The Prevalence of Prostate Cancer in Organ Donors With Increased Prostate-Specific Antigen.

Elevated prostate-specific antigen (PSA) levels were found in 139 of 472 kidney donors from our transplant center tested between 2009 and 2022, representing 29%. The mean age of these donors was 47.3 years. PSA values ranged from 2.8 to 160.4 ng/mL (mean 13.9 ng/mL). The recommended range is <2.5 ng/mL. Prostate histopathologic examination was performed in 38 of the 139 (27%). We found 14 cases of prostate cancer (PCa), with Gleason 3+3 in 8 cases, 3+4 in 4 cases (one donor disqualification), 1 case Gleason 4+3 (donor disqualification), and 1 case Gleason 4+5 (donor disqualification). Thirty-three patients met the criteria, were aged ≥50 years, and had a PSA level >10 mg/mL. Of these, prostate histopathologic examination was performed in 24 cases. PCa was found in 10 cases (42%). There was no difference between donors ≥50 years of age, with PSA>10 ng/mL with and without pathomorphologic diagnosis of PCa regarding age (mean 60.4 vs 60.6 years), creatinine clearance according to the Cockroft-Gaulta formula (mean 101.6 vs 94.8 mL/min) and PSA levels (mean 34.1 vs 29.3 ng/mL). Among other donors with PCa, 3 were <50 years with PSA >10 ng/mL, and 1 was ≥50 years with PSA<8 ng/mL. Kidneys from donors with PCa were transplanted into 10 men and 9 women. Follow-up time was 1 to 10 years. No cases of PCa transmission were reported. One of the recipients died of neoplasm-breast cancer. Donors ≥50 years of age with PSA>10 ng/mL have a higher risk for Pca. Accepting donors with Pca (Gleason 3+3 and 3+4) possesses minimal risk for transmission. All donors ≥50 years with increased PSA require further diagnostic procedures (eg, digital rectal examination, ultrasound, and eventually histologic examination).

Increased Circulating Irisin Levels in Kidney Transplant Patients: Is There a Connection with Glycaemic Control?

Irisin is a myokine with potential effects on glucose metabolism and the development of diabetes in humans. We analysed irisin serum levels (ISL) in 47 patients without diabetes before and 1, 2, 3, 4 and 5 weeks after kidney transplantation (KTx). All measurements of irisin before KTx levels were lower than 25 ng/mL (median 8.4 ng/mL). We found an outstanding increase in ISL measured after KTx, reaching more than 1000 times in 44% of patients (HIL-high irisin level group). The increase appeared at the first measurement (one week after KTx). Factors connected to the large growth of ISL were, i.e., BMI > 30 (p = 0.04) and subsequent KTx-second and third (p < 0.001). The global mean blood glucose level during the first two weeks after KTx was significantly lower in the HIL group (p = 0.002), the same as the day-by-day analysed mean fasting and postprandial serum glucose in the first days after KTx. In 12 months of observation, diabetes requiring insulin therapy occurred in the HIL group at a rate of 19%, while in the rest of the patients, the rate was 27%, p = 0.526. Irisin levels increase significantly in some patients after kidney transplantation, accompanied by lower blood glucose levels in the early post-transplant period. Whether an increase in irisin levels results in better glycaemic control remains questionable and requires further research, as well as the relationship between irisin levels and the occurrence of PTDM.

Nanoparticle Tracking Analysis of Urinary Extracellular Vesicle Proteins as a New Challenge in Laboratory Medicine.

Urinary extracellular vesicle (uEV) proteins may be used as specific markers of kidney damage in various pathophysiological conditions. The nanoparticle-tracking analysis (NTA) appears to be the most useful method for the analysis of uEVs due to its ability to analyze particles below 300 nm. The NTA method has been used to measure the size and concentration of uEVs and also allows for a deeper analysis of uEVs based on their protein composition using fluorescence measurements. However, despite much interest in the clinical application of uEVs, their analysis using the NTA method is poorly described and requires meticulous sample preparation, experimental adjustment of instrument settings, and above all, an understanding of the limitations of the method. In the present work, we demonstrate the usefulness of an NTA. We also present problems encountered during analysis with possible solutions: the choice of sample dilution, the method of the presentation and comparison of results, photobleaching, and the adjustment of instrument settings for a specific analysis. We show that the NTA method appears to be a promising method for the determination of uEVs. However, it is important to be aware of potential problems that may affect the results.

Pretransplant BMI Significantly Affects Perioperative Course and Graft Survival after Kidney Transplantation: A Retrospective Analysis.

Background. The number of kidney transplant recipients (KTRs) with overweight and obesity is increasing. It was shown that obesity is related to inferior patient and graft survival. We aimed to analyze intraoperative parameters and postoperative short and long-term course of kidney transplantation (KT) in body mass index (BMI)-stratified cohorts of KTRs. Methods. A retrospective analysis of a prospectively built database of 433 KTRs from 2014 to 2017 from a single transplant center was performed. The objective of the study was to analyze the association between BMI at the time of transplantation with intraoperative parameters, adverse events in early postoperative course, and the overall mortality and graft loss in BMI-stratified cohorts: normal (18.5 and 24.9 kg/m2), overweight (25−29.9 kg/m2) and obese (≥30 kg/m2). Results. Obesity was related to longer total procedure time (p = 0.0025) and longer warm ischemia time (p = 0.0003). The postoperative course in obese patients was complicated by higher incidence of DGF (delayed graft function), early surgical complications (defined as surgical complications <30 days from KT), reoperation rate, vascular complications, incidence of lymphocele and wound dehiscence. There was no difference between the normal weight and overweight KTRs. The one-month kidney function (p = 0.0001) and allograft survival (p = 0.029) were significantly inferior in obese patients with no difference between normal weight and overweight patients. One-year death-censored graft survival was better in patients with BMI < 30 (88.6 vs. 94.8% p = 0.05). BMI was a significant predictor of graft loss in univariate (p = 0.04) but not in multivariate analysis (p = 0.09). Conclusion. Pretransplant obesity significantly affects the intraoperative and postoperative course of kidney transplantation and graft function and survival. The course of transplantation of overweight is comparable to normal BMI KTRs, and presumably pretransplant weight reduction to the BMI < 30 kg/m2 may improve the short-term postoperative course of transplantation as well as may improve graft survival. Thus, pretransplant weight reduction in obese KTRs may significantly improve the results of kidney transplantation. Metabolic surgery may play a role in improving results of KT.

Kidney Transplantation in Patients After Bariatric Surgery: High-Volume Bariatric and Transplant Center Experience.

BACKGROUND: Kidney transplantation (KTx) is the best type of treatment for patients with end-stage renal disease (ESRD). Unfortunately, obesity may be a contraindication for transplantation. Our study aimed to evaluate the results of KTx in patients who had bariatric surgery (BS) prior to transplantation. METHODS: A single center, with experience in bariatric and transplant surgery, presents a retrospective study of 13 patients who received a kidney transplant after a gastric bypass (GB) operation between 2012 and 2019. RESULTS: Thirteen patients, who were potential candidates for KTx, were previously qualified for BS because of a body mass index (BMI) > 35 kg/m2. Additionally, all patients had arterial hypertension, 60% of patients had diabetes, and 30% of patients had coronary artery disease. Patients were activated on the waiting list when their BMI was < 35 kg/m2. KTx was performed between 5 and 29 months after BS. One patient needed reoperation due to a urinary leak and another patient needed reoperation because of a high-pressure lymphocele. We diagnosed 2 delayed graft functions (DGFs) and 1 acute rejection. One patient died for reasons independent of surgery. The KTx observation period ranged from 3 to 8 years. Currently, 11 patients has stable renal function: creatinine concentration is 0.8-1.8 mg/dL and BMI is between 23 and 35 kg/m2. CONCLUSIONS: Despite the small group of patients, we can assume that kidney transplantation can be safely performed in patients with end-stage renal disease (ESRD) who have previously undergone gastric bypass (GB) as a graft bridging procedure. In some cases, BS may be the only chance of getting an organ.

Early outcomes and long-term survival after kidney transplantation in elderly versus younger recipients from the same donor in a matched-pairs analysis.

ABSTRACT: The elderly are the fastest-growing population on waiting lists for kidney transplantation (KTx). Recognized barriers to KTx in the elderly is early post-transplant mortality and morbidity. To analyze the outcomes of KTx in recipients older than 60 years and, simultaneously, in their younger paired recipients, receiving a graft from the same donor.We included 328 kidney transplant recipients in the study. The elderly kidney transplant recipients (EKT) group included 164 patients aged 65 standard deviation (SD4) years. They were paired with younger kidney transplant recipients (YKT) aged 45 (SD12) years.The studied groups (EKT vs YKT) did not differ from the graft function estimated 1 year after the transplantation (50.7 mL/min vs 54.0 mL/min), while the estimated glomerular filtration rate decline was significantly faster in the YKT group. One-year patient survival (93.9% vs 97.0%), 1-year graft survival (90.4% vs 82.3%), and incidences of delayed graft function and acute rejection did not differ between the EKT and YKT groups. Significantly more cardiovascular complications and post-transplant diabetes mellitus were noticed in the EKT group. The long-term patient and graft survivals were poorer in the EKT group versus the YKT group, but death-censored graft survivals were the same. After having excluded donor-derived graft factors, there were no differences in the first-year outcome of KTx between recipients younger and older than 60 years. As life expectancy is lower in the EKT group, the probability of patient and graft survival was also significantly lower in this group. However, death-censored graft survival was not different in the EKT and YKT groups.

The utility of cytolytic flow cytometry crossmatch before kidney transplantation.

The donor/recipient matching in kidney transplantation is based on approved laboratory tests, which are complement-dependent cytotoxic crossmatch (CDC-XM) and flow cytometry crossmatch (FCXM). Both have some disadvantages: CDC-XM has low sensitivity, whereas FCXM does not differentiate between lytic vs. non-lytic alloantibodies. To find an improved method, we have developed a new crossmatch technique of cytolytic flow cytometry crossmatch (cFCXM), which allows for sensitive detection of clinically relevant complement-binding antibodies. The cFCXM assay detects dead cells with viability dye that ensue from the binding of allospecific lytic antibodies. In our study, 135 unsensitized kidney transplant recipients were recruited based on the CDC-XM and FCXM results and the clinical utility of cFCXM was evaluated. The 5-year follow-up for acute rejection incidents revealed that cFCXM could verify the clinical relevance of positive FCXM results as recipients with positive FCXM but negative CDC-XM had the same risk of rejection as patients with both negative CDC-XM/FCXM results. These findings suggest that cFCXM assay may provide more precise immunological risk assessment in kidney transplant recipients.

Pregnancy After Kidney Transplantation With Maternal and Pediatric Outcomes: A Single-Center Experience.

Outcomes of pregnancies after kidney transplantation were evaluated. Thirty-one pregnancies in 26 women were noted. The mean maternal age at pregnancy was 31 ± 5 years (range, 23-44 years). The interval between transplantation and conception was 54 ± 51 months (range, 7-213 months). The mean serum creatinine concentration before conception was 1.28 ± 0.4 mg/dL (range, 0.8-2.45 mg/dL), and mean estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was 62 ± 18 mL/min/1.73 m2 (range, 27-106 mL/min/1.73 m2). There were no maternal deaths. There was 1 case of suspected acute rejection after delivery. There was 1 case of graft loss during pregnancy. Maternal complications included edema (6/26), hypertension (7/26), increase of (2/26) or appearance of proteinuria (5/26), and preeclampsia (4/26). Mean creatinine increase during pregnancy was 0.02 mg/dL. Mean creatinine 1 year after pregnancy was 1.54 mg/dL (±0.8 mg/dL). There were 19 cesarean sections. Fetal outcomes included 25 live births, 4 abortions, and 2 stillbirths. Out of 25 live births, 22 children were considered healthy, 2 children had congenital defects, and there were 2 deaths at neonatal age. Mean pregnancy age was 35 ± 4 weeks (range, 24-40 weeks). The rate of premature deliveries was 15 of 25. Mean neonate birth weight was 2363 ± 1029 grams (range, 490-4100 grams). The rate of babies small for gestational age was 19%. During follow-up (range, 0.5-30 years) 5 of 26 patients lost grafts (between 3 and 15 years after pregnancy); most (20) of the children previously considered healthy had good long-term development. Our results confirm that risk of pregnancy in kidney transplant recipients can be accepted, and children considered healthy at delivery develop well.

Ophthalmologic Diseases in Kidney Transplant Recipients: A Single-Center Prospective Study.

BACKGROUND: Kidney transplant (KTx) recipients usually experience many comorbidities (eg, hypertension, diabetes, cardiovascular disease, glaucoma). They usually are older and have some ophthalmologic disorders, which may deteriorate after Ktx and some others may develop. OBJECTIVE: We aimed to review a 1-year examination of the eyesight characteristics in patients after KTx. METHODS: The study encompassed 82 eyes in 41 patients who underwent KTx in the years 2014 to 2018. All patients had visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography. RESULTS: The most frequently observed changes during the 1-year observation were cataract (46%), hypertensive angiopathy (20%), and glaucoma (20%). One year after the renal transplant visual acuity declined in 22 patients (54%). In 45% of those with eyesight deterioration the cause was cataract, while in patients with no changes in eyesight (n = 9) cataract was not diagnosed. Patients with cataracts had been more often treated with high doses of steroids (steroid boluses), mainly because of acute rejection, which was significantly associated with cataract developing after Ktx (42% vs 11%; P = .019). On univariate analysis Charlson Comorbidity Index, total ischemic time, and steroid boluses were significantly associated with cataract developing after Ktx; none of these factors were an independent predictor on multivariate analysis. CONCLUSIONS: The most common ophthalmologic diagnoses in patients after Ktx include cataract, glaucoma, and hypertensive angiopathy. Visual acuity deterioration, seen so often in the studied group of the patients, was mainly the effect of cataract progress. The effect of steroid boluses on cataract progress was meaningful.

The Pre-Transplant Drop in Panel-Reactive Antibodies Titer Evaluated Using Complement-Dependent Cytotoxicity (PRA-CDC) and the Risk of Early Acute Rejection in Sensitized Kidney Transplant Recipients.

Background: The panel-reactive antibodies that use the complement-dependent cytotoxicity test (PRA-CDC) are still a standard method for monitoring the degree of immunization in kidney transplant candidates on active waiting lists in some countries, including Poland. The aim of this study was to analyze the relationship between the maximum and the last pre-transplant PRA titer on the percentage of positive cross-matches and rate of early acute rejection episodes. Material and methods: The retrospective analysis included 528 patients from two transplant centers. All patients were divided into three groups, depending on their peak and last pre-transplant PRA titers. There were 437 (82.8%) patients with peak PRA <20% (non-sensitized group, non-ST) and 91 (17.2%) patients with peak PRA >20%. Among the latter group, 38 had maintained PRA level >20% at the time of transplantation (sensitized patients, ST), whereas 53 had pre-transplant PRA ≤20% (previously sensitized patients, prev-ST). Results: The percentages of positive crossmatches were 76.9% in ST and 53.7% in prev-ST groups versus 18.4 in non-ST group (both p < 0.001). The acute rejection rates were 18.9, 17.6 and 6.8%, respectively (p < 0.001 for ST or prev-ST versus non-ST). The pre-transplant PRA titer drop did not decrease the risk of early acute rejection [OR = 1.09 (95% CI: 0.31⁻3.85)] in a multiple logistic regression analysis. The occurrences of primary graft non-function and delayed graft function were similar in all study groups. Conclusions: Previously immunized kidney transplant candidates even with substantial decrease in pre-transplant PRA-CDC levels are still at high immunological risk when compared with non-immunized patients, and they should receive lymphocyte-depleting induction therapy.

Pilot Study of Eyesight Characteristics and Thickness of the Retinal Nerve Fiber and Ganglion Cell-inner Plexiform Layers in Adolescent Patients with Type one Diabetes Mellitus on an Insulin Pump.

AIM: Estimation of the ocular status in adolescents with diabetes mellitus type 1 (DM1) treated with continuous subcutaneous insulin infusion (CSII), assessment of the development of the diabetic retinopathy (DR) and nephropathy (DN) within 10 years. METHODS: 37 patients (74 eyes) aged 16-33 years, treated with CSII were enrolled to the study. Baseline, and a 10- year follow-up evaluation included: best corrected visual acuity (BCVA), tonometry, slit lamp exam and fluorescein angiography (FLA). Additionally, spectral-domain optical coherence tomography (SD-OCT) was done in the 7th year of observation to assess the thickness of the retinal nerve fiber (RNFL) and the ganglion cellinner plexiform layers (GCL-IPL) complex thickness. Glycated haemoglobin (HbA1) and albuminuria were also analysed. RESULTS: During the 10-year observation period DR (non-proliferative - NPDR, proliferative - PDR, diabetic macular edema - DME) was diagnosed in 3 (8%) patients. In the DR group: BCVA was significantly lower, intraocular pressure (IOP) levels and albuminuria were higher. There were no differences in HbA1 in both groups. The thinning of RNFL was observed in both groups. Macular RNFL, GCL-IPL complex thickness assessment showed a significantly higher number of borderline results in the group with DR. CONCLUSIONS: Diabetic patients treated with CSII are at a lower risk of developing vascular complications even with poor metabolic control. Increased albuminuria may be a predictive sign for early ocular complications, and requires intense observation. Diagnosis of RNFL and GCL-IPL decreased values is crucial prior to diabetic retinopathy development. SD-OCT is a non-invasive, easy-to-perform, relatively inexpensive procedure, and can be a useful tool to monitor neuropathy progression.

A 10-year monitoring of the eyesight in patients after kidney transplantation.

A pilot study of a 10-year analysis of the eyesight characteristics in patients after renal transplantation with a view to a later wider study of the same population.The study encompassed 50 eyes in 25 patients who underwent renal transplantation in the years 2007 and 2008. All patients underwent: visual acuity measurement, tonometry, slit lamp examination, and spectroscopic optical coherence tomography.Changes in the eyes observed during the 10-year observation period included mostly: cataract (48%), hypertensive angiopathy (28%), diabetic macular edema (16%), and glaucoma (16%). Ten years after the renal transplant visual acuity declined in 15 patients (60%). In 67% of those with eyesight deterioration the cause was cataract, while in patients with no changes in the eyesight (n = 10) cataract was diagnosed only in one. Patients with cataracts had been more often treated with cyclosporine, and that difference was statistically significant (73% vs 21%; P < .05). Comparing patients with hypertensive angiopathy with controls has shown that in the first group creatinine levels were statistically significantly higher (1.6 vs 1.16 mg/dL; P < .05). Patients with angiopathy had been also longer on renal replacement therapy before transplant (57 vs 26 months, P > .05), and this group included also statistically more persons after retransplantation (43% vs 5%, P < .05).Most frequent ophthalmological diagnoses in patients after a kidney transplant include cataract, diabetic retinopathy, and hypertensive angiopathy. Visual acuity deterioration was seen in 60% of patients and was mainly the effect of cataract progress. The effect of cyclosporine on cataract progress was significant. The diagnosis of hypertensive angiopathy corresponded with poorer function of the transplanted kidney.

Immunosuppressive regimens containing generic mycophenolate mofetil (Myfenax) in de novo renal transplant recipients--preliminary results of 6-month observation.

BACKGROUND: The aim of the findings presented below is to show the preliminary outcomes of transplantation in patients treated with the generic formulation of mycophenolate mofetil (Myfenax, Teva). MATERIAL/METHODS: Over the past 2 years 34 patients received generic mycophenolate mofetil (Myfenax) after renal transplantation at the Gdansk Transplantology Center. During the same time period another 127 kidney transplantations were performed in our Department and these patients were treated with other formulations of mycophenolate (CellCept, Myfortic or Mycophenolate mofetil Apotex) as a part of the immunosuppressive scheme. Fifteen of the Myfenax patients received a pair of kidneys from the same donor and received original mycophenolate mofetil Cell-Cept. RESULTS: The outcomes of the renal transplants in both groups (Myfenax vs. pair) were good; with satisfactory function of grafts, and no instances of graft loss were reported. There was no difference in the incidence of acute renal graft rejection (AR) in either group. Moderate adverse reactions to immunosupression were observed in both groups. On the other hand, a comparison between the 34 patients with Myfenax and the 127 other patients with other formulations of mycophenolate revealed no differences in the incidence of AR, delayed graft function (DGF), graft loss and death. CONCLUSIONS: There were no differences in the incidence of AR, DGF, graft loss and death in patients with Myfenax vs. original CellCept and other formulations of mycophenolate. In order to confirm its complete biological and pharmacokinetic equivalence with the reference medicine, long-term, randomized observations carried out on larger renal transplant patients groups are needed.

Immunosenescence increases the rate of acceptance of kidney allotransplants in elderly recipients through exhaustion of CD4+ T-cells.

Compromised immunity is the hallmark of ageing. Paradoxically, it may be "an ally" in facilitating acceptance of allogeneic grafts in the elderly. In this retrospective study we looked for biomarkers of immunosenescence that distinguish elderly recipients less prone to reject kidney allografts. Recruited kidney recipients aged > or = 60 or < 60 were designated 'elderly' and 'young', respectively. Both age-groups were divided according to the history of acute rejection. The phenotype, length of telomeres, expression of FoxP3 and proliferative responses were assessed in CD4(+) and CD8(+) T-cell subsets. In addition, IL6, IL10 and TGFbeta were measured on the level of mRNA and serum protein. Acute-rejection-free history in elderly transplant recipients was associated with short telomeres, a decreased proportion of CD28(+) T-cells associated with CMV-seropositivity and low proliferation of CD4(+) T-cells. In contrast, elderly recipients who experienced acute rejection kept preserved telomere length, had a higher number of functional CD4(+)CD28(+) cells and exhibited vigorous proliferation in vitro. These differences were not found in the young group. The major conclusion of this study is that the impaired condition of CD4(+) T-cells, so-called immunosenescence, renders transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients of > 60 years of age.

[Genetic predisposition to systemic complications of arterial hypertension in maintenance haemodialysis patients]. / Potencjalne predyspozycje genetyczne do powiklan nadcisnienia tetniczego u chorych leczonych powtarzanymi hemodializami.

UNLABELLED: Cardiovascular disease is the most common cause of a high morbidity and mortality in patients on renal replacement therapy and is responsible for about 50% of deaths. Hypertension is the main risk factor for cardiovascular events in the general population as well as in haemodialysed (HD) patients. The hypertension in HD patients is caused by excess extracellular fluid volume (ECV) on the other hand hypertension resistant to normalization of ECV may result from the accelerated activity of the systemic and local--vascular renin-angiotensin-aldosteron system (RAAS). RAAS genes are potential etiological candidates for cardiovascular damage. The aim of the study was to evaluate the prevalence of hypertension, left ventricular hypertrophy, hypertensive retinopathy in patients treated with haemodialysis and to evaluate the association between the polymorphism of RAAS genes: ACE I/D, AGT M235T AT1R A1166C, CYP112 (-344) and the systemic complications of arterial hypertension such as hypertensive retinopathy, left ventricular hypertrophy and also mortality in haemodialysis patients. MATERIAL AND METHODS: The studied population consisted of 302 HD patients (175 men, 127 women) age 21-87, mean 56, at four dialysis units. Patients with cardiac defect, advanced coronary artery disease and atrial fibrillation were excluded from the study. 62 patients died during 3,5 years of observation. Methods consisted of tree times repeated blood pressure measurements before and post dialysis, echocardiography, direct opthalmoscopy (Keith-Wegener-Barker classification of hypertensive retinopathy) and DNA analysis--genotypes ACE I/D, AGT M235T AT1R A1166C, CYP11B2 T(-344)C were determined through PCR or PCR-RFLP method. RESULTS: Hypertension was present in 72%, LVH in 84% haemodialysed patients. Arterial pressure correlated with LVMI values and hypertension was connected with LVH. Insufficient control of blood pressure and LVH were connected with worse survival in HD patients. CONCLUSIONS: It seems that I/D polymorphism ACE gene and AC AT1 gene influence the development of hypertension and LVH in HD patients. The most dangerous in the development of hypertension and LVH was DD genotype ACE gene and CC AT1 gene. ACE I/D, AGT M/T, AT1 A/C, CYP11B2 T/C polymorphism appears to have no relation to the short-term prognosis in HD patients. The mortality did not differ among groups with different genotypes of ACE I/D, AGT M/T AT1 A/C, CYP11B2 T/C polymorphisms. Direct ophtalmoscopy seems to be an insufficient method in the estimation of the systemic complications of hypertension in haemodialysed patients.