). In this study, serum fetuin-A levels were associated with total CACS. This Fetuin-A may play a role in increased mortality in this group of patients via facilitating CAC.

Successful peritoneal dialysis in a hemophilia A patient with factor VIII inhibitor.

Chronic kidney disease and need for renal replacement therapy in hemophiliacs are relatively rare occurrences. Successful hemodialysis and peritoneal dialysis applications have been reported in the literature. We report a difficult-to-manage patient with hemophilia A plus factor VIII inhibitor who presented with gastrointestinal bleeding complicated by uremia. We admitted this hemophilia A patient with gastrointestinal bleeding who did not take regular factor infusions. He also had chronic kidney disease due to urinary stone disease. Since uremia might have contributed to bleeding, we chose hemodialysis along with factor VIII supplementation. His factor VIII and factor VIII inhibitor levels were 4% and 5 Bethesda units respectively. In order to bypass the inhibitor, we applied factor VIIA and prothrombin complex concentrate. After cessation of the hemorrhage, we placed a Tenckhoff catheter under prothrombin complex concentrate infusion. We did not observe any perioperative complication. To our knowledge, this is the first report of successful peritoneal dialysis in a hemophilia A patient who had factor VIII inhibitors.

Assessment of adrenal functions in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and extrarenal manifestations may be observed in many organ systems. Hypothalamus-pituitary-adrenal axis was not evaluated extensively in patients with ADPKD. We aimed to evaluate this axis in these patients. METHODS: Twenty two patients with ADPKD and 27 healthy subjects were enrolled. Basal dehydroepiandrosterone sulfate (DHEAS) levels and cortisol and DHEA responses to low dose short adrenocorticotropin stimulation test were assessed. Correlation analyses of these parameters with glomerular filtration rates (GFR), renal volumes and pain characteristics in patients with ADPKD were performed. RESULTS: Patients with ADPKD had higher basal cortisol levels (12.1 ± 3.4 vs. 9.6 ± 4.3 µg/dL, p=0.033), and higher basal cortisol/DHEAS ratios (0.073 ± 0.05 vs. 0.045 ± 0.02, p=0.015) compared to controls. None of the subjects had inadequate response to adrenocorticotropin stimulation. Patients with ADPKD had lower delta cortisol (absolute increase between peak and basal) levels (10.3 ± 2.8 vs. 12.6 ± 4.2 µg/dL, p=0.026) compared to controls. Subgroup analysis showed that significant differences existed only between female patients and female controls. There was no significant correlation between cortisol levels and renal volumes or GFR. A significant correlation was found only between delta cortisol and pain frequency in female patients. CONCLUSIONS: Patients with ADPKD had higher basal cortisol levels, higher basal cortisol/DHEAS ratios and lower delta cortisol levels compared to controls, indicating promptly stimulated zona fasciculata function. Further studies are needed to confirm these results and to investigate possible underlying mechanisms.

Milk of calcium hydronephrosis.

There are very few reported cases of 'milk of renal calcium' since Holm's first presentation of this rare condition in 1948 [Rosenberg, J. Urol., 101: 714, 1967]. We recently had the opportunity to study 2 more cases, which are described herein.