Regulatory T Cells in the Context of New-Onset Diabetes After Renal Transplant: A Single-Center Experience.

BACKGROUND: New-onset diabetes mellitus after transplant (NODAT) is a well-known complication of renal transplant that severely affects graft and patient survival. It is necessary to explore further risk factors and reveal the underlying pathomechanism. METHODS: Renal transplants performed between January 2010 and June 2018 were involved. Exclusion criteria were the recipient age younger than 18 years, follow-up period less than 6 months, and patients with diabetes at the time of transplant. Only primary kidney transplants were involved in our study, which totaled 223 cases. Besides donor and recipient demographic data, the type of immunosuppression, the average fasting glucose level, and T-subset profiles were compared. RESULTS: Of 223 cases there were 33 patients (14.8%) with NODAT (17 female; mean age, 54.2 [SD, 10.3] years; mean body mass index [calculated as weight in kilograms divided by height in meters squared], 27.8 [SD, 5.1]; mean follow-up, 43.3 [SD, 25.5] months). The control group consisted of 190 patients. The average fasting blood glucose level was higher in the NODAT group vs the control group (P < .001). The average fasting blood glucose level above diabetic threshold (≥7 mmol/L) was in association with a 6-fold higher risk of NODAT (odds ratio, 5.86; 95% CI, 2.46-13.97; P < .001). Absolute value of CD4+CD25brightCD127dim regulatory T cells was lower in the NODAT group at the first month after transplant (P = .048) Immunosuppressive protocol and survival data did not differ. CONCLUSIONS: Intensive management of the carbohydrate excursions during the early post-transplant period may decrease the incidence of NODAT. Further investigations will be required to decide whether the reduced CD4+CD25brightCD127dim/regulatory T-cell count contributes the development of NODAT.

Surgical Treatment of Hyperparathyroidism After Kidney Transplant.

Chronic renal impairment is often associated with complex bone disorders. Improvement of secondary hyperparathyroidism (HPT) is expected after kidney transplant (KT) if the glomerular filtration rate is normalized. PATIENTS AND METHODS: There were 888 KTs performed between 1996 and 2017 at our department. A total of 558 general patients have been operated on for HPT during the same period. The 2 populations had a common part: out of the 558, a total of 69 (12.4%) were in end-stage renal failure when operated on because of secondary HPT. That also means that 7.8% of all KTs were associated with HPT. Retrospective, single-center analysis was performed using the patients' medical records. The aim of our study was to analyze the results of parathyroidectomies after KT. RESULTS: Parathyroid surgery was performed on 19 patients (2.14%) because of HPT after KT. The applied surgical technique was total parathyroidectomy with autotransplant in 6 cases, subtotal parathyroidectomy in 3 cases, and selective parathyroidectomy in 10 cases. In all cases, histology revealed benign disease. Complications were observed in 10 cases (52%); there were 6 cases of postoperative hypocalcaemia (31.58%), 1 case of transient laryngeal recurrent nerve paresis (5.26%), and 6 cases of recurrent HPT (31.58%). SUMMARY: The first step of HPT management is calcimimetic drug treatment. It is essential to prevent possible complications with regular laboratory monitoring. If the proper conservative therapy is refractory or severe in complications, surgery should be chosen. If the patient is already waiting for a KT, it is worth performing the parathyroid surgery before KT. Close collaboration with endocrinologists and nephrologists is needed to achieve successful therapy.

Autosomal Dominant Polycystic Kidney Disease Transplant Recipients After Kidney Transplantation: A Single-center Experience.

Kidney transplantation is indicated for end-stage renal disease. Autosomal dominant polycystic kidney disease (ADPKD) causes structural degeneration of the kidney and eventually becomes end-stage renal disease. ADPKD patients usually have several renal and nonrenal complications. We analyzed our kidney transplantation activities between 1991 and 2010 regarding ADPKD. We followed up with patients to December 31, 2016. Data were collected as patient and graft survival rates, the prevalence of polycystic manifestation of the gastrointestinal tract and other organs, and the attendance of urinary tract infection. Among the 734 kidney transplantations, 10.9% (n = 80) had an ADPKD. Four patients (5%) had diverticulum perforation. The prevalence of post-transplantation urinary tract infection was higher in ADPKD patients (55.9%) compared to non-ADPKD patients (44.1%). The 1-, 3-, and 5-year overall survival rates in ADPKD recipients versus non-ADPKD patients are 77.5%, 70.0%, and 67.5% versus 86.4%, 83.0%, and 80.1%, respectively. Patients with ADPKD were transplanted at an elder age compared to others (median: 47.5 years vs. 39.9 years). Female patients had longer graft survival times than males. ADPKD implies multiple cystic degeneration of the kidneys; however, it can cause structural degeneration in other organs. It is typical for ADPKD patients to have an acute abdominal-like syndrome. Immunosuppressive drugs can hide the clinical picture, which makes early diagnosis difficult.

Ophthalmic Findings in Patients After Renal Transplantation.

The aim of the study was to perform complete ophthalmic examinations in patients after renal transplantation to determine ocular alterations and condition of the eyes. Moreover, ophthalmic findings were correlated with certain clinical characteristics related to transplantation such as post-operative renal functions and immunosuppressive regimen. The study was performed on 84 eyes of 42 patients who had received a renal transplant at least 6 months earlier. All patients underwent a complete ophthalmologic examination. In addition, in 33 (78.6%) patients peripapillary retinal nerve fiber layer (RNFL) thickness was determined using optical coherence tomography (Stratus OCT, Zeiss, Germany), which is a unique finding among renal transplantation patients. Recipients received immunosuppressive therapy consisting of tacrolimus, mycophenolate mofetil, and corticosteroid. Of 42 patients, 19 (45%) were women and 23 (55%) were men. The age of the patients ranged from 26 to 74 years, the mean age was 53.4 years. At least one ocular abnormality could be detected in 37 patients (88%), including impaired visual acuity (n = 31, 74%), keratoconjunctivitis sicca (n = 6, 14.3%), pinguecula (n = 3, 7.1%), arcus lipoides (n = 1, 2.4%), cataracts (n = 24, 57.1%), glaucoma (n = 2, 5%), retinal drusen (n = 6, 14.3%), and hypertensive or atherosclerotic retinopathy (n = 22, 52.4%). Twenty-five patients (75.8%) have reduced RNFL thickness. Cataract formation was positively correlated with age and usage of methylprednisolone. Moreover, RNFL thickness loss was correlated with transplantation duration and postoperative infections. Our study suggests that ocular disorders are frequent among renal transplantation patients. Besides immunosuppression and postoperative infection, aging is a high-risk factor in such cases.

Bacterial Infections After Kidney Transplantation: A Single-Center Experience.

BACKGROUND: Bacterial infections significantly affect graft loss and mortality after kidney transplantation (KT). We reviewed the frequencies, risk factors, and sources of bacterial infections after KT and their impact on graft and patient survivals. METHODS: The data of 154 kidney recipients who underwent transplantation from 2010 to 2015 were explored. Donor, recipient, and surgical parameters were collected, and source, type, and frequency of infectious complications, number of infective episodes, multidrug-resistant (MDR) bacteria, and the bacterial spectrum were established. RESULTS: The most common infection was urinary tract infection, which is in line with the literature. Out of the 154 recipients, 72.1% (n = 111) had at least 1 occasion of a bacterial infection episode with clinical symptoms. It occurred 0-43 months (mean, 19.5 mo) after transplantation. Ninety-three KT recipients (67.9%) developed 274 episodes of infection in the postoperative 1st year (1.8 episodes/patient/y), and 42 patients had admission to the hospital ward (5.2 d/patient/y). MDR was detected in 19.8% of the infections. CONCLUSIONS: A bacterial infection had no significant impact on survival by itself. However, in case of sepsis graft and patient survivals were lower compared with normal control subjects.

Cardiovascular Screening and Management Among Kidney Transplant Candidates in Hungary.

INTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease patients on dialysis and the most common cause of death in the immediate post-transplantation period. The aim of our study was to describe a novel approach of cardiovascular screening and management of dialysis patients evaluated for the transplant waiting list. METHODS: Twenty-eight patients with end-stage renal disease put on the waiting list between July 2013 and July 2014 were subjected to a prespecified cardiovascular screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently divided into 3 strata in terms of their estimated cardiovascular risk. Each of these groups were then prescribed interventions aiming to improve their cardiovascular condition. RESULTS: According to our prespecified protocol of cardiovascular screening studies, 15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four (14%) patients were current smokers. In the low-risk group, we initiated a patient education program involving counseling on regular exercise such as swimming or cycling to improve their functional capacity. In the high-risk group revascularization was done in 5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA) with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG) for triple-vessel disease in 2 cases. In the medium-risk group medical management was opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management, indices of bone-mineral disease, and fluid status. CONCLUSION: In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening protocol. Further studies are needed to correlate this novel strategy with post-transplantation outcomes.

Oxidation of hemoglobin by lipid hydroperoxide associated with low-density lipoprotein (LDL) and increased cytotoxic effect by LDL oxidation in heme oxygenase-1 (HO-1) deficiency.

Heme-catalyzed oxidation of low-density lipoprotein (LDL) is one of the relevant mechanisms involved in LDL modification. We previously revealed a substantial oxidation of plasma hemoglobin to methemoglobin and a subsequent heme-catalyzed LDL oxidation generating moieties toxic to endothelium in heme oxygenase-1 (HO-1)-deficiency in human. Drawing upon our previous observation we posited a pathway for oxidation of plasma hemoglobin in the HO-1-deficient child involving LDL-associated lipid hydroperoxide. In support, LDL-associated lipid hydroperoxide oxidized ferrohemoglobin to methemoglobin--known to readily release its heme moieties--in a dose-dependent manner. Repeated heme exposure of the child s LDL further increased its lipid hydroperoxide content within min leading to additional cytotoxic effect on endothelium. Both cytotoxicity and HO-1 inducing ability of the oxidized LDL were strongly dependent on its lipid hydroperoxide content. We wondered if cells of the HO-1-deficient patient were prone to oxidative damage arising from heme-mediated oxidation of LDL. Indeed, we found elevated cytotoxicity induced by heme-catalyzed oxidation of LDL in lymphoblastoid cells derived from the HO-1-deficient patient. We conclude that oxidation of hemoglobin to methemoglobin by LDL-associated lipid hydroperoxide and increased sensitivity of cells of the HO-1-deficient child to stress of oxidized LDL might contribute to the vascular disorders reported earlier.