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.

Pain Control, Glucose Control, and Quality of Life in Patients With Chronic Pancreatitis After Total Pancreatectomy With Islet Autotransplantation: A Preliminary Report.

BACKGROUND: Total pancreatectomy (TP) is offered as a last treatment option for pain relief in patients with chronic pancreatitis. Concurrent islets autotransplantation (TP-IAT) may improve glucose control. METHODS: We analyzed results in 20 recent patients who underwent TP-IAT at The University of Chicago. The median observation period was 28 months (2-38). Data were collected prospectively then analyzed retrospectively. RESULTS: The number of patients requiring opioids daily for pain control decreased from 16 (80%) prior to surgery to 2 (13%) 1 year after, with only 1 (6.5%) patient experiencing persistent phantom pancreatic pain. Opioid requirements decreased from a median 56.3 (0-240) morphine equivalent dose to 5 (0-130) on day 75 and to 0 (0-30) at 1-year follow up. Five patients (25%) completely stopped insulin support prior to day 75 while maintaining hemoglobin A1c of 5.9% (5-6.3). Eight (53%) patients were insulin free at 1 year with A1c of 6% (5.5-6.8) and a similar rate persisted in next 2 years. For the remaining patients, the more islet function that was preserved, the less insulin they required and A1c was closer to optimal. Quality of Life (QoL) measured by SF36 Physical (PCS) and Mental (MCS) Component Score improved on day 75 (P < .001) and maintained improvement later on. Both PCS and MCS improved regardless of whether patient requires insulin support or not. CONCLUSIONS: Improvements of QoL with pain resolution and good glucose control can be achieved after TP-IAT in properly selected patients with CP and intractable pain, regardless of patient insulin support status.

External Validation of the Newly Developed BETA-2 Scoring System for Pancreatic Islet Graft Function Assessment.

BACKGROUND: BETA-2 score using a single fasting blood sample was developed to estimate beta-cell function after islet transplantation (ITx) and was validated internally by a high ITx volume center (Edmonton). The goal was to validate BETA-2 externally, in our center. METHODS: Areas under receiver operating characteristic curves (AUROCs) were obtained to see if beta score or BETA-2 would better detect insulin independence and glucose intolerance. RESULTS: We analyzed values from 48 mixed meal tolerance tests (MMTTs) in 4 ITx recipients with a long-term follow-up to 140 months (LT group) and from 54 MMTTs in 13 short-term group patients (ST group). AUROC for no need for insulin support was 0.776 (95% confidence interval [CI] 0.539-1, P = .02) and 0.922 (95% CI 0.848-0.996, P < .001) for beta score and 0.79 (95% CI 0.596-0.983, P = .003) and 0.941 (95% CI 0.86-1, P < .001) for BETA-2, in LT and ST groups, respectively, and did not differ significantly. In LT group BETA-2 score ≥ 13.03 predicted no need for insulin supplementation with sensitivity of 98%, specificity of 50%, positive predictive value (PPV) of 93%, and negative predictive value (NPV) of 75%. In ST group the optimal cutoff was ≥13.63 with sensitivity of 92% and specificity, PPV, and NPV 82% to 95%. For the detection of glucose intolerance BETA-2 cutoffs were <19.43 in LT group and <17.23 in ST group with sensitivity > 76% and specificity, PPV, and NPV > 80% in both groups. CONCLUSION: BETA-2 score was successfully validated externally and is a practical tool allowing for frequent and reliable assessments of islet graft function based on a single fasting blood sample.

Outcomes in Renal Transplant Recipients With Lupus Nephritis-A Single-Center Experience and Review of the Literature.

BACKGROUND: Renal transplantation is the renal replacement therapy of choice in patients with end-stage lupus nephritis (LN). The aim of this study was to evaluate the early and late outcomes of renal transplantation in LN patients in a single transplant center. PATIENTS AND METHODS: This study analyzed the clinical data of patients who received a renal transplant (RTx) at Gdansk Transplantation Centre between January 1999 and December 2014. RESULTS: There were 1296 RTx performed between January 1999 and December 2014, including 21 RTx in 19 LN patients (mean age 40 ± 10 years, 89% female). During the follow-up period (between 1 month and 10.5 years), 1 patient died of urosepsis and 1 of pneumonia. Three RTx recipients with antiphospholipid syndrome lost 5 kidney allografts, including 3 due to acute rejection (AR) during the first posttransplantation month. Kidney allograft survival median was 64 months. Delayed graft function (DGF) and AR were observed in 48% and 33% vs 31% and 21% of LN patients and other RTx patients, respectively (P = .1 and P = .16 for DGF and AR, respectively). The most common early posttransplantation complications were AR (31%) and perirenal hematomas (29%), and late complications were urinary tract infections (75%). Recurrence of LN in renal allograft was observed in 1 patient and was successfully treated by increasing the basic immunosuppression. CONCLUSIONS: Secondary antiphospholipid syndrome has a major influence on the outcomes of RTx in LN patients. Recurrence of LN has no clinical significance.

Acute graft pyelonephritis during the first year after renal transplantation.

INTRODUCTION: Urinary tract infections are the most common infections in renal transplant recipients. Acute graft pyelonephritis (AGPN) is considered a potential risk factor for poorer graft outcomes; however, its clinical impact still remains controversial. METHODS: This study analyzed urine cultures performed within the first 12 months after renal transplantation with reference to clinical data of patients who received a renal transplant at Gdansk Transplantation Centre between January 2007 and December 2009. Renal function assessed by creatinine concentration and estimated glomerular filtration rate was recorded 24 months after renal transplantation. RESULTS: This study examined urine cultures and clinical data from 209 renal transplant recipients, including 59.3% men, with a mean age of 46 ± 14 years. We observed 70 AGPN episodes defined as the presence of significant bacteriuria, fever >38°, and/or graft pain and/or acute graft function impairment, including 13 cases of bacteremia, in 46 patients. This accounted for 22% of all diagnosed urinary tract infections. Over 80% of all AGPN episodes were diagnosed beginning from the second month posttransplantation, and the most frequently isolated uropathogen was Escherichia coli (65.7%, n = 46). Female sex, vesicoureteral reflux, or strictures at the ureterovesical junction and a history of cytomegalovirus infection emerged as independent predictors of AGPN. The evolution of renal graft function measured by serum creatinine concentration and MDRG eGFR rate did not differ significantly between patients with and without AGPN. CONCLUSIONS: AGPN may be a marker of an underlying impairment of urine flow, eg, due to vesicoureteral reflux or strictures at the ureterovesical junction, whereas it does not affect graft function in renal transplant recipients.

Klebsiella spp urinary tract infections during first year after renal transplantation.

BACKGROUND: Urinary tract infections (UTIs) are the most common infections in renal transplant recipients (RTR). Klebsiella spp is a well-recognized source of nosocomial infections in immunocompromised patients and is also the most common pathogen capable of producing extended-spectrum ß-lactamases (ESBLs). METHODS: We performed a retrospective cohort study reviewing medical records of patients followed-up at Gdansk Transplantation Centre. We analyzed urine cultures performed within the first 12 months after renal transplantation (RT) with reference to clinical data. We recorded all Klebsiella spp UTIs. RESULTS: We studied urine cultures and clinical data from 335 RTRs. We observed 59 Klebsiella spp episodes in 24 RT patients, including 10 cases of acute graft pyelonephritis and 8 of urosepsis. More than half were caused by ESBL+, whereas there were no carbapenemase-producing strains. Almost 80% of episodes were diagnosed beginning from the second month post-transplantation. More than 60% of upper Klebsiella spp UTIs were due to ESBL+ strains, although we did not identify any host risk factors including vesico-ureteral reflux, strictures at the uretero-vesical junction, history of recurrent UTIs before RT, comorbidity measured by Charlson Comorbidity Index, history of acute rejection, use of induction, and type of immunosuppression used. Upper Klebsiella spp UTIs were slightly more prevalent in males with urinary flow impairment due to various reasons. CONCLUSIONS: Klebsiella spp virulence factors, not the host factors, seem to be mostly responsible for developing upper UTIs in RT patients.

Tako-tsubo cardiomyopathy on the first day after renal transplantation - case report and literature review.

BACKGROUND: The etiology of tako-tsubo cardiomyopathy, defined as a transient left ventricular dysfunction in the absence of significant coronary artery stenosis, still remains unclear. This syndrome mainly occurs in postmenopausal women and is often associated with emotional stress or miscellaneous diagnostic and therapeutic procedures. Estimated prevalence of tako-tsubo cardiomyopathy is found in 1% to 2% of patients presenting with suspected acute coronary syndrome. So far there has been only one case report of tako-tsubo cardiomyopathy in a renal transplant recipient. CASE REPORT: We describe the case of a 68-year-old woman with a history of coronary artery disease and coronary artery bypass grafting in whom unspecific transient chest pain and hypotension were observed on the first day after renal transplantation. After transplantation, the patient was anuric with pulmonary congestion and toxic tacrolimus concentrations were observed. Electrocardiogram showed sinus rhythm with left bundle branch block (LBBB) that has not been described before. Plasma cardiac necrosis markers troponin I and creatine kinase MB were mildly elevated. Echocardiography showed severe left ventricular function impairment with characteristic shape of left ventricle. Subsequent cardiac catheterization revealed the absence of angiographic evidence of acute plaque rupture within both coronary arteries and bypass grafts. During the next few days there was marked clinical improvement with resolution of LBBB and full recovery of all biochemical parameters. On discharge, full functional recovery of the left ventricle in echocardiography was observed. Postulated mechanisms of tako-tsubo cardiomyopathy include catecholamine excess, coronary artery spasm, and microvascular dysfunction. On the other hand calcineurin inhibitors are known factors causing coronary epicardial endothelial dysfunction and negatively affecting vasomotor function. CONCLUSIONS: Tako-tsubo cardiomyopathy in patients after renal transplantation may be at least in part a manifestation of calcineurin inhibitor cardiotoxicity.

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.

Changes of PBP5 gene expression in enterococcal isolates from renal transplantation recipients.

The aim of the study was to evaluate changes in expression of PBP5 gene associated with immunosuppression. A linear locked nucleic acid (LNA) probe was used to measure resistance gene expression by the Flow-FISH method. Expression of the PBP5 gene measured by Flow-FISH was higher in enterococcal strains isolated from renal transplantation (RTx) recipients than in commensal strains. Additionally, in contrast to commensal strains in isolates from RTx patients, PBP5 gene expression was 17.45% higher in biofilms than in planktonic cells. Detailed comparison also showed that cyclosporine seemed to induce higher expression of PBP5 as compared to tacrolimus.

Urinary tract infections in renal transplant recipients.

INTRODUCTION: Urinary tract infections (UTIs) are most common infections in renal transplant recipients and are considered a potential risk factor for poorer graft outcomes. AIM: To evaluate incidence, clinical manifestations, microbiology, risk factors for UTIs, and the influence of UTIs on long-term renal graft function. PATIENTS AND METHODS: We analyzed urine cultures with reference to clinical data of patients who received a renal transplantation from January to December 2009 with a 12-month follow-up. RESULTS: The 1170 urine cultures were correlated with clinical data from 89 renal transplant recipients, including 58.4% males and on overall mean age of 48±14 years. The 151 episodes in 49 patients consisted of asymptomatic bacteriuria (65%, n=98); lower UTIs (13%, n=19); and upper UTIs (22%, n=34), as well as five cases of bacteremia. Nearly 48% of UTIs were diagnosed during the first month posttransplantation. The most frequently isolated uropathogens were Enterococcus faecium (33%, n=24) and Escherichia coli (31%, n=23). Beginning from the second month, most frequently found bacterium in urine cultures was E coli (65% n=51). Risk factors for posttransplant UTIs were female gender and a history of an acute rejection episode and/or a cytomegalovirus (CMV) infection. All patients with vesicoureteral reflux of strictures at the ureterovesical junction suffered recurrent UTIs (n=7). The evolution of renal graft function did not differ significantly between patients with versus without UTIs. CONCLUSIONS: UTIs a frequent problem after kidney transplantation most commonly exist as asymptomatic bacteriuria. E coli and E faecium are ther predominant pathogens. Exposure to intensified immunosuppression due to acute rejection episodes or CMV infections represents a risk factor for UTIs. Vesicoureteral reflux or strictures at the ureterovesical junction are risk factors for recurrent UTIs. UTIs did not impair 1-year graft function.

The Y111 H (T415C) polymorphism in exon 3 of the gene encoding adiponectin is uncommon in Polish obese patients.

The genetic background of obesity is under research. Obesity-related phenotype candidate genes include the gene encoding adiponectin (AdipoQ). In this study, exon 3 of the adiponectin gene was screened for the Y111 H (Tyr111His, or T415C, rs17366743) polymorphism, and adiponectin serum concentrations were measured in 206 obese subjects (110 women and 96 men, aged 50.5+/-16.9 years). Their BMI, % of body fat, plasma glucose, insulin, and glycosylated hemoglobin were measured. Adiponectin was determined by enzyme-linked immunosorbent assay. Genomic DNA was extracted from peripheral blood leukocytes. A fragment of exon 3 of the adiponectin gene was amplified in PCR and screened for the Y111 H polymorphism in SSCP analysis. Genetic screening revealed a different SSCP pattern in 2 subjects. Subsequent genotyping disclosed the TC genotype in both subjects, resulting in Y111 H heterozygote variant frequency of 0.01 in the whole cohort. Other results for SNP (single nucleotide polymorphism) positive and negative subjects were as follows, respectively: BMI (kg/m (2)) 39.95+/-9.83 vs. 38.12+/-8.56; waist circumference (cm) 122+/-18.4 vs.115+/-16; glucose (mmol/l) 7.51+/-1.86 vs. 5.56+/-0.74; HbA1c (%) 7.55+/-1.86 vs. 6.58+/-1.36; body fat (%) 51+/-2 vs. 44+/-10; plasma insulin (mU/l) 28.92+/-16.50 vs. 37.59+/-47.34; adiponectin (ng/ml) 1301+/-15.8 vs. 5682+/-4156. Due to a proportion of 2 vs. 204, statistical calculations were not possible. The Y111 H adiponectin gene variant is uncommon in Polish obese subjects. Although we observed low adiponectin concentrations in Y111 H SNP heterozygote carriers, this finding was not confirmed by statistics.