Antiviral prophylaxis, male sex, and killer immunoglobulin-like receptor KIR2DL3 as markers for stratifying the risk of BK polyomavirus-associated nephropathy in kidney transplant recipients.

INTRODUCTION: The risk of polyomavirus­associated nephropathy (PyVAN) currently ranges from 1% to 10%, and the risk of graft loss is 10% to 50% within 2 years post­diagnosis. There is currently no specific antiviral therapy against BK polyomavirus (BKPyV), and no therapeutic approach has been proven superior. Natural killer cells play a key role in the defense against viral infections. OBJECTIVES: A retrospective, single­center cohort study was performed to investigate the association between the kidney transplant recipients' killer­cell immunoglobulin­like receptor (KIR) genotype and PyVAN. We also evaluated other possible risk factors for the occurrence of PyVAN in a population of kidney transplant recipients. PATIENTS AND METHODS: DNA samples from 134 kidney transplant recipients were identified for the presence or absence of variable KIR genes and their HLA ligands using polymerase chain reaction with sequence­specific primers. RESULTS: The analysis revealed that the presence of the inhibitory KIR2DL3 (P = 0.03) was a risk factor for posttransplant PyVAN. We also found that the presence of acute rejection before PyVAN (P = 0.02), male sex (P = 0.04), and the lack of antiviral prophylaxis (P = 0.01) were additional risk factors for posttransplant PyVAN. CONCLUSIONS: Our findings confirm that the KIR/HLA genotype plays a significant role in the development of PyVAN and suggest the contribution of both environmental and genetic factors to the incidence of BKPyV infection after kidney transplantation.

Overcoming Inequity in Access to Kidney Transplantation: A Quality Improvement Project.

BACKGROUND: In 2018, DaVita dialysis clinics in Poland introduced a new pathway to improve the referral of dialysis patients for kidney transplantation. It was designed to meet formal requirements for timely referral for transplant assessment and measures to have the patient "active" on the waiting list. The pathway aimed to mitigate the existing inequitable access to transplantation surgery for patients with end stage kidney disease under the care of ambulatory dialysis clinics. The consequences to the patient of lack of contact with nephrologist when called in for transplant surgery during out-of-office hours was a major concern. We reviewed the effectiveness of whether the new procedure impacted facilitating a patient's call for a transplant surgery when dialysis clinics were not operating. METHODS: We collected data on the number of transplantations performed and the number of calls for surgery according to a conventional or new procedure over a 30-month period. RESULTS: In our study, 269 patients received a deceased donor kidney transplant, and 205 candidates (75%) were called for transplantation during the working hours of dialysis clinics, according to the standard procedure, of which 4 patients were discharged for various reasons. In addition, 69 candidates (25%) were called outside clinic working hours through the new procedure process, of which 1 patient was discharged during a phone call due to infection. CONCLUSIONS: DaVita's Poland new transplant access procedure effectively supports a patient's call for transplantation during outpatient dialysis clinics' closure hours.

Type 1 diabetes: genes associated with disease development.

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Based on the World Health Organization (WHO) report from 2014 the number of people suffering from all types of diabetes ascended to 422 million, compared to 108 million in 1980. It was calculated that this number will double by the end of 2030. In 2015 American Diabetes Association (ADA) announced that 30.3 million Americans (that is 9.4% of the overall population) had diabetes of which only approximately 1.25 million had T1D. Nowadays, T1D represents roughly 10% of adult diabetes cases total. Multiple genetic abnormalities at different loci have been found to contribute to type 1 diabetes development. The analysis of genome-wide association studies (GWAS) of T1D has identified over 50 susceptible regions (and genes within these regions). Many of these regions are defined by single nucleotide polymorphisms (SNPs) but molecular mechanisms through which they increase or lower the risk of diabetes remain unknown. Genetic factors (in existence since birth) can be detected long before the emergence of immunological or clinical markers. Therefore, a comprehensive understanding of the multiple genetic factors underlying T1D is extremely important for further clinical trials and development of personalized medicine for diabetic patients. We present an overview of current studies and information about regions in the human genome associated with T1D. Moreover, we also put forward information about epigenetic modifications, non-coding RNAs and environmental factors involved in T1D development and onset.

Reoperation in Early Kidney Post-transplant Period as a Strong Risk Factor of Surgical Site Infection Occurrence.

BACKGROUND: One of the most common infective complications after kidney transplant (KTx) is surgical site infection (SSI). Providing indications of improvement of perioperative antibiotic prophylaxis (PAP) and allowing the characterization of risk factors are critical to reduce SSI. The purpose of this study was to evaluate the SSI risk factors and impact of reoperation in the early post-transplant period on SSI occurrence and assess if standard PAP in those cases is a best consideration. METHODS: Between April 2014 and October 2015, a total of 236 KTxs were performed in our center. Deceased donor data, recipient data, and data related to surgical procedures were collected. RESULTS: Surgical site infections were reported in 5.6% (12/214) of patients. Seven patients were diagnosed as having superficial SSI (7/12; 58.3%), 2 with deep SSI (2/12; 16.6%), and 4 with organ-specific SSI (4/12; 33.3%). Extended criteria donor-related transplant, cold ischemia time > 22 hours, dialysis period > 30 months, recipient age older than 45 years, recipient body mass index > 27, induction therapy prior to transplant, diabetes prior to transplant, and ≥ 1 reoperation during 30 days of observation were independent risk factors of SSI occurrence. A total of 19 reoperations were performed in 17 patients. In 8 of all 12 patients with SSI diagnosis, the reoperation was performed (66.7%). In 202 patients of non-SSI patients, only 9 reoperations were performed (4.5%). CONCLUSIONS: Early reoperation after Ktx is a strong risk factor of SSI occurrence. There is a probability that > 4 SSI risk factors and reoperation in the early post-transplant period could require different and more aggressive proceeding, as standard PAP in those cases is insufficient.

Should Immunosuppression After Kidney Transplant Be Adjusted Based on Renal Resistance During Pretransplant Hypothermic Machine Perfusion?

BACKGROUND: The hypothermic machine perfusion reduces delayed graft function after kidney transplant and allows, to some extent, predicting early graft function. However, it is difficult to identify exact perfusion criteria with which to exclude kidneys from transplant or modify post-transplant care. The aim of this study was to analyze whether renal resistance during the fourth hour of hypothermic machine perfusion is useful in the prediction of graft survival and acute rejection. PATIENTS AND METHODS: Data on pretransplant hypothermic machine perfusion parameters of 407 transplanted kidneys were available. Receiver operating characteristic curve analysis was performed to find an optimal cutoff value of ratio for predicting a higher risk class of considered group of patients. According to this, patients were divided into 2 groups: those who received kidneys with renal resistance lower than 0.19 mm Hg/mL/min (R1; n = 187) and those who received kidneys with renal resistance equal to or higher than 0.19 mm Hg/mL/min (R2; n = 220). Within R2, we additionally analyzed 2 subgroups: patients who received induction therapy (R2-Ind+; n = 124) and those who did not received induction therapy (R2-Ind-; n = 96). RESULTS: Acute rejection in R1 within 1 month post transplant was 2-fold lower compared with R2 and was 6.4% vs 13.1% (P = .03), respectively. One-year graft survival was higher in R1 compared with R2 and was 94.6% vs 88.5% (P = .03), respectively. Acute rejection in the R2-Ind+ subgroup within 1 month post transplant was 2.46-fold lower compared with the R2-Ind- subgroup and was 8% vs 19.7% (P = .01), respectively. CONCLUSION: Immunosuppression treatment after transplant should be adjusted to perfusion parameters.

Do We Need Insulin Independence After Islet Transplantation?

INTRODUCTION: Most life-threatening diabetes-related complications involve the kidneys, eyes, cardiovascular system, and autonomic nervous system. Clinical islet transplantation (CITx) may be a therapeutic option for some patients. In this study, we analyzed the progression of diabetic complications after CITx and in patients waiting for islet transplantation. METHODS: From 2008 to 2015, 67 patients were listed for pancreatic or islet transplantation. We compared beta scores, islet scores, and secondary complications between patients who underwent islet allotransplantation (CITx group, n = 6) and the patients awaiting islet transplantation (wait group, n = 19) at baseline and during the 1-year follow-up. RESULTS: In the CITx group, good islet function was observed in 80% of patients 1 month post-transplantation and 40% of patients 1 year post-transplantation; however, no patient achieved insulin independence. One patient who underwent simultaneous islet-kidney transplantation died on day 8 because of severe bleeding in the retroperitoneal space. In 1 case, islet primary nonfunction was observed. Mean islet score in the CITx group 1 year post-transplantation was significantly higher than the pretransplant score and wait group scores at enrollment and 1 year later (P < .01). Increased albuminuria was observed in 3 of 11 (27%) patients in the wait group and 0 patients in the CITx group (P = .08). One patient (9%) in the wait group developed chronic renal failure requiring hemodialysis. Ophthalmologic procedures were required by 47% of patients in the wait group and 0 patients in the CITx group in the first year after transplantation (P < .01). CONCLUSION: Successful islet transplantation slows the progression of diabetic complications.

Islet Autotransplantation in Diabetic Patients.

INTRODUCTION: Painful chronic pancreatitis (CP) is the main indication for analgesic pancreatectomy with simultaneous islet autotransplantation to prevent postoperative diabetes mellitus (DM). However, advanced CP may lead to insulin secretion disorders and DM. There are doubts as to whether islet autotransplantation in such cases is an appropriate procedure. The aim of this study was to analyze the results of islet autotransplantation in patients with CP with already diagnosed with DM. METHOD: Between 2008 and 2015, at the Department of General and Transplantation Surgery, patients with CP and unsatisfying pain treatment with positive fasting C-peptide ( > 0.3 ng/mL) level were qualified for simultaneous pancreatectomy and islet autotransplantation. Eight procedures were performed. In 5 cases patients had DM diagnosed prior to the procedure (DM group n = 5). Three patients without DM diagnosed prior to surgery were the control group (n = 3). RESULT: There were no cases of procedure-related deaths in either group. Pain relief without analgesics was reported by all patients. Good islet function was observed in 80% (4/5) of the DM group vs 100% (3/3) in the control group (P = ns). Brittle diabetes was diagnosed in 1 patient in the DM group as a result of islet primary non-function. CONCLUSION: Patients with CP-related severe pain and DM patients with positive C-peptides should be considered for pancreatectomy and islet autotransplantation.

Changes in Gene Expression of Selected Genes in Patients with Type 1 Diabetes and Pancreas Transplant in Peripheral Blood.

BACKGROUND: Diabetes is an autoimmunologic disease that may have a different background. The aim of our study was to show that type 1 diabetes is accompanied by changes in gene expression in peripheral blood mononuclear cells. We analyzed the genes characteristic of pancreatic islet cells and genes playing a big part in autoimmune diseases and cancer. DESIGN: The study included 21 patients and was performed to examine the expression of 9 genes. The patients were divided into 3 research groups: people with type 1 diabetes, people with diabetes after pancreas transplant, and a control group of healthy patients. To assess the level of expression, RNA material was obtained from peripheral blood collected from individuals qualified for the study. RESULTS: The results of the study showed many interesting changes in the expression level of the analyzed genes. It was demonstrated that CASR gene expression was significantly higher in transplant patients than in diabetic patients. Differences in the level of activity are also noted in genes that take part in autoimmune diseases. PROPOSAL: Profiling gene expression in peripheral blood samples may be a useful and noninvasive diagnostic tool that allows early detection of changes leading to the onset or resumption of diabetes.

Diagnostic utility of monitoring cytomegalovirus-specific immunity by QuantiFERON-cytomegalovirus assay in kidney transplant recipients.

BACKGROUND: Despite universal prophylaxis, late cytomegalovirus (CMV) infection occurs in a high proportion of kidney transplant recipients. We evaluated whether a specific viral T-cell response allows for the better identification of recipients who are at high risk of CMV infection after prophylaxis withdrawal. METHODS: We conducted a prospective study in 19 pretransplant anti-CMV seronegative kidney graft recipients R- (18 from seropositive donors [D+] and one from a seronegative donor [D-]) and 67 seropositive recipients R(+) (59 from seropositive donors and eight from seronegative donors) who received antiviral prophylaxis with valganciclovir. The QuantiFERON-CMV (QF-CMV) assay was performed within the first and third months after transplantation. Blood samples were monitored for CMV DNAemia using a commercial quantitative nucleic acid amplification test (QNAT) that was calibrated to the World Health Organization International Standard. RESULTS: Twenty-one of the 86 patients (24%) developed CMV viremia after prophylaxis withdrawal within 12 months posttransplantation. In the CMV R(+) group, the QF-CMV assay yielded reactive results (QF-CMV[+]) in 51 of 67 patients (76%) compared with 7 of 19 patients (37%) in the CMV R(-) group (p = 0.001). In the CMV R(+) group, infection occurred in seven of 16 recipients (44%) who were QF-CMV(-) and eight of 51 recipients (16%) who were QF-CMV(+). In the CMV R(-) group, infection evolved in five of 12 recipients (42%) who were QF-CMV(-) and one of 7 recipients (14%) who were QF-CMV(+). No difference was found in the incidence of CMV infection stratified according to the QF-CMV results with regard to the recipients' pretransplant CMV IgG serology (p = 0.985). Cytomegalovirus infection occurred in 15 of 36 patients (42%) with hypogammaglobulinemia (HGG) 90 days posttransplantation compared with two of 34 patients (6%) without HGG (p = 0.0004). Cytomegalovirus infection occurred in seven of 13 patients (54%) with lymphocytopenia compared with 14 of 70 patients (20%) without lymphocytopenia (p = 0.015). The multivariate analysis revealed that the nonreactive QuantiFERON-CMV assay was an independent risk factor for postprophylaxis CMV infection. CONCLUSIONS: In kidney transplant recipients who received posttransplantation prophylaxis, negative QF-CMV results better defined the risk of CMV infection than initial CMV IgG status after prophylaxis withdrawal. Hypogammaglobulinemia and lymphocytopenia were risk factors for CMV infection.