Insights into IL-1 family cytokines in kidney allograft transplantation: IL-18BP and free IL-18 as emerging biomarkers.

Proinflammatory cytokines and their inhibitors are involved in the regulation of multiple immune reactions including response to transplanted organs. In this prospective study, we evaluated changes in serum concentrations of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-1RA, IL-18, IL-18BP, and IL-36 beta) in 138 kidney allograft recipients and 48 healthy donors. Samples were collected before transplantation and then after one week, three months and one year, additional sera were obtained at the day of biopsy positive for acute rejection. We have shown, that concentrations of proinflammatory members of the IL-1 family (IL-1ß, IL-18, IL-36 ß) and anti-inflammatory IL-18BP decreased immediately after the transplantation. The decline of serum IL-1RA and IL-1α was not observed in subjects with acute rejection. IL-18, including specifically its free form, is the only cytokine which increase serum concentrations in the period between one week and three months in both groups of patients without upregulation of its inhibitor, IL-18BP. Serum concentrations of calculated free IL-18 were upregulated in the acute rejection group at the time of acute rejection. We conclude that IL-1 family cytokines are involved mainly in early phases of the response to kidney allograft. Serum concentrations of free IL-18 and IL-18BP represent possible biomarkers of acute rejection, and targeting IL-18 might be of therapeutic value.

The relationship between lower urinary tract dysfunctions and urinary leakage from ureterocystoneoanastomosis in male patients after kidney transplantation.

OBJECTIVES: The aim of this study was to investigate the association of lower urinary tract dysfunctions with urinary leakage from ureterocystoneoanastomosis (UCNA) after kidney transplantation. BACKGROUND: The UCNA leakage after kidney transplantation can be associated with various conditions while severe lower urinary tract dysfunctions could be one of them. METHODS: The analysis included all men who underwent kidney transplantation between January 2009 and December 2014. The parameters of storage and voiding functions were evaluated. All patients were monitored during their post-transplantation period for the incidence of urinary leakage from UCNA. Urodynamic parameters were compared between men with and without a documented leakage. RESULTS: The study cohort included 127 male patients, while UCNA leakage was observed in 11 (8.7 %) patients. Significant differences between both groups of patients were found for storage parameters (patients with leakage had smaller volume at first and a normal desire to void, smaller maximal cystometric capacity, and lower detrusor compliance) and voiding parameters (patients with leakage had a lower maximal flow rate, higher detrusor pressure at maximal flow rate and higher bladder outlet obstruction index). CONCLUSION: This study shows an association between lower urinary tract dysfunction and UCNA leakage in men without previous urological history (Tab. 2, Fig. 2, Ref. 24). Text in PDF www.elis.sk Keywords: urinary leakage, ureterocystoneoanastomosis, lower urinary tract dysfunctions, kidney transplantation.

Genome-Wide Association Study of Acute Renal Graft Rejection.

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long-term graft loss. We performed a genome-wide association study to detect loci associated with biopsy-proven acute T cell-mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort. In the discovery cohort, we found five candidate loci tagged by a number of contiguous SNPs (more than five) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor-type tyrosine kinase essential for B cell receptor signaling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium.

Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management.

Kidney transplant early venous complications managed by reperfusion and re-transplantation - salvage procedure.

We report five cases of early venous complications, all successfully rescued by graft removal, re-perfusion and re-transplantation, these kidneys would have been lost otherwise. All kidneys were from deceased donors, mean donor age was 39 years (range 29-55), with serum creatitine levels on harvesting being 81 µmol/l (65-108), glomerular filtration of 1.46 ml/s (0.82-1.83). Reasons for venous complications were following: Two cases of renal vein stenosis, another two with renal vein laceration, one renal vein thrombosis for unknown reason. All the five kidney grafts have been rescued successfully. One year's results in this group comes as mean serum creatinine level of 127 µmol/l. The described approach gives a chance to the patients with early vein thrombosis and offers the kidney graft salvage (Ref. 4).

Mechanisms and rescue strategies of calcineurin inhibitor mediated tolerance abrogation induced by anti-CD4 mAb treatment.

To ensure safety tolerance induction protocols are accompanied by conventional immunosuppressive drugs (IS). But IS such as calcineurin inhibitors (CNI), for example, cyclosporin A (CsA), can interfere with tolerance induction. We investigated the effect of an additional transient CsA treatment on anti-CD4mAb-induced tolerance induction upon rat kidney transplantation. Additional CsA treatment induced deteriorated graft function, resulting in chronic rejection characterized by glomerulosclerosis, interstitial fibrosis, tubular atrophy and vascular changes. Microarray analysis revealed enhanced intragraft expression of the B cell attracting chemokine CXCL13 early during CsA treatment. Increase in CXCL13 expression is accompanied by enhanced B cell infiltration with local and systemic IgG production and C3d deposition as early as 5 days upon CsA withdrawal. Adding different CNIs to cultures of primary mesangial cells isolated from glomeruli resulted in a concentration-dependent increase in CXCL13 transcription. CsA in synergy with TNF-α can enhance the B cell attracting and activating potential of mesangial cells. Transient B cell depletion or transfer of splenocytes from tolerant recipients 3 weeks after transplantation could rescue tolerance induction and did inhibit intragraft B cell accumulation, alloantibody production and ameliorate chronic rejection.

[Recent possibilities of treatment of End Stage Renal Disease]. / Soucasné moznosti lécby nezvratného selhání ledvin.

The End Stage Renal Disease (ESRD) represents a significant medical and economic problem. The success of longterm outcome of ESRD is dependent on the adequate nephrological care. The treatment of choice represents a kidney transplantation from a living donor or in those who haven't got such possibility, a deceased donor kidney transplantation. Recently, number of living donor kidney transplants has been increasing during last years in Europe and USA, mainly because of large awareness campaign and by using incompatible pairs. There were 361 (34.3 pmp) deceased donor and 71 (6.7 pmp) living donor kidney transplants performed while 4,050 patients benefit the life with functioning kidney graft in the Czech Republic in 2012. Hemodialysis therapy had undergone 5,772 (550 pmp) while peritoneal dialysis 489 (47 pmp) patients on December 31st, 2012.

[Biological treatment following renal transplantation]. / Biologická lécba po transplantaci ledvinv.

Renal transplantation represents a method of choice in irreversible renal failure. The outcome of renal transplantation is affected by acute or chronic rejection and long-term evaluation also suggest a role of adverse effects of immunosuppressive therapy, mainly the incidence of cardiovascular complications and tumours. Immunosuppressive therapy with biologic agents aims to reduce the incidence of acute rejections, prolong allograft survival and, consequently, patient survival. Apart from a reduction in acute rejection incidence, biological agents are used in a selected group of patients to eliminate the need for an adjunctive treatment with steroids and to reduce consequences of ischemic-reperfusion damage in older donors who suffer from a range ofco-morbidities. The most frequently used therapies include induction and anti-rejection therapy with a rabbit polyclonal anti-human thymocyte globulin (rATG) or an induction therapy with monoclonal anti-interleukin-2 receptor antibody (anti-IL2R), basiliximab. Considering the high immunosuppressive effect of rATG, adverse effects, mainly opportunistic infections and more frequent delayed tumourigenesis, have to be taken into account.

[An overview of the results of renal transplantation in the Czech Republic]. / Piehled výsledku transplantací ledvin v Ceské republice.

Renal (kidney) transplantation is now a routine and the most successful form of renal replacement therapy. There is a long tradition of renal transplantation in the Czech Republic, The first was performed as early as 1961 in Hradec Kralove, and the programme as such was launched in 1966 with the first successful transplantation at the Institute of Experimental Surgery (later Institute for Clinical and Experimental Medicine, Prague). At present, transplantations are being performed at 7 transplantation centres (IKEM Prague, Centre for Cardiovascular and Transplantation Surgery Brno, Faculty Hospitals Hradec Kralove, Plzen, Olomouc and Ostrava and Faculty Hospital Motol for children). From the programme launch until the end of 2010, 8,761 renal transplantations were performed, 364 in 2010 alone. One-year patient and cadaver renal allograft survival, transplanted in the CR between 2000 and 2009, is around 95% and 92%, respectively, and 5-year survival is 87% and 81%, respectively. As of 31st December 2009, a total of 3,771 patients lived with functional renal allograft in the Czech Republic and the proportion of patients with irreversible renal failure treated with transplantation has recently been around 40%.

Antibody-mediated rejection of renal allografts: diagnostic pitfalls and challenges.

Antibody-mediated rejection (ABMR) is a major obstacle to the long-term success in kidney transplantation. Diagnosis of ABMR is determined according to the internationally recognized Banff criteria. However, a significant proportion of patients does not meet all the defined criteria, and the outcome of such cases remains poorly understood. The histology of ABMR frequently lacks sensitivity and specificity. More importantly, mixed forms of ABMR and T cell-mediated rejection as well as findings of nonspecific injury are common in clinical settings. Donor-specific anti-HLA antibodies (DSA) are detectable only in half of the ABMR cases by histology. Prognostic role of non-HLA antibodies against various endothelial proteins has been discussed. Antibody independent NK cell activation reflecting killer-cells' inhibitory receptor incompatibility is suggested in microvascular inflammation in DSA negative patients. Molecular assessment of ABMR has been prioritized to overcome high interobserver variability and improve diagnostics in mixed forms of rejections and in DSA negative cases. Finally, donor-derived cell-free DNA detected in a recipient's peripheral blood sample has been proposed as a noninvasive marker for diagnosis of graft rejection, and thus might serve as a liquid biopsy in the near future. Despite all achievements, diagnosing ABMR in kidney allografts remains to be a challenge in a significant number of cases.

Changes in phenotypic patterns of blood monocytes after kidney transplantation and during acute rejection.

Peripheral blood monocytes, which serve as precursors for tissue macrophages and dendritic cells (DC), play a key role in the immune response to kidney allograft, reparation processes and homeostasis regulation. In this prospective study, we used multicolor flow cytometry to monitor the phenotypic patterns of peripheral monocytes in subjects with uncomplicated outcomes and those with acute rejection. We found a reciprocal increase in the proportion of "classical monocytes" (CD14+CD16-) along with a decline in pro-inflammatory "intermediary" (CD14+CD16+) and "non-classical" (CD14lowCD16+) monocytes in subjects with normal outcomes. In subjects with acute rejection, we observed no reduction in "intermediary" monocytes and no increase in "classical" monocytes. Patients with uncomplicated outcomes exhibited downregulated HLA-DR in all three monocyte subpopulations. However, non-classical monocytes were unaffected in subjects with acute rejection. Expression of CD47 was downregulated after transplantation, while patients with antibody-mediated rejection and donor-specific antibodies showed higher pre-transplant values. In monocytes isolated at the time of biopsy, CD47 expression was higher in individuals with acute rejection compared to patients with normal outcomes one year post-transplant. Expression of CD209 (DC-SIGN) and the proportion of CD163+CD206+ subpopulations were upregulated during the first week after kidney transplantation. CD209 was also upregulated in samples taken on the day of biopsy confirming acute rejection. Our data demonstrate that kidney allograft transplantation is associated with phenotypic changes in peripheral blood monocytes during acute rejection.

SARS-CoV-2 viral load assessment in lung transplantation.

In the era of COVID-19 pandemic, organ transplantation programs were facing serious challenges. The lung transplantation donor pool was extremely limited and SARS-CoV-2 viral load assessment has become a crucial part of selecting an optimal organ donor. Since COVID-19 is a respiratory disease, the viral load is thought to be more important in lung transplantations as compared to other solid organ transplantations. We present two challenging cases of potential lung donors with a questionable COVID-19 status. Based on these cases, we suggest that the cycle threshold (Ct) value should always be requested from the laboratory and the decision whether to proceed with transplantation should be made upon complex evaluation of diverse criteria, including the nasopharyngeal swab and bronchoalveolar lavage PCR results, the Ct value, imaging findings and the medical history. However, as the presence of viral RNA does not ensure infectivity, it is still to be clarified which Ct values are associated with the viral viability. Anti-SARS-CoV-2 IgA antibodies may support the diagnosis and moreover, novel methods, such as quantifying SARS-CoV-2 nucleocapsid antigen in serum may provide important answers in organ transplantations and donor selections.

Leflunomide derivate FK 778 in accelerated renal injury in transgenic rat.

Renal ischaemia/reperfusion (I/R) injury and hypertension represent major alloantigen-independent risk factors contributing to the development of chronic allograft nephropathy. In a model of accelerated major histocompatibility complex-independent renal injury, we evaluated the effect of leflunomide derivate - FK778 - on the progression of accelerated nephropathy. Thirty-six uninephrectomized hypertensive transgenic (m-REN-2)-27 rats received a clip on renal pedicle for 45 minutes. Animals were treated with FK778 3 mg/kg/day (I/R 3 mg, N = 12), 10 mg/kg/day (I/R 10 mg, N = 12) or placebo (N = 12) via gavage for 16 weeks. Eighteen animals were sham-operated and treated with FK778 3 mg/kg/day (sham 3 mg, N = 6), 10 mg/kg/day (sham 10 mg, N = 6) or were untreated (sham, N = 6). Proteinuria and blood pressure were evaluated throughout and the kidneys were harvested for morphological and immunohistochemical analysis at the end of the experiment. At week 16, rats with I/R injury and FK778 treatment had lower proteinuria compared with placebo-treated rats (I/R 3 mg: 48.42 +/- 26.16, I/R 10 mg 27.28 +/- 21.86 vs. Placebo: 70.13 +/- 50.19 mg/day, P < 0.05). The untreated sham group exhibited lower proteinuria compared with FK778-treated sham groups (Sham 3 mg: 24.23 +/- 10.89; Sham 10 mg: 17.37 +/- 4.13; Sham: 14.23 +/- 1.18) There was no difference in glomerulosclerosis and interstitial fibrosis among the treated groups. In the untreated animals the rate of interstitial fibrosis decline reached statistical significance (Placebo vs. Sham: 1.125 +/- 0.641 % vs. 0.250 +/- 0.500 %, P < 0.05). There was higher CD5+ leukocyte infiltration in the placebotreated group. FK778-treated rats displayed amelioration of some changes induced by the I/R injury. Our observation also suggests potential nephrotoxicity of FK778.

Molecular Assessment of Kidney Allografts: Are We Closer to a Daily Routine?

Kidney allograft pathology assessment has been traditionally based on clinical and histological criteria. Despite improvements in Banff histological classification, the diagnostics in particular cases is problematic reflecting a complex pathogenesis of graft injuries. With the advent of molecular techniques, polymerase-chain reaction, oligo- and microarray technologies allowed to study molecular phenotypes of graft injuries, especially acute and chronic rejections. Moreover, development of the molecular microscope diagnostic system (MMDx) to assess kidney graft biopsies, represents the first clinical application of a microarray-based method in transplantation. Whether MMDx may replace conventional pathology is the subject of ongoing research, however this platform is particularly useful in complex histological findings and may help clinicians to guide the therapy.

Up-regulation of CD163 expression in subpopulations of blood monocytes after kidney allograft transplantation.

M2 macrophages expressing CD163 are known to suppress immune responses but have been also found in biopsies of patients with chronic kidney allograft injury associated with interstitial fibrosis. The aim of our study was to evaluate the expression of CD163 in blood monocytes, precursors of tissue macrophages, in kidney allograft recipients with uncomplicated outcome (n=94) compared with those developing acute rejection (n=44). Blood samples were collected before the transplantation and at 1 week, 1 month and 1 year. The expression of CD163 increased during the first week after the transplantation not only in classical (CD14+CD16-) but also in intermediate (CD14+CD16+) and nonclassical (CD14lowCD16+) monocytes in all patients regardless of their rejection status. In patients developing acute rejection, higher pre-transplant expression of CD163 on blood monocytes was found. In vitro experiments confirmed strong induction of membrane CD163 on monocytes together with CD206 (an alternative marker of M2 macrophages) in response to IL-10. We assume from our data that dramatic upregulation of CD163 by peripheral blood monocytes may have a pathophysiological role in early phases after kidney allograft transplantation and high pre-transplant expression of CD163 on blood monocytes might be involved in events leading to acute rejection.

Fetuin-A early after renal transplantation.

BACKGROUND: Fetuin-A is a major inhibitor of ectopic calcium phosphate precipitation and an acute phase reactant. Its deficiency, common in end-stage renal disease, has been suggested to be associated with cardiovascular complications. The aim of this study was to monitor fetuin-A levels in the early period after renal transplantation. METHODS: 30 deceased donor kidney recipients treated with calcineurin inhibitor-based immunosuppression were followed prospectively for the first 3 months and the association of fetuin-A levels with clinical and laboratory parameters was evaluated. RESULTS: Despite a correlation of fetuin-A levels with creatinine clearance (r = 0.348, p < 0.01) and estimated GFR (r = 0.331, p < 0.01), no significant increase in fetuin-A levels over the first 3 months was observed. Moreover, a significant decrease in serum fetuin-A levels was noted at 2 weeks (p < 0.001). Subsequently, fetuin-A levels increased (p < 0.001) reaching pretransplant values at month 3. CONCLUSIONS: In this study there was no increase of fetuin-A levels during the first 3 months, but a decrease 2 weeks after transplantation was observed.

Long-term peritoneal dialysis treatment provokes activation of genes related to adaptive immunity.

Permanent irritation of the peritoneum during peritoneal dialysis (PD) treatment leads to local chronic inflammation and subsequently activation of processes driving fibrogenesis in the long-term. The aim of the study was to compare the peritoneal effluent transcriptome of 20 patients treated less and 13 patients treated more than 2 years using microarray analysis. An increased expression of genes associated with an immune response was observed in long-term treated patients with well preserved peritoneal function, when compared to patients treated less than 2 years. From 100 genes highly expressed in long-term patients, a significant up-regulation of six was found by RT-qPCR: LY9 (lymphocyte antigen 9), TNSFR4 (tumor necrosis factor receptor superfamily, member 4), CD 79A (CD79a molecule), CCR7 (chemokine C-C receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor alpha chain). Furthermore, the effluent cell population was analysed. A positive relationship between the number of granulocytes and NK cells on one hand, and duration of PD treatment on the other, was shown. We conclude, that the mechanisms of adaptive immunity promoting T helper 2 cells response are activated in the long-term before functional alterations develop. It consequently might trigger the fibrosis promoting processes.

The incidence of infectious diseases after renal transplantation: a single-centre experience.

This single-centre study was designed to investigate the incidence of infections and their causative pathogens during the first three months after renal transplantation (RTx) in patients who had undergone the procedure in 2005 (n=174). We compared this group of patients with a previous one (1998-2000, n=437). In 2005, infection was diagnosed in 82 patients (47%). Symptomatic lower urinary tract infection (UTI) was present in 43 patients (25%), pyelonephritis in 15 (8.6%), and urosepsis in 7 (4%). Wound infection developed in 21 patients (12%), cytomegalovirus (CMV) disease in 15 (8.6%), and pneumonia in 5 (3%). The most frequent pathogens in UTI were Klebsiella pneumoniae and Enterococcus faecalis. Pathogens of wound infection included Staphylococcus coagulase negative and K. pneumoniae. Pneumonia was frequently caused by Mycoplasma pneumophila. Compared with the previous group, we noted decreases in the total number of infections (77.7 vs. 47%, P<0.001), pneumonia (8.5 vs. 3%, P<0.02) and UTI (33.3 vs. 24.7%, P<0.05). We observed an increased incidence of multiresistant Klebsiella. Based on these results, we have changed our scheme of antibiotic prophylaxis and the algorithms of antibiotic treatment. We reduced the use of antibiotics with an adverse epidemiological effect (quinolones, third-generation cephalosporins) and increased the use of relatively safe antibiotics (penicillins, aminopenicillins, with and without beta-lactam inhibitors).

Aortoiliac reconstruction with allograft and kidney transplantation as a one-stage procedure: long term results.

OBJECTIVES: An increasing number of aortoiliac lesions and abdominal aortic aneurysms occur in renal failure patients waiting for renal transplantation. The aim of our study was to assess long term results of simultaneous renal transplantation and surgical repair of aortoiliac lesions with arterial allografts. DESIGN: A retrospective observational study. PATIENTS AND METHODS: From October 1997 to June 2007, we performed simultaneous aortoiliac reconstructions using fresh arterial allografts and kidney transplantation in 14 patients with chronic renal failure (men 9, women 5, mean age 53 years). The indication for vascular reconstruction was an asymptomatic abdominal aneurysm in 6 patients or aortoiliac stenosis/occlusion in 8 patients. The median follow up period for the cohort was 55.5 months (range from 1 to 116 months). RESULTS: Three patients died during the follow up period. In none of them there was an allograft (neither arterial nor renal) related death. No signs of arterial grafts infection or aneurysmal formation and no need for secondary intervention (angioplasty and/or thrombolysis) of any arterial reconstruction was observed during the follow up period in any patient. The renal grafts failed in three patients. CONCLUSIONS: Our experience suggests that it is possible and safe to use arterial allografts in the treatment of arterial occlusive disease or abdominal aortic aneurysm simultaneously with renal transplantation.

Influence of VEGF polymorphism on progression of autosomal dominant polycystic kidney disease.

BACKGROUND: Significant phenotypical variability is observed in autosomal dominant polycystic kidney disease (ADPKD). Dysregulation of vascular endothelial growth factor (VEGF) expression in the kidney has been demonstrated in a wide range of renal diseases. The aim of the present study was to assess the influence of the -2578 C/A and the -1154 G/A polymorphisms in the regulatory region of the VEGF gene upon the progression of ADPKD toward end-stage renal disease (ESRD). METHODS: The study was performed on 283 ADPKD patients (145 males, 138 females, mean age 51.7 +/- 10.3 years) who had reached ESRD. Patients were divided into three groups: (1) ESRD development later than in 63 years (slow progressors, n = 47), (2) ESRD development before 45 years (rapid progressors, n = 69), and (3) ESRD development between 45 and 63 years (intermediate progressors, n = 167). Genetically unrelated healthy Czech individuals were analyzed as a control group (n = 311, 153 males, 158 females, mean age 44.6 +/- 9.2 years). DNA samples were genotyped for the -2578 C/A and for the -1154 G/A polymorphisms of the VEGF gene promoter. The serum levels of VEGF were established in 111 healthy Czech individuals from the control group. RESULTS: The VEGF -2578 C/A and -1154 G/A genotype distribution showed no differences among the groups of slow, rapid and intermediate progressors. The age of ESRD with regard to different genotypes was not significantly different in all ADPKD patients. However, the AA genotype of the -2578 C/A polymorphism was associated with a significantly higher age of ESRD than other genotypes in rapid progressors (42.7 vs. 40.5 years, p = 0.01). The CG haplotype was found significantly more frequent in ADPKD rapid progressors than in slow progressors (p = 0.047). Serum levels of VEGF did not significantly differ in the control group, according to different genotypes of both polymorphisms. CONCLUSION: To conclude, AA genotype of the -2578 C/A polymorphism was related to better prognosis of the disease in a limited group of ADPKD patients. Classical genetic recessive and dominant model did not find significant influence of separate VEGF polymorphisms on the progression of ADPKD. Accordingly, CG haplotype was associated with earlier onset of ESRD in ADPKD patients.