Everolimus-Related Chylothorax: A Rare Case Report.

Everolimus is an orally administered mechanistic target of rapamycin inhibitor in solid-organ transplant patients. In addition to the common adverse side effects of this treatment, such as hyperlipidemia, rash, stomatitis, anorexia, diarrhea, anemia, thrombocytopenia, and leukopenia, pulmonary toxicity is also an important adverse side effect. Although pulmonary toxicity due to everolimus has been reported mostly as pneumonitis, cases of pleural effusion due to everolimus have also been reported rarely. Chylothorax is defined as the accumulation of lymphatic fluid in the pleural space. It may develop secondary to trauma or malignancy. In this case report, we present a patient with chylothorax after everolimus treatment.

Allogeneic bone marrow mesenchymal stem cell-derived exosomes alleviate human hypoxic AKI-on-a-Chip within a tight treatment window.

BACKGROUND: Acute hypoxic proximal tubule (PT) injury and subsequent maladaptive repair present high mortality and increased risk of acute kidney injury (AKI) - chronic kidney disease (CKD) transition. Human bone marrow mesenchymal stem cell-derived exosomes (hBMMSC-Exos) as potential cell therapeutics can be translated into clinics if drawbacks on safety and efficacy are clarified. Here, we determined the real-time effective dose and treatment window of allogeneic hBMMSC-Exos, evaluated their performance on the structural and functional integrity of 3D microfluidic acute hypoxic PT injury platform. METHODS: hBMMSC-Exos were isolated and characterized. Real-time impedance-based cell proliferation analysis (RTCA) determined the effective dose and treatment window for acute hypoxic PT injury. A 2-lane 3D gravity-driven microfluidic platform was set to mimic PT in vitro. ZO-1, acetylated α-tubulin immunolabelling, and permeability index assessed structural; cell proliferation by WST-1 measured functional integrity of PT. RESULTS: hBMMSC-Exos induced PT proliferation with ED50 of 172,582 µg/ml at the 26th hour. Hypoxia significantly decreased ZO-1, increased permeability index, and decreased cell proliferation rate on 24-48 h in the microfluidic platform. hBMMSC-Exos reinforced polarity by a 1.72-fold increase in ZO-1, restored permeability by 20/45-fold against 20/155 kDa dextran and increased epithelial proliferation 3-fold compared to control. CONCLUSIONS: The real-time potency assay and 3D gravity-driven microfluidic acute hypoxic PT injury platform precisely demonstrated the therapeutic performance window of allogeneic hBMMSC-Exos on ischemic AKI based on structural and functional cellular data. The novel standardized, non-invasive two-step system validates the cell-based personalized theragnostic tool in a real-time physiological microenvironment prior to safe and efficient clinical usage in nephrology.

A comparative urinary proteomic and metabolomic analysis between renal aa amyloidosis and membranous nephropathy with clinicopathologic correlations.

Urinary omics has become a powerful tool for elucidating pathophysiology of glomerular diseases. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urine proteomic and metabolomic analysis between recently diagnosed renal AA amyloidosis (AA) and membranous nephropathy (MN) patients. Urine samples of 22 (8 AA, 8 MN and 6 healthy control) patients were analyzed with nLC-MS/MS and GC/MS for proteomic and metabolomic studies, respectively. Pathological specimens were scored for glomerulosclerosis and tubulointerstitial fibrosis grades. Functional enrichment analysis between AA and control groups showed enrichment in cell adhesion related sub-domains. Uromodulin (UMOD) was lower, whereas ribonuclease 1 (RNase1) and α-1-microglobulin/bikunin precursor (AMBP) were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03) and AMBP-eGFR (r = -0.69, p = 0.003) variables. Metabolomic analysis showed myo-inositol and urate were higher in AA compared to MN group. A positive correlation was detected between RNase1 and urate independent of eGFR values (r = 0.63, p = 0.01). Enrichment in cell adhesion related domains suggested a possible increased urinary shear stress due to amyloid fibrils. UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be related with systemic inflammation in AA amyloidosis. SIGNIFICANCE: Urinary omics studies have become a standard tool for biomarker studies. However, no urinary omics analysis has been performed yet on renal AA amyloidosis. Here, we performed a comparative urinary omics analysis between recently diagnosed renal AA amyloidosis (AA), membranous nephropathy (MN) patients and healthy controls. Pathological specimens were scored with glomerulosclerosis (G) and tubulointerstitial fibrosis (IF) grades to consolidate the results of the omics studies and correlation analyzes. Functional enrichment analysis showed enrichment in cell adhesion related sub-domains due to downregulation of cadherins; which could be related with increased urinary shear stress due to amyloid deposition and disruption of tissue micro-architecture. In comparative proteomic analyzes UMOD was lower, whereas RNase1 and AMBP were higher in AA compared to MN group. Whereas in metabolomic analyzes; myo-inositol, urate and maltose were higher in AA compared to MN group. Correlations were demonstrated between UMOD-proteinuria (r = -0.48, p = 0.03), AMBP-eGFR (r = -0.69, p = 0.003) and between RNase1-Urate independent of eGFR values (r = 0.63, p = 0.01). This study is the first comprehensive urinary omics analysis focusing on renal AA Amyloidosis to the best of our knowledge. Based on physiologic roles and clinicopathologic correlations of the molecules; UMOD, AMBP and myo-inositol were related with tubulointerstitial damage, whereas RNase1 and urate were believed to be increased with systemic inflammation and endothelial damage in AA amyloidosis.

Evaluation of renal fibrosis in various causes of glomerulonephritis by MR elastography: a clinicopathologic comparative analysis.

BACKGROUND: Renal parenchymal fibrosis is the most important determinant of kidney disease progression and it is determined via biopsy. The aim of this study is to evaluate the renal stiffness noninvasively by magnetic resonance elastography (MRE) and to compare it with clinicopathologic parameters in glomerulonephritis and AA amyloidosis patients. METHODS: Thirty-four patients with glomerular filtration rate (GFR) over 20 ml/min/1.73m2 had non-contrast MRE prospectively. Kidney stiffness values were obtained from whole kidney, cortex, and medulla. Values were correlated with GFR, albuminuria, proteinuria, and degree of fibrosis that are assessed via renal biopsy. Patients were grouped clinicopathologically to assess the relation between stiffness and chronicity. RESULTS: Mean whole kidney, cortex, and medulla stiffnesses were 3.78 (± 1.26), 3.63 (± 1.25), and 4.77 (± 2.03) kPa, respectively. Mean global glomerulosclerosis was 22% (± 18%) and median segmental glomerulosclerosis was 4% (min-max: 0%-100%). Extent of tubulointerstitial fibrosis was less than 25% in 26 of the patients (76.5%), 25%-50% in 6 of the patients (17.6%), and higher than 50% in 2 of the patients (5.9%). Fourteen patients were defined to have chronic renal parenchymal injury. MRE-derived stiffness values correlated negatively with parameters of fibrosis. Lower stiffness values were observed in patients with chronic renal injury compared to those without (P < 0.05 for whole kidney and medulla MRE-derived stiffness). CONCLUSION: MRE-derived stiffness values were lower in patients with chronic injury. Stiffness decreases as glomerulosclerosis and tubulointerstitial fibrosis progresses in patients with primary glomerulonephritis and AA amyloidosis. With future studies, there may be a role for MRE to assess renal function in concert with conventional markers.

The relationship between glomerular IgG staining and poor prognostic findings in patients with IgA nephropathy: the data from TSN-GOLD working group.

BACKGROUND: Galactose-deficient IgA1 (Gd-IgA1) has an increased tendency to form immunocomplexes with IgG in the serum, contributing to IgAN pathogenesis by accumulating in the glomerular mesangium. Several studies showed that glomerular IgG deposition in IgAN is an important cause of mesangial proliferation and glomerular damage. This study aims to determine the association of the positivity of IgG and the intensity of IgG staining with a poor renal prognosis. METHODS: A total of 943 IgAN patients were included in the study. Glomerular IgG staining negative and positive patients were compared using Oxford classification scores, histopathological evaluations, proteinuria, eGFR, albumin, blood pressures. IgG positive patients were classified as (+), (++), (+++) based on their staining intensity, and the association with the prognostic criteria was also evaluated. RESULTS: 81% (n = 764) of the patients were detected as IgG negative, while 19% (n = 179) were positive. Age, gender, body mass index, blood pressure, proteinuria, eGFR, uric acid values were similar in IgG positive and negative patients who underwent biopsy (p > 0.05). Intensity of glomerular IgG positivity was not found to be associated with diastolic and systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p > 0.05 for all, r = - 0.084, r = - 0.102, r = - 0.006, r = 0.062, r = 0.014, r = - 0.044, r = - 0.061, r = - 0.066, r = 0.150, respectively). There was no difference for histopathological findings between IgG (+), IgG (++), IgG (+++) groups (for all, p > 0.05). CONCLUSION: Glomerular IgG negativity and positivity detected by routine IFM in IgAN patients is not associated with poor renal prognostic risk factors.

Characteristics of primary glomerular diseases patients with hematuria in Turkey: the data from TSN-GOLD Working Group.

PURPOSE: Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country. METHODS: Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded. RESULTS: Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001). CONCLUSION: This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients.

INTRODUCTION: HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. METHODS: 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. FINDINGS: Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). DISCUSSION: Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation.

Kidney transplantation for end-stage renal disease secondary to familial Mediterranean fever.

Although kidney transplantation (KT) is widely used for treating renal amyloidosis secondary to familial Mediterranean fever (FMF), data concerning transplant outcome are limited and inconsistent. The aim of this study was to determine the long-term outcome of KT in patients with amyloidosis secondary to FMF. Kidney transplantation outcome in 24 patients with FMF was compared to that in 72 controls matched for age, gender of recipient, and type of the donor that underwent KT due to end-stage renal disease (ESRD) not caused by FMF. Mean follow-up time was 80.3 ± 55.1 months in the FMF group, vs. 86.5 ± 47.6 months in the control group. Death-censored graft survival at five and 10 yr in the FMF group was 95.8% and 78.4%, respectively, and was comparable to that in the control group. In the FMF group, five- and 10-yr patient survival (87.5 and 65.6%) was shorter than in the control group, but the difference was not statistically significant. The findings show that long-term outcome of KT in the patients with amyloidosis secondary to FMF was comparable to that in patients with ESRD not caused by FMF. Recurrence of amyloidosis in the allograft, gastrointestinal intolerance, and fatal infections remain as major complications during the post-transplant period.

Safety of Percutaneous Ultrasound-Guided Kidney Biopsy in Patients with AA Amyloidosis.

BACKGROUND: Bleeding is the most frequent complication of kidney biopsy. Although bleeding risk in patients with AA amyloidosis after kidney biopsy has not been studied in a large population, AA amyloidosis has long been perceived as a risk factor for bleeding. The aim of the present study was to evaluate post-biopsy bleeding risk in patients with AA amyloidosis. METHODS: We retrospectively analyzed bleeding complications in 88 patients with AA amyloidosis and 202 controls after percutaneous kidney biopsy. All the kidney biopsies were performed under the guidance of real-time ultrasound with the use of an automated core biopsy system after a standard pre-biopsy screening protocol. Bleeding events were classified as major when transfusion of blood products or surgical or radiological intervention was required, or if the bleeding caused hypovolemic shock or death. Bleeding events that did not meet these criteria were accepted as minor. RESULTS: The incidence of post-biopsy bleeding was comparable between AA amyloidosis and control groups (5.7 vs. 5.0%, p = 0.796). Major bleeding events were observed in 3 patients from each group (p = 0.372). Selective renal angiography and embolization were applied to 2 patients from the AA amyloidosis group. One of these patients underwent colectomy and died because of infectious complications. Bleeding events were minor in 2.3% of the patients with AA amyloidosis and 3.5% of the controls (p = 0.728). CONCLUSIONS: AA amyloidosis was not associated with increased post-biopsy bleeding risk. Kidney biopsy is safe in AA amyloidosis when standard pre-biopsy screening is applied. Further data are needed to confirm these findings.

Demographic and clinical characteristics of primary glomerular diseases in Turkey.

BACKGROUND: The aim of our study was to delineate the demographic and clinical properties of primary glomerular diseases of adult population in our country in the light of global knowledge. METHODS: All over the country, a total of 25 centers entered data between May 2009 and July 2012 to the database created by 'Glomerulonephritis Study Group' of Turkish Society of Nephrology. Demographic and clinical characteristics, specific diagnoses of glomerular diseases and biopsy findings recorded to the database were analyzed. RESULTS: Among the 1,274 patients, who had renal biopsy within the defined time period, 55 % were male and 45 % were female. The mean age was 40.8 ± 14.6 years. The most frequent indication for biopsy was nephrotic syndrome (57.8 %), followed by nephritic syndrome including rapidly progressive glomerulonephritis (16.6 %) and asymptomatic urinary abnormalities (10.8 %). The most frequent primary glomerular disease was membranous nephropathy (28.8 %), followed by focal segmental glomerulosclerosis (19.3 %) and IgA nephropathy (17.2 %). CONCLUSION: The presented study displayed important data about the epidemiology of primary glomerular diseases among adults in our country. The predominance of membranous nephropathy in contrast to other countries, in which the most frequent etiology is IgA nephropathy, seems to be due to differences in the indications for renal biopsy.

An uninvestigated risk factor for contrast-induced nephropathy in chronic kidney disease: proteinuria.

BACKGROUND: Contrast-induced nephropathy (CIN) is one of the most frequent causes of acute renal failure in hospitalized patients with the incremental use of contrast media. We aimed to investigate whether proteinuria may act as a risk factor for CIN in patients with chronic kidney disease. METHODS: Seventy hospitalized patients (37 men, 33 women) with chronic kidney disease, proteinuria, and/or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, who were exposed to contrast media were investigated prospectively. Thirty patients were diabetic. All patients received prophylaxis against CIN with acetylcysteine and 0.9% intravenous saline. CIN is defined as either a 25% higher increase in serum creatinine (sCr) from the baseline levels or a 0.5 mg/dL increase in sCr at 72 h after contrast media exposure. RESULTS: CIN was detected in 26 (37.1%) patients. Advanced age, diabetes, heart failure, anemia, baseline sCr of >1.5 mg/dL, baseline eGFR of <60 mL/min/1.73 m(2), proteinuria of ≥1 g/day, hypoalbuminemia, and the volume of contrast media of ≥100 mL correlated significantly with CIN. The frequency of CIN was significantly higher in patients with proteinuria of ≥1 g/day compared to patients with proteinuria of <1 g/day (p = 0.009). CONCLUSION: Proteinuria may be a new risk factor for the development of CIN in patients with chronic kidney disease.

Major barriers against renin-angiotensin-aldosterone system blocker use in chronic kidney disease stages 3-5 in clinical practice: a safety concern?

Renin-angiotensin-aldosterone system (RAAS) blockers are underutilized in patients with chronic kidney disease (CKD). We aimed to determine barriers against the use of RAAS blockers in these patients. Patients with stage 3-5 CKD referred to Hacettepe University Hospital Nephrology Unit during a 1 year period were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166 male, 113 female) were analyzed. The mean age of the patients was 56.7 ± 15.2 years, mean serum creatinine was 2.45 ± 1.44 mg/dL, and mean glomerular filtration rate was 33.3 ± 15.1 mL/min. The mean follow-up time was 22.0 ± 21.9 months and the clinical visit number was 4.0 ± 3.5. Angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of patients, RAAS blockers had either been used earlier or were being used. Hyperkalemia was the principal reason for both not starting and also discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for not starting RAAS blockers were unclear. This study showed that hyperkalemia is the major barrier against the use of RAAS blockers in patients with CKD. There was, however, a subset of patients who did not receive RAAS blockers even without clear contraindications.

Use of mesenchymal stem cells and darbepoetin improve ischemia-induced acute kidney injury outcomes.

BACKGROUND: Interest has recently been focused on the possible role of bone marrow-originating stem cells and the therapeutic role of erythropoietin in the recovery of ischemia-induced acute kidney injury (AKI). The aim of the present study was to compare treatment with mesenchymal stem cells (MSCs) to treatment with darbepoetin-α (DPO) or both concomitantly in a rat model of ischemia/reperfusion (I/R) AKI. METHODS: Forty male Sprague-Dawley rats were included, and 28 of them were randomly assigned to controls (treated with serum physiologic) or one of the three treatment groups treated with either DPO, MSCs, or both (MSCs and DPO concomitantly) after the induction of I/R injury. Hematocrit, serum creatinine, and BUN levels were obtained at 0, 24, 48, and 72 h of surgery, and renal tissue was obtained at 72 h after nephrectomy for histological analysis. Tissue injury was quantified by standardized histological scoring systems, using light and electron microscopes. RESULTS: Treatment with MSCs or DPO improved renal function compared with controls. However, the improvement observed in renal function in the MSC/DPO group was better than that in the other groups. Histological analysis demonstrated that tissue injury was significantly decreased in rats in the MSC or DPO groups compared to that of the controls; however the best recovery was observed in rats treated with MSCs and DPO concomitantly. CONCLUSION: These results suggest that concomitant application of DPO and MSCs may be a potential novel renoprotective therapy for patients after having sustained an ischemic renal insult.

The relation between urinary angiotensinogen and proteinuria in renal AA amyloidosis patients.

OBJECTIVE: The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with proteinuria in patients with renal AA amyloidosis. METHODS: Thirty-two patients with renal AA amyloidosis (19 male, mean age: 45 ± 13 years) and sixteen healthy controls (5 male, mean age: 32 ± 5 years) were included in this study. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT-ELISA, urinary creatinine and protein levels. Logarithmic transformations of urinary AGT-creatinine ratio log(UAGT/Ucre) and urinary protein-to-creatinine ratio (UPCR) were done to obtain the normal distributions of these parameters. RESULTS: Log(UAGT/UCre) was significantly higher in patients compared with the controls (1.88 ± 0.92 µg/g vs. 1.25 ± 0.70 µg/g; p = 0.023). Importantly a significantly positive correlation was found between log(UAGT/Ucre) and logUPCR in patients (r = 0.595, p = 0.006). CONCLUSIONS: Urinary AGT levels are higher in renal AA amyloidosis patients than in controls. Also, there is a significant positive correlation between urinary AGT and proteinuria in renal AA amyloidosis.

Postural epigastric pain: a challenging symptom for cytomegalovirus (CMV) gastritis.

Abstract Postural epigastric pain is an uncommon symptom and is hardly acquired unless specifically asked to the patient. Here we present a cytomegalovirus (CMV) gastritis case in a renal transplant patient with postural epigastric pain. A 36-year-old male was admitted to our clinic on the 50th day of renal transplantation with postural epigastric pain. All investigations were unremarkable except biopsy-proven CMV gastritis and increased CMV viral load. The patient was free of symptom after ganciclovir treatment. Postural epigastric pain has not been described together with a clinical entity. Although not proved yet, it can be regarded as a unique symptom of CMV gastritis. Renal transplant patients presenting with postural epigastric pain which is not relieved with acid suppression should raise suspicion of CMV gastritis and this has to be confirmed by endoscopy and biopsy.

A population-based survey of Chronic REnal Disease In Turkey--the CREDIT study.

BACKGROUND: Chronic kidney disease (CKD) is a growing health problem worldwide that leads to end-stage kidney failure and cardiovascular complications. We aimed to determine the prevalence of CKD in Turkey, and to evaluate relationships between CKD and cardiovascular risk factors in a population-based survey. METHODS: Medical data were collected through home visits and interviews. Serum creatinine, blood glucose, total cholesterol, triglycerides, HDL, LDL and uric acid were determined from 12-h fasting blood samples, and spot urine tests were performed for subjects who gave consent to laboratory evaluation. RESULTS: A total of 10 872 participants were included in the study. The final analysis was performed on 10 748 subjects (mean age 40.5 ± 16.3 years; 55.7% women) and excluded 124 pregnant women. A low glomerular filtration rate (GFR) (< 60 mL/min/1.73 m(2)) was present in 5.2% of the subjects who were evaluated for GFR, while microalbuminuria and macroalbuminuria were observed in 10.2% and 2% of the subjects, respectively. The presence of CKD was assessed in subjects who gave consent for urinary albumin excretion measurement (n = 8765). The overall prevalence of CKD was 15.7%; it was higher in women than men (18.4% vs. 12.8%, P < 0.001) and increased with increasing age of the subjects. The prevalence of hypertension (32.7% in the general population), diabetes (12.7%), dyslipidaemia (76.3%), obesity (20.1%) and metabolic syndrome (31.3%) was significantly higher in subjects with CKD than subjects without CKD (P < 0.001 for all). CONCLUSIONS: The prevalence of CKD in Turkey is 15.7%. Cardiovascular risk factors were significantly more prevalent in CKD patients.

Impact of cytokine genotype on cardiovascular surrogate markers in hemodialysis patients.

BACKGROUND/AIMS: Cytokine gene polymorphisms have been implicated as potential genetic risk factors for cardiovascular diseases (CVDs). Atherosclerosis and left ventricular hypertrophy (LVH) are surrogate markers for CVDs in uremic patients. The aim of this study was to assess the role of cytokine gene polymorphisms in carotid intima-media thickness (CIMT) and left ventricular mass index (LVMI) progression in nondiabetic hemodialysis (HD) patients. METHODS: About 102 nondiabetic patients on maintenance HD were included in this study. Patients were followed up for 2 years. Genetic polymorphisms of TNF-alpha (-308 G/A, -238A/G) and IL-10 (-1082 A/G, -819 C/T, -592 A/C) were determined by polymerase chain reaction. Biochemical parameters and inflammatory markers and ambulatory blood pressure (BP) measurements were determined during the study period. CIMT and LVMI were also determined at baseline and after the first and second year. RESULTS: Cardiovascular risk factors did not differ between TNF-alpha -308 high-/low-producer genotype groups. However, CIMT and LVMI progression were detected at higher levels in patients with high-producer genotypes (AA+AG) than in patients with the low-producer genotype (GG) during the study period. The TNF-alpha -308 G/A polymorphism was closely associated with C-reactive protein (CRP), a marker of systemic inflammation in the study population. Analysis also showed that the combination of high production of TNF-alpha and low production of IL-10 was associated with higher average IMT and LVMI progression and elevated average CRP levels compared with a combination of low production of TNF-alpha and high production of IL-10. CONCLUSION: Polymorphisms in inflammatory genes may represent an additional factor affecting inflammation and CVD progression in nondiabetic HD patients.

Serum stem cell factor level in renal transplant recipients with posttransplant erythrocytosis.

The etiology of posttransplant erythrocytosis (PTE) remains unclear, and the most frequently suggested causative factors are still a matter of controversy. We aimed to investigate serum-soluble stem cell factor (sSCF) along with serum erythropoietin (EPO) levels in renal transplant recipients (RTRs) with PTE. Thirteen RTRs with PTE, 42 RTRs without PTE, and 42 healthy controls were included. Serum sSCF and EPO levels were determined using an enzyme-linked immunosorbent assay kit. Expected and observed/expected EPO levels were calculated. Serum sSCF levels and observed/expected EPO were significantly higher in RTRs with PTE than both RTRs without PTE and controls. In RTRs with PTE, sSCF level was significantly correlated with hematocrit and observed/expected EPO, respectively. Significant correlation was also observed between hematocrit level and observed/expected EPO in RTRs with PTE. Increased sSCF level and inadequate suppression of EPO production seem to have a role in the pathogenesis of PTE.

Association among serum fetuin-A level, coronary artery calcification, and bone mineral densitometry in maintenance hemodialysis patients.

Patients with end-stage renal disease have a very high prevalence and extent of arterial calcification. A number of studies suggest that similar pathophysiologic mechanisms are responsible for development and progression of calcification of atherosclerotic plaque and bone formation. Fetuin-A is a potent calcification inhibitor and is expressed in bone, with not-yet well-defined functions. The aim of this study was to investigate the relation between bone mineral densitometry parameters, coronary artery calcification, and serum fetuin-A levels. In a cross-sectional design, we included 72 maintenance hemodialysis (HD) patients and 30 age- and gender-matched healthy controls. Serum fetuin-A levels were studied both in maintenance HD patients and healthy controls. Maintenance HD patients had radius, hip, and lumbar spine bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry and coronary artery calcification score (CACS) measured by electron-beam computed tomography. The associations between site-specific BMD parameters, CACS, and serum fetuin-A levels were studied in maintenance HD patients. CACS, mass, and volume of plaques in coronary arteries were significantly higher in patients with a T-score below -2.5 than above in the proximal region of the radius, neck and trochanter of the femur, and the lumbar spine. Mean serum fetuin-A concentration was 0.636 +/- 0.118 g/L in maintenance HD patients and it was less than healthy controls (0.829 +/- 0.100 g/L, P < 0.0001). CACS, mass, and volume of plaques in coronary arteries correlated significantly with the serum fetuin-A levels. Moreover, significant positive correlations were shown between the serum fetuin-A levels, BMD values, and T-scores of proximal radius, neck, and trochanter of the femur, but not with the lumbar spine. The present study demonstrates an association between serum fetuin-A levels, coronary artery calcification, and bone mineral densities--except for the lumbar spine, in maintenance HD patients. However, the results should be interpreted with caution because of the cross-sectional design of the study.

Concomitant amyloidosis, renal papillary carcinoma and ipsilateral pelvicalyceal urothelial carcinoma in a patient with familial Mediterranean fever.

We report a case of a 58-year-old man with a history of long standing familial Mediterranean fever (FMF) and AA amyloidosis, who developed renal papillary carcinoma and renal pelvic urothelial carcinoma simultaneously. Although the association between chronic inflammatory states like FMF and AA amyloidosis has been well established, the relationship between amyloidosis and solid tumors is not defined as clearly. Furthermore, to the best of our knowledge, co-existence of two different types of kidney malignancy with amyloidosis in a patient with FMF has not been reported. Our patient was admitted to hospital with gross hematuria and renal insufficiency. Imaging studies revealed mass lesions in the middle portion of the right kidney. Right radical nephrectomy showed extensive amyloid deposition, co-existing with renal papillary carcinoma and poorly differentiated invasive urothelial carcinoma.