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Background: We would like to present an unusual case of simultaneous stenosis of renal graft artery and vein diagnosed four months after transplantation. both treated by stent placement. Our aim is to point at the fact that renal graft venous stenosis is very rarely reported in the literature and - as it is not easy to diagnose by routine US - it could be overlooked. If early detected it can be treated by stent placement., Case Presentation: We present a case of 36-old-male with renal failure who received a kidney graft from deceased donor. The patient experienced delayed graft function. No rejection was found in the biopsy. Four months after transplantation the kidney function deteriorated to sCr 280 µmol/l. Graft artery stenosis together with graft vein stenosis was revealed. Both lesions were dilated with stent placement, the graft function returned to 230 µmol/l and became stable for 10 years. Ten years after stent placement graft function deteriorated to 300 µmol/l. An in stent restenosis of arterial stent was detected. It was successfully dilated by the balloon, the graft function returned to 230 µmol/l and stays stable for another 5 years., Conclusions: An unusual simultaneous transplanted kidney artery and vein stenosis treated by stent placement is presented. The patient had stable graft function for 15 years after the procedure with one re-intervention on arterial stent., (© 2024. The Author(s).)

Introduction: Monoallelic variants in the ALG5 gene encoding asparagine-linked glycosylation protein 5 homolog (ALG5) have been recently shown to disrupt polycystin-1 (PC1) maturation and trafficking via underglycosylation, causing an autosomal dominant polycystic kidney disease-like (ADPKD-like) phenotype and interstitial fibrosis. In this report, we present clinical, genetic, histopathologic, and protein structure and functional correlates of a new ALG5 variant, p.R79W, that we identified in 2 distant genetically related Irish families displaying an atypical late-onset ADPKD phenotype combined with tubulointerstitial damage., Methods: Whole exome and targeted sequencing were used for segregation analysis of available relatives. This was followed by immunohistochemistry examinations of kidney biopsies, and targeted (UMOD, MUC1) and untargeted plasma proteome and N-glycomic studies., Results: We identified a monoallelic ALG5 variant [GRCh37 (NM_013338.5): g.37569565G>A, c.235C>T; p.R79W] that cosegregates in 23 individuals, of whom 18 were clinically affected. We detected abnormal localization of ALG5 in the Golgi apparatus of renal tubular cells in patients' kidney specimens. Further, we detected the pathological accumulation of uromodulin, an N-glycosylated glycosylphosphatidylinositol (GPI)-anchored protein, in the endoplasmic reticulum (ER), but not mucin-1, an O- and N-glycosylated protein. Biochemical investigation revealed decreased plasma and urinary uromodulin levels in clinically affected individuals. Proteomic and glycoproteomic profiling revealed the dysregulation of chronic kidney disease (CKD)-associated proteins., Conclusion: ALG5 dysfunction adversely affects maturation and trafficking of N-glycosylated and GPI anchored protein uromodulin, leading to structural and functional changes in the kidney. Our findings confirm ALG5 as a cause of late-onset ADPKD and provide additional insight into the molecular mechanisms of ADPKD- ALG5 ., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Kidney transplant recipients are a very vulnerable population at risk of severe course and death from Covid-19. Several antiviral drugs are now available for the treatment of nonhospitalized individuals with mild to moderate Covid-19 and hospitalized patients with severe disease. The combination of monoclonal antibodies is also available to be used as pre-exposure prophylaxis in elderly patients. Previously used monoclonal antibodies for post-exposure prophylaxis are no longer effective because of the new mutations and are no longer recommended. Although the immune response to Covid-19 vaccines is impaired in kidney transplant recipients, the effectiveness of the Covid-19 vaccines was described even in this immunocompromised group. Therefore vaccination, together with anti-epidemic measures, remains the most important tool to prevent Covid-19.

Chronic kidney disease (CKD) affects 10% of the population of developed countries and significantly affects the population health. In addition to the well-known renoprotection tools slowing down the progression of CKD, SGLT2 inhibitors have been newly introduced into clinical practice based on the results of extensive studies, both in diabetics and non-diabetics. This expert opinion discusses the classification of CKD, current renoprotection options, and the recent role of SGLT2 inhibitors in the care of patients with CKD.

BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Saláková, Ludvíková, Hamšíková, Kolářová, Šroller, Viklický and Wohlfahrtová.)

Despite an increasing quality of life after renal transplantation, the number of recipients undertaking paid professional work remains relatively low. Employment after kidney transplantation became a new important marker of clinically significant health recovery. Furthermore, for social and economic reasons, returning to work and participation in social life may be considered as an objective parameter that demonstrate the effectiveness of transplantation. The objectives of the following study were to evaluate the factors that determine resuming paid work after renal transplantation, to assess a patient's decision about returning to professional activity by comparative analysis of renal transplant recipients from Poland, Czech Republic and Germany, and to identify groups of patients exposed to professional exclusion in those EU countries. Five hundred renal transplant recipients from three EU countries were included into the study. The two main research methods used in the study were the SF-36 questionnaire, constructed and validated to assess the quality of life after kidney transplantation and a questionnaire constructed for the purposes of this study. Multifactorial analysis identified several risk factors associated with professional exclusions after kidney transplantation, namely young or advanced age, female gender, lack of education, place of residence in rural areas, long period of illness, and lack of occupational activity before transplantation. Despite the high standards of social care and rehabilitation support, patients in Germany failed to take up professional activity after kidney transplantation in more cases than those in Poland and Czech Republic. Surprisingly, the objective function of the kidney (creatinine level) and the multidimensional assessment of quality of life (SF-36 survey) did not have a significant association with the employment status after renal transplantation.

Background: Complement may contribute to donor-specific antibody (DSA)-triggered transplant injury. Here, we investigated whether the intrinsic strength of classical pathway and alternative pathway (AP) relates to the pathogenicity of DSA., Methods: Classical pathway and AP high-activity genotypes were defined according to C4 gene copy number and the presence of functional polymorphisms in C3 (C3 102G ), factor B (fB 32R ), and factor H (fH 62V ) genes. Associations of these genotypes with blood complement profiles and morphologic/molecular rejection features were evaluated in a cohort of 83 DSA-positive patients (antibody-mediated rejection [AMR], n = 47) identified upon cross-sectional screening of 741 kidney allograft recipients ≥180 days posttransplantation. Associations with long-term graft survival were evaluated in a larger kidney transplant cohort (n = 660) not enriched for a specific type of rejection., Results: In the cohort of DSA-positive subjects, the number of C4 gene copies was related to C4 protein levels in serum and capillary C4d staining, but not AMR activity. Patients with a high-activity AP complotype, which was associated with complement consumption in serum, showed enhanced microcirculation inflammation (median glomerulitis plus peritubular capillaritis score, 2 [interquartile range, 0-4 versus 1 0-2]; P = 0.037). In the larger transplant cohort, this complotype was associated with a slightly increased risk of graft loss (hazard ratio, 1.52; 95% confidence interval, 1.02-2.25; P = 0.038 and multivariable Cox model, 1.55; 1.04-2.32; P = 0.031)., Conclusions: Our study suggests a contribution of complement genetics to the phenotypic presentation of AMR. Future studies will have to clarify whether a possible association of AP strength with graft survival relates to enhanced antibody-triggered injury., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Active infection with BK polyomavirus (BKPyV) may cause serious complications in transplantation settings. Recently, the level of BKPyV IgG seroreactivity in graft donors has been shown to predict viremia and BKPyV-associated nephropathy in kidney transplant (KTx) recipients. Pretransplantation testing of the donor and recipient BKPyV serostatus could, therefore, identify patients at high risk. For the development of serological immunoassays, antibody response to the predominant BKPyV subtypes (BKPyV-I and BKPyV-IV) was studied using virus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). VLPs made from the capsid protein, VP1, derived from BKPyV-I and BKPyV-IV subtypes were produced using a baculovirus expression system and used as antigens. The tests were used for IgG antibody determination in 50 KTx recipients and 111 healthy blood donors. While 87% of samples reacted with mixed BKPyV-I and BKPyV-IV antigens, only 49% of samples were reactive in both ELISA tests when using BKPyV-I or BKPyV-IV antigens separately. Twenty-seven percent of healthy blood donors and 26% of KTx recipients were reactive only with BKPyV-I, while 9% and 20% were reactive only with BKPyV-IV, respectively. To determine the specificities of the antigens, selected seropositive samples were retested after preadsorption with soluble BKPyV-I, BKPyV-IV, or JC polyomavirus antigens. The experiments confirmed that recombinant VP1 VLP-based ELISAs predominantly detected BKPyV type-specific antibodies. The results imply that anti-BKPyV antibody ELISA tests should contain a mixture of subtype-specific VLP-based antigens instead of antigen derived from the most prevalent BKPyV-I subtype. The tests can be used for serological surveys of BKPyV infection and improved KTx patient management., (© 2019 Wiley Periodicals, Inc.)

Background: Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene ( MUC1 ) mutations (ADTKD- MUC1 ) is characterized by progressive kidney failure. Genetic evaluation for ADTKD- MUC1 specifically tests for a cytosine duplication that creates a unique frameshift protein (MUC1fs). Our goal was to develop immunohistochemical methods to detect the MUC1fs created by the cytosine duplication and, possibly, by other similar frameshift mutations and to identify novel MUC1 mutations in individuals with positive immunohistochemical staining for the MUC1fs protein., Methods: We performed MUC1fs immunostaining on urinary cell smears and various tissues from ADTKD- MUC1- positive and -negative controls as well as in individuals from 37 ADTKD families that were negative for mutations in known ADTKD genes. We used novel analytic methods to identify MUC1 frameshift mutations., Results: After technique refinement, the sensitivity and specificity for MUC1fs immunostaining of urinary cell smears were 94.2% and 88.6%, respectively. Further genetic testing on 17 families with positive MUC1fs immunostaining revealed six families with five novel MUC1 frameshift mutations that all predict production of the identical MUC1fs protein., Conclusions: We developed a noninvasive immunohistochemical method to detect MUC1fs that, after further validation, may be useful in the future for diagnostic testing. Production of the MUC1fs protein may be central to the pathogenesis of ADTKD- MUC1 ., (Copyright © 2018 by the American Society of Nephrology.)

Kidney transplantation represents the best treatment of end stage renal diseases in respect of patient survival and quality of life. Despite many advances in immunosuppression and surgical techniques, many kidney grafts are being lost in the long term, mainly due to chronic rejection and recurrence of glomerulonephritis. Calcineurin drug nephrotoxicity, which was overestimated in last decades, seems to have only minor impact on graft survival if any. Despite better understanding of mechanisms of kidney graft injuries, which are reflected by never-ending changes in histological classification systems, optimal treatment strategies are not available for majority of cases. Prospective randomized trials generated from transplant community are therefore warranted to solve many questions about the therapy.Key words: chronic rejection - kidney transplantation - nephrotoxicity - recurrence.

Aims: To determine the incidence of malignancies in renal transplant recipients (RTRs) and to analyze the association between the risk of skin cancer and immunosuppressive regiments used in the posttransplant period., Materials and Methods: A cohort study was performed on 797 RTRs. Standardized morbidity ratio (SMR) was calculated for the most common types of cancer developed in the posttransplant period and different types of immunosuppressive therapy used in the cohort., Results: 192 cases of malignancies were diagnosed in 86 RTRs (10.8%). Nonmelanoma skin cancer (NMSC) was the most frequent type of cancer (SMR = 6.42, p = 0.000), followed by renal cancer (SMR = 5.9, p = 0.000), malignant melanoma (SMR = 2.59, p = 0.080), and prostate cancer (SMR = 1.21, p = 0.593). The risk to develop NMSC was significantly higher in the group where cyclosporine has been used besides tacrolimus, mycophenolatemophetil and steroids as well as in the group treated with the combination without cyclosporine (SMR = 9.62, p = 0.001 and SMR = 5.18, p = 0.000). Furthermore, the risk was significantly higher in RTRs receiving anti-thymocyte globulin within induction therapy (SMR = 4.14, p = 0.000)., Conclusion: The preliminary results indicate that the risk of NMSC in RTRs is significantly higher than in the general population and thus emphasize the need to improve preventive strategies in the Czech transplant population., (© 2016 Wiley Periodicals, Inc.)

Secondary hyperparathyroidism is a well-known complication of end-stage renal disease (ESRD). Both nodular and diffuse parathyroid hyperplasia occur in ESRD patients. However, their distinct molecular mechanisms remain poorly understood. Parathyroid tissue obtained from ESRD patients who had undergone parathyroidectomy was used for Illumina transcriptome screening and subsequently for discriminatory gene analysis, pathway mapping, and gene annotation enrichment analysis. Results were further validated using quantitative RT-PCR on the independent larger cohort. Microarray screening proved homogeneity of gene transcripts in hemodialysis patients compared with the transplant cohort and primary hyperparathyroidism; therefore, further experiments were performed in hemodialysis patients only. Enrichment analysis conducted on 485 differentially expressed genes between nodular and diffuse parathyroid hyperplasia revealed highly significant differences in Gene Ontology terms and the Kyoto Encyclopedia of Genes and Genomes database in ribosome structure (P = 3.70 × 10 -18 ). Next, quantitative RT-PCR validation of the top differently expressed genes from microarray analysis proved higher expression of RAN guanine nucleotide release factor (RANGRF; P < 0.001), calcyclin-binding protein (CACYBP; P < 0.05), and exocyst complex component 8 (EXOC8; P < 0.05) and lower expression of peptidylprolyl cis/trans-isomerase and NIMA-interacting 1 (PIN1; P < 0.01) mRNA in nodular hyperplasia. Multivariate analysis revealed higher RANGRF and lower PIN1 expression along with parathyroid weight to be associated with nodular hyperplasia. In conclusion, our study suggests the RANGRF transcript, which controls RNA metabolism, to be likely involved in pathways associated with the switch to nodular parathyroid growth. This transcript, along with PIN1 transcript, which influences parathyroid hormone secretion, may represent new therapeutical targets to cure secondary hyperparathyroidism., (Copyright © 2016 the American Physiological Society.)

BACKGROUND Acute kidney injury (AKI) is a risk factor for adverse hospital outcomes in recipients of a heart transplantation (HTx). Timely recognition of AKI is crucial for the initiation of proper treatment. We hypothesized that serum or urine biomarkers can predict AKI. MATERIAL AND METHODS In this prospective study we evaluated 117 consecutive patients after HTx. AKI was defined as an increase of the serum creatinine level by ≥50% or a worsening of the renal function requiring renal replacement therapy during the first post-HTx week. We serially sampled serum cystatin C (S-cystatin C) as a marker of glomerular filtration and urinary neutrophil gelatinase-associated lipocalin (U-NGAL) as a marker of tubular damage. RESULTS A cohort of 30 patients (25.6%) fulfilled the criteria of AKI. S-cystatin C allowed the earliest separation between the AKI and non-AKI groups, with a significant difference present as soon as 3 h after surgery and it persisted on days 7, 10, and 30. The increase in S-cystatin C preceded the serum creatinine elevation by 4 days. In a multivariate analysis, S-cystatin C >1.6 mg/L at 3 h after HTx predicted AKI with OR 4.3 (95% CI: 1.6-11.5). U-NGAL was significantly higher at day 3 in the AKI group (p=0.003) and elevated S-cystatin C (≥2.54 mg/L on day 7) could predict 1-year mortality in these HTx recipients. CONCLUSIONS Our study showed that the measurement of S-cystatin C at 3 h after surgery may help to identify patients with high risk for renal complications. A persistent elevation of S-cystatin C also predicts 1-year mortality.

Malignant melanoma is considered to be an immunogenic tumor, which is expected to change its behaviour in the field of immunosuppression. Although the incidence of melanoma in organ transplant recipients is increased to a smaller degree than in non-melanoma skin cancer, its potential morbidity and mortality has to be considered in the posttransplant care. The aim of this review is to investigate the relationship between melanoma and immunosuppression and to discuss management strategies for different melanoma scenarios in pre-transplant as well as posttransplant period., (© 2015 Wiley Periodicals, Inc.)

The significance of borderline changes in kidney allograft biopsies is widely debated. To help resolve this, we studied differences in intrarenal gene expression patterns between early clinical and 3-month protocol biopsies, all of which had borderline histologic changes. The gene expression profiles in training set of patients by microarray analysis and data were validated in a larger cohort using RT-qPCR. There was greater expression of immunity- and inflammation-related genes in the early clinical biopsies compared to the 3-month protocol biopsies with borderline changes. In early clinically manifested borderline changes, graft deterioration within 24 months due to chronic rejection was associated with increased activation of immune, defense, and inflammatory processes. Regression modeling identified higher donor age and expression of macrophage receptor CLEC5A as risk factors for progression. In the 3-month protocol biopsies with borderline changes, graft dysfunction was associated with increased expression of fibrinogen complex transcripts. The discrimination power of fibrinogen was confirmed by cross-validation on two independent cohorts. Thus, our study highlights variations in gene expression between clinical and subclinical borderline changes despite similar histological findings. The data also support a recommendation for frequent patient monitoring, especially in those with borderline changes who received grafts from older donors.

Living donor AB0 incompatible kidney transplantation represents a new tool how to improve the access to transplantation. Majority of European protocols are based on desensitization with rituximab, triple drug immunosuppression, intravenous immunoglobulins and specific immunoads option (IA) which eliminates isohaemaglutinins. AB0i kidney transplant program was initiated in our centre in 2011 and 21 patients have received grafts from incompatible donors until recently. Highest accepted isohaemaglutinins titers before rituximab were 1 : 64 and corresponding pretransplant immunoadsorption procedures varied from 2 to 9. In 5 patients 1-2 IA procedures were performed also after transplantation. With the advent of paired exchange program the AB0i transplantation is offered to patients with unsuccessful matching run or with aim to improve HLA match between donor and recipient. The main complications were postoperative bleeding and urinary tract infections in patients at risk. Majority of protocol biopsies exhibited positivity of C4d staining. Neither graft loss nor patient death were noticed.

Background: Gene SLCO1B1, encoding solute organic anionic transport polypeptide OATP1B1, belongs to the group of candidates potentially influencing statin treatment safety. OATP1B1 regulates (not only) the hepatic uptake of statins. Its genetic variation was described as an important predictor of statin-associated myopathy in a cohort of patients treated with a maximum dose of simvastatin. However, the impact of SLCO1B1 gene polymorphism on this risk in patients treated with other statins or lower doses of simvastatin needs to be assessed. Therefore, we performed the present study., Material/methods: SLCO1B1 tagging rs4363657 polymorphism was analyzed in 2 groups of patients with dyslipidemia (treated with simvastatin or atorvastatin, 10 or 20 mg per day), subgroup with statin-induced myalgia (N=286), and subgroup (N=707) without myalgia/myopathy, and in 2301 population controls without lipid-lowering treatment., Results: Frequency of the individual genotypes in patients with myalgia/myopathy (TT=62.3%, CT=34.5%, CC=2.8%) did not significantly differ (both P values over 0.19) from that in patients without muscle symptoms (TT=61.4%, CT=32.9%, CC=5.7%) or from the population controls (TT=63.9%, CT=32.5%, CC=3.6%). Null results were also obtained for the dominant and recessive models of the analysis., Conclusions: In Czech patients treated with low statin doses, there is no association between SLCO1B1 gene polymorphism and risk of myalgia/myopathy.

Background: The purpose of our study was to determine whether renal function can be restored by early nephrostomy in patients who fail to develop renal function immediately after transplantation., Methods: Between 2001 and 2010, we have performed external/internal nephrostomy in 13 patients during the early posttransplant period. The reason for the procedure was graft nonfunction with oliguria/anuria in the presence of normal renal perfusion, absence of signs of rejection, and/or renal collecting system dilation. The nephrostomy was created under ultrasound/fluoroscopic guidance., Results: Nephrostomy was technically successful in all cases. On days 1-3 following nephrostomy creation, 10 of 13 patients showed an increase in diuresis and subsequent graft function development. Once the obstruction had been removed, the graft remained functional for months up to years posttransplantation. Three patients failed to respond to nephrostomy. There were no nephrostomy-related complications., Conclusions: Our study documents that, in patients who failed to develop graft function posttransplant for unknown reasons, nephrostomy may result in graft function development.