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Purpose An outbreak of a novel respiratory disease due to coronavirus species was emerged in 2019 and named as Coronavirus Disease-2019 (COVID-19). Clinical and immunological factors affecting the course of COVID-19 in kidney transplant recipients (KTR) are not well-known. Methods In this prospective observational study, we presented 20 KTR with COVID-19 pnemonia and examined the factors predicting the severity of COVID-19. A total of 10 KTR without COVID-19 was used as control group. Lymphocyte subsets were determined by flow cytometry. In 13/20 patients, immunophenotyping was repeated 1 week later. Results Mean age of the patients was 50 ± 9 years. Patients were classified as mild–moderate (oxygen saturation: SO2 > 90%) and severe disease groups (SO2 ≤ 90%). Serum albumin and hemoglobin were lower and CRP, fibrinogen and peak d-dimer were higher in severe group. Peak CRP was inversely associated with nadir SO2 (r = − 0.68, p = 0.001). Neutrophil/lymphocyte ratio was higher in severe group (p = 0.01). CD3 + and CD4 + cells were lower and NK cell percentage (CD16 + 56 +) was higher in severe group. Percentage of spontaneously activated CD8 cells (CD8 + CD69 +) was higher in severe group. In comparison of KTR with and without COVID-19, CD8 + cells were lower but NK cell percentage was higher in KTR with COVID-19. Conclusion In this pilot study, increased NK cells, activated CD8 + cells and decreased CD3 + and CD4 + cells were associated with severity of COVID-19 in KTR. Peripheral immunophenotyping of lymphocyte subtypes may provide prognostic information about the clinical course of COVID-19 in KTR. Supplementary Information The online version contains supplementary material available at 10.1007/s11255-021-02947-y.

Primary focal segmental glomerulosclerosis (FSGS) treatment is based on immunosuppressive therapies. Since refractory disease is common, alternative methods are emerging. One of these methods is plasmapheresis with intravenous cyclosporine and corticosteroids, and it could be an option in post-transplant recurrent FSGS. We retrospectively investigated the efficacy of this combined treatment in adult patients with refractory primary FSGS.Seven refractory primary FSGS patients were included. Demographics, estimated glomerular filtration rates, serum albumin levels, urine protein/creatinine ratios, and previous treatments were evaluated. Also, complications and remission rates were assessed.Median patient age was 23 years. Median duration of diagnosis was 2 years. Median number of plasmapheresis sessions was 14. Five of seven patients (71.4%, one complete, four partial remissions) were responders after the protocol. Changes in serum albumin levels and proteinuria after protocol were statistically significant (P = 0.018 and P = 0.018, respectively). eGFR levels did not change statistically (P = 0.753). Median follow-up duration after the treatment was 17 months. However, two patients experienced disease relapse (28.5%). End-stage kidney disease was developed in two patients. Sustained remission rate was 42.8% during follow-up (One complete and two partial remissions). Also, 42.8% of patients experienced catheter infections. Catheter-associated thrombosis that required surgery was observed in a patient.Plasmapheresis combined with intravenous cyclosporine and corticosteroids could be an option in refractory primary FSGS. High response rates after this protocol were encouraging. However, the relapsing disease was observed after the cessation of apheresis. Also, complications of the protocol could limit the applicability.

The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN).A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining.Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021].An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.

Introduction Early diagnosis of rejection in kidney transplant (KTx) recipients is of paramount importance for long-term graft survival. Cytokines play an important role in rejection via activating T cells. Neutrophil accumulation in the graft indicates cell-mediated rejection. Cellular infiltration is mediated through chemoattractant factors. The aim of this study was to investigate the relationship between graft function and serum levels of interleukin 2 (IL-2) and interleukin 8 (IL-8) in KTx. Method Sixty-five patients undergoing KTx were enrolled in the study. Serum samples of IL-2 and IL-8 were collected the day before the operation, on postoperative days 1 and 7 day, and during the first and third month after the onset of rejection. The enzyme-linked immunosorbent assay method was used to determine the IL-2 and IL-8 values. Results A total of 9 (13.8%) patients had rejection documented on biopsy samples. Fifty-six patients had stable graft function (SGF). IL-2 and IL-8 values before KTx of both the rejected and SGF patients were not statistically different. Univariate analysis revealed that IL-2 and IL-8 were correlated with rejection (P = .046, P = .015). IL-8 levels were higher in the rejection group compared to the SGF group on the seventh day and first month postoperatively (P = .023, P = .038). The rejection group maintained higher levels of IL-8 for 11 days (range: 7–30) compared to the SGF group (P = .002) and the IL-8 levels correlated with serum creatinine levels (r = 0.621, P = .001). IL-2 levels were higher in the rejection group on days 1 and 7 compared to the SGF group (P = .042, P = .031). IL-2 and IL-8 levels were correlated with low eGFR in the third month in the rejection group (r = 0.421, P = .037; r = 0.518, P = .008). Conclusion Determining the cytokine levels in the early post-KTx period may be helpful in tailoring immunosuppressive regimens in patients with a risk of rejection.

Background The prognostic factors for COVID-19 in patients with chronic kidney disease (CKD) are uncertain. We conducted a study to compare clinical and prognostic features between hospitalized COVID-19 patients with and without CKD. Methods Fifty-six patients with stage 3–5 CKD and propensity score-matched fifty-six patients without CKD were included in the study. Patients were followed-up at least fifteen days or until death after COVID-19 diagnosis. The endpoints were death from all causes, development of acute kidney injury (AKI) or cytokine release syndrome or respiratory failure, or admission to the intensive care unit (ICU). Results All patients were reviewed retrospectively over a median follow-up of 44 days (IQR, 36–52) after diagnosis of COVID-19. Patients with CKD had higher intensive care unit admission and mortality rates than the patients without CKD, but these results did not reach statistical significance (16 vs. 19; p = 0.54 and 11 vs. 16, p = 0.269, respectively). The frequency of AKI development was significantly higher in predialysis patients with CKD compared to the other group (8 vs. 5; p

Introduction: Management of COVID-19 in kidney transplant recipients should include treatment of the infection, regulation of immunosuppression, and supportive therapy. However, there is no consensus on this issue yet. This study aimed to our experiences with kidney transplant recipients diagnosed with COVID-19. Material and Methods: Kidney transplant recipients diagnosed with COVID-19 from five major transplant centers in Istanbul, Turkey, were included in this retrospective cohort study. Patients were classified as having moderate or severe pneumonia for the analysis. The primary endpoint was all-cause mortality. The secondary endpoints were acute kidney injury, the average length of hospital stay, admission to intensive care, and mechanical ventilation. Results: Forty patients were reviewed retrospectively over a follow-up period of 32 days after being diagnosed with COVID-19. Cough, fever, and dyspnea were the most frequent symptoms in all patients. The frequency of previous induction and rejection therapy was significantly higher in the group with severe pneumonia compared to the moderate pneumonia group. None of the patients using cyclosporine A developed severe pneumonia. Five patients died during follow-up in the intensive care unit. None of the patients developed graft loss during follow-up. Discussion: COVID-19 has been seen to more commonly cause moderate or severe pneumonia in kidney transplant recipients. Immunosuppression should be carefully reduced in these patients. Induction therapy with lymphocyte-depleting agents should be carefully avoided in kidney transplant recipients during the pandemic period., NA

Objectives TNF-like weak inducer of apoptosis (TWEAK), monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) are proinflammatory cytokines/chemokines that are considered as potential biomarkers reflecting disease activity in systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of serum (s) and urine (u) levels of TWEAK, MCP-1 and NGAL with disease activity in both renal and extra-renal SLE. Methods Thirty active patients with SLE (15 renal and 15 extra-renal) were recruited. Thirty-one inactive patients with SLE (16 renal and 15 extra-renal), 14 patients with ANCA-associated vasculitis (AAV) all of whom had active renal involvement and 20 healthy volunteers were selected as control groups. Serum and urine levels of TWEAK, MCP-1 and NGAL were tested using ELISA. Results Serum and urine levels of TWEAK and NGAL were significantly higher in the active SLE group compared to the inactive SLE group (sTWEAK p = 0.005; uTWEAK p = 0.026; sNGAL p Conclusion sTWEAK, uTWEAK, sNGAL and uNGAL are biomarkers showing disease activity in SLE. However, our results implicate that these biomarkers may not be specific for SLE, and can be elevated in patients with active renal involvement of AAV.

Background The largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. Methods Data of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study. Results The mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467–6307) mg/day, 1.0 (IQR: 0.7–1.6) mg/dL, 82.9 (IQR: 47.0–113.0) mL/min and 3.2 ± 0.9 g/dL, respectively. Conclusions The distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic acid (MPA) in the perioperative period. PPIs are metabolized by cytochrome (CYP) 2C19 enzymes. Mycophenolate sodium (MYF) and mycophenolate mofetil (MMF) have been used in immunosuppression. Clinically relevant drug-drug interactions have been described between immunosuppressive drugs. In the present study, we investigated the drug interaction between MPA and lansoparazole or rabeprazole and the impact of CYP2C19 polymorphisms on these drug interactions after renal transplantation.A total of 125 renal transplant patients taking MPA derivatives between 2012 and 2016 were included in this study. The 125 patients were divided into 6 groups: MMF/tacrolimus/steroid together with lansoprazole or rabeprazole; MYF/tacrolimus/steroid together with lansoprazole or rabeprazole and without PPI. The single nucleotide polymorphisms of CYP2C19 were determined by the polymerase chain reaction-restriction fragment length polymorphism. Plasma concentrations of MPA were measured by cloned enzyme donor immunoassay. Clinical parameters such as incidence of delayed graft function and acute rejection, the rate of change of serum creatinine, toxicity, and gastrointestinal adverse effects were analyzed retrospectively.The mean concentrations of MPA in the MYF group were higher than those in the MMF group. The mean dose-adjusted blood concentration of MPA coadministered with lansoprazole was lower than that of MPA with rabeprazole or without PPI in MMF and MYF groups (P .05). In patients with the CYP2C19*2/*2 genotype, the mean concentrations of MMF with lansoprazole were significantly lower than those with rabeprazole with MMF or without PPI (P .05). Gastrointestinal side effects were significantly higher in MMF with lansoprazole group than in MYF with lansoprazole group (P .05). However, no differences were found according to genotype distribution in all groups (P.05).Polymorphisms in CYP2C19 are related to the metabolic oxidation of drugs to varying degrees. Both genetic and clinical factors in pharmacokinetics may help to make further progress toward individualized therapy to yield maximum efficacy with minimal side effects.

Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation candidates.Anti-HLA class I/II antibody screening tests were performed in 906 renal transplantation candidates with the use of a microbead-based assay (Luminex).Two hundred ninety-seven (32.8%) of the patients were determined as positive in terms of PRA, and 609 (67.2%) were negative. Sensitized and non-sensitized patients were compared separately in terms of each sensitization type. The anti-HLA class I, II, and I+II positivity rates in patients sensitized only by blood transfusion were 13.1%, 6.3%, and 14.1%, the rates with pregnancy sensitization were 35.5%, 29%, and 45.2%, and rates with previous transplantation sensitization were 15.6%, 34.4%, and 38.9%, respectively. Prevalence of PRA positivity was significantly higher in patients with previous pregnancy than with transplantation and transfusion (odds ratio, 1.003; 95% confidence interval, 0.441-2.281; P = .031). The risk of developing HLA class I antibodies was higher in pregnancies (P .001), and the risk of developing anti-HLA class II antibodies was higher in patients who had undergone a previous transplantation (P .001). The rate of developing HLA-B antibodies in patients sensitized by pregnancy were significantly higher compared with sensitization after transfusion (P = .015), as was the rate of developing HLA-DQ antibodies in patients sensitized by previous transplantation compared with sensitization through pregnancy (P = .042).In patients who are waiting for kidney transplantation, sensitization by pregnancy and transplantation have a significant impact on development of HLA class I and class II antibodies.

Background The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. Methods Serum Gd-IgA1 levels of 18 patients with recurrent IgAN were compared with control renal transplant recipients (n = 23) with non-recurrent IgAN and control non-transplant IgAN patients (n = 44) and healthy relatives (n = 11). Serum Gd-IgA1 levels of patients were measured with the use of KM55 enzyme-linked immunosorbent assay (ELISA). The effects of serum Gd-IgA1 concentrations on IgAN recurrence, post-transplant events, and graft survival were evaluated. Results All recurrent IgAN patients presented with renal dysfunction (mean serum creatinine, 1.62 ± 0.39 mg/dL) and detectable proteinuria at the time of diagnosis. Serum Gd-IgA1 levels of recurrent IgAN patients (8735 ± 10854 ng/mL [log10: 3.71 ± 0.45]) were significantly higher than those of non-recurrent IgAN patients (4790 ± 6089 ng/μL [log10: 3.31 ± 0.64]) ( P = .027). Serum Gd-IgA1 levels of non-transplant IgAN patients were significantly higher (8791 ± 8700 ng/μL [log10: 3.79 ± 0.36]) than those of non-recurrent IgAN patients (4790 ± 6089 ng/μL [log10: 3.31 ± 0.64]) and healthy relatives (2615 ± 1611 ng/μL [log10: 3.34 ± 0.27]) ( P P = .021, respectively). Receiver-operating characteristic curve analysis revealed that the area under the curve for recurrence of IgAN was 0.69 (0.53–0.85) for serum Gd-IgA1 ( P = .038). Biopsy-confirmed allograft rejection rates were similar in the recurrent IgAN group [3 (17%)] compared with the non-recurrent IgAN [6 (26%)] group ( P = .47). Graft failure rate was not also significantly different in the recurrent IgAN group [4 (22.2%)] compared with the non-recurrent IgAN group [2 (8.7%)] ( P = .224). Conclusions This novel lectin-independent Gd-IgA1 ELISA that can detect serum Gd-IgA1 in patients with recurrent IgAN can be used as a biomarker for diagnosis and activity assessment of post-transplant recurrent IgAN.

Background/Aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS). Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM– C3–, IgM+ C3–, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes. Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77–8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3–27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3– and IgM– C3– groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349–8.344, p = 0.009). Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS.

Introduction Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Rituximab is widely used in kidney transplantation for a variety of situations, and rituximab may inhibit some cytokines and antibodies that may play an active role in the atherosclerotic process. The aim of the study was to evaluate the efficacy of rituximab on atherosclerosis biomarkers in kidney transplant recipients. Methods All patients, 18 years of age and older, who underwent kidney transplantation and received at least 1 dose of 375 mg/m2 rituximab were considered for participation in this study. The primary study endpoint was the development of cardiovascular diseases after rituximab therapy. The secondary endpoint was the onset of cytomegalovirus (CMV) disease or biopsy-confirmed BK virus nephropathy. In addition, comparison of atherosclerosis biomarkers was performed between study and control groups. Results There were no cardiovascular events observed during follow up. Only 8 patients in the study group suffered from CMV disease during follow up. Serum interleukin 10 levels were significantly higher in the rituximab group compared with the control group, although anti–oxidized low-density lipoprotein levels were lower in the rituximab group compared with the control group, though this did not achieve statistical significance. Discussion Rituximab treatment may increase the risk of CMV reactivation and decrease lymphocyte counts and interleukin 10 levels; however, significant decreases in all atherosclerotic-related biomarkers have not been shown in our study.

Introduction Seasonal influenza is an important cause of morbidity and mortality in the post-transplant period; therefore, the influenza vaccination has been recommended for all kidney transplant recipients before the influenza season. However, at least theoretically, the introduction of antigens via vaccines may trigger rejection attacks by causing an antibody response. In this study, we examined the development of de novo panel reactive antibody (PRA) development against the influenza vaccine in kidney transplant recipients. Materials and Methods Overall, 41 kidney transplant recipients who received the influenza vaccination and 50 kidney transplant recipients (study group) who refused to receive the influenza vaccination (control group) were enrolled in the study. Following basal biochemistry examination, the inactivated trivalent influenza vaccine was administered intramuscularly. Panel reactive antibodies were screened in all patients before and after vaccination on days 30 and 180. The primary outcome variable was development of de novo panel reactive antibodies. Results One patient in the study group developed de novo class I and II PRA at 6 months after vaccination (P > .05), while no antibody development was noted in the control group. Graft dysfunction or biopsy-confirmed rejection was not observed during the follow-up period in both groups. Conclusion The influenza vaccination is generally effective and safe in solid organ transplant recipients. The vaccination procedure has the potential to trigger antibody development and occurrence of rejection. Therefore, vaccinated kidney transplant recipients should be monitored more carefully with regard to PRA; if the graft deteriorates, a rapid transplant biopsy should be performed.

Ozluk, Yasemin/0000-0002-7191-0488; WOS: 000394441100004 PubMed: 27776435 Background: Antibody-mediated rejection is a frequent cause of graft failure; however, prognostic indications of this complication have not been well defined. The aim of this study was to evaluate the association of histopathological and clinical features and to determine the effect of these findings on allograft survival in patients with AMR. Methods: Fifty-two patients suffered from AMR (30 male; mean age 39 +/- 11 years) were included in the study. Data were investigated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff 2009 classification. Results: Of the 52 cases, 45 were transplanted from living-donors. Twenty-one patients were diagnosed in the first 3-months after transplantation. Graft survival was 65% at 12 months and 54% at 36 months. Mean serum creatinine at time of biopsy was 3.8 +/- 3.6 mg/dL. Thirty-five of the 52 cases showed diffuse C4d positivity, 12 cases showed focal and 5 remained C4d negative. One of the patients died, 13 experienced graft loss and 38 survived with functioning grafts. Serum creatinine levels at time of biopsy were correlated with graft survival (p = .021: OR = 1.10: 95 % CI = 1.015-1.199). In terms of the impact of pathological findings; tubulitis (p =.007: OR = 2.62: 95 % CI = 1.301-5.276), intimal arteritis (p = .017: OR = 2.85: 95% CI = 1.205-6.744) and interstitial infiltration (p = .004: OR = 3.37: 95% CI = 1.465-7.752) were associated with graft survival. Conclusions: Serum creatinine at time of biopsy, tubulitis, intimal arteritis and interstitial infiltration were significantly associated with graft survival. Antibody-mediated rejection is associated with reduced long-term graft survival.

Background/Aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN). Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2. Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression.

Background Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). Methods Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo DSAs and C1q binding. Clinical and biopsy data were retrospectively obtained. Results The analysis included 118 patients (68 tacrolimus, 50 CsA), with mean age and follow-up of 36.1 ± 11.4 and 7.2 ± 4.8 years, respectively. As compared with tacrolimus, the CsA group had higher rates of both class II DSAs and C1q-binding DSAs (20% vs 4.4%, P = .008, and 18% vs 0%, P = .003, respectively). Rates of chronic antibody-mediated rejection (cAMR), proteinuria >500 mg/g, and levels of creatinine both at last visits were also higher in the CsA group (20% vs 0%, P = .002, 30% vs 5.9%, P = .005, 1.67 ± 1.31 vs 1.18 ± 0.45 mg/dL, P = .019, respectively).Class II DSAs and C1q-binding class II DSAs were significantly correlated with the clinical outcomes (creatinine levels, proteinuria, and cAMR). Conclusions Compared with tacrolimus, CsA appears to pose a higher risk for the development of de novo anti-HLA antibodies with C1q-binding properties and, consequently, adverse graft-related outcomes.

Hepatitis B surface antigen-positive allografts may be a source of transmission in patients who undergo renal transplantation. Treatment of hepatitis B virus infection with nucleoside/nucleotide analogs in kidney recipients who have hepatitis B virus infection or who have received transplants from hepatitis B surface antigen-positive donors improves long-term patient survival. Antiviral agents are administered as a preemptive or prophylactic therapy at the time of kidney transplantation, rather than as salvage treatment. In this report, we present 2 renal transplant recipients who had hepatitis B virus reinfection or who had developed seroconversion with immunosuppressive treatment. These case reports also demonstrate the unexpectedly different courses of hepatitis B reinfection after kidney transplantation.

QT dispersion (QTd) was shown to be an independent predictor of mortality in hemodialysis (HD) patients. It may be hypothesized that coronary artery calcification is related to QTd in HD patients because widespread calcification may also involve the cardiac conducting system in these patients. In this study, we aimed to investigate the relationships of corrected QTd (QTcd) with coronary artery calcification score (CACS), carotid plaque score (CPS) and possible influence of these parameters on survival of HD patients.Seventy-two HD patients (33 male, 39 female) were enrolled into the study. Mean age of the patients was 44 ± 12 years. Mean follow-up duration was 77 ± 24 months. CACS was determined by computed tomography. QTcd values were calculated as the difference of maximum and minimum QT intervals. Left ventricular mass index (LVMI) and CPS were measured by echocardiography.QTcd was significantly correlated with CACS (r = 0.233, p = 0.049), CPS (r = 0.354, p = 0.003) and LVMI (p = 0.011, r = 0.299). CPS was found to be significantly higher in the group with high QTcd (60 ms) [2 (1-4) versus 0 (0-1), p = 0.02]. CACS was significantly correlated with age (r = 0.44, p0.001), LVMI (r = 0.52, p0.001) and CPS (r = 0.32, p = 0.003). In Kaplan-Meier analysis, survival of patients with high QTcd was significantly lower than the patients with low QTcd. In Cox regression analysis for predicting mortality, age, serum albumin and QTcd were found to be the independent predictors of mortality.QTcd independently predicted mortality, and it was significantly associated with coronary artery calcification, left ventricular hypertrophy and atherosclerosis in HD patients.

Background Amyloid A (AA) amyloidosis is a multisystemic, progressive, and severe disease. Renal involvement is a prominent feature of the disease, and the outcome of patients on dialysis is poor. We aimed to analyze the outcomes of kidney transplantation in patients with AA amyloidosis in comparison with chronic glomerulonephritis (CGN). Methods Charts of patients who underwent kidney transplantation between 1988 and 2012 were reviewed; 41 patients with AA amyloidosis were identified, and 41 age- and sex-matched control patients with chronic CGN were included. Baseline characteristics, immunosuppressive regimens, and transplantation-related outcomes were retrieved using a standardized form. Results The mean follow-up period was 70.9 ± 44.9 months. The 10-year patient survival was found to be significantly worse in the AA amyloidosis group (62.5%) compared to CGN group (100%) (P = .008). During the follow-up period, three of the 41 patients (9.7%) died of sepsis and one patient died of cardiac complications in the amyloidosis group, whereas there was no patients were lost in the CGN group. The first-year, fifth-year, and tenth-year mean graft survival rates, acute and chronic rejections, and mean creatinine levels at last visits were not significantly different between the groups. Proteinuria >1 g/d, cytomegalovirus and tuberculosis infections, and rhabdomyolysis were recorded at a significantly higher rate in patients with amyloidosis. Conclusion As compared to patients with CGN, patients with AA amyloidosis had a lower patient survival; equal graft survival and rejection rates; and higher risks of developing proteinuria, cytomegalovirus and tuberculosis infections, and rhabdomyolysis.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The course and progression of the disease is highly variable. In this study, we aimed to investigate the impact of clinical characteristics and basic biochemical parameters on progression of chronic kidney disease (CKD) in ADPKD patients. A total of 323 consecutive patients with ADPKD were enrolled into the study and followed with a mean duration of 100 ± 38 months. Patients were grouped as rapid progressors (RP) and slow progressors (SP) according to median rates of decline in glomerular filtration rate (ΔGFR) per year, namely 1 ml/min/year. History of macroscopic hematuria, urinary stone and smoking were more common in male patients; hepatic and other organ cysts were more common in female patients. ∆GFR/year was similar between males and females [0.95 (0–3.02) vs. 1.11 (0.10–2.74) ml/min/year, p = 0.21]. History of smoking and pack-year of cigarettes smoked were significantly higher in the RP compared to the SP group (36 vs. 18 %, p = 0.01 and 5.24 ± 1.20 vs. 3 ± 1.32 pack-year, p = 0.02, respectively). Baseline 24 h-proteinuria was found to be significantly correlated with the percent decline of GFR (∆%GFR) per year (r = 0.303, 0.001). In Cox regression analysis for predicting the progression of CKD, age, hypertension, urinary stone and proteinuria were retained as the significant independent factors predicting progression of CKD in the model. Baseline proteinuria was significantly correlated with ∆%GFR per year. Hypertension and proteinuria were found to be the major treatable risk factors for the progression of CKD in ADPKD patients.

Background: Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the non-uremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD. Methods: In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) non-diabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment. Results: Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8 th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 ± 8.3% at baseline to 11.37 ± 9% (p < 0.001). At the 8 th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 ± 8%, p < 0.001). Conclusion: Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.

Objective The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation. Methods Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed. Results There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group. Conclusions Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts.

Aims: The prognostic outcome of patients with amyloidosis who receive a kidney transplant is controversial. The aim of the study was to analyze the renal transplantation outcome of patients with amyloidosis compared to transplant recipients with other kidney diseases. Methods: Among 940 patients who had renal transplantation in our unit between 1983 and 2009, 44 patients with amyloidosis were compared regarding early and late complications and survival, retrospectively, with a control group of 41 consecutive patients with the same donor type and a matched renal transplantation date. Results: The groups were similar regarding demographic parameters, HLA mismatch numbers and mean follow-up period. Groups were similar regarding early and late infectious and non-infectious complications, except recurrence of the primary disease, which was more common in the amyloidosis group. As the cause of graft loss, rejection (acute or chronic) was more common in the control group; whereas primary non-functioning graft, and death with a functioning graft were more common in the amyloidosis group. Patient survival rates at 1, 5, and 10 years were 87.6%, 78.1%, and 62.3 in the amyloidosis group; and 93.2%, 82.6%, and 69.3% in the control group. Graft survival rates at 1, 5 and 10 years were 87.6%, 75.4%, 56.4% in the amyloidosis group; and 93.2%, 80.3%, and 60.6% in the control group, respectively. These values did not show any statistical difference. Conclusions: The outcomes of renal transplantation in patients with amyloidosis are comparable with recipients whose primary problems are due to other kidney diseases; therefore, amyloidosis patients should be accepted as good candidates for transplantation.

Background In this prospective study, we sought to investigate the long-term prognostic value of coronary flow reserve (CFR) and carotid intima media thickness (IMT) estimates in renal transplant recipients without known coronary artery disease. Methods The 20 renal transplant recipients included in this study underwent CFR recordings performed by trans-thoracic Doppler echocardiography (TTDE) and carotid IMT measured by carotid Doppler ultrasonography. Results During a 3-year follow-up only one patient experienced a cardiac event. The baseline CFR and carotid IMT values of the patients were 1.77 ± 0.47 and 0.67 ± 0.15 mm, respectively. After 3 years of follow-up, there were no significant differences compared with baseline measurements with regard to CFR and IMT values. CFR values at the third year of follow-up showed significant correlation with age as well as IMT at baseline and at the third year. Upon multivariate analysis, baseline carotid IMT (β = −0.562; P = .05) was a significant independent predictor of CFR at the third year. Conclusion Carotid IMT showed a greater predictive value for impaired CFR in renal transplant recipients. CFR was not an independent predictor for cardiovascular events among renal transplant recipients within the first 3 years of follow-up measurements.

Pulse pressure (PP) has been reported as an independent predictor of cardiovascular mortality in hemodialysis patients. In this study, we aimed to investigate association of PP with echocardiographic and vascular structural changes such as atherosclerosis and arterial calcifications in HD patients. In this cross-sectional study, 108 chronic hemodialysis patients (49 male, 59 female, mean age: 46 ± 13 years) were included. Biochemical analyses, echocardiographic and high-resolution carotid Doppler examinations were done. Aortic wall and coronary artery calcifications were measured with electron beam computed tomography. The degree of carotid artery stenosis was measured at four different sites (communis, bulbus, interna and externa) in both carotid arteries. PP was strongly correlated with systolic (r: 0.82) and diastolic (r: 0.33) blood pressure, left ventricular mass index (r: 0.58), left ventricle end diastolic diameter (r: 0.38) and weakly correlated with aortic wall calcification score (r: 0.26) and carotid plaque score (r: 0.27), but not with coronary artery calcification score. Patients with carotid plaque had higher PP than patients without plaque (50 ± 16 mmHg versus 44 ± 14 mmHg, P = 0.05). Patients were divided into three groups according to aortic wall calcification score. PP was significantly higher in patients with higher aortic wall calcification (54 ± 16 mmHg) than patients with lower aortic wall calcification (44 ± 15 mmHg, P = 0.04). However, on multivariate linear regression analysis for predicting PP, the only significant factor retained was left ventricle end diastolic diameter. PP was weakly associated with large vessel calcification and atherosclerosis in hemodialysis patients. The bulk of the effect on PP seems to be due to hypervolemia.

Patients with pre-transplantation high levels of panel reactive antibody (PRA) have an increased risk of graft failure, and renal transplantation in sensitized patients remains a highly significant challenge worldwide. The influence of anti-human leukocyte antigen (HLA) antibodies on the development of rejection episodes depends on patient-specific clinical factors and differs from patient to patient. The HLA typing of the recipient might influence the development of anti-HLA antibodies. Some HLA antigens appear to be more immunogenic than others. The aim of this study is to demonstrate the distribution of HLA phenotypes in PRA-positive and PRA-negative end-stage renal disease (ESRD) patients on the basis of having sensitizing events or not. Our study included 642 (mean age: 41.54; female/male: 310/332) ESRD patients preparing for the first transplantation and who are on the cadaveric kidney transplantation waiting list of Istanbul Medical Faculty in 2008-2009. Class I HLA-A,B typing was performed by complement-dependent cytotoxicity (CDC) method, whereas class II HLA-DRB1 typing was performed by low-resolution polymerase chain reaction (PCR)-sequence-specific primer (SSP). All serum samples were screened for the presence of IgG type of anti-HLA class I- and II-specific antibodies by enzyme-linked-immunosorbent assay (ELISA). PRA-negative group consisted of 558 (86.9%) and PRA-positive group included 84 (13.1%) patients. We have found statistically significant frequency of HLA-A3 (p=0.018), HLA-A66 (p=0.04), and HLA-B18 (p=0.006) antigens in PRA-positive patients and DRB1*07 (p=0.02) having the highest frequency in patients with sensitizing event history but no anti-HLA development suggesting that DRB1*07 might be associated with low risk of anti-HLA antibody formation.

Background The effect of pre-transplant dialysis modality on early graft function is a matter of debate. Although some authors deny the existence of a significant influence, others suggest that peritoneal dialysis (PD) affects early graft function favorably, possibly by contributing to a more physiologic water balance. In the present study, we evaluated the influence of pre-transplant dialysis modality on early and late graft function. Patients and Methods We studied 745 patients who underwent a first renal transplantation during 1983 – 2006, comparing the records of 44 PD patients [26 male; mean age: 26 ± 9 years (range: 8 – 56 years)] who received 36 living related and 8 cadaveric renal transplantations with those of a control group of 44 consecutive hemodialysis (HD) patients [26 male; mean age: 27 ± 11 years (range: 7 – 49 years)] for the index cases. Results The groups showed no significant differences in donor type, human leukocyte antigen matching, immunosuppressive protocols, and duration of dialysis. Also, neither group differed significantly with regard to incidence of delayed graft function, acute tubular necrosis, wound infection, systemic viral and bacterial infections, or acute rejection in the early post-transplant period. In the late post-transplant period, incidences of chronic rejection, graft failure, and malignancies were also similar. During the follow-up period, 3 patients in the PD group experienced acute rejection, 2 developed cytomegalovirus (CMV) disease, and 5 developed various other infections. In the HD group, 4 patients experienced acute rejection, 1 developed CMV disease, and 8 experienced other infections. Five patients in the PD group and one in the HD group died with functioning grafts ( p = 0.09). No differences were noted between the groups in the incidences of post-transplant cardiovascular complications, malignancies, and diabetes mellitus. In the PD group, 33 patients with functioning grafts are still being followed, 6 have returned to dialysis, and 5 have died. In the HD group, 38 patients with functioning grafts are still being followed, 5 have returned to dialysis, and 1 has died. Conclusions As a pre-transplant dialysis modality, neither HD nor PD affects the outcome of renal transplantation.

Background. Despite the developments in haemodialysis, there are still some difficulties in maintaining the haemodynamic stability. Bioimpedance analysis (BIA) has been proposed for the estimation of dry weight in haemodialysis patients. We aimed to investigate the effects of dialysate sodium and glucose contents on volume distribution in body compartments after haemodialysis by using BIA, a sensitive and reliable method. Methods. Seventeen chronic haemodialysis patients [11 males, 6 females, mean age: 36.9 (18-64) years] were included in the study. Patients were evaluated in three periods. The patients (period 1-P1) underwent haemodialysis with dialysate of 200 mg/dL glucose and 140 mmol/dL sodium for 4.5 h in the middle session of the first week. At the beginning and the end of the session, haematocrit, vital parameters (blood pressure, pulse), ultrafiltrated volume, plasma osmolarity and plasma renin activity were recorded. Also multi-frequency bioelectric impedance analyses (Bodystat®Quadscan 4000) were applied to all patients at 5, 50, 100 and 200 kHz, including the impedance index (Z200/Z5). In the second midweek session the same procedure was repeated with same glucose concentration and 135 mmol/dL sodium including dialysate (period 2-P2), and in the third week, it was performed with a dialysate that included 140 mmol/dL sodium and no glucose (period 3-P3). Results. The change of the ratio of the intracellular volume to total body weight (ICV/TBW) at the beginning and the end of the session was same in all periods. However, there were significant differences in the change (after/before session) ratio for the extracellular volume/total body weight (ECV/TBW) in P2 compared to other periods (P values for P1-P2

Increased cardiovascular disease risk is very well known in nephrotic syndrome. Coronary flow reserve measurement by trans-thoracic echocardiography reflects coronary microvascular and endothelial function. However, diastolic filling abnormalities by echocardiography may indicate diastolic dysfunction. Our aim was to evaluate endothelial and diastolic functions by trans-thoracic echocardiography in nephrotic syndrome.Eighteen patients with nephrotic syndrome (five females, 34 +/- 17 years) and 30 controls (10 females, 35 +/- 10 years) were evaluated in this cross-sectional observational study. Age, weight, lipid profile, glucose, blood urea nitrogen, creatinine, serum albumin, total protein, C-reactive protein, erythrocyte sedimentation rate, blood pressures, 24-hour urine volume, and protein were recorded. Glomerular filtration rate was estimated by Cockcroft-Gault Formula. Doppler flow and other echocardiographic parameters were measured by Vivid 7 echocardiography.Coronary flow reserve was significantly lower in patients than controls (p0.001) and was negatively correlated with proteinuria (p0. 001), creatinine levels (p = 0.03), total cholesterol (p = 0.02), C-reactive protein (p = 0.02), and erythrocyte sedimentation rate (p = 0.005). E/A ratio was significantly lower in patients than in controls (p = 0.005). DT was significantly higher in patients than in controls (p = 0.01) and isovolumic relaxation time was similar in both groups.Coronary flow reserve and left ventricular diastolic filling are significantly impaired in nephrotic syndrome. Proteinuria, serum creatinine, total cholesterol and inflammation may have all contributory effects on endothelial dysfunction. Early evaluation of patients with nephrotic syndrome should include coronary flow and diastolic function by echocardiography.

Fever of unknown origin (FUO) in hemodialysis (HD) patients represents a diagnostic challenge because differential diagnosis includes diverse etiologies. Causes of FUO in the general population can be classified into 3 diagnostic categories: infections, tumors, and noninfectious inflammatory diseases. Also, chronic HD patients may have additional problems such as infections, the risk for which may be increased by the immunosuppression associated with uremia, vascular access-related infections, and nosocomial infections. Moreover, patients with chronically failed kidney transplants can have low-grade fever and abdominal pain, and if inflammation of the allograft is severe enough, it may result in a spontaneous rupture. Hence, it is important to rapidly recognize, diagnose, and manage these complications. In the present study, we report a case of FUO in an HD patient with a failed graft and discuss clinical approach and management of these patients.

Fibroblast growth factor (FGF)-23 is a recently discovered phosphaturic hormone that increases in chronic kidney disease (CKD). It has been accepted as a determinant of mortality and a therapeutic target in these patients. Ghrelin is a hormone that has roles in energy and nutrient metabolism. Ghrelin level was found to be increased in CKD patients. This is a controlled study in which the relationship between FGF-23 and ghrelin levels in CKD patients has been studied.Three groups were involved: 88 individuals. Dialysis group (DG, 33 patients) including patients on hemodialysis (21 patients) or peritoneal dialysis program (12 patients); predialysis group (PG, 29 patients) consisting of patients with stage-3 CKD; and the control group (CG, 29 individuals) of healthy adults. Serum FGF-23 and ghrelin levels were measured as well as routine biochemical parameters.FGF-23 levels were similar within the groups (CG: 268±45 pg/mL, PG: 284±94 pg/mL, DG: 259±87 pg/mL, P=0.11). Ghrelin level was higher in the PG group compared with the DG and CG, while DG had higher ghrelin level than the CG (CG: 2.79±0.38 ng/mL, PG: 4.53±1.18 ng/mL, DG: 3.98±0.89 ng/mL). When all groups were studied together; a strong correlation was found between FGF-23 and ghrelin levels. When the analysis was repeated with PG and DG accepted as CKD group; this strong correlation persisted; while it was not true for the CG.There might be a strong correlation between FGF-23 and ghrelin levels irrespective of the stage of CKD and the dialysis modality. There is need for further studies to clarify the pathophysiological link between these parameters.

Objective Behcet's syndrome (BS), a common chronic inflammatory disease in Turkey, results in considerable morbidity and increased mortality. We aimed to estimate its direct and indirect costs. Methods We studied 119 (78 male/41 female) patients with BS at our multidisciplinary BS out-patient clinic in Istanbul, between March and July 2005. The mean age and disease duration were 35 +/- 9 and 10 +/- 6 S.D. yrs. According to the primary clinical problem, patients were divided into: (i) ocular; (ii) vascular; (iii) neurological and (iv) mucocutaneous-joint disease subgroups. They were interviewed with a standardized questionnaire addressing: (a) direct costs such as medication, diagnostic tests, hospital visits, hospitalization fees and lodging and transportation expenses and (b) indirect costs such as lost workdays and wages. The costs were assessed retrospectively by assessing the expenses within a year of the survey and were expressed as US$ mean +/- S.D. Results The mean annual total cost per patient was US$ 3226 +/- 3488 (S.D.). The direct cost accounted for 68% of the total cost. Medication expenses made up 79% of the total direct cost. About 42% of the patients reported lost workdays that averaged 119 +/- 96 days S.D. Among the clinical subgroups mucocutaneous-joint involvement (US$ 1180 +/- 1053) had the lowest economic impact while the neurological disease (US$ 5005 +/- 2707) had the highest. Conclusion In this first cost of illness study in BS, the neurological involvement had the highest annual cost. Direct costs were higher than the indirect costs. Drug costs were the major cost driver. BS causes considerable economic burden for the health care system in Turkey.

Familial Mediterranean fever (FMF) is an inherited inflammatory disease characterized by recurrent febrile polyserositis. Central nervous system (CNS) involvement in FMF is uncommon, but recently cases with multiple sclerosis (MS) and FMF have been reported. Here we assess patients with both FMF and MS, in order to clarify any relationship between FMF and MS, and to evaluate disease characteristics. Our MS database between 1986–2005 was screened retrospectively, and patients with both FMF and inflammatory/demyelinating CNS disease were evaluated among a total of 2800 patients including definite MS (n = 2268) and other demyelinating disorders. There were 12 patients with FMF, who developed a CNS disorder with multifocal white matter lesions. Median age at onset of FMF was 7 years, and median age at neurological onset was 26.8 years. Nine patients (including two siblings) had definite MS according to clinical and MRI findings, whereas 3 patients had atypical features suggesting other demyelinating disorders. Disease severity varied among the patients between very mild to a fatal course. All 8 patients evaluated for oligoclonal IgG bands in CSF were positive. The rate of FMF among our patients with definite MS is almost 4 times the expected prevalence in Turkey. Our series including a sibling pair concordant for FMF and MS may suggest that similar genetic susceptibility and environmental factors might be responsible, although coincidence still remains a possibility. A prospective study on a larger sample seems to be justified.

Background. Accelerated atherosclerosis and vascular calcification are common in chronic haemodialysis (HD) patients. In this study, we aimed to investigate the relationship between left ventricular hypertrophy (LVH) in HD patients and atherosclerosis and vascular calcification measured by electron beam computed tomography (EBCT). Methods. In a cohort of 118 HD patients (52 male, 66 female, mean age: 46±13 years), we measured biochemical parameters, including BUN, creatinine, albumin, haemoglobin, C-reactive protein and fibrinogen levels, and performed echocardiography, highresolution B-mode carotid ultrasonography and EBCT in 85 of them. The degree of stenosis was measured at four different sites (communis, bulbus, interna and externa) in both carotid arteries. Carotid plaque scores were calculated by summing the degrees of stenosis measured at all locations. Results. LVH was detected in 89 of the patients (75%). Plaque-positive patients had higher left ventricular mass index (LVMI) than plaque-negative patients (175±59 vs 143±46 g/m 2 , P ¼ 0.003). LVMI was correlated with systolic blood pressure (r ¼ 0.62, P

Insulin resistance (IR) in chronic renal failure (CRF) is well-known. In this randomized-controlled study, we aimed to compare the effect of doxazosin and amlodipine on IR in patients with CRF. Fifteen patients with CRF (male/female: 5/10, mean age: 46 +/- 13 years) and 9 controls (male/female: 3/6, mean age: 35 +/- 8 years) were included. Patients and controls had no family history of diabetes mellitus. Homeostasis model assessment (HOMA) was calculated as a marker of IR. Patients were grouped randomly to doxazosin (n = 8; 2-4 mg/day) and amlodipine (n = 7; 5-10 mg/day) arms. Baseline biochemical analysis (fasting serum glucose, BUN, creatinine, uric acid, cholesterol and cholesterol subgroups) and parameters related with insulin metabolism (insulin, C peptide, HOMA) were similar between amlodipine and doxazosin groups. There was no difference in age, gender and body mass index among study groups. The follow-up time was 12 weeks. Patients with CRF had higher HOMA (1.83 +/- 0.55 vs 1.00 +/- 0.36, p = 0.001), fasting insulin (8.06 +/- 1.98 vs 4.46 +/- 1.31 IU/l, p < 0.001) and serum triglyceride levels (197 +/- 136 vs 112 +/- 67 mg/dl, p = 0.04) as compared to controls. Serum HDL cholesterol levels were significantly lower in patients with CRF than controls (40 +/- 10 vs 57 +/- 14 mg/dl, p = 0.02). HOMA significantly decreased after doxazosin (1.91 +/- 0.45 vs 1.41 +/- 0.21, p = 0.02), however, no difference was found after amlodipine. Also, fasting insulin levels were decreased after a 12-week doxazosin therapy from 8.17 +/- 1.22 vs 6.58 +/- 0.84 IU/l, p = 0.02), but no change was seen after amlodipine. Lipid parameters did not significantly change during the study period in 2 groups. No adverse effect requiring drug discontinuation was observed during the 12-week period in the study groups. In conclusion, doxazosin decreases IR in patients with CRF, whereas amlodipine has no effect. This may be of advantage in the treatment of hypertension in this group of patients for preventing some long-term complication of IR.

There is increasing evidence that long-term peritoneal dialysis (PD) is associated with structural changes in the peritoneal membrane. Inhibition of the renin-angiotensin system has been demonstrated to lessen peritoneal injury and to slow the decline in residual renal function. Whether spironolactone affects residual renal function in addition to the peritoneal membrane is unknown. We evaluated 23 patients (13 women) with a glomerular filtration rate of 2 mL/min/1.73 m2 or more who were receiving PD. Patients with an active infection or peritonitis episode were excluded. Baseline measurements were obtained for serum high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta), and connective tissue growth factor (CTGF); for daily ultrafiltration (in milliliters); for end-to-initial dialysate concentration of glucose (4/D0 glucose), Kt/V, and peritoneal transport status; and for dialysate cancer antigen 125 (CA125). Spironolactone therapy (25 mg) was given daily for 6 months, after which all measurements were repeated. Mean age of the patients was 46 +/- 13 years. Duration of PD was 15 +/- 21 months (range: 2-88 months). After spironolactone therapy, mean dialysate CA125 was significantly increased compared with baseline (20.52 +/- 12.06 U/mL vs. 24.44 +/- 13.97 U/mL, p = 0.028). Serum hs-CRP, VEGF, TGF-beta, CTGF, daily ultrafiltration, D/Do glucose, Kt/V and peritoneal transport status were similar at both times. At the end of the study period, residual glomerular filtration rate in the patients was lower. In PD patients, treatment with spironolactone seems to slow the decline of peritoneal function, suppress the elevation of profibrotic markers, and increase mesothelial cell mass.

Chronic granulomatous disease (CGD) is a genetic disease caused by structural mutations in the enzyme NADPH oxidase that results in severe immunodeficiency. End-stage renal disease occurs in this patient population and is attributed to various factors, including infections, amyloidosis, and nephrotoxic anti-infective agents. In this report, we present our experience in transplantation for a patient with CGD complicated by isolated hepatic tuberculosis abscess. The course of the case demonstrates the absolute requirements for a multidisciplinary and compulsive approach before, during, and after transplantation. This case report also highlights the unexpectedly benign effects of immunosuppressive therapy in this patient population.

Objectives. We had noted cogwheel rigidity in a number of patients with rheumatoid arthritis (RA). Based on this finding, we aimed to investigate formally the presence of rigidity and cogwheeling in RA patients. Our secondary aim was to survey the co-existence of RA and Parkinson’s disease (PD). Methods. A total of 87 consecutive patients with a diagnosis of RA, 78 patients with PD and 67 otherwise healthy patients attending a dedicated headache clinic participated in the study. Results. Rigidity was observed in 24% of RA, 60% of PD and 2% of headache patients. The frequency among the RA patients was significantly higher compared to that of patients with headache (x2 = 15.2; P= 0.00009). The frequency of PD among the RA patients was 2/87 (2.3%), while the frequency of RA among the PD patients was 6/78 (7.7%). Conclusion. Rigidity can be observed in approximately a quarter of patients with RA.

Our objective was to compare the therapeutic approaches of German and Turkish physicians to rheumatoid arthritis (RA) and to osteoarthritis (OA) of the knee, by means of a mailed survey. The survey contained four case histories representing a mild, a moderate and a severe case of RA and a case of OA of the knee. One hundred and thirty-two physicians from Germany (internal medicine based (IR) and orthopaedics based (OR) rheumatologists) and thirty-three from Turkey (rheumatologists and physical medicine and rehabilitation specialists (PT) participated in the study. German respondents would give more disease-modifying drugs (DMARD) in early RA (48.7% vs 18.2%, p

Background Patients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection. Methods Sixty patients (27 male, 33 female, mean age 50 ±15 years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-α and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight. Results Serum prohepcidin levels of HCV positive patients (135 ± 25 ng/mL) were significantly lower than HCV negative patients [148 ± 18 ng/mL, (p = 0.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (p = 0.016). Serum prohepcidin levels were positively correlated with ferritin (r = 0.405, p = 0.001) and IL-6 (r = 0.271, p = 0.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (r = 0.514 p = 0.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (r = 0.418, p = 0.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (r = 0.28, p = 0.008). Conclusions HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients.

Pulmonary arterial involvement is an important complication of Behçet's syndrome (BS). Among 2179 patients with BS, 24 (1.1%) were diagnosed as having pulmonary arterial aneurysms (PAAs). Haemoptysis was the presenting symptom in all but one. All were male. The mean age at the time of the diagnosis of PAA was 30 +/- 11 S.D. yr (range 17-59 yr). Their mean disease duration was 5 +/- 4 yr (range 3 months-16 yr). There was a high prevalence of thrombophlebitis (21/24, 88%). Histopathological examination showed pulmonary vasculitis involving all layers of pulmonary arteries and veins. Twelve patients (50%) died after a mean of 9.5 +/- 11 S.D. months (range 1-36 months) after the onset of haemoptysis. The mean duration of follow-up of the remaining 12 patients was 25.5 +/- 24 S.D. months (range 1-78 months). The treatment consisted mainly of pulsed or oral cyclophosphamide alone or with prednisolone. As is true with other severe manifestations of Behçet's syndrome, PAAs are more common among males. They are associated with a prevalence of thrombophlebitis and there is high mortality despite treatment.

Objective: To test the hypothesis that not all acute phase reactants respond in the same way during attacks of familial Mediterranean fever (FMF) and that there is a subclinical acute phase response (APR) in a proportion of patients during the interval between attacks. Methods: Blood and urine samples were obtained from 49 patients with FMF during an attack and the attack-free period that followed, to test for erythrocyte sedimentation rate, C reactive protein (CRP), fibrinogen, white blood cell count, platelet count, factor VIII related antigen, haptoglobin, protein electrophoresis, ferritin, proteinuria, and haematuria. Control groups comprised 29 patients with juvenile idiopathic arthritis, 10 patients with various infectious diseases, and 19 healthy subjects. Results: A marked APR was seen during the FMF attacks which was comparable with that obtained in the diseased control groups. CRP was the only acute phase protein that was raised during all attacks. Neither thrombocytosis nor an increase in ferritin levels (except one) was noted in any attack. Serum albumin levels remained unchanged. In two thirds of the patients with FMF a continuing APR was seen in between the attacks. Conclusion: Platelet, ferritin, and albumin responses are not part of the significant APR seen during short lived attacks of FMF, and inflammation continues in about two thirds of the patients during an attack-free period.

Background Reflux nephropathy (RN) has an important place among the etiologies of end-stage renal disease (ESRD). In this retrospective study we sought to analyze posttransplantation complications among renal transplant recipients whose primary disease was RN. Methods Seven hundred forty-five patients who underwent transplantation in our institution between 1983 and 2006 were included in the study. The outcomes of patients with RN (Group 1) were compared with a control group (Group 2) that consisted of age-matched, nondiabetic patients whose primary disease was chronic glomerulonephritis or unknown etiologies. Results Group 1 consisted of 52 patients, including 20 males with a mean overall age of 25 years. Group 2 included 47 patients, including 21 males with a mean age of 27 years. There was no significant difference with regard to age, gender, donor type, donor age, modality of hemodialysis, or HLA match between the 2 groups. Group 1 graft survival rates in the first and fifth years were 95% and 90%, respectively, and in Group 2 they were 86% and 70%, respectively ( P = .302 and P = .072, respectively). There was no significant difference with respect to follow-up duration, hospital stay, or incidence of biopsy-proven or clinically suspected acute rejection episodes between the groups. During the 6-year follow-up, the incidence of biopsy-proven chronic allograft nephropathy was the same in both groups. One patient in Group 1 and 2 in Group 2 died of cardiovascular issues; 1 Group 2 patient died of infection. The frequency of urinary tract infection in Group 1 was greater than that of Group 2 (40% vs, 23%; P = NS). Conclusion Despite the higher incidence of urinary tract infections, there was no significant difference in posttransplantation complications or patient and graft survival rates between RN patients compared with the control group.

Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 +/- 71 months. Mean serum creatinine level was 1.63 +/- 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 +/- 0.58 mg/dL (P = 0.67), 1.52 +/- 0.53 mg/dL (P = 0.414), 1.62 +/- 0.62 mg/dL (P = 0.734), and 1.48 +/- 0.58 mg/dL (P = 0.065), 1.58 +/- 0.53 mg/dL (P = 0.854), 1.88 +/- 0.77 mg/dL (P = 0.083), respectively. Daily proteinuria levels increased from 0.04 +/- 0.11 g/day at baseline to 0.55 +/- 1.33 g/day (P = 0.037) after conversion, in the responders group. In the nonresponders group, baseline proteinuria was 0.13 +/- 0.25 g/day, and increased to 1.44 +/- 2.44 g/day after conversion (P = 0.008). SRL was discontinued in 16 patients (31%) because of the occurrence of severe side effects. The proportion of patients remaining on SRL therapy over time was 43.1% at 1 year, 15.5% at 2 years after conversion, and 10.3% at 3 years after conversion. SRL conversion may be very useful in patients suffering from neoplasia; however, frequent side effects related with this intervention should be considered, and routine conversion from CNI to SRL to reduce nephrotoxicity should be discouraged.

Serum uric acid (UA) level as a significant and independent risk factor for cardiovascular disease, and the link between this marker and left ventricular hypertrophy (LVH) in renal transplant recipients remains to be clarified. A total of 141 renal transplant recipients (83 men), between ages of 18 and 69 (mean age 37 ± 11), were included in this single center study. In addition to demographic, clinical, and laboratory parameters, serum UA concentrations were evaluated. LVH was determined by two-dimensional and M-mode echocardiography. Serum UA levels were significantly higher (6.14 ± 1.15 mg/dL) in patients with LVH (n = 54) when compared to patients (n = 87) who did not have this abnormality (5.29 ± 1.43 mg/dL) (p = 0.006). Serum UA levels were significantly correlated with septal wall thickness, LV posterior wall thickness, LV mass index (LVMI), and pulmonary arterial pressure. Multiple linear regression analysis revealed that UA predicted LVMI (r(2) = 0.150, β = 0.369, p = 0.001). However, serum creatinine (β = 0.060, p = 0.593) and age (β = 0.146, p = 0.175) were not predictors of LVMI. High serum UA levels are associated with LVH in renal transplant recipients, which underlines the importance of treating hyperuricemia.

Endothelial dysfunction (ED) is a common precursor and denominator of cardiovascular events including development of atherosclerosis. In this cross-sectional study, we aimed to investigate ED, measured by coronary flow reserve (CFR) in hemodialysis (nHD) patients who were never transplanted and patients with failed renal transplants restarting hemodialysis (fTx-HD).Forty nHD (24 males, mean age 39 ± 9 yr) and 43 fTx-HD patients (27 males, mean age 36 ± 9 yr) were included in the study. Clinical and biochemical parameters, including high-sensitive C-reactive protein (hs-CRP) levels were determined. Also, CFR measurements were used to evaluate ED.There were no significant differences regarding age, gender, smoking status, systolic and diastolic blood pressure levels, mean duration of HD treatment as well as Kt/V((urea)) values between the two groups. Time spent on dialysis in the nHD group and dialysis duration following failure of renal allograft in the fTx-HD group were similar. Serum creatinine, hemoglobin, hematocrit, calcium and phosphorus levels were similar between the two groups as well. When compared to nHD group, serum total cholesterol (139 ± 3 vs. 154 ± 3 mg/dL, p = 0.045), serum albumin (3.8 ± 0.3 g/dL vs. 4.1 ± 0.2 g/dL, p0.0001) and CFR (1.60 ± 0.2 vs. 1.75 ± 0.3, p = 0.028) levels were significantly lower, while serum hs-CRP levels (11 ± 15 mg/L vs. 3 ± 4 mg/L, p = 0.001) were significantly higher in the fTx-HD group. Serum hs-CRP negatively correlated (r = -0254, p = 0.021), while serum albumin positively correlated (r = 0402, p = 0.001) with CFR values.ED is more prominent in fTx-HD than the nHD patients. Inflammation, caused by failed renal allograft can be responsible for this abnormality.

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED) is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 +/- 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR2 andor= 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 +/- 82.1 pg/mL) in patients with CFRor= 2 were significantly higher than those in patients with CFR2 (63.3 +/- 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 +/- 37.81 ng/mL vs. 63.95 +/- 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.

Serum albumin levels have been used as a representative marker for morbidity and mortality in the dialysis population. We evaluated the significance of various biochemical values in peritoneal dialysis (PD) patients with a history of peritonitis. In 51 patients [27 women, 24 men; mean age: 42.6 years (range: 19 - 70 years); average duration of PD: 28.26 +/- 23.1 months] with history of peritonitis, we recorded serum albumin and cholesterol levels at the beginning of PD, at the last visit (1 month) before the peritonitis episode, and at months 1, 6, and 12 after the peritonitis episode. Routine data from peritoneal equilibration tests were also obtained. Serum albumin showed a significant decline from the basal measurement at the measurements 1 month before and after the peritonitis episode (p = 0.026 and 0.025 respectively). Serum cholesterol levels and dialysate-to-plasma creatinine at hours 2 and 4 revealed no significant alterations at the same time points. The decline in serum albumin relative to the first visit (basal level) may be a factor showing the likelihood of peritonitis. A decline in serum albumin during follow-up may be an indicator for subsequent peritonitis. The absence of a similar decline in serum cholesterol levels (mimicking albumin) may rule out low dietary intake or malnutrition. Pathophysiologic explanations for these relationships are not obvious. If the leading complication of PD is peritonitis, efforts should be focused on improving the factors that influence serum albumin levels.

We investigated peritoneal leukocyte count (PLC) and culture results for correlations with inflammation, nutrition, microbiologic parameters, and the effects of peritonitis on peritoneal equilibration tests (PETs) and clinical outcomes in peritoneal dialysis (PD) patients. The study group consisted of patients who had experienced peritonitis for the first time and who had been on PD for at least 6 months, with a PET performed both before and after the peritonitis episode. Only patients with an increased PLC were analyzed. In the 70 patients analyzed (35 men; mean age: 45.1 +/- 13.5 years), 7 (10.0%) underwent PD catheter removal, 60 (85.7%) responded well to treatment, and 3 (4.3%) died. Cultures of peritoneal fluid were positive in 25 patients (35.7%), and these patients had a significantly higher PLC than did the culture-negative patients. After the peritonitis episode, C-reactive protein (CRP) increased significantly in affected patients. Residual urine declined after peritonitis. We observed no significant difference in PET results. Clearly, more micro-organisms are present in the peritoneal fluid in patients with a positive culture than in those with a negative culture, meaning that they have severe peritonitis, which responds poorly to treatment. Beyond a consideration of possibly inappropriate culturing techniques, the variations in effluent culture results might reflect geographic or ethnic differences. Positive culture results and a high PLC should be considered risk factors for catheter loss and mortality in PD. Moreover, culture results might show geographic and ethnic differences. In peritonitis follow-up, CRP may be a better marker than erythrocyte sedimentation rate is.