Combined Liver-Pancreas Transplantation as Novel Treatment for Patient With Cystic Fibrosis: A Case Report.

BACKGROUND: A 21-year-old woman diagnosed with cystic fibrosis developed cirrhosis, exocrine pancreatic insufficiency, and insulin-dependent diabetes mellitus. The patient qualified for double organ liver-pancreas transplantation beyond typical indications. The respiratory symptoms of cystic fibrosis were moderate and well-treated. The patient was endangered mainly by liver insufficiency and recurrent hypoglycemia, which was due to the treatment of diabetes with high doses of insulin. Computed tomography showed mild bronchiectasis, cirrhotic liver, splenomegaly, and atrophy of the pancreas. Pseudomonas aeruginosa colonized the upper respiratory tract. Gastrointestinal complications were sufficient for the patient to be qualified for combined liver-pancreas transplantation. METHODS: First, a standard hepatectomy was performed. The liver was transplanted orthotopically. Subsequently, the team performed pancreas transplantation through a separate incision. The donor's duodenum was anastomosed to the recipient's jejunum, close to the ligament of Treitz. RESULTS: No serious complications were noted during the postoperative period. Transplanted organs started functioning without delay. The patient was discharged after 6 weeks in general good condition. Twenty months later, the patient felt well, and the grafts kept functioning properly. CONCLUSION: Combined liver-pancreas transplantation in patients with CF restores exocrine and endocrine pancreatic function and minimizes the risk of life-threatening complications associated with liver insufficiency. Improvement of life quality coincides with the possibility of discontinuing insulin and pancreatic enzyme supplementation. The combination of liver and pancreas transplantation may prevent advanced pulmonary complications, extend the prognosis of survival, and improve the long-term life quality.

Comparison of Long-Term Outcomes of Surgical Treatment of Human Papillomavirus-Dependent Neoplastic Lesions in Patients With Chronic Immunosuppression After Allogenic Organ Transplantation and Patients With Primary or Acquired Immunodeficiency-A One-Center Experience.

Immunodeficiency predisposes to severe manifestations of human papillomavirus (HPV) infection, including extensive, recalcitrant anogenital lesions and their progression towards carcinomas. This holds for primary and acquired immunodeficiencies, and post-transplant immunosuppressive therapy. About 50% to 90% of patients receiving chronic immunosuppression after allogenic transplantation develop HPV-associated lesions within 4 to 5 years, comprising 10% to 15% of patients presenting with (pre)cancerous HPV-dependent anogenital lesions. Immunodeficiency is one of the highest risk factors associated with severe clinical manifestations of HPV-associated cancers. The primary objective of this work is to compare the long-term therapeutic effectiveness of surgical intervention for HPV-dependent lesions in transplant recipients undergoing chronic immunosuppression and patients burdened with primary or acquired immunodeficiencies. Two groups of 30 patients (selected for most extensive presentations of HPV-dependent neoplastic anogenital lesions), who underwent surgical treatment of these lesions were followed up for 3 to 5 years. The first group comprised patients who qualified and underwent kidney or liver transplantation (10 for a rare disease indication) and are under chronic immunosuppressive regimens. The second group comprised patients burdened by primary or acquired immunodeficiency (15 each). The recurrence rate in the follow-up period was the primary compared parameter. The recurrence rate was higher in the second group, amounting to >15%. For the first group a <5% recurrence rate was observed for recipients without rare disease indications, compared to <15% for recipients with such indications. The importance of rapid surgical intervention and the need for postoperative monitoring for recurrence is highlighted. Chronic immunosuppression demonstrates high relative safety and efficacy in terms of HPV-dependent anogenital lesion recurrence.

The Importance of 1-Year Protocol Biopsy in the Long-Term Prognosis of Kidney Transplants-5-Years Follow-Up.

BACKGROUND: Protocol biopsies are performed to detect subclinical pathologies that may lead to future graft dysfunction. However, they are not routinely performed interventions in every transplant center. There is no established regimen for performing them. PURPOSE: The study aimed to evaluate if protocol biopsies can improve long-term patient outcomes after detecting early disorders and modifying treatment. MATERIAL AND METHODS: Our observational study included 61 patients who underwent protocol biopsy 12 months after the transplantation. Based on the biopsy results, patients with abnormal histologic material (n = 37) were divided into 3 study groups as follows: patients with mild inflammatory lesions (n = 21), patients with interstitial fibrosis and tubular atrophy (IFTA) grade II to III (n = 12), and patients with BK virus nephropathy (n = 4). The control group (n = 24) included kidney recipients with IFTA 0 to I grade. Outcomes after 5-year follow-up were evaluated. RESULTS: Five years after the biopsy, patients in the control group had stable graft function (5-year change in serum creatinine was -0.09 mg/dL). An increase in serum creatinine levels was observed in patients with IFTA II to III compared with the control group (0.14 mg/dL, P = .04). Immunosuppressive treatment was modified in the group with mild inflammatory changes and in the BKV group after the biopsy result. In the group with mild inflammatory lesions, renal function was stable (change of serum creatinine was -0.01 mg/dL, P = .51). In the BKV nephropathy group, there was a significant reduction in serum creatine levels (-0.48 mg/dL, P = .016). The analysis showed no diagnostic value for serum creatinine concentration (95% CI 0.49-0.78, P = .08). CONCLUSIONS: Protocol biopsies are useful for detecting early pathologies and preventing allograft failure. They greatly benefit patients with detectable pathology that can be treated or in whom therapy modification is possible.

Potential utility of urinary chemokine CCL2 to creatinine ratio in prognosis of 5-year graft failure and mortality post 1-year protocol biopsy in kidney transplant recipients.

BACKGROUND: Chemokines (chemotactic cytokines) are small proteins which are engaged in many pathophysiological processes, including inflammation and homeostasis. In recent years, application of chemokines in transplant medicine was intensively studied. The aim of this study was to determine the utility of urinary chemokines CCL2 (C-C motif ligand 2) and CXCL10 (C-X-C motif chemokine ligand 10) in prognosis of 5-year graft failure and mortality post 1-year protocol biopsy in renal transplant recipients. METHODS: Forty patients who had a protocol biopsy 1 year after renal transplantation were included. Concentrations of CCL2 and CXCL10 in urine with reference to urine creatinine were measured. All patients were under the supervision of one transplant center. Long-term outcomes within 5 years after 1-year posttransplant biopsy were analyzed. RESULTS: Urinary CCL2:Cr at the time of biopsy was significantly increased in patients who died or had graft failure. CCL2:Cr was proven to be a significant predictor of 5-year graft failure and mortality (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 1.02-1.19, p = .02; OR: 1.08, 95% CI: 1.02-1.16, p = .04; respectively). CONCLUSION: Chemokines are easily detected by current methods. In the era of personalized medicine, urinary CCL2:Cr can be considered as a factor providing complementary information regarding risk of graft failure or increased mortality.

Difficulties in the Diagnosis of Fibrinogen Aα-Chain Amyloidosis-Literature Review and Case Report of a Patient After Kidney Transplantation.

BACKGROUND: Amyloidosis is a very heterogeneous disease. Correct diagnosis is extremely important because of the various treatment options for different types of amyloidosis. This study presents a case report and literature review of the misdiagnosis of fibrinogen Aα-chain amyloidosis (AFib amyloidosis). CASE PRESENTATION: We report a 65-year-old man diagnosed with proteinuria in 2009. The kidney biopsy revealed the presence of Congo red-stained amyloid deposits. During differential diagnosis, amyloid deposits were discovered in adipose tissue and gingiva. Bone marrow trephine biopsy showed a predominance of lambda chains presenting plasmocytes. Based on performed medical examination, light chain amyloidosis was identified. Therefore, the patient received high-dose melphalan and underwent successful autologous peripheral blood stem cell transplantation. However, proteinuria, worsening of the kidneys' function, and incorrect levels of free light chains were still observed. In 2019, due to continuous treatment failure, a previously acquired kidney biopsy was examined by mass spectrometry, and numerous fibrinogen deposits were identified. Recommended DNA analysis revealed that the patient had AFib amyloidosis. Therefore, chemotherapy treatment was abandoned, and successful kidney transplantation was performed. CONCLUSION: Today, it is essential for medical practitioners to remember the possibility of rare and hereditary types of amyloidosis. There are multiple cases where a diagnosis was wrong or delayed because of the atypical course of the disease, the coexistence of another disease, and the rarity of AFib amyloidosis, and all of these reasons may result in the wrong treatment that will delay the right therapy. However, with the new, more precise diagnostics methods, such situations will become rare.

CYP3A5 Expressor Genotype of the Transplanted Kidney Increases the Risk of Preterm Graft Loss and Acute Rejection.

INTRODUCTION: Tacrolimus is metabolized mainly in the liver by the CYP3A enzyme family, with a particularly well-documented role of CYP3A5. CYP3A5 is also expressed in the renal tissue and is present in the transplanted kidney. To date, the association between donor CYP3A5 polymorphisms and transplant outcome remains poorly understood. The aim of this study was to assess the effect of donor CYP3A5 expression on early and long-term transplant outcomes. METHODS: A retrospective cohort study including 207 patients who received kidney grafts from 110 deceased donors was conducted at a single Central European Center. Tissue samples from all donors were studied for CYP3A5 single-nucleotide polymorphism (rs776746). Death-censored graft loss within 5-year follow-up, acute rejection occurrence, and kidney function, measured using serum creatinine and MDRD eGFR, were compared between groups of patients with allografts from rs776746 carriers (CYP3A5 expressors) and noncarriers (CYP3A5 nonexpressors). RESULTS: Recipients who received kidneys from CYP3A5 expressors (n = 24) were at significantly higher risk of death-censored graft loss within 5-year follow-up (adjusted HR, 95% CI: 6.82, 2.01-23.12; p = 0.002) and acute rejection within the 1st posttransplant year (adjusted OR, 95% CI: 4.62, 1.67-12.77; p = 0.003) than those who did not (n = 183). The median time to loss of function was 1.93 [IQR; 0.77-3.19] years. CONCLUSIONS: Donor CYP3A5 expressor status is associated with worse renal graft survival and a higher risk of acute rejection. Determination of donor CYP3A5 genotype is a potentially useful tool that may improve kidney transplant outcomes.

Donor CYP3A5 Expression Decreases Renal Transplantation Outcomes in White Renal Transplant Recipients.

BACKGROUND After renal transplantation, immunosuppressants should be administered to prevent organ rejection and prolong graft survival. One of them is tacrolimus, which is metabolized by the CYP3A enzyme family. The variability of the CYP3A5 gene in renal transplant recipients has been previously studied for its correlation with acute rejection and allogeneic kidney function. CYP3A5 enzyme is also present in the renal tissue, and its relevance has not yet been extensively investigated. This study aimed to evaluate the effect of donor and recipient CYP3A5 expression status on early and long-term transplant outcomes. MATERIAL AND METHODS Single-nucleotide polymorphism in CYP3A5 (rs776746) was analyzed in 95 kidney transplant recipients and their grafts. The effect of donor and recipient genotypes on the primary endpoint, which was the loss of the renal graft over 5-year follow-up, was assessed. The secondary endpoints were biopsy-proven acute rejection, proteinuria, delayed graft function, and renal function. RESULTS Patients who received a CYP3A5*1 allele-carrying kidney (n=16) were at greater risk of graft loss (adjusted hazard ratio, 95% CI: 10.61, 2.28-49.42, P=.003) than those with the CYP3A5*3/*3 genotype (n=79). Renal CYP3A5 expression was also a predictor of acute rejection between the 2nd and 12th post-transplant months (adjusted odds ratio, 95% CI: 4.36; 1.08-17.6, P=.038) and proteinuria at different time intervals. No effect of the recipient CYP3A5 genotype was observed. CONCLUSIONS The donor CYP3A5 genotype is associated with inferior transplantation outcomes. Local renal tacrolimus metabolism is a potential target for improving long-term transplantation outcomes.

Renal Cyp3a5-Expressing Genotype Decreases Tacrolimus-to-Dose Ratio in Small Cohort of Renal Transplant Recipients-Preliminary Report.

BACKGROUND: Previous reports have established that patient CYP3A5 allelic variability may be the most important genetic contributor to interindividual variation in tacrolimus exposure in renal transplant recipients. However, CYP3A5 protein is expressed in the allogenic kidney. The aim of this study was to investigate the role of the renal CYP3A5 genotype in tacrolimus concentration-to-dose ratio within 3 years posttransplant. METHODS: A retrospective cohort study of 90 renal transplant recipients and their donors evaluated the effect of the CYP3A5 single-nucleotide polymorphism (rs776746) on tacrolimus exposure. The area under the curve for tacrolimus concentration-to-dose ratio within 3-year follow-up was calculated and compared in kidneys carrying at least 1 CYP3A5*1 allele and those carrying the CYP3A5*3/*3 genotype. RESULTS: A significant effect of CYP3A5 expression on tacrolimus exposure was observed in both donors (mean ± SD: 23.8 ± 7.9 vs 32.6 ± 7.4 ng/mL/mg, respectively; P < .001) and recipients (mean ± SD: 27.1 ± 8.0 vs 32.2 ± 7.9 ng/mL/mg, respectively; P = .034) and was lower when CYP3A5 enzyme occurred. Thus, new groups were formed: the group in which at least 1 of the pairs, donor or recipient, had a CYP3A5 expressing allele (n = 23) had lower exposure to tacrolimus compared with nonexpressors (n = 67; mean ± SD: 26.2 ± 7.6 vs 33.2 ± 7.4 ng/mL/mg, respectively; P < .001). CONCLUSION: Intrarenal metabolism of tacrolimus may affect both local and systemic drug exposure. Nonexpressors receiving kidneys with the CYP3A5*1 allele may benefit from higher tacrolimus doses to hasten achievement of target drug concentrations.

Comparison of Post-Transplantation Lymphoproliferative Disorder Risk and Prognostic Factors between Kidney and Liver Transplant Recipients.

Post-transplantation lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation (SOT). Its development risk varies among organ graft recipients. In this study, retrospective data were analyzed to compare PTLD's risk and prognostic factors between adult kidney and liver transplant recipients (KTRs and LTRs, respectively). Over 15 years, 2598 KTRs and 1378 LTRs were under observation at our center. Sixteen KTRs (0.62%) and twenty-three LTRs (1.67%) were diagnosed with PTLD. PTLD developed earlier in LTRs (p < 0.001), SOT patients > 45 years old (p = 0.002), and patients receiving tacrolimus (p < 0.001) or not receiving cyclosporin (p = 0.03) at diagnosis. Tacrolimus use, male sex, and age > 45 years old significantly affected the time of PTLD onset in KTRs (hazard ratio (HR) = 18.6, 7.9 and 5.2, respectively). Survival was longer in LTRs < 45 years old (p < 0.009). LTRs were more likely than KTRs to achieve complete remission (p = 0.039). Factors affecting PTLD development and outcome differ between KTRs and LTRs; thus, these populations should be separately evaluated in future studies.

Development and Validation of the New Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Unbound Tacrolimus in the Plasma Ultrafiltrate of Transplant Recipients.

(1) Background: Only unbound tacrolimus particles are considered to be active and capable of crossing cellular membranes. Thus, the free-drug concentration might be better associated with clinical effects than the total drug concentration used for dosage adjustment. We propose a new, fully validated online liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for unbound tacrolimus concentration measurement. (2) Methods: The determination of the unbound tacrolimus concentration in plasma ultrafiltrate was performed with the Nexera LC system with LCMS-8050 triple quadrupole MS using ascomycin as an internal standard. Chromatographic separation was made using a HypurityC18 analytical column. MS/MS with electrospray ionization and positive-ion multiple-reaction monitoring was used. The unbound tacrolimus level was determined in 36 patients after solid organ transplantation (n = 140). (3) Results: A lower limit of quantification 0.1 pg/mL was achieved, and the assay was linear between 0.1 and 20 pg/mL (R2 = 0.991). No carry-over was detected. The within-run and between-run accuracies ranged between 97.8-109.7% and 98.3-107.1%, while the greatest imprecision was 10.6% and 10.7%, respectively. Free tacrolimus in patients' plasma ultrafiltrate varied between 0.06 and 18.25 pg/mL (median: 0.98 pg/mL). (4) Conclusions: The proposed method can be easily implemented. The significance of the unbound tacrolimus concentration needs to be investigated. This may facilitate the individualization and optimization of immunosuppressive treatment.

Organization of Post-Transplant Care and the 5-Year Outcomes of Kidney Transplantation.

The outcomes of kidney transplantation depend on numerous factors and vary between transplant centers. The aim of this study is to assess the relationship between selected organizational factors, comorbidities, and patient and graft survival. This is a retrospective analysis of 438 renal transplant recipients (RTR) followed for 5 years. Patient and graft survival were evaluated in relation to hospitalization length, distance from the patient's residence to the transplant center, the frequency of outpatient transplant visits, and the number and type of comorbidities. Five-year patient and graft survival rates were 93% and 90%, respectively. We found significant associations of patient survival with the prevalence of pre-transplant diabetes, cardiovascular diseases, malignancies, the number of comorbidities, and the first post-transplant hospitalization length. The incidence of infections, cardiovascular diseases, and transplanted kidney diseases was 60%, 40%, and 33%, respectively. As many as 41% of RTR had unknown etiology of primary kidney disease. In conclusion, the organization of post-transplant care needs to be adapted to the multi-morbidity of contemporary RTR and include multi-specialist care, especially in the context of current problems related to the COVID-19pandemic. The high proportion of patients with undetermined etiology of their primary renal disease carry the risk for additional complications during their long-term follow-up.

Effects of the COVID-19 Pandemic on Solid Organ Transplantation During 2020 in Poland Compared with Countries in Western Europe, Asia, and North America: A Review.

The coronavirus disease 2019 (COVID-19) pandemic, due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began in March 2020, affected organ donor acceptance and rates of heart, lung, kidney, and liver transplants worldwide. According to data reported to POLTRANSPLANT, the number of solid organ transplants decreased by over 35% and the number of patients enlisted de novo for organ transplantation was reduced to 70% of its pre-COVID-19 volume in Poland. Most transplant centers in Western Europe and the USA have also drastically reduced their activity when compared to the pre-pandemic era. Areas of high SARS-CoV-2 infection incidence, like Italy, Spain, and France, were most affected. Significant decreases in organ donation and number of transplant procedures and increase in waitlist deaths have been noted due to overload of the healthcare system as well as uncertainty of donor SARS-CoV-2 status. Intensive care unit bed shortages and less intensive care resources available for donor management are major factors limiting access to organ procurement. The impact of the COVID-19 outbreak on transplant activities was not so adverse in Asia, as a result of a strategy based on experience gained during a previous SARS pandemic. This review aims to compare the effects of the COVID-19 pandemic on solid organ transplantation during 2020 in Poland with countries in Western Europe, North America, and Asia.

Review of the Latest Methods of Epidermolysis Bullosa and Other Chronic Wounds Treatment Including BIOOPA Dressing.

Epidermolysis bullosa (EB) is a hereditary genetic skin disorder, classified as a type of genodermatosis, which causes severe, chronic skin blisters associated with painful and potentially life-threatening complications. Currently, there is no effective therapy or cure for EB. However, over the past decade, there have been several important advances in treatment methods, which are now approaching clinical application, including gene therapy, protein replacement therapy, cell therapy (allogeneic fibroblasts, mesenchymal stromal cells), bone marrow stem cell transplant, culture/vaccination of revertant mosaic keratinocytes, gene editing/engineering, and the clinical application of inducible pluripotent stem cells. Tissue engineering scientists are developing materials that mimic the structure and natural healing process to promote skin reconstruction in the event of an incurable injury. Although a cure for EB remains elusive, recent data from animal models and preliminary human clinical trials have raised the expectations of patients, clinicians, and researchers, where modifying the disease and improving patients' quality of life are now considered attainable goals. In addition, the lessons learned from the treatment of EB may improve the treatment of other genetic diseases.

Replacing centrifugation with mixing in urine analysis enriches protein pool in the urine samples.

Urine is the basic diagnostic material, easy to collect, not requiring invasive approach. During standard procedure the urine samples are centrifuged and the supernatant analysed physically, biochemically, and microscopically. The centrifugation step removes proteins including those forming aggregates especially in the state of illness and after transplantation. Here, we analysed the effect of urine centrifuging on specific protein content in urine samples obtained from cardiovascular patients (CVD) and after kidney or liver transplantation. We tested homogeneous whole urine samples, standardly centrifuge one, and the pellet after centrifuging. Protein content was examined using Western blot analysis and mass spectrometry (MS) of samples from CVD patients or the one after transplantation. The average of 21% proteins from non-centrifuged samples were found in the pellet removed after standard centrifugation. MS analysis confirmed that diagnostically important proteins were located there in. In 90% of cases whole urine samples contained more proteins than standard supernatant, among them e.g. proteins involved in immunological response like immunoglobulins and complement compounds secreted by leucocytes. Replacing centrifuging with intensive mixing of urine samples provides a method of enriching the samples with proteins removed during standard procedure, thus increasing possibility of finding new biomarkers for diseases undiagnosable with classic urine analysis.

Post-Traumatic Growth among Patients after Living and Cadaveric Donor Kidney Transplantation: The Role of Resilience and Alexithymia.

The aim of this study was to determine the role of resilience and alexithymia in the post-traumatic growth as a response to extreme stress in patients after kidney transplantation and to determine whether there are differences in the level of posttraumatic growth in patients after living and cadaveric donor kidney transplantation. The relationships between these variables were also evaluated. The questionnaire survey of 91 kidney recipients took place in 2018 and 2019. The following tools were used: authorial post-transplant questionnaire for recipients and validated questionnaires, Post Traumatic Growth Inventory (PTGI-R), Resilience Coping Scale Questionnaire, and Toronto Alexithymia Scale Questionnaire (TAS20). The results obtained showed significant differences between the group of kidney recipients from living donors and recipients from cadaveric donors, in terms of overall post-traumatic growth, as well as changes in self-perception and a greater appreciation for life. Post-traumatic growth in both groups was related to the level of resilience and the level of alexithymia. Resilience is an accurate predictor of posttraumatic growth in general and for each of the groups of recipients separately.

Applicability of Augmented Reality in an Organ Transplantation.

Augmented reality (AR) delivers virtual information or some of its elements to the real world. This technology, which has been used primarily for entertainment and military applications, has vigorously entered medicine, especially in radiology and surgery, yet has never been used in organ transplantation. AR could be useful in training transplant surgeons, promoting organ donations, graft retrieval and allocation, and microscopic diagnosis of rejection, treatment of complications, and post-transplantation neoplasms. The availability of AR display tools such as Smartphone screens and head-mounted goggles, accessibility of software for automated image segmentation and 3-dimensional reconstruction, and algorithms allowing registration, make augmented reality an attractive tool for surgery including transplantation. The shortage of hospital IT specialists and insufficient investments from medical equipment manufacturers into the development of AR technology remain the most significant obstacles in its broader application.

Retrospective Analysis of Pancreas Transplants in Poland in Years 1998-2015.

Transplantation of the pancreas is an established method for the treatment of complicated diabetes mellitus. As the numbers of diabetic patients increase so does the need for efficient treatment methods. Despite significant perioperative risk and complications related to immunosuppression, pancreas transplant remains the best therapeutic option for selected patients. METHODS: The analysis was based on the comparison of characteristics of all organ donors and recipients in years 1998 to 2015. The collected data were divided into 2 periods to facilitate identification of populational changes. RESULTS: The total number of pancreas transplants in Poland was 139 in years 1998 to 2006 and 268 in years 2007 to 2015. The largest differences revealed by the comparison of donor-related variables in both periods were those related to the doses of pressor amines, duration of circulatory arrest, and duration of stay at the intensive care unit. The critical finding consisted in the improvement of short-term survival of recipients and organs being observed in contrast to the surprising lack of improvement in long-term survival. Reduced likelihood of transplantation success was observed already in overweight patients (body mass index 25-29.99 kg/m2). CONCLUSIONS: No significant changes were observed with regard to pancreas transplant outcomes over the period of many years. Transplantation success is determined by 1-year survival of the organ, and the therapeutic success is measured by long-term disease-free survival of the patient. In the era of rapid advances in numerous areas of medicine, the lack of significant extension of patient survival times warrants a closer look of our knowledge on pancreas transplants.

Donor Klotho KL-VS Polymorphism Predicts Allograft Glomerulosclerosis and Early Post-Transplant Kidney Function.

BACKGROUND: The Klotho protein, encoded by the KL (Klotho) gene, exerts antiaging and antifibrotic effects. The KL-VS genotype diminishes Klotho expression and correlates with cardiovascular death, heart failure, and chronic kidney disease progression. The aim of this study was to analyze the contribution of donor Klotho rs9536314 and rs9527025 polymorphisms (KL-VS genotype) to renal allograft morphology and function in the early post-transplant period. METHODS: Clinical data and biopsy reports of 170 deceased donor transplantations were retrieved from standard medical files. Donor DNA was genotyped for rs9527025 and rs9536314 SNPs using custom TaqMan assays. RESULTS: As rs9527025 remained in full linkage with rs9536314, we report results for the latter. The analyses were performed for G dominant model (GG+GT vs TT). We found an association between reported SNP alleles, morphologic changes in the peritransplant biopsy, and kidney function 3 months after engraftment. A chronic glomerulopathy score of >0 was found in 12.2% of GG+GT cases and in 3.2% of TT cases (P = .023). For G allele carriers, the third month's median estimated glomerular filtration rate value was 35.0 (range, 20.4-76.6 mL/min), while for TT haplotype, the value was 46.3 (range, 15.5-96.8 mL/min), P = .001. At the third post-transplant month, proteinuria incidence was higher for organs with G allele than with TT haplotype (24.4% vs 9.5%; P = .030; odds ratio 3.09; 95% confidence interval 1.22-7.69). CONCLUSION: Deceased donor KL-VS polymorphism, altering protein dimerization and coreceptor function, predicts early renal transplant glomerular lesions and function. Further analyses for mentioned effect durability are necessary. ETHICS STATEMENT: This study complies with the Helsinki Congress and the Istanbul Declaration regarding donor source. Donors were not prisoners, and were not paid or coerced.

How Early Postoperative Urinary Tract Infections Affect Renal Graft Function at 1-Year Follow-up.

BACKGROUND: Urinary tract infection (UTI) occurs in 21% of kidney recipients within the first 3 months after transplantation (KTx). It is associated with impaired graft function. Ureteral stent placement increases the occurrence of UTIs. The aim of this study was to assess the correlation between double-J placement, UTI incidence, and graft function. MATERIAL AND METHODS: We conducted an observational study in 753 patients transplanted between 2010 and 2017 in compliance with the Helsinki Congress and the Istanbul Declaration. Recipients with preserved graft function at the 1-year follow-up were included. Medical records were searched for intraoperative double-J placement, UTI incidence, and estimated glomerular filtration rate (eGFR) on the 30th and 360th days post-transplant. Pretransplant hypothetical estimated GFR (heGFR) of each donor was calculated from donors' age and physiological age-dependent loss of functional nephrons. Spearman's correlation and linear regression analyses were applied. P < .05 was considered significant. RESULTS: UTIs occurred in 239 (31.8%) patients. On the 30th day after KTx, eGFR was significantly lower in the UTI group (median, 39.5 vs 43.2; P < .01). A similar pattern was seen 1 year after KTx (47.5 vs 54.2; P < .01). Urinary stents were placed in 213 (28.3%) patients. UTIs occurred in 92 (43.2%) of them and in 147 (27.2%) of nonstented patients (odds ratio: 2; 95% confidence interval [CI], 1.5-2.8; P < .01). Median donor heGFR was 105.8 mL/min/1.73 m2, whereas median donor Modification of Diet in Renal Disease (MDRD) GFR was 64.2 mL/min/1.73 m2. A moderate correlation between age-adjusted heGFR and 1-year transplant function (r = .47) was noted. CONCLUSIONS: UTIs in the early post-transplant period decreased 1-year eGFR by 4 to 5 mL/min/1.73 m2. UTIs occurred twice as often when a urinary stent was placed.

Correlation of Cancer Development and Human Papilloma Virus Infection in Patients After Organ Transplantation.

Immunosuppressed patients are at higher risk of developing human papilloma virus (HPV) cancerous and precancerous lesions in the anogenital region Carcinogenesis after organ transplantation due to immunosuppressive therapy is the major cause of long-term negative transplantation results. This is a rationale for the improvement of transplantation programs with carcinogenesis risk stratification in patients referred for transplantation. There is a need for a study on HPV-related carcinogenesis also in terms of its risk factors in the population after organ transplantation. This study aimed to assess the morbidity of anogenital carcinoma in patients with HPV infection, including those after organ transplantation and evaluate risk factors for carcinoma occurrence in patients after organ transplantation and with HPV infection. Our analysis directly indicates the group of patients with a high risk of HPV-related oncological complications of immunosuppression in anogenital region.