Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study.

BACKGROUND: Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient-reported warning signal for invasive SCCs in OTRs. OBJECTIVES: To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. METHODS: We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient-reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan-Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. RESULTS: There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97-2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0-2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. CONCLUSIONS: We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.

Candida arteritis in kidney transplant recipients: case report and review of the literature.

Multi-organ procurement is a risk factor for contamination of preservation fluid with intestinal flora including fungi (e.g., Candida). Transmission of fungal species to the graft vessel can cause mycotic arteritis. This is a very rare but life-threatening complication of renal transplantation. We present 2 cases of renal transplant recipients from the same multi-organ donor. Both recipients suffered from severe hemorrhages from renal graft anastomosis and renal artery pseudoaneurysm due to Candida albicans arteritis (CAA). The culture of the preservation fluid revealed growth of Escherichia coli, but neither preservation fluid nor multiple routine blood cultures performed before hemorrhagic complications revealed fungal growth (media non-selective for fungal growth were applied). The first recipient suffered from sudden severe hemorrhage in the area of graft anastomosis on day 10 post surgery (without any preceding clinical or radiological symptoms). This led to urgent surgery and graftectomy, which was complicated by cardio-respiratory arrest with resuscitation in the operating room; despite resuscitation, irreversible brain damage, and subsequent death occurred in the intensive care unit (ICU) 2 weeks later (on day 24 after transplantation). The second patient underwent urgent vascular surgery on day 22 (after transplantation), because of hemorrhage from a pseudoaneurysm of the graft artery. She required repeated vascular operations, extended antimicrobial and antifungal therapy, and ICU monitoring and, despite these interventions, she died on day 80 after transplantation as a result of Pseudomonas aeruginosa sepsis. Arteritis of the renal artery in both patients was caused by C. albicans. This was confirmed by histopathology: infiltration of renal artery with budding yeast forming pseudohyphae (Case 1), and the presence of C. albicans in the culture of the renal artery and surrounding tissue (Case 2). We conclude that organ preservation solution should be cultured with use of media selective for fungal growth. As soon as the positive culture is detected, appropriate measures protecting patients against CAA should be undertaken.

Treated asymptomatic bacteriuria during first year after renal transplantation.

BACKGROUND: Urinary tract infections (UTIs) are widespread in renal transplant (RTx) recipients with asymptomatic bacteriuria (AB) as the predominant form. It is necessary to determine if AB is a risk factor for symptomatic UTIs. METHODS: We analyzed clinical data and urine cultures performed within the first 12 months after RTx in 209 consecutive patients undergoing RTx at Gdansk Transplantation Center between January 2007 and December 2009. RESULTS: We observed 170 AB episodes in 83 patients. This accounted for 53% of all diagnosed UTIs in 111 patients, with more than half of AB episodes occurring during the first month post transplant. The most prevalent uropathogen was Enterococcus faecium (36.8%, n = 32) and, from the second month after RTx, Escherichia coli (54.2%, n = 45). Female gender, use of induction with anti-thymocyte globulin, comorbidity measured by Charlson Comorbidity Index, history of acute rejection, and cytomegalovirus infection were risk factors for developing AB, and no differences in risk factors were seen for developing a symptomatic UTI vs. an AB after RTx. All patients with AB received antibiotic therapy. AB was an independent risk factor for symptomatic UTIs, but only 21 of 152 episodes of symptomatic UTIs were preceded by AB with the same causative agent. CONCLUSIONS: AB is a common finding in the RTx population and AB episodes may be considered a risk factor for symptomatic infections. It remains to be determined if the treatment of AB in RTx patients is in fact helpful or harmful in preventing symptomatic infections.

Adipokines and nutritional status for patients on maintenance hemodialysis.

OBJECTIVES: The aim of this study was to investigate the serum concentration of adipokines, such as leptin, adiponectin, and resistin, and assess its relation to nutritional and inflammatory parameters in both overweight and normal weight patients on maintenance hemodialysis. METHODS: A total of 36 hemodialysis patients (27 M, 9 F; mean age 55.3 +/- 12 yr.) were examined and 23 additional healthy volunteers were recruited as the control group. The concentrations of leptin, leptin receptor, adiponectin, resistin, IL-6, TNFa and CRP were measured by ELISA. Assessment of nutritional status was determined by the levels of albumin, BMI, percentage of body fat (%F), lean body mass (LBM), and Subjective Global Assessment Score (SGA). RESULTS: According to the SGA 7-points score and the albumin level, 20 patients were of good nutritional status (6-7 points), while 16 patients were mildly malnourished (4-5 points). The concentrations of CRP, resistin, adiponectin, and TNFa were statistically higher in hemodialysis patients than in the control group (p pound 0.05). The adiponectin level was inversely correlated with %F (R Spearman=-0.3; p pound 0.05). The level of leptin was positively correlated with %F as well as with BMI and SGA scores (R Spearman=0.4; p pound 0.05). Although there was no significant difference in the nutritional status between the nonoverweight (BMI 18.5-24.99) and overweight (BMI (3)25.0) groups of patients, in the nonoverweight group there were 12 patients (54.5%) with signs of mild malnutrition compared to 4 malnourished patients (28.5%) in the overweight group. Nonoverweight patients presented significantly lower leptin concentration (12.7 vs 27.8 ug/l) and higher adiponectin level (38.9 vs 32.5 ng/ml) when compared to overweight patients. The levels of IL-6 and TNFa were higher in the nonoverweight group of patients. Overweight patients also had shorter durations of stay in the hemodialysis program (30.5 vs. 87.6 months). CONCLUSION: The results of our study indicate that lean hemodialysis patients are more prone to malnutrition and inflammation. The increased levels of leptin and decreased levels of adiponectin in the overweight hemodialysis patients support the idea of a reverse epidemiology phenomenon in this group of patients.

Lipoxin (LTX A4 5S, 6R, 15R) levels drastically decrease after 5 years of hemodialysis treatment.

The increased risk of atherosclerosis in patients with chronic kidney disease (CKD) is associated with the increased concentration of fatty acids from the omega-6 family. Products of arachidonic acid oxidation, including prostaglandins, thromboxanes, hydroxyleicosa-tetraenoic acids (HETES) and hydroxyoctadecadienoic acids (HODES) are involved in the pathogenesis of cancer and cardiovascular diseases due to increased oxidative stress. The aim of our study was to determine the relations resulting from the duration of CKD treatment. One of our main concerns is, whether and when the cascade of synthesis of inflammatory mediators may be insufficient in patients with CKD during many years of treatment. The study involved 121 patients with CKD and 87 healthy volunteers. Eicosanoid profiles 9(S)-HODE, 13(S)-HODE, 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 5(S)-oxoETE, 16(RS)-HETE, and 5(S),6(R)-lipoxinA4, 5(S),6(R),15(R)-lipoxinA4 were extracted in plasma. The HPLC separations were performed by means of 1260 liquid chromatography. Patients with CKD have a significantly higher concentration of the following inflammatory mediators: 13(S)-HODE, 5(S)-HETE, 12(S)-HETE, 15(S)-HETE, 5(S)-oxoETE, 16(RS)-HETE, and 5(S),6(R), 15(R)-lipoxinA4 relative to the control group. However, the concentrations of 9(S)-HODE were lower in the CKD group. The comparison of sexes did not show significant differences in terms of CKD. A tendency for lower concentrations of HETE and HODE were observed in the group of men. 15LOX, 12LOX and 5LOX pathways in chronic kidney disease are increased, while COX are suppressed (9-HODE). The analysis of the treatment time of patients with CKD shows that incorrect levels of 5(S), 6(R) and 15(R)-lipoxinA4 are developed. We present a new evidence of possible concepts and future clinical interventions in patients suffering from chronic kidney disease for many years. These data for the first time demonstrate that lipoxin levels drastically decrease in the course of CKD. Therefore, synthetic LXA4 analogues may be used as an antioxidant therapy in CKD, which requires further research.

Islet Transplantation - perspective from Poland.

The article describes impact of advanced research in the USA and collaborative approach of US scientists and clinicians on development of the field of islet transplantation in Poland and all over the world. At the same time, it presents negative consequences of islet regulation by FDA as a biological drug leading to decline and extinction of the field in the US, while it is on the rise worldwide.

Clinical characteristics of Polish patients with ANCA-associated vasculitides-retrospective analysis of POLVAS registry.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare small to medium-size vessel systemic diseases. As their clinical picture, organ involvement, and factors influencing outcome may differ between countries and geographical areas, we decided to describe a large cohort of Polish AAV patients coming from several referral centers-members of the Scientific Consortium of the Polish Vasculitis Registry (POLVAS). METHODS: We conducted a systematic multicenter retrospective study of adult patients diagnosed with AAV between Jan 1990 and Dec 2016 to analyze their clinical picture, organ involvement, and factors influencing outcome. Patients were enrolled to the study by nine centers (14 clinical wards) from seven Voivodeships populated by 22.3 mln inhabitants (58.2% of the Polish population). RESULTS: Participating centers included 625 AAV patients into the registry. Their distribution was as follows: 417 patients (66.7%) with GPA, 106 (17.0%) with MPA, and 102 (16.3%) with EGPA. Male-to-female ratios were almost 1:1 for GPA (210/207) and MPA (54/52), but EGPA was twice more frequent among women (34/68). Clinical manifestations and organ involvement were analyzed by clinical phenotype. Their clinical manifestations seem very similar to other European countries, but interestingly, men with GPA appeared to follow a more severe course than the women. Fifty five patients died. In GPA, two variables were significantly associated with death: permanent renal replacement therapy (PRRT) and respiratory involvement (univariate analysis). In multivariate analysis, PRRT (OR = 5.3; 95% confidence interval (CI) = 2.3-12.2), respiratory involvement (OR = 3.2; 95% CI = 1.06-9.7), and, in addition, age > 65 (OR = 2.6; 95% CI = 1.05-6.6) were independently associated with death. In MPA, also three variables were observed to be independent predictors of death: PRRT (OR = 5.7; 95% CI = 1.3-25.5), skin involvement (OR = 4.4; 95% CI = 1.02-19.6), and age > 65 (OR = 6.3; 95% CI = 1.18-33.7). CONCLUSIONS: In this first multicenter retrospective study of the Polish AAV patients, we have shown that their demographic characteristics, disease manifestations, and predictors of fatal outcome follow the same pattern as those from other European countries, with men possibly suffering from more severe course of the disease.

Cardiovascular and Renal Outcomes of Renin-Angiotensin System Blockade in Renal Transplant Recipients.

BACKGROUND: There is considerable controversy over the benefits of renin-angiotensin system (RAS) blockade in renal transplant recipients (RTRs). The aim of the study was to research the effects of RAS blockade on allograft and patient outcome. METHODS: A retrospective analysis of the effects of RAS blockade on allograft and patient outcome in 53 pairs of RTRs receiving grafts from the same donor was performed. The 106 RTRs (53 pairs), transplanted from 2002 to 2012, were included in the study when 1 patient from the pair used an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for a minimum period of 36 months (RAS[+]) and the second one did not use it (RAS[-]). RESULTS: There were no differences between RAS(+) and RAS(-) subjects in terms of age, body mass index, reason of end-stage renal disease, mismatches number, total ischemic time, episodes of cytomegalovirus infections, acute rejections, and immunosuppressive treatment. The mean time of observations was 66.28 months ± 24.39 months. RAS inhibitors were given in a mean dose of 23.1% (ACEI) and 27.08% (ARB) of the maximum recommended. The main reasons for the therapy were as follows: hypertension (39.62%), nephroprotection/proteinuria (39.62%), and polyglobulia (28.3%). The composite cardiorenal endpoint was reached by 6 (11.32%) and 7 (13.21%) patients in RAS(+) and RAS(-) group, respectively. There were no differences in changes of creatinine, potassium serum level, or estimated glomerular filtration rate between RAS(+) and RAS(-) patients in the early period after RAS blockade commencement. CONCLUSION: Agents inhibiting the RAS system neither improved nor deteriorated patients and graft survival in RTRs.

Influence of Renin-Angiotensin System Blockers on Graft Function in Retrospective Analysis of Pairs of Renal Transplant Recipients From the Same Donor.

BACKGROUND: Renin-angiotensin system (RAS) blocking agents efficiently control hypertension in renal transplant recipients (RTRs), and reduce proteinuria and post-transplant erythrocytosis. A beneficial effect on the retardation of the long-term decline in renal function has not yet been demonstrated. The aim of the study was to evaluate the effects of RAS blockade on allograft function. METHODS: In order to minimize donor variability and bias, 33 pairs of RTRs receiving grafts from the same donor were included into the retrospective analysis. A total of 66 RTRs were enrolled in which 1 patient from the pair used an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for a minimum period of 60 months (RAS[+]) and the second one did not use it at all (RAS[-]). RESULTS: There were no differences between RAS(+) and RAS(-) subjects in terms of age, body mass index, mismatches number, duration of total ischemia, episodes of cytomegalovirus infections, acute rejections, or immunosuppressive treatment. Significantly, more RAS(+) patients presented with diabetes and cardiovascular complications. Among RAS(+) patients, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were used in 28 (84.84%) and 5 (15.15%) patients in a mean dose of 23.03 ± 16.83% and 30 ± 11.18% of their maximum doses, respectively. There were no significant differences in estimated glomerular filtration rate changes (-0.37 ± 12.68 vs 2.54 ± 20.76 mL/min) and serum creatinine changes (0.05 ± 0.39 vs 0.14 ± 0.79 mg/dL) between RAS(+) and RAS(-) patients during the 60 months follow-up. CONCLUSION: Agents inhibiting the RAS did not significantly affect graft function in RTRs during 60 months of observation.

Risk of Skin Diseases in Maintenance Hemodialysis.

INTRODUCTION: Maintenance hemodialysis (HD) patients are potential transplant recipients. One of the most common cancers in the population of kidney recipients is skin neoplasm. Skin infections are also of a particular importance. In this population, especially in patients on the transplant waiting list, full dermatological examination, including dermatoscopy, should be carried out routinely. MATERIALS AND METHODS: The research was comprised of 105 HD patients (57 men, 48 women) with a mean age of 60.8 (range 25-94) years. The patients' skin condition was assessed and a dermatoscopic examination was performed. We compared the incidence of skin diseases in the two subpopulations: HD patients (n = 89) and HD patients active on the transplant waiting list (n = 16). RESULTS: Bacterial, fungal, and viral infections in the group of HD patients occurred in 24.7%, 14.6%, and 6.7% of patients, respectively. In HD patients on the waiting list, bacterial skin diseases were reported in 12.5% of patients, and neither fungal nor viral infections were noticed. Malignant skin lesions and precancerous conditions, such as basal cell carcinoma and keratosis actinic, developed in 4.5% and 3.4% of the HD patients. These malignancies did not occur in HD patients on the waiting list. The results show proper qualification for transplantation in maintenance HD patients before the waiting list. In the group of dialysis patients, 67.4% required dermatological care, while in the HD waiting group only 12.5% required dermatological care. CONCLUSIONS: The presented results prove the necessity of performing dermatological examinations on HD patients. Some dermatological skin lesions, if not diagnosed and treated, could progress to cancer after organ transplantation.

Level of Education and Knowledge of Skin Cancer Risk Factors in Patients Undergoing Maintenance Hemodialysis.

INTRODUCTION: An increased risk of skin cancer is particularly important in patients undergoing maintenance hemodialysis (HD), who are potential transplant recipients. In transplant recipients who are exposed to immunosuppressive therapy, neoplastic skin disease my take a more aggressive course. Increased exposure to photoradiation, elderly age, a low skin phototype, sunburn during childhood, and a history of smoking are the main factors contributing to the development of skin neoplasms. Knowledge of these risk factors as well as education on sun protection should be important for such patients. PATIENTS AND METHODS: We studied 105 HD patients (57 men, 48 women) with a mean age of 60.8 (range 25-94) years. Knowledge of skin cancer risk factors was assessed on the basis of a questionnaire regarding skin cancer risk factors. RESULTS: In the study group, 23.8% of patients claimed that they frequently and intensively engage in sunlight exposure. However, only 11.4% have started to apply sunblockers recently. Sunburn during adolescence was reported by 12.4% patients. Among the patients studied, 65.7% had skin phototype I or II, and only 34.3% had phototype III. In the investigated study group, 55.2% admitted smoking: 30.5% smoked more than 20 pack-years. Among the patients studied only 2.86% could name 3 skin cancer risk factors, 29.5% 2 risk factors, 60% 1 risk factor, and 7.6% could not name any risk factor. CONCLUSIONS: The results presented prove that patients undergoing HD lack knowledge regarding skin cancer risk factors, which explains the necessity of education, particularly on the dangers of sun radiation.

Clinical Consequences of Diabetes Mellitus in Patients After Kidney Transplantation: A Paired Kidney Analysis.

BACKGROUND: Diabetes mellitus (DM) has been acknowledged as the most common disorder leading to end-stage renal failure in adults. Diabetic patients show higher survival rates after kidney transplantation (KTx) compared with dialysis therapy. The aim of the study was to evaluate follow-up after KTx in patients with DM as a reason of end-stage renal disease (ESRD), or with long-lasting diabetes before transplantation, compared with patients without DM. METHODS: We retrospectively analyzed the clinical consequences of DM in patients after KTx performed at the Gdansk Transplantation Centre between 2000 and 2016. To minimize donor bias, a paired kidney analysis was applied. RESULTS: The incidence of DM (types 1 and 2) was 13%; 145 patients with DM had pairs of nondiabetic patients, who received kidneys from the same donor and were included to the analysis. The DM group was older. The incidence of AR was similar among the 2 groups, DGF was observed more often in patients with diabetes. Kidney graft function 1 month after transplantation was equal in both groups (mean serum creatinine concentration 1.4 mg/dL). Five-year patient survival was better in the non-DM group (96.7% vs 81.5%). Kaplan-Meier survival curves did not differ significantly between the DM and non-DM groups. DM was not associated graft loss. In the univariate analysis age was the only factor associated with death. CONCLUSION: Diabetic patient survival after KTx seems to be worse than in patients without diabetes, but generally the follow-up among diabetics is good, with graft survival similar to that observed in patients without DM.

Assessment of Cardiovascular Risk in Renal Transplant Recipients: Preliminary Results.

BACKGROUND: Cardiovascular (CV) diseases are the most common cause of death in patients with chronic kidney disease, including patients after kidney transplantation. The aim of the study was to do a retrospective analysis of CV risk in renal transplant recipients (RTRs). METHODS: The analysis of CV risk was based on the following scales: QRISK2, Framingham (assessment of development of CV disease), PROCAM (assessment of any CV incident), and Pol-SCORE (assessment of CV death) within a 10-year period. Out of 150 RTRs transplanted in 2007-2009, 100 RTRs (65 male/35 female) with an average age of 48.4 years were enrolled in the study. Coronary heart disease and diabetes mellitus were diagnosed in 7% and 15% of participants, respectively. Coronarography was performed in 38% of patients. Hypertension was diagnosed in 98% of participants, myocardial infarction was diagnosed in 6% of participants, and stroke was diagnosed in 2% of participants. RESULTS: High and very high risk of CV endpoint according to QRISK2, PROCAM, Framingham, and Pol-SCORE scales was found in 41%, 8%, 10%, and 41% of patients, respectively. After 5 years of follow-up, a total of 13 CV events (myocardial infarction and stroke) were observed in 11 patients. Among these patients, the highest risk of endpoint according to QRISK2, PROCAM, Framingham, and Pol-SCORE scales was found in 36%, 9%, 18%, and 45% of patients, respectively. CONCLUSIONS: The QRISK2 and Pol-SCORE scales seem to be the most predictive in assessing CV risk in RTRs.

Cytomegalovirus Status of Kidney Transplant Recipients and Cardiovascular Risk.

BACKGROUND: Cytomegalovirus (CMV) infection is associated with an increased risk of cardiac complications in kidney transplant recipients (KTRs). Some data suggest that CMV may be involved in atherogenesis. The aim of the study was the analysis of CMV medical history in KTRs and its influence on cardiovascular (CV) incidents. MATERIALS AND METHODS: The study observed 254 patients (165 male/89 female) with mean age of 47.2 (range, 15-81) years and duration of dialysis before transplantation 29.2 months who received transplants in 1 university unit (2007-2013). Thirty-six patients were transplanted preemptively. The mean time of observation lasted 7 years. KTRs suffered from diabetes, hypertension, and hyperlipidemia (17.3%, 88.5%, and 61%, respectively). Coronary artery disease was diagnosed in 19.6% patients, 3.5% underwent elective coronary surgery operation, and 9.05% had CV incidents before transplantation. The following CMV donor/recipient (D/R) viral statuses were noticed in the study group: D+/R+ (68.9%), D+/R- (16.9%), D-/R+ (10.2%), and D-/B- (3.9%). D+/R- received universal CMV prophylaxis; the rest were under preemptive CMV prophylaxis. CMV infection affected 87 (34.25%) patients; there were 24 primary infections and 85 secondary infections (some patients had more than 1 CMV). Mean time of diagnosis of the primary and secondary CMV infection was 190.7 and 160.5 days, respectively. RESULTS: During observation 22 patients experienced 26 CV incidents: 15 were D+/R+, 6 were D+/R-, and 1 was D-/R+. CMV infections occurred in 40.9% of patients with CV incidents after kidney transplantation. In comparison, 33.6% patients without CV incidents after kidney transplantation suffered from CMV infection. CONCLUSIONS: CMV infection in KTRs was not a crucial risk factor for CV incidents.

Native Nephrectomy in Renal Transplant Recipients With Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Patients with autosomal dominant polycystic kidney disease (ADPKD) represent about 10% of kidney transplant recipients (KTR) and have unique needs regarding acceptance for this procedure. Whether native kidney nephrectomy (NKN) affects kidney transplantation (KT) outcomes remains a matter of debate, and more data is needed to establish a standard approach to KTR with ADPKD. AIM: To analyze the prevalence, timing, and short- and long-term outcomes of NKN in a cohort of ADPKD recipients in a single institution. METHOD: Retrospective, observational study. RESULTS: In the years 1993 to 2016 we identified 162 KTR with ADPKD; of those, 149 had known NKN status. A high proportion of ADPKD KTR (n = 72) underwent NKN, the majority of which (69.4%) were performed before KT. There was no difference in short-term and long-term transplantation outcomes (including death, graft loss, delayed graft function, acute rejection, bacterial and cytomegalovirus [CMV] infection, and post-transplant diabetes mellitus) between NKN and non-NKN groups in a median of 98 months of follow-up. However, we found a significant difference in time on a waiting list, which was longer in the NKN group vs non-NKN. CONCLUSIONS: There is a need for a consensus regarding indications and timing for NKN in recipients with ADPKD. The systematic acquisition, sharing, and analysis of accessible data on NKN between institutions is an important step toward meeting this need. In our cohort, we found no impact of the NKN procedure on KT impact. However, undergoing NKN significantly prolonged the time on the waiting list.

Efficacy and Safety of Mammalian Target of Rapamycin Inhibitor Use-Long-term Follow-up of First Tuberous Sclerosis Complex Patient Treated De Novo With Sirolimus After Kidney Transplantation: A Case Report.

Mammalian target of rapamycin inhibitors (mTORI) are increasingly used in the treatment of tuberous sclerosis complex (TSC) and as immunosuppressants after organ transplantation. In TSC patients, mTORI are the treatment of choice after kidney transplantation. It is still under debate if benefits from long-term mTORI use will not be limited by side effects. MATERIALS AND METHODS: We report long-term follow-up data of the first TSC patient after kidney transplantation treated with sirolimus de novo. In 2005, a female patient was transplanted with a kidney graft after bilateral nephrectomy due to angiomyolipoma. Initial immunosuppressive treatment consisted of antithymocyte globulin, methylprednisolone, tacrolimus, and, due to TSC diagnosis, sirolimus. Creatinine level at discharge was 1.2 mg/dL. RESULTS: Long-term mTORI use resulted in skin lesion regression (angiofibromas, "confetti" skin lesions, shagreen patch) and disease stabilization in brain, abdominal, and chest magnetic resonance imaging/computed tomography scans. Pulmonary function tests showed improvement in restriction and slow deterioration in obstruction and diffusion parameters. Sirolimus related adverse reactions were hyperlipidemia and hypertriglyceridemia and respiratory and urinary tract infections. No gastrointestinal or hematologic symptoms occurred. Sirolimus concentrations ranged between 1.7 and 8.2 ng/mL (mean 4.01 ± 2.09 ng/mL). Since 2009 proteinuria and slow increase in creatinine level have been observed. No biopsy was performed to establish etiology and potential association with mTORI. In 2017 creatinine level was 2.2 mg/dL. CONCLUSION: The case of the patient confirms clinical effectiveness and acceptable safety of long-term mTORI treatment. Long-term mTORI use requires meticulous patient observation to optimize dosage, achieve immunosuppressive effect, and improve TSC manifestations with minimal side effects.

Obesity Risk Factors in Patients After Kidney Transplantation.

BACKGROUND: Kidney transplantation is currently the best approach for renal replacement therapy. Compared with dialysis, it provides a better quality of life and improves patient prognosis. However, some evidence suggests that body composition could play a role in the complications observed in kidney transplant recipients (KTRs), and may influence survival. The purpose of this study was to assess the eating habits and body composition of KTRs. METHODS: Seventy KTRs were included in this study. Anthropometry and body composition were performed using electronic-scale, dynamometer, and bioimpedance analyses. Dietary habits were investigated using the Food Frequency Questionnaire (FFQ6). Biochemical parameters were also determined. RESULTS: Overweight and obesity were found in 33.8% and 21.1% of KTRs, respectively. High body mass index (BMI, >25) correlated positively with high body fat (r = 0.8, P < .05) and waist circumference (r = 0.7, P < .05). The mean percentage of body fat was 30.8 ± 9.3% (range, 13%-52%), fat tissue index was 12.4 ± 4.9, and lean tissue index (LTI) was 13.2 ± 2.2. Sarcopenia was recognized based on decreased LTI and decreased handgrip strength in 33.3% of KTRs with excess body weight. Patients with excess body mass consumed significantly (P < .05) more sugar and fruits. CONCLUSION: A significant percentage of KTRs present with sarcopenic obesity. Excess body weight is associated with many factors, such as immunosuppressive therapy, low physical activity, and abnormal diet. Results based on the FFQ6 indicate a relationship between carbohydrate intake and excess body weight among those in the study group.

Evaluation of Pretransplant Donor-Specific Alloantibodies With Different Crossmatch Techniques.

Donor-recipient crossmatching for kidney transplantation is an obligatory step for the transplant work-up process. Attention is currently put on single bead assay (SBA) that enables virtual crossmatching. In contrast, methods developed for complement binding capacity are still not routinely established. We compared modified, cytolytic flow cytometry crossmatch (cFC-XM) with complement-dependent serological crossmatch (CDC-XM), SBA, and flow cytometry crossmatch (FC-XM) to verify whether newly developed techniques may be beneficial for transplant immunological matching. Also, the cutoff value for donor-specific alloantibodies levels currently used for virtual crossmatch was verified. Serum from 22 sensitized patients was crossmatched with surrogate donors by CDC-XM, FC-XM, and cFC-XM, while anti-HLA antibodies were measured by SBA. In all cases, virtual crossmatch was positive at 5000 mean fluorescence intensity cutoff. Among 22 tested sera with donor-specific alloantibodies above 5000 mean fluorescence intensity, the positive CDC-XM result was noted only in 41% of patients (n = 9), but positive FC-XM was noted in 86% (n = 19), and further lytic antibodies (cFC-XM) were confirmed in 27% of cases (n = 6). Our results suggest that donor-recipient immunological matching for kidney transplantation requires different methods to verify the importance of alloantibodies, and improvement in laboratory investigation is needed. This is especially important for immunized patients that have many types of alloantibodies and virtual crossmatching used as a tool for deceased donor allocation should balance between the likelihood of transplantation and risk of positive crossmatch result.

New-onset Diabetes Mellitus After Kidney Transplantation-A Paired Kidney Analysis.

BACKGROUND: New-onset diabetes mellitus (NODAT) is a severe complication after kidney transplantation. It is associated with increased risk of graft failure, cardiovascular disease, mortality and infections. METHODS: We retrospectively (partially using the registry database) analyzed risk factors and clinical consequences of NODAT in patients after kidney transplantation performed at the University Transplant Centre between 2001 and 2016. To minimize the donor variability and bias, a paired kidney analysis was applied. Diabetes was defined as the need for insulin therapy for a minimum 30 days after transplantation. RESULTS: The incidence of NODAT was 7.6% (109 of 1424), but only 74 patients with NODAT had their pairs of patients without NODAT, who received kidneys from the same donor and were included to the analysis. The NODAT group was older, and with a significantly higher Charlson Comorbidity Index (2.97 vs 3.39; P = .02). The groups did not differ significantly with respect to immunosuppressive protocols and number of mismatches (2.65 vs 2.78). The incidence of acute rejection (AR; not biopsy proven) was significantly higher in the NODAT group (30% vs 13%), but the incidence of delayed graft function (DGF) was similar (40%). Creatinine concentration and estimated glomerular filration rate (using the Modified Diet in End-stage Renal Disease equation) 1-month after kidney transplantation did not differ: 1.5 vs 1.54 mg/dL and 49.3 vs 50.2 mL/min, respectively. Body mass index (BMI) was higher in the NODAT group. On multivariate analysis, factors significantly associated with NODAT were: age; AR; Charlson Comorbidity Index; and pretransplant dialysis time. BMI was higher in the NODAT group. NODAT was not a predictor of early graft loss and patient survival in the short-term analysis. CONCLUSION: AR, older age, higher comorbidity index, and BMI were risk factors for NODAT. We did not identify an influence of NODAT on early graft function and loss, but further analysis with a longer follow-up is necessary.