3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

3D Echocardiography - A Useful Method for Cardiovascular Risk Assessment in End-Stage Renal Disease Patients.

Patients with chronic kidney disease (CKD) have an increased risk of premature mortality, mainly due to cardiovascular causes. The association between hemodialysis and accelerated atherosclerosis has long been described. The ankle-brachial index (ABI) is a surrogate marker of atherosclerosis and recent studies indicate its utility as a predictor of future cardiovascular disease and all-cause mortality. The clinical implications of ABI cut-points are not well defined in patients with CKD. Echocardiography is the most widely used imaging method for cardiac evaluation. Structural and functional myocardial abnormalities are common in patients with CKD due to pressure and volume overload as well as non-hemodynamic factors associated with CKD. Our study aimed to identify markers of subclinical cardiovascular risk assessed using ABI and 2D and 3D echocardiographic parameters evaluating left ventricular (LV) structure and function in patients with end-stage renal disease (ESRD) (patients undergoing dialysis), patients after kidney transplantation and non-ESRD patients (control). In ESRD, particularly in hemodialysis patients, changes in cardiac structure, rather than function, seems to be more pronounced. 3D echocardiography appears to be more sensitive than 2D echocardiography in the assessment of myocardial structure and function in CKD patients. Particularly 3D derived end-diastolic volume and 3D derived LV mass indexed for body surface appears to deteriorate in dialyzed and transplanted patients. In 2D echocardiography, myocardial mass represented by left ventricular mass/body surface area index (LVMI) appears to be a more sensitive marker of cardiac structural changes, compared to relative wall thickness (RWT), left ventricle and diastolic diameter index (LVEDDI) and left atrial volume index (LAVI). We observed a generally favorable impact of kidney transplantation on cardiac structure and function; however, the differences were non-significant. The improvement seems to be more pronounced in cardiac function parameters, peak early diastolic velocity/average peak early diastolic velocity of mitral valve annulus (E/e´), 3D left ventricle ejection fraction (LV EF) and global longitudinal strain (GLS). We conclude that ABI is not an appropriate screening test to determine the cardiovascular risk in patients with ESRD.

Preparation and processing of human allogenic dermal matrix for utilization in reconstructive surgical procedures.

AIM: This article presents the development of a novel preparation and processing method as well as indication for clinical applications of human allogeneic acellular dermal matrix, which was developed originally in the Central Tissue Bank (CTB) for use in burn medicine and reconstructive surgery. METHODS: Acellular dermal matrix (ADM) is a biological material assigned for utilization in several surgical procedures due to its unique structure and advantageous properties. The article focuses on a novel preparation and processing method developed by CTB, which differs in its impact on the structure, biological and biomechanical properties of the final ADM compared to the wide range of commercially available ADM products and currently available ADM products of other tissue banks. RESULTS: The ubiquitous acellular allogeneic dermal collagen matrix is the main substance participating in advantageous properties facilitating the use of ADM in numerous indications from dermal replacement and soft tissue augmentation to more extensive surgical reconstructive procedures. Dermal substitutes play an essential role in the reconstruction of full-thickness skin defects, both in acute and chronic wounds, defects of fasciae, peritoneum, etc., and there is a strong evidence that they can improve the final scar quality as well. Differences in preparation methods of ADMs are recently causing concerns among surgeons utilizing the ADMs. We present three different cases with favourable outcomes by using human acellular ADM grafts. CONCLUSIONS: Although ADMs did not fulfil all of the requirements for an ideal dermal substitute, their applications have been advanced for diverse indications in soft tissue reconstructions and augmentations. Early revascularization of the allografts reduces bacterial contamination. Research and development of new generation of acellular dermal matrices with incorporated autologous in vitro cultured cells will likely yield new products and give new hope for continued improve-ments in functional and cosmetic outcomes (Fig. 9, Ref. 60).

Radiotherapy of prostate cancer in renal transplant recipients: single-center experience.

This study analyzed the long-term outcomes of localized prostate cancer in renal transplant recipients after radiotherapy treatment - mainly brachytherapy. We retrospectively analyzed clinical data of renal transplant recipients between 2003 and 2016 at a single tertiary center, and identified four patients with high serum PSA level during regular follow-up, 1-108 months after primary renal transplantation. The mean age of patients with detected high serum PSA level with 9.25µg/l median was 59.05 years. All four patients had functioning grafts. To prove prostate cancer, they underwent trans-rectal prostate biopsy, with no complications. Histological evaluation identified prostate adenocarcinoma (Gleason 6-7, stage T1-2cN0M0) in three patients. The biopsy in the fourth patient was negative and he therefore had trans-urethral prostate resection. Histological evaluation of resected prostate tissue revealed prostate adenocarcinoma (Gleason 7, 4+3). All patients began treatment with androgen deprivation therapy. Three patients were indicated for permanent prostate brachytherapy (BT) with iodine-125 (125I) seeds and the trans-urethral resection patient was referred for external beam radiotherapy (EBRT). After a mean follow-up of 49 months (range, 30-73), all patients, irrespective of type of radiotherapy, were in complete clinical and biochemical remission, with undetectable PSA levels. The kidney grafts remained functional, with a mean creatinine level of 99 µmol/l (range 64-123) and a glomerular filtration rate of 1.17 ml/s/1.73 m2 (range, 0.89-1.59). Radiation-induced late adverse effects were reported in two BT patients; one had clinically significant urine incontinency and the other suffered urethral stricture. Localized prostate tumor was identified in all reported patients, and all received radiotherapy plus androgen deprivation. All patients were disease-free at the time of the last follow-up. Therefore, combined BT and twelve months androgen deprivation appears both safe and effective for patients with prostate cancer after kidney transplantation.

Occurrence of malignancies after kidney transplantation in adults: Slovak multicenter experience.

Malignancies are one of the three major causes of renal recipient´s death with a functioning graft after cardiovascular diseases and infections. Among the variety of risk factors, including conventional and specific to transplant recipients, the duration of immunosuppressive therapy, the intensity of therapy, and the type of immunosuppressive agent all have an impact on development of post-transplant malignancy. The aim of our retrospective study was to document the incidence, the type of malignancies, the patient/graft survival in the group of kidney transplant recipients in Slovak Republic, and to identify the factors which influenced the outcome. We analyzed the data of 1421 patients who underwent renal transplantation from deceased or living donors in the period from 2007 to 2015 in the Slovak transplant centers. The incidence of malignant tumors was 6%, the malignancy was diagnosed in 85 patients at the age of 54.1 ± 9.8 years, more frequently in men (68.2 %; P < 0.0001). The mean time of malignancy occurrence was 45 months after transplantation. The most frequent malignancies were skin cancers- basal cell carcinoma (BCC) in 17.6%, squamous cell carcinoma (SCC) in 8.2%, and malignant melanoma (MM) in 2.4% of patients, followed by non-skin tumors such as renal cell carcinoma (RCC) in 16.5%, cancer of colon in 12.9%, prostatic cancer in 9.4%, breast cancer in 9.4%, cancer of lung in 7.1%, post-transplant lymphoproliferative disease (PTLD) in 2.4%, cancer of urine bladder in 2.4%, and cancer of sublingual gland in 1.17% of patients. Surgical treatment was used in 40% of patients, chemotherapy in 7.1%, radiotherapy in 2.4%, treatment with biological agents in 15.3%, combined therapy in 29.4% and palliative treatment in 5.9% of patients. 55.3% of patients underwent conversion from other immunosuppressive agents into mTORi at the time of malignancy occurrence. The remission was achieved in 48.2% of patients, 28.2% of patients were in the oncology treatment in the end of the year 2015, and 23.5% of patients died. There was no difference in the kidney function at the time of malignancy occurrence (s-creat 133.7 ± 59.8 µmol/l) and one year later (s-creat 131.1 ± 47.9 µmol/l) (P = 0.7768). The patients after successful treatment more frequently suffered from BCC (P = 0.0140), did not undergo palliative treatment (P = 0.0033), but were more frequently treated surgically (P < 0.0001).

Pilot Study of the Occurrence of Somatic Mutations in Ciliary Signalling Pathways as a Contribution Factor to Autosomal Dominant Polycystic Kidney Development.

Autosomal-dominant polycystic kidney disease (ADPKD) is an inherited disease that results in multiple kidney cysts, and it is a common cause of end-stage renal disease. Recent studies have shown that disease progression can be slowed by simultaneous disruption of the primary cilium and polycystins. The exact genetic mechanism of this process is still unknown. The aim of the present study was to characterize the mutation profile of ciliary signalling pathways in the renal epithelial cells of ADPKD patients. In our study, we performed an analysis of 110 genes encoding the components of Sonic Hedgehog, Hippo, Notch, Wnt and planar cell polarity signalling (PCP) by targeted next-generation sequencing. We analysed 10 formalin-fixed, paraffinembedded (FFPE) tissue samples of patients with ADPKD. We identified a unique mutation profile in each of the analysed ADPKD samples, which was characterized by the presence of pathogenic variants in eight to 11 genes involved in different signalling pathways. Despite the significant genetic heterogeneity of ADPKD, we detected five genes whose genetic variants affected most ADPKD samples. The pathogenic variants in NCOR2 and LRP2 genes were present in all analysed samples of ADPKD. In addition, eight out of 10 samples showed a pathogenic variant in the MAML2 and FAT4 genes, and six out of 10 samples in the CELSR1 gene. In our study, we identified the signalling molecules that may contribute to the cystogenesis and may represent potential targets for the development of new ADPKD treatments.

Incidence of Diabetes Mellitus After Kidney Transplantation in Slovakia: Multicentric, Prospective Analysis.

BACKGROUND: The incidence rate of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT) is 5% to 40%. The objective of this analysis was to identify the risk factors of PTDM after KT in the Slovak Republic (SR). METHODS: In the group of 133 patients/non-diabetics, we identified the risk factors of PTDM in the monitored period of 12 months from transplantation. RESULTS: The incidence of PTDM in the SR in 2014 was 38.3%. By logistic regression, we discovered that the age at the time of KT [odds ratio, 1.0885; 95% CI, 1.0222-1.1592; P = .0082], the value of body mass index (BMI) at the time of KT [odds ratio, 1.4606; 95% CI, 1.0099-2.1125; P = .0442], and the value of insulin resistance index (homeostatic model assessment for insulin resistance) at the time of KT [odds ratio, 2.5183; 95% CI, 1.7119-3.4692; P < .0001] represented predictive factors of PTDM. The independent risk factors of PTDM in our group were age at the time of KT of more than 60 years [HR 0.3871; 95% CI 0.1659-1.7767; P = .0281], waist circumference at the time of KT in men more than 94 cm and in women more than 80 cm [HR, 3.4833; 95% CI, 1.2789-9.4878 (P = .0146)], BMI at the time of KT [HR 3.0011; 95% CI 1.0725-8.3977 (P = .0363)], and triacylglycerols at the time of KT more than 1.7 mmol/L [HR, 2.9763; 95% CI, 1.0141-8.7352; P = .0471]. CONCLUSIONS: In the group of Slovak patients after kidney transplantation, the dominating risk factor for PTDM development was insulin resistance prior to KT.

Impact of Trough Levels of Tacrolimus on Kidney Function and Graft Survival in Short and Longer Periods After Renal Transplantation.

BACKGROUND: Optimizing immunosuppressive treatment in the early posttransplant period is important for achieving long-term graft function and survival. MATERIAL AND METHODS: There were 205 renal transplant recipients involved in this study. Patients were divided into groups according to the induction therapy (no induction vs basiliximab/daclizumab vs rabbit antithymocyte globulin), maintenance therapy at the time of transplantation (tacrolimus [TAC] vs cyclosporine), the average trough TAC levels in months 4 to 6 after TO and serum creatinine 5 years after renal transplantation. RESULTS: The incidence of acute rejection was significantly higher in cyclosporine than in TAC group of patients (P = .0364). The average TAC levels on elapsed time after transplantation significantly decreased (P < .0001). Five years after renal transplantation, there were higher TAC levels (5.6 ± 0.7 ng/mL) in the group with "zero" low levels than in the group with "zero" high levels (4.6 ± 1.1 ng/mL), which was statistically significant (P < .0001). We did not find any difference in graft and patient survival in posttransplant years 2 to 5 according to TAC levels or the induction treatment. CONCLUSIONS: In our study, we have confirmed that better graft function 5 years after transplantation was connected with higher trough tacrolimus levels on elapsed time after renal transplantation.

Impact of kidney transplantation on restless legs syndrome.

AIM: Our study was to assess the impact of kidney transplantation on restless legs syndrome (RLS) in end stage renal disease (ESRD) patients. METHODS: A total of 75 patients after a successful kidney transplantation (39 males, 36 females) were assessed consecutively. All patients completed the self reported questionnaire focused on RLS 6 months after kidney transplantation with investigation of selected laboratory parameters. The questionnaire met the International Restless Legs Syndrome Study Group criteria for RLS diagnosis. RESULTS: 30 (40.54%) out of 75 patients met the RLS diagnostic criteria. From this RLS positive group, 8 (26.7%) of them reported a complete regression of symptoms, 13 (43.3%) reported symptoms relief, 6 (20.0%) were without any change and 3 (10.0%) reported worsening of symptoms after kidney transplantation. In the RLS positive group, the majority of patients (26-86.7%) reported the occurrence of the symptoms in the evening and 21 (70.0%) of RLS positive patients reported the onset of symptoms after the onset of renal disease. CONCLUSION: Although the secondary RLS in EDRS patients is very common, it is often unrecognized or misdiagnosed. We concluded that kidney transplantation, except the primary benefit to kidney replacement and to its function, has a secondary impact on other conditions such as RLS (Tab. 5, Fig. 4, Ref. 17).

Analysis of HLA-G expression in serum and biopsy samples of kidney transplant recipients.

In this study, we analyzed HLA-G expression in serum and graft biopsies of renal transplant patients to find out whether there is any relationship between HLA-G and renal graft acceptance. The transplant patients were divided into two groups: those without any rejection episode (n=32) and those with acute rejection (n=33). Patient sera were collected 1 day before and at various intervals after transplantation. Soluble HLA-G (sHLA-G) in serum was determined using ELISA. In time-course experiment we found that in all patients (with and without rejection) the pre-transplantation level of sHLA-G declined in the early post-transplant period (1-2 weeks). In sera collected over 1-12 months after transplantation, a substantial increase of sHLA-G was detected in patients without rejection while no change or additional decline was observed in recipients with graft rejection. In sera collected after more than 1 year post-transplantation, sHLA-G levels increased in both groups of patients (with or without graft rejection). The time-course of serum sHLA-G antigens in patients with graft rejection was in good correlation with the course of total HLA-G mRNA determined in graft biopsy samples isolated from patients with acute rejection. We further demonstrated that serum sHLA-G values were significantly higher in patients without graft rejection than with rejection (P=0.0058). This observation supports the assumption that the increase of serum sHLA-G may contribute to allograft acceptance.

[Parvovirus B19 infection--the cause of severe anaemia after renal transplantation]. / Infekcia parvovírusom B19--prícina závaznej anémie po transplantácíi oblicky.

Anaemia belongs to the most frequent, mutlifactorial complications after kidney transplantation. Blood loss during surgery, iron deficiency, inflammation, bone marrow suppression by immunosuppressants and antiviral medication, use of angiotensin-converting enzyme and/or angiotensin receptor blockers, hyperparathyroidism, allograft dysfunction and at last viral infections participate in the development of posttransplant anaemia. Persistent aplastic anaemia after kidney transplantation could be caused by parvovirus 819 infection.

Vascular complications after renal transplantation.

BACKGROUND: Vascular complications in renal transplant recipients are uncommon but important causes of graft dysfunction and graft loss after kidney transplantation. OBJECTIVES: To document vascular complications that occurred following kidney transplantations in order to assess the incidence of these complications at our center as well as to identify possible treatment approach. METHODS: 103 kidney transplantations were performed in the period from 1 January 2008 to 31 December 2009. All patients after kidney transplantation underwent ultrasound examination (included colour Doppler flow and duplex Doppler ultrasound) immediately after surgery--especially in condition of anuria, then regularly according to an internal schedule and always in patients with worsened graft function. RESULTS: We detected renal vein thrombosis in 3 cases (2.9%), artery thrombosis in 4 cases (3.9%), one time intrarenal pseudoaneurysm (1%) and renal artery stenosis in 10 patients (9.7%). There was no extrarenal pseudoaneurysm or arteriovenous fistula in our group of patients. CONCLUSION: The incidence of vascular complications in our department correlates with the incidence of these complications referred in literature. We confirmed the importance of established immediate diagnosis and fast intervention once the diagnosis of vascular complication is established (Fig. 8, Ref. 12). Full Text in free PDF www.bmj.sk.