Sibel Ersan

Tuberculosis in renal transplant recipients.

Abstract Background: Renal transplant recipients should be considered at high risk for development of Mycobacterium tuberculosis infection (tuberculosis, TB). TB is relatively more frequent among transplant recipients than general population, depending on its epidemicity in the geographic region. Clinical manifestations in this group of patients may be atypical and deserve aggressive investigations for diagnosis. Tuberculin skin test has several limitations regarding diagnosis in chronic renal failure patients. In this retrospective study, we aimed to explore the prevalence and clinical manifestations of TB in renal transplant patients. Materials and methods: We retrospectively analyzed the data for TB prevalence, clinical presentations, and patient and graft survivals of total 320 pediatric and adult renal transplant recipients in our center between 1992 and 2010. Results: The prevalence of TB was 2.8%. Five patients received kidney from living-donor related and four from cadaveric donors. Cadaveric-donor patients received antithymocyte globulin for induction, and four patients received pulse steroid for acute rejection. The median duration of time between transplantation and TB was 21 (1–150) months, and between induction/pulse therapy and infection was 5 (1–100) months. The immunosuppressive protocols included prednisolone and cyclosporine/rapamycin with or without mycophenolate mofetil/azathioprine. The major symptoms were fever (77%), cough (66%), and abdominal pain (22%). Extrapulmonary TB with intestinal (2/9), pericardial (1/9), lymph node (1/9), and cerebral (1/9) involvements developed in five patients. One patient had both pulmonary and testicular involvements. All patients received quartet of anti-TB therapy for a median duration of 9 months. One patient died at the second month of therapy because of dissemination of TB, and one patient returned to hemodialysis because of chronic allograft nephropathy. Conclusion: The prevalence of TB was 2.8% in our renal transplant patients. The quartet of anti-TB treatment including rifampicin resulted in success in a majority of patients.

Incidence of thyroid dysfunction and thyroid cancer in renal transplant recipients: a single center experience.

Background. The prevalence of thyroid cancer in renal transplant population has not been widely studied, and there is no consensus on the management of thyroid cancer in transplant patients. The aim of this study was to evaluate changes in thyroid hormone levels and investigate the incidence of the thyroid cancer after renal transplantation. Materials and methods. From October 1989 to April 2007, 122 renal allograft recipients that were being followed underwent thyroid ultrasonography to determine nodules together with thyroid hormone levels. Ultrasound-guided fine-needle aspiration biopsy (FNAB) was performed to the nodules > 10 mm or those with 8–10 mm diameter but with calcifications. Results. One hundred and eight patients (88.5%) had normal thyroid function. None of the patients had overt hypothyroidism, 2 had subclinical hypothyroidism, 10 subclinical thyrotoxicosis, and 2 low T3 syndrome. Mean thyroid volume was 14.2 ± 7.2 ml. In all, 91.8% was diagnosed with goiter (n = 112). Seventy-two thyroid nodules were detected in 49 kidney allograft recipients (single nodule in 30, multiple in 19 patients). Eighty-four biopsy samples were reported as benign (n = 21, 87.5%), 8 as suspicious (n = 2, 8.3%), and 4 as inadequate (n = 1, 4.1%). After surgery, one of the patients (0.8%) with suspicious FNAB was reported as papillary thyroid carcinoma. Conclusion. Because of the high incidence of thyroid dysfunction in transplant patients, screening of thyroid function should be a part of follow-up. Our results suggest that although frequency of nodules is increased in kidney transplant patients, prevalence of thyroid cancer is slightly, but not significantly, higher than that of the normal population.

Unusual case of severe late-onset cytomegalovirus-induced hemorrhagic cystitis and ureteritis in a renal transplant patient.

Abstract Cytomegalovirus (CMV) infection is common in solid organ transplant recipients and accounts for the majority of graft compromise. Major risk factors include primary exposure to CMV infection at the time of transplantation and the use of antilymphocyte agents such as OKT3 (the monoclonal antibody muromonab-CD3) and antithymocyte globulin. It most often develops during the first 6 months after transplantation. Although current prophylactic strategies and antiviral agents have led to decreased occurrence of CMV disease in early posttransplant period, the incidence of late-onset CMV disease ranges from 2% to 7% even in the patients receiving prophylaxis with oral ganciclovir. The most common presentation of CMV disease in transplant patients is CMV pneumonitis followed by gastrointestinal disease. Hemorrhagic cystitis is a common complication following hematopoietic stem cell transplantation. The condition is usually due to cyclophosphamide-based myeloablative regimens and infectious agents. Even in these settings, CMV-induced cases occur only sporadically. Ureteritis and hemorrhagic cystitis due to CMV infection after kidney transplantation is reported very rarely on a case basis in the literature so far. We report here a case of late-onset CMV-induced hemorrhagic cystitis and ureteritis presenting with painful macroscopic hematuria and ureteral obstruction after 4 years of renal transplantation. The diagnosis is pathologically confirmed by the demonstration of immunohistochemical staining specific for CMV in a resected ureteral section. We draw attention to this very particular presentation of CMV hemorrhagic cystitis with ureteral obstruction in order to emphasize atypical presentation of tissue-invasive CMV disease far beyond the timetable for posttransplant CMV infection.

PRETREATMENT WITH NEBIVOLOL ATTENUATES LEVEL AND EXPRESSION OF MATRIX METALLOPROTEINASES IN A RAT MODEL OF RENAL ISCHEMIA-REPERFUSION INJURY.

Matrix metalloproteinases (MMPs) are zinc‐containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischaemic organ injuries. In the present study, we aimed to determine the expression and level of MMP‐2 and MMP‐9 in renal ischaemia–reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a β1‐adrenergic receptor blocker, on both MMP‐2 and ‐9 level and expression and tubular injury caused by IRI.

Results of 4-Year Analysis of Conversion from Calcineurin Inhibitors to mTOR Inhibitors in Renal Transplant Patients: Single-Center Experience

Abstract In this retrospective study, 83 patients were accepted. Mammalian target of rapamycin (mTOR) group consisting of 37 patients were converted from calcineurin inhibitors (CNI), and the control group included 46 patients (initially CNI-receiving patients). As a control-match of each mTOR inhibitor patient, the succeeding patient with transplantation who continued CNI therapy was chosen. All patients received CNI, MMF, and prednisolone as an immunosuppressive therapy initially. In comparison of two groups, there was no significant difference between sex, donor organ source, donor organ ischemia time, or mismatches. However, mean age between groups was significantly different (mTOR group: 48.3 ± 12, CNI group: 38.6 ± 11, p < 0.001). Decision of conversion to mTOR inhibitors in 30 patients was made by biopsy. The reasons for conversion were determined as CNI nephrotoxicity in 15 patients, chronic allograft nephropathy in 15 patients, malignancy in 6 patients, and renal artery stenosis in 1 patient. Basal glomerular filtration rates (GFRs) were markedly lower in mTOR group than in CNI group (38.8 mL/min vs. 72.7 mL/min). At the end of 48-month follow-ups, GFR increased from 38 mL/min to 54 mL/min in mTOR group; however, it decreased to 53 mL/min from 72 mL/min in CNI group. There was no difference left between the two groups in GFR after 4-year follow-up. Hyperlipidemia was higher in mTOR group. Acute rejection rates were similar. Cytomegalovirus (CMV) disease was more prevalent in CNI group. Graft failure developed due to secondary reasons, causing mortality in both groups. We suggest that conversion to mTOR inhibitors maintains and improves graft functions well.

Complement Factor H and Complement Factor H-Related Protein 5 Mutations Associated with Atypical Hemolytic Uremic Syndrome in a Systemic Lupus Erythematosus Patient: Efficacy of Eculizumab

The pathophysiology of aHUS involves endothelial injury caused by uncontrolled activation of the alternative complement pathway mostly due to mutations in genes coding for regulatory and activatory proteins (1-3). Mutations in the CFH/CFHR gene cluster have been reported in other disorders including C3 glomerulopathy, SLE, and age related macular degeneration (4,5). CFH gene mutation is the most common one with a frequency of 12-20% in sporadic, and 32-42% in familial cases (6-9). In SLE patients, certain mutations in the regulatory complement proteins related with aHUS have been reported to increase susceptibility to SLE and early onset of nephritis (10,11).

Risk factors for colistin-associated nephrotoxicity and mortality in critically ill patients

Background/aim: Colistin is gaining popularity against multidrug-resistant bacteria. The primary concern with colistin is its nephrotoxicity (NT). The aim of this study was to evaluate the incidence and risk factors for NT and to evaluate the risk factors for mortality in the toxicity group. Materials and methods: NT was defined according to the RIFLE criteria. Data of patients who did or did not develop NT were compared. Positive and negative predictive values, risk ratio, and correlation coefficients were calculated. Results: NT was seen in 39 patients (70%). Hypoalbuminemia, old age, and the use of vasopressors (VPs) were associated with NT. The use of VPs had the highest positive predictive value, while age had the highest negative predictive value and risk ratio. The only variable that was associated with mortality in the toxicity group was VP use. Conclusion: Aging, hypoalbuminemia, and the use of VPs were shown to be risk factors for NT, while the last of these was the only significant risk factor for mortality in the toxicity group.

Prevalence and Causes of Proteinuria in Kidney Transplant Recipients: Data from a Single Center

Abstract Introduction. Proteinuria after renal transplantation increases the risk of graft failure and mortality. The aim of the study was to determine the prevalence and causes of proteinuria in kidney transplant recipients. Methods. All kidney transplant recipients followed up in our clinic were included in the study. As a center protocol 24-hour urine collections were used to quantify protein excretion with 3-month intervals posttransplantation during the first year, and yearly thereafter. The etiology of chronic kidney disease and demographic characteristics of the study group were obtained from outpatient records. Data regarding the immunosuppressive regimens used, 24-hour proteinuria levels and creatinine clearences, new-onset hypertension, new-onset diabetes mellitus, rejection episodes, infections like cytomegalovirus (CMV) and polyoma (BK), and biopsy findings were noted. Results. A total of 260 kidney transplant recipients (97 females, mean age 42.3±12.3 years) were evaluated. Median follow-up period was 36 months; 137 of all transplantations were from living donors. Mean age of donors was 42.7±15 years and 133 were female. Proteinuria with protein excretion ≥300 mg/d was present in 35.4% of patients. The most common cause of biopsy-proven proteinuria was transplant-specific conditions (acute rejection, and borderline changes). Conclusion. The prevalence of proteinuria was 35.4%. The transplant-specific diagnoses were the most likely causes. Even in nonnephrotic ranges it was associated with decreased graft survival.

The Effect of Steroid-Sirolimus Combination on the Experimental Model of Encapsulating Peritoneal Sclerosis in Rats

ABS TRACT Objective: Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis terminating with peritoneal sclerosis and coccooning of intestinal loops. The inhibitors of mammalian target of rapamycin (mTOR), everolimus and sirolimus, have attenuated EPS findings in experimental animal models. The effect of combination of sirolimus with steroid has not been documented so far. The aim of the study was to determine the effect of combination of sirolimus and steroid on experimental sclerosing peritonitis model. Material and Methods: 41 wistar albino male rats were divided into 6 groups : control group (C; isotonic saline injected intraperitoneally), chlorhexidine gluconate group (CG; model group), resting group (R; CG then peritoneal rest, prednisolone group (P; CG then prednisolone), sirolimus group (Sir; CG then sirolimus), and prednisolone-sirolimus group (P-Sir; CG then prednisolone plus sirolimus). Peritoneal specimens obtained after sacrification at the end of study were examined for peritoneal thickness, fibrosis, and vascular intensities under light microscopy. Results: In the CG and R groups there was a significant increase in peritoneal thickness, fibrosis score and vascular intensity compared to C, P, Sir, and P-Sir groups in both parietal and visceral peritoneum (p<0.05). The parameters at the end of the study were not different in C, P, Sir, and P-Sir groups. The difference between P, Sir, and P-Sir groups were not significant. Resting was shown to be ineffective in attenuating EPS parameters. Conclusion: In this study we observed that sirolimus-prednisolone combination was equally effective in experimental EPS model compared to prednisolone and sirolimus only regimens.