Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.

The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.

Orchestrating the Impact of KIR/HLA Interactions on Kidney Transplant.

This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.

Association between Human Leukocyte Antigen and End-Stage Renal Disease in Patients from Transylvania, Romania.

End-stage renal disease (ESRD) is the final stage of chronic kidney disease. This study explored the association between human leukocyte antigen (HLA) and ESRD. The interaction between genetic and environmental factors may also play a role in the development of ESRD. The study included 2392 ESRD patients who were awaiting renal transplantation. Blood samples were genotyped by SSOP and SSP-PCR methods. Multivariate logistic regression analysis showed that HLA-A*11 (p = 0.027), HLA-A*34 (p = 0.017), HLA-A*69 (p = 0.012), HLA-B*41 (p < 0.001), HLA-B*50 (p = 0.004), HLA-DRB1*10 (p = 0.027), and HLA-DRB1*14 (p = 0.004) were positively associated with ESRD (OR > 1); HLA-DRB1*07 (p < 0.001), HLA-DRB1*08 (p = 0.005), and HLA-DRB1*13 (p < 0.001) were protective against ESRD (OR < 1); and the three-locus haplotype HLA-A*02-B*41-DRB1*03, containing one susceptible allele, was strongly associated with ESRD (p < 0.001, OR = 3.15). In conclusion, this retrospective analysis of HLA typing in patients with ESRD of various etiologies suggests that molecular data on the HLA polymorphism should be collected in order to identify high-risk ESRD patients and to improve graft survival after kidney transplantation.

Comparing the First and Second Wave of COVID-19 in Kidney Transplant Recipients: An East-European Perspective.

BACKGROUND: The present study examined whether patient characteristics, management, and outcome of kidney transplant recipients (KTx) with COVID-19 changed in the second versus the first pandemic wave. METHODS: We reviewed all available data (demographics, medical history, comorbidities, therapeutic interventions, and outcome) on our KTx with COVID-19 during the first wave (March-September 2020, n = 33) and the second wave (October 2020-February 2021, n = 149) of the COVID-19 pandemic. RESULTS: One hundred eighty-two out of our 1,503 KTx in active follow-up got COVID-19 during 12-month period, corresponding to a prevalence of 12.1%. No difference was found in age, gender distribution, comorbidities, body mass index, or baseline immunosuppression between the 2 COVID-19 waves. Bilateral COVID pneumonia was more frequent during the first wave. More KTx were managed as outpatients during the second wave (15 vs. 39%, p < 0.01). Calcineurin inhibitors were more sparingly reduced during the second wave, whereas antimetabolites were similarly reduced (91 vs. 86, p = ns). Admission to intensive care units was comparable between the first (27%) and second waves (23%). During the first wave, 8 out of 9 patients (89%) requiring intensive care died, whereas the mortality of the ICU patients in the second wave was 68% (23 deaths) (p = 0.2). The overall mortality was 24% during the first wave and 16% during the second wave (p = 0.21), while in-hospital mortality was identical between the CO-VID-19 waves (27%). Increasing age and poor allograft function were significant predictors of mortality. CONCLUSIONS: Most patient characteristics and outcome were comparable between the first 2 COVID-19 waves. More KTx were managed as outpatients without an overall negative impact on outcome.

Maximizing Nephron Mass in Horseshoe Kidney Transplantation Using Inferior Epigastric Artery: Case Report.

Due to the progressive shortage of donors, kidneys with congenital anomalies are considered for transplantation. We report a successful transplantation of a split horseshoe kidney from a deceased donor by using the inferior epigastric artery with an end-to-end anastomosis, supplying the isthmus. Thus, we preserved as much as possible the functional parenchyma for a good long-term outcome. The learning point is that the use of the right inferior epigastric artery seems to be a good solution to perfuse the lower artery in order to avoid its ligation, thus reducing the nephron mass of the graft.

The use of metabolomics and machine learning algorithms to predict post-transplant diabetes mellitus in renal transplant patients on Tacrolimus therapy.

Background and aim: Tacrolimus (TAC) has significantly improved kidney graft survival following transplantation, though it is associated with adverse side effects. The most prevalent complication resulting from excessive TAC exposure is the onset of de novo diabetes mellitus (DM), a condition that can negatively impact both renal graft function and patient outcomes. De novo DM is linked to an increased risk of chronic transplant dysfunction, as well as cardiovascular morbidity and mortality. Although the underlying mechanisms remain unclear, emerging research in the field of omics shows promise. The aim of this study was to investigate the metabolomic profile of kidney transplant patients who developed de novo DM, in comparison to those who did not, following TAC exposure, using untargeted metabolomic analysis through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and machine learning algorithms. Methods: A cohort of 34 kidney transplant patients on a Tacrolimus regimen for at least 6 months was enrolled in the study, with serum samples collected from each patient. Comprehensive profiling of serum metabolites was performed, enabling the classification of patients into de novo diabetes mellitus and non diabetes groups. The metabolomic analysis of serum was conducted using UHPLC-MS. Results: Of the 34 patients, 16 were diagnosed with TAC-induced diabetes. A total of 334 metabolites were identified in the serum samples, of which 10 demonstrated a significant correlation with the de novo diabetes mellitus group. Most of these metabolites were linked to alterations in lipid metabolism. Conclusion: The application of metabolomics in kidney transplant patients undergoing a Tacrolimus regimen is both feasible and effective in identifying metabolites associated with de novo diabetes mellitus. This approach may provide valuable insights into the metabolic alterations underlying TAC-induced diabetes.

Machine learning analysis of contrast-enhanced ultrasound (CEUS) for the diagnosis of acute graft dysfunction in kidney transplant recipients.

AIM: The aim of the study was to develop machine learning algorithms (MLA) for diagnosing acute graft dysfunction (AGD) in kidney transplant recipients based on contrast-enhanced ultrasound (CEUS) analysis of the graft.Materials and methods: This prospective study involved 71 patients with kidney transplant undergoing CEUS during follow-up. AGD wasdefined as an increase in serum creatinine levels of at least 25% compared to the baseline of the last three months. The control group consisted of patients with stable kidney graft function (SGF). The top five CEUS parameters that achieved the best discrimination between the AGD and SGF groups were selected based on ANOVA testing and then employed as input for training MLA (naïve Bayes (NB), k-nearest neighbors (k-NN), and logistic regression (LR)). The models were validated by leave-one-out cross-validation. RESULTS: Among the 111 CEUS analyses, 21 corresponded to the AGD group and 90 to the SGF group. CEUS analyses yielded 44 parameters, from which five were selected: the wash out rate in segmental arteries,time to peak in segmental arteries, medullary mean transit time, renal mean transit time, and medullary time to fall. These five parameters were employed as input for MLA, yielding an AUROC of 0.68 for NB and k-NN and 0.72 for LR. The inclusion of graft survival in the MLA significantly improved discrimination accuracy, yielding an AUROC of 0.79 for NB, 0.76 for k-NN,and 0.81 for LR. CONCLUSIONS: The use of MLA represents a promising strategy for analyzing CEUS-derived parameters in the setting AGD.

HLA Diversity in Transylvanian Ethnic Groups: Consequences for Hematopoietic Cell Transplantation.

The HLA profile is essential in cell and tissue transplantation, particularly in patients with autoimmune conditions and infections. Due to the extreme polymorphism in certain HLA loci, it also serves as a key tool for population genetic analysis. This study aimed to identify the allele and haplotype distributions of HLA class I (A, B, and C) and class II (DRB1) genotypes in unrelated hematopoietic stem cell donors. A retrospective analysis was conducted between 2016 and 2020 on 9832 Transylvanian volunteers, divided into Romanian and Hungarian groups based on self-reported ethnicity. Using PCR-SSO for HLA typing, significant differences were found in allele frequencies between ethnic groups. A total of 19 HLA-A, 31 HLA-B, 14 HLA-C, and 13 HLA-DRB1 distinct allele groups were identified between ethnic groups. Notably, B*18, B*51, and C*12 were more frequent in Romanians, while B*44, B*40, and C*07 were more common in Hungarians. Differences in haplotype distributions were also observed, with HLA-A*02~B*18~C*07~DRB1*11 being significantly more frequent in Romanians. Understanding these population-specific HLA profiles can improve donor matching for hematologic diseases, enhancing patient outcomes and access to life-saving hematopoietic stem cell transplantation.

The immunologically high-risk kidney recipient in the early post-COVID-19 period. To do or not to do? A case report.

Kidney transplantation is nowadays the treatment of choice for end-stage kidney disease (ESKD), and it is the most performed organ transplantation. During the COVID-19 pandemic, kidney-transplant recipients appeared to be at higher risk of morbidity and mortality due to severe forms of illness. The result was a decrease in the number of solid organs transplants worldwide, with patients' reduced chance of receiving transplants. The best timing for surgery after COVID-19 infection is still controversial since most of the available data come from study periods with zero or low prevalence of vaccination and COVID-19 variants with high mortality rates. The American Society of Anesthesiologists (ASA) and the Anesthesia Patient Safety Foundation (APSF) Joint Statement on Elective Surgery/Procedures and Anesthesia for Patients after COVID-19 Infection states that elective surgery should be delayed for 7 weeks after a SARS-CoV-2 infection in unvaccinated patients while making no clear statement for vaccinated ones, or those which have already been infected with the virus. Kidney transplant, as opposed to tissue transplant, is not an elective surgery, so the question raised is whether to do it or not. We present the case of a hyper-immunized 47-year-old male patient with end-stage chronic kidney disease who received a second kidney transplant, despite having a mild SARS-COV 2 infection just 2 weeks before his transplantation surgery.

An Integrated Approach Using HLAMatchmaker and Pirche II for Epitopic Matching in Pediatric Kidney Transplant-A Romanian Single-Center Study.

(1) Background: Renal transplantation (KT) is the most efficient treatment for chronic kidney disease among pediatric patients. Antigenic matching and epitopic load should be the main criteria for choosing a renal graft in pediatric transplantation. Our study aims to compare the integration of new histocompatibility predictive algorithms with classical human leukocyte antigen (HLA) matching regarding different types of pediatric renal transplants. (2) Methods: We categorized our cohort of pediatric patients depending on their risk level, type of donor and type of transplantation, delving into discussions surrounding their mismatching values in relation to both the human leukocyte antigen Matchmaker software (versions 4.0. and 3.1.) and the most recent version of the predicted indirectly identifiable HLA epitopes (PIRCHE) II score. (3) Results: We determined that the higher the antigen mismatch, the higher the epitopic load for both algorithms. The HLAMatchmaker algorithm reveals a noticeable difference in eplet load between living and deceased donors, whereas PIRCHE II does not show the same distinction. Dialysis recipients have a higher count of eplet mismatches, which demonstrates a significant difference according to the transplantation type. Our results are similar to those of four similar studies available in the current literature. (4) Conclusions: We suggest that an integrated data approach employing PIRCHE II and HLAMatchmaker algorithms better predicts histocompatibility in KT than classical HLA matching.

Favipiravir in Kidney Transplant Recipients With COVID-19: A Romanian Case Series.

BACKGROUND: Favipiravir (FPV) is an orally administrable antiviral drug that selectively inhibits RNA-dependent RNA polymerase and has been repurposed for COVID-19 treatment. There is limited information on the use of FPV in kidney transplant recipients (KTx), who often have multiple comorbidities and run a higher risk for death from COVID-19. METHODS: We retrospectively reviewed all KTx at our institution who got sick with COVID-19 between March 1, 2020, and May 31, 2021, and who received FPV (loading dose of 1800 mg × 2 on day 1, maintenance dose 2  ×  800 mg/d for 5-14 days) as part of their COVID treatment. We analyzed demographics, clinical course, laboratory data, management, and outcome. RESULTS: Nine KTx with COVID-19 received FPV; all were hospitalized. The median age was 52 years (range, 32-60 years), and women were predominant (77.7%). Eight KTx had pulmonary involvement on chest radiograph. On admission 1 patient had mild, 5 had moderate, 2 had severe, and 1 had critical disease. Leukopenia and increased creatinine were universally noted. Three patients had disease progression under treatment. Seven patients (77.7%) required additional oxygen, and 4 (57.1%) needed intensive care unit admission. Three KTx died, resulting in an overall mortality of 33.3%. Survivors did not show increased transaminases or creatinine during or after FPV treatment; leukocytes, neutrophils, and platelets improved on discharge compared with admission values. CONCLUSIONS: FPV appears well tolerated by KTx with COVID-19, but its clinical benefit remains unclear. Larger analyses are needed.

The Use of Machine Learning Algorithms and the Mass Spectrometry Lipidomic Profile of Serum for the Evaluation of Tacrolimus Exposure and Toxicity in Kidney Transplant Recipients.

Tacrolimus has a narrow therapeutic window; a whole-blood trough target concentration of between 5 and 8 ng/mL is considered a safe level for stable kidney transplant recipients. Tacrolimus serum levels must be closely monitored to obtain a balance between maximizing efficacy and minimizing dose-related toxic effects. Currently, there is no specific tacrolimus toxicity biomarker except a graft biopsy. Our study aimed to identify specific serum metabolites correlated with tacrolinemia levels using serum high-precision liquid chromatography-mass spectrometry and standard laboratory evaluation. Three machine learning algorithms were used (Naïve Bayes, logistic regression, and Random Forest) in 19 patients with high tacrolinemia (8 ng/mL) and 23 patients with low tacrolinemia (5 ng/mL). Using a selected panel of five lipid metabolites (phosphatidylserine, phosphatidylglycerol, phosphatidylethanolamine, arachidyl palmitoleate, and ceramide), Mg2+, and uric acid, all three machine learning algorithms yielded excellent classification accuracies between the two groups. The highest classification accuracy was obtained by Naïve Bayes, with an area under the curve of 0.799 and a classification accuracy of 0.756. Our results show that using our identified five lipid metabolites combined with Mg2+ and uric acid serum levels may provide a novel tool for diagnosing tacrolimus toxicity in kidney transplant recipients. Further validation with targeted MS and biopsy-proven TAC toxicity is needed.

The Perspectives of Biomarkers in Predicting the Survival of the Renal Graft.

Kidney transplantation (KT) is currently the elective approach for patients with end-stage renal disease. Although it is a safe choice for these patients, the early complications can lead to graft dysfunction. One of the most redoubtable complications is delayed graft function (DGF), having no specific treatment. The effects of DGF on the graft survival are large enough to justify the formulation of specific biological protocols. Therefore, discovering biomarkers of acute impairment in renal transplanted patients is required. Creatinine is a poor marker to establish the kidney injury. Estimated glomerular filtration rate together with creatinine is ready to approximately measure the kidney function. Different serum and urine proteins are being studied as possible predictive biomarkers for delayed graft function. This review will concentrate on recent and existing research which provide insight concerning the contribution of some molecules for the estimation and evaluation of graft function after kidney transplantation. Further studies examining various aspects of DGF after KT are urgently needed to address a hitherto less-known clinical question.

COVID-19 after kidney transplantation: Early outcomes and renal function following antiviral treatment.

OBJECTIVES: The lack of effective treatments for coronavirus disease 2019 (COVID-19) has mandated the repurposing of several drugs, including antiretrovirals and remdesivir (RDV). These compounds may induce acute kidney injury and are not recommended in patients with poor renal function, such as kidney transplant (KTx) recipients. METHODS: The records of 42 KTx recipients with COVID-19 were reviewed. Some of them were receiving antiretrovirals (n = 10) or RDV (n = 8) as part of COVID-19 management. Most patients were male (71%) and their median age was 52 years. The median glomerular filtration rate in these patients was 56 ml/min. Regarding disease severity, 36% had mild disease, 19% had moderate disease, 31% had severe disease, and 12% had critical disease. Subgroups, i.e., patients receiving antiretrovirals, RDV, or no antivirals, were comparable in terms of patient age, comorbidities, and immunosuppression. RESULTS: Seven patients (16.6%) died during hospitalization. Acute kidney injury was found in 24% of KTx recipients at admission. Upon discharge, estimated glomerular filtration rate (eGFR) increased in 32% and decreased in 39% of the KTx recipients compared with the admission rate. The decrease was more prevalent in the RDV group (80%) compared with KTx recipients without any antiviral treatment (29%) (p < 0.05). Most patients (62%) returned to baseline eGFR values within 1 month of discharge. The proportion was similar between the patients receiving antiviral treatment and those not receiving this treatment. CONCLUSIONS: KTx recipients run a high risk of COVID-19-related renal impairment. Antivirals appear to be safe for use without major risks for kidney injury.

Angle grinder as surgical tool for incarcerated penoscrotal steel ring.

Penile strangulation with concomitant scrotal entrapment by a steel ring is an extremely rare urological emergency that requires immediate intervention. Any delay may lead to irreversible complications. Metal rings increase penile engorgement and are usually associated with an attempt to improve sexual pleasure or to maintain a prolonged erection. The removal of steel rings can be challenging and may require a multidisciplinary approach. We present a unique case report of an 18-year-old male with a penoscrotal steel ring retained for 24 hours that was safely removed using an angle grinder as a surgical tool.

Renal Tumors in Young Adults: Is Preoperative Computer Tomography Imaging Suggestive for the Nature of the Tumors?

Renal cell carcinoma (RCC) accounts for 2-3% of all adult malignant neoplasms and is even rarer in patients under 45 years old. Clear-cell carcinoma represents most of the pathological subtypes. Our study aimed to investigate the association between preoperative computer tomography imagistic evaluation and histopathological diagnosis of renal tumors in young adults. Patients younger than 45 years old with renal tumors who were referred for medical treatment at the Clinical Institute of Urology and Renal Transplantation Cluj-Napoca from 2012 to 2019 were considered eligible for the study. Medical charts were retrospectively reviewed, and patients with complete data regarding preoperative diagnostic, histopathological evaluation, and follow-up data, regardless of gender, were included in the study. Sixteen patients younger than 45 years fulfilled all the inclusion criteria and were evaluated. With two exceptions, the evaluated patients were in a T1 and T2 stage, with no vascular invasion or of the adjacent organs. Two-thirds of our patients had a clear-cell renal cell carcinoma. None of our patients fitted in the low complexity surgery category of the R.E.N.A.L. Nephrometry Score and 37.5% of them benefited from partial nephrectomy. Half of the suppositions made based on imaging were concordant with the histopathology report. Fifteen of the patients showed no recurrence during the respective follow-up interval. Computer tomography imaging reports showed on our sample a higher concordance with the histopathological report in the more common subtypes (namely Renal Clear Cell RCC), with typical appearances.

Difficulties in diagnosing HIV-associated nephropathy in kidney transplanted patients. The role of ultrasound and CEUS.

A 62-year-old woman who underwent kidney transplantation in 2014 was diagnosed with HIV infection in 2018. Grey scale and Doppler ultrasound evaluation revealed a normal aspect of the allograft. Contrast-enhanced ultrasound detected a quick cortical contrast uptake followed by a rapid cortical wash-out. This behavior was interpreted as a sign of inflammation. Ten months after ultrasound evaluation the graft presented severe disfunction and the patient was reintroduced into the hemodialysis program.

Contrast-enhanced ultrasonography in the initial evaluation of the kidney graft function: a pilot study.

AIM: Our study aimed to assess the usefulness of contrast-enhanced ultrasound (CEUS) in the initial evaluation of the graft function. MATERIALS AND METHOD: A cross-sectional study was conducted in the early postoperative period on patients with kidney transplantation, between September 2017 to November 2018. Two groups of patients were investigated; delayed graft function (DGF) and early graft function (EGF). All patients were examined by grey scale, Doppler ultrasound and CEUS. RESULTS: Nineteen patients, aged from 23 to 64 years (mean age 50 years), 7 in the DGF group and 12 in the EGF group were evaluated. The resistive index (RI) show significantly higher values in the DGF group at the level of upper interlobar artery (p=0.025) and medium interlobar artery (p=0.02). The CEUS investigation shows a greater region of interest (ROI) area (p=0.02) and lower values for wash-out area under the curve (WoAUC) (p=0.047) and respectively wash-in and wash-out area under the curve (WiWoAUC) (p=0.031) for the DGF group. The quality of fit (QoF) proved lower in the DGF group either for evaluation of global graft (p=0.012), cortex (p=0.025), or medulla (p=0.009).A significant relationship among all patients was found between the glomerular filtration rate (GFR) [ml/min] and the renal artery fall time (FT) [s] (p=0.012), WoAUC [a.u.] (p=0.03), and WiWoAUC [a.u.] (p=0.024). The arterial QoF [%] was associated with the arterial ROI area (p=0.048). CONCLUSIONS: Intensity CEUS parameters WoAUC and WiWoAUC may be useful to diagnose and follow-up grafts with delayed function. Additional studies on larger cohorts are required for the recommendation of CEUS as a routine evaluation of the transplanted kidney.

Shear-Wave Elastography Variability Analysis and Relation with Kidney Allograft Dysfunction: A Single-Center Study.

Shear-wave elastography (SWE) showed the absence or presence of significant differences among stable kidney allograft function and allograft dysfunction. We evaluated the variability of kidney allograft stiffness in relation to allograft dysfunction, respectively, in terms of a correlation of stiffness with patients' characteristics. A single-center prospective study on patients who had undergone renal transplantation was conducted between October 2017 and November 2018. Patients were clinically classified as having a stable allograft function or allograft dysfunction. SWE examinations performed by the same radiologist with a LOGIQ E9 were evaluated. Ten measurements were done for Young's modulus (kPa) at the level of allograft cortex and another ten at the level of medulla. Eighty-three SWE examinations from 63 patients, 69 stable allografts, and 14 allografts with dysfunction were included in the analysis. The intra-examinations stiffness showed high variability, with the quantile covariation coefficient ranging from 2.21% to 45.04%. The inter-examinations stiffness showed heterogeneity (from 28.66% to 42.38%). The kidney allograft cortex stiffness showed significantly higher values in cases with dysfunction (median = 28.70 kPa, interquartile range (IQR) = (25.68-31.98) kPa) as compared to those with stable function (median = 20.99 kPa, interquartile range = (16.08-27.68) kPa; p-value = 0.0142). Allograft tissue stiffness (both cortex and medulla) was significantly negatively correlated with body mass index (-0.44, p-value < 0.0001 for allograft cortex and -0.42, p-value = 0.0001 for allograft medulla), and positively correlated with Proteinuria/Creatinuria ratio (0.33, p-value = 0.0021 for allograft cortex and 0.28, p-value = 0.0105 for allograft medulla) but remained statistically significant only in cases with stable function. The cortical tissue stiffness proved significantly higher values for patients with allograft dysfunction as compared to patients with stable function, but to evolve as an additional tool for the evaluation of patients with a kidney transplant and to change the clinical practice, more extensive studies are needed.

Quadruple primary urogenital cancers - A case report.

INTRODUCTION: Urogenital cancers are not an uncommon occurrence in daily practice. Prostate cancer is the second most frequent cancer in men, kidney cancer accounts for 2.4% of all cancers and bladder cancers represent 3.1% of cancers in both men and women [1]. However, the cases of a simultaneous development of all three cancers, including one with a neuroendocrine component, are very few and far between. PRESENTATION OF CASE: Our case report involves a case of a patient with prostate adenocarcinoma, clear-cell renal carcinoma, papillary renal carcinoma and small-cell bladder cancer. The patient was treated as if he had separate pathologies by a multidisciplinary team: surgical and oncological, performing radical cystoprostatectomy with left perifascial nephroureterectomy, right ureterostomy and adjuvant chemotherapy, with excellent outcome even four years after the initial diagnosis. DISCUSSION: The distinct features of this case are the occurence of four different malignancies of the urogenital system, the family history of colon cancer, the development of small-cell carcinoma of the bladder, which is extremely rare and the good outcome, despite the quadruple malignancies and the aggresivity of the small-cell carcinoma. CONCLUSION: Mutiple primary malignancies are a relatively rare pathology, but should be considered as a possibility in patients who already had a second malignancy. Cases of patients with MPMs should be supervised by a multidisciplinary team and should be followed closely.