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Percutaneous nephrostomy is a first-line minimal invasive treatment option for ureteral obstruction following kidney transplantation, with high effectiveness and a low complication rate. Percutaneous nephrostomy might be used as a temporary salvage therapy, providing acute decompression of the kidney collecting system and preventing graft loss. It can also function as a permanent and sometimes only possible option in transplant patients with frequent recurrences of ureteral stenosis who either fail an open surgical reconstruction or who are not good candidates for these procedures. We present two patients with acute decline in urine output after renal transplantation with radiologically verified hydroureteronephrosis of the transplanted kidney (graft) caused by stenosis of distal ureter. In both cases, nephrostomy was placed within 48 hours as a temporary salvage treatment that ameliorates renal function and prevents graft loss. The permanent nephrostomy was the only possible solution for the preservation of the graft’s function in the first case because of the recurrences of ureteral stenosis after several percutaneous interventions and open-surgery ureteral reconstruction. A few episodes of nephrostomy tube-related infections were resolved with antibiotics in the first case. The second case was treated with open ureteroneocystostomy with resection of stenotic segment and reinsertion of the ureter into the bladder (ureterocystoneostomy) because of the length of the involved ureteral segment. Both patients had stable graft function in the follow-up period.

Background Diabetic retinopathy (DR) is a microvascular complication of diabetes highly associated to cardiovascular disease and diabetic kidney disease. However, these associations are not thoroughly investigated at an early type 2 diabetes disease stage. This study therefore evaluated the association between baseline DR status and development of cardiovascular events (CVEs), microalbuminuria, and kidney function decline and in persons with type 2 diabetes and normal urinary albumin excretion. Methods Post-hoc analysis of the PRIORITY study including 1758 persons with type 2 diabetes and normoalbuminuria followed for a median of 2.5 (IQR: 2.0–3.0) years. The study was originally designed to investigate a urinary proteomic risk classifier predictor of microalbuminuria development. DR at baseline was defined as non-proliferative and proliferative abnormalities, macular oedema, or history of laser treatment. Cox models were fitted to investigate the association of DR status with development of 1) a CVE composite defined as non-fatal myocardial infarction, stroke, coronary artery bypass graft, percutaneous coronary intervention, hospitalization for heart failure, or all-cause mortality; 2) persistent microalbuminuria (urinary albumin-creatinine ratio > 30mg/g); and 3) chronic kidney disease (CKD) G3 (eGFR 2). Models were adjusted for relevant risk factors. Results At baseline, 304 (17.3%) had DR. Compared to persons without DR, they were older (mean ± SD: 62.7 ± 7.7 vs 61.4 ± 8.3 years, p = 0.019), had longer diabetes duration (17.9 ± 8.4 vs. 10.6 ± 7.0 years, p 1c (62 ± 13 vs. 56 ± 12 mmol/mol, p

Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced mainly in osteocytes. In chronic kidney disease (CKD) FGF23 levels increase due to higher production, but also as the result of impaired cleavage and reduced excretion from the body. FGF23 has a significant role in disturbed bone and mineral metabolism in CKD, which leads to a higher cardiovascular risk and mortality in these patients. Current research has emphasized the expression of FGF23 in cardiac myocytes, fibroblasts, and endothelial cells, and in addition to the effects on the kidney, its primary role is in cardiac remodeling in CKD patients. Recent discoveries found a significant link between increased FGF23 levels and anemia development in CKD. This review describes the FGF23 role in cardiac hypertrophy and anemia in the setting of CKD and discusses the best therapeutical approach for lowering FGF23 levels.

Although kidney transplantation is the best treatment option for end stage kidney disease, it is still associated with long-term graft failure. One of the greater challenges for transplant professionals is the ability to identify grafts with a high risk of failure before initial decline of eGFR with irreversible graft changes. Transplantation medicine is facing an emerging need for novel disease end point-specific biomarkers, with practical application in preventive screening, early diagnostic, and improved prognostic and therapeutic utility. The aim of our review was to evaluate the clinical application of urinary proteomics in kidney transplant recipients at risk for any type of future graft failure.

Complex coronary artery disease is the leading cause of death in patients with end-stage renal disease. We report a case of a patient on peritoneal dialysis, preloaded with Prasugrel and acetylsalicylic acid as а potent dual antiplatelet therapy (DAPT). The patient underwent a high-risk percutaneous coronary intervention (PCI) due to bifurcation stenosis of the left main stem branch. A “double kiss crush” bifurcation stenting technique was performed. This case provides additional data about the treatment of this group of patients, a group that is often excluded from randomized control trials, but is frequently encountered in cardiovascular practice. Furthermore, it helps to advance PCI treatment along with exploring the safety of potent DAPT in a group that is susceptible to both ischemia and bleeding, thus presenting a great challenge in the decision for treatment.

The determination of blood flow rate (BFR) is a useful tool for assessing the function of arteriovenous fistula (AVF).Eighty patients with a newly created radio cephalic AVF were analyzed. Hemodynamics and morphological characteristics of the blood vessels were assessed by Doppler ultrasound.The mean age of patients was 59.9 ± 13.5 years. A successful rate of AVF maturation was 62.5% at 8 weeks. Six adjusted models of multivariate analysis showed that BFR at Day 1 was a predictor for AVF maturation both at 4 weeks (p 0.001) and 8 weeks (p 0.001). Receiver operating characteristic analysis showed an optimal cut-off point for BFR at Day 1 of 395 ml/min for successful maturation at 4 weeks (sensitivity 0.714, specificity 0.889) and 344 ml/min for successful maturation at 8 weeks (sensitivity 0.860, specificity 0.867).BFR at Day 1 is a powerful predictor for successful AVF maturation at 4 and 8 weeks.

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients., Graphical Abstract Graphical abstract

Although early rejection episodes are successfully controlled, the problem of unrecognized production of de novo anti-HLA antibodies and associated chronic rejection still persists.In addition to the standard induction and maintenance therapy, we present a couple of new drugs as induction (Alemtuzumab), CNI-free protocol (Belatacept, Sirolimus, and Everolimus), and maintenance treatment in transplant patients with various types of malignancies (T cell-targeted immunomodulators blocking the immune checkpoints CTLA-4 and PD1/PDL1) and TMA (aHUS)-eculizumab and IL6 receptor antagonists in antibody-mediated rejection (AMR).There are a couple of issues still preventing improvement in kidney transplant long-term outcomes with current and anticipated future immunosuppression: patients more susceptible to infection and CNI nephrotoxicity in kidneys obtained from elderly donors and highly sensitized patients with limited chances to get appropriate kidney and a higher risk for late AMR. A lower rate of CMV/BK virus infections has been observed in everolimus-treated patients. Belatacept use has been justified only in EBV-seropositive kidney transplants due to the increased risk of PTLD. Eculizumab upon recurrence of aHUS is a sole cost-effective option. A new IL-6 blocking drug (clazakizumab/tocilizumab) is a promising option for prevention/treatment of AMR. Clinical experience in tailoring immunosuppression for improving as long as possible graft and patient survival is inevitable.

The discovery of nephrin in 1998 has launched a new era in glomerular diseases research, emphasizing its crucial role in the structure and function of the glomerular filtration barrier. In the past 20 years, substantial advances have been made in understanding podocyte structure and function as well as the discovery of several podocyte-related proteins including nephrin. The glomerular filtration barrier is comprised of podocytes, the glomerular basement membrane and endothelial cells. Podocytes, with their specialized slit diaphragm, form the essential backbone of the glomerular filtration barrier. Nephrin is a crucial structural and functional feature of the slit diaphragm that prevents plasma protein, blood cell and macromolecule leakage into the urine. Podocyte damage results in nephrin release. Podocytopathies are kidney diseases in which podocyte damage drives proteinuria, i.e., nephrotic syndrome. Many kidney diseases involve podocytopathy including congenital nephrotic syndrome of Finnish type, diffuse mesangial sclerosis, minimal change disease, focal segmental glomerulosclerosis, collapsing glomerulonephropathy, diabetic nephropathy, lupus nephropathy, hypertensive nephropathy and preeclampsia. Recently, urinary nephrin measurement has become important in the early detection of podocytopathies. In this chapter, we elaborate the main structural and functional features of nephrin as a podocyte-specific protein, pathomechanisms of podocytopathies which result in nephrinuria, highlight the most commonly used methods for detecting urinary nephrin and investigate the diagnostic, prognostic and potential therapeutic relevance of urinary nephrin in primary and secondary proteinuric kidney diseases.

BACKGROUND AND AIMS Doppler Ultrasound (DUS) is a superior tool for the assessment of arteriovenous fistula (AVF) functionality. The aim of the study was to determine the association between morphological and haemodynamic characteristics of the blood vessels with AVF maturation. METHOD The study was prospective that analysed 80 patients with chronic kidney disease (CKD) stage 4/5 and CKD stage 5 on haemodialysis (CKD5D) with newly created radio cephalic AVF. Haemodynamics and morphological evaluation of blood vessels by DUS was performed in all patients. The diameter of the cephalic vein, radial and brachial artery was measured: before creation, on the first day (24-h after creation) and at 4 weeks. The blood flow (BF) rate of AVF was calculated by DUS on day 1, at 4 and 8 weeks. The successful maturation of AVF was defined with BF ≥ 600 mL/min. RESULTS The mean age of the patients was 59.9 ± 13.5 years, of which 46 (57.50%) were males. Successful AVF maturation at 4 weeks was 43.75% and 62.5% at 8 weeks. The results of six adjusted models in multivariate analyses showed BF rate on day 1 was a predictor for AVF maturation at 4 (P CONCLUSION Our study showed that BF rate of AVF on day 1 was a predictor for AVF maturation at 4 and 8 weeks. The diameter of blood vessels and male gender were statistically associated with AVF maturation.

Background: A new medium cut-off (MCO) membranes has been designed to achieve better removal capacities for middle and large middle molecules in hemodialysis (HD) treatment. Aim: The aim of this study was to evaluate the removal efficacy of Theranova® in standard HD in comparison with standard high-flux HD. Methods: Four HD patients (M/F 1/4) were included in 12-week observational pilot study in HD with Theranova® 400 and Theranova® 500 dialyzers. Each patient was assessed 4 times, T0 with high-flux dialyzers, T1 at 1 month, T2 at second month, and T3 at third month, by measuring pre- and post-HD samples of urea, Cr, β2-microglobilin (β2M), myoglobin, albumin, free light chains kappa (FLC-k), and free light chains lambda (FLC-λ). Results: The data showed a higher average removal rate for all the uremic toxins with Theranova® dialyzers for β2M, myoglobin, FLC-k, and FLC-λ (62.7, 56.9, 63.5, and 54.6%, respectively) during the 3 months. Albumin retention was observed and did not change between T0 and T3 (p = 0.379). Conclusion: Compared to high-flux membranes, MCO membranes show greater permeability for middle molecules in midterm report.

Introduction. Podocyte injury has been reported as an early feature of DN therefore, the assessment of podocyte injury can be accomplished by estimation of podocalyxin in urine. This study aimed to estimate the urinary podocalyxin levels and to determine the sensitivity and specificity of this biomarker for early detection of DN. Materials and methods. A total of 90 patients with type 2 diabetes mellitus (T2DM) were included in this cross-sectional study. Sixty of them were without diagnosed DN, and 30 with diagnosed DN. A control group consisted of 30 healthy subjects. All patients with T2DM were divided into three subgroups according to urinary microalbumin/creatinine ratio (UM/CR): normoalbuminuric, microalbuminuric and macroalbuminuric patients. Urine samples, were used for measurement of podocalyxin by ELISA, creatinine and microalbumin. Fasting venous blood samples was collected for biochemical analyses. Results. The levels of urinary podocalyxin (u-PDX) were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied subgroups regarding u-PDX was found (p < 0.05). Levels of u-PDX are increasing gradually with the degree of DN (p < 0.029). u-PDX levels were positively correlated with UM/CR (r = 0.227, p = 0.002). A cut-off level of 43.8 ng/ml u-PDX showed 73.3% sensitivity and 93.3% specificity to detect DN in early stage. A cut-off level of 30 mg/g UM/CR showed 41.5% sensitivity and 90% specificity in predicting DN. u-PDX was elevated in 48,2% of normoalbuminuric patients. Conclusion. Urinary podocalyxin be useful and more sensitive and specific marker in early detection of DN than microalbuminuria.

The Macedonian Society for Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) was established on September 1, 1992 in order to stimulate the development of nephrology and to unite experts from all professions interested in the research and treatment of kidney patients. Momir H. Polenakovic was elected President of MSNDTAO. The First congress of MSNTAO was held in Ohrid from October, 7 to 10, 1993 in hotel “Desaret” under the auspices of the first President of R. Macedonia, Kiro Gligorov. During the Congress, the Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was formed on October 9, 1993. The idea of cooperation with the Department of Nephrology from the Ege University, Izmir, R. Turkey was promoted. Some of the presented papers were published in the Proceedings “Nephrology ’93” as a supplement to the Macedonian medical review. The “Doctrine for performing nephrological activity in the Republic of Macedonia” was also promoted. The Second congress of MSNDTAO was held in Struga, R. Macedonia from September, 6 to 10, 1997 together with the Second BANTAO Congress. Selected papers were printed in the Macedonian Medical Review. The Third congress of MSNDTAO was held from May, 30 to June 2, 2001 in Skopje, at the Macedonian Academy of Sciences and Arts (MASA). Proceedings of papers was also published. In 2011 M. H. Polenakovic was elected Honorary President of MSNDTAO for life, and Goce Spasovski was elected the current President of MSNDTAO. The Fourth congress of MSNDTAO was held in Ohrid from June, 21 to 24, 2012 together with the Fourth Meeting of the South-Eastern European Pediatric Nephrology Working Group (SEEPNWG). The Fifth congress of MSNDTAO was held from June, 9 to 12, 2016 in Skopje, at MASA together with the 6th Southeastern European Pediatric Nephrology Working Group (SEPNWG) Meeting and IPNA (International Pediatric Nephrology Association) Teaching Course. The VIII Macedonian-Croatian Nephrology Days were also held during the Congress. The Sixth congress of MSNDTAO was held from September, 26 to 29, 2019 along with the 15th BANTAO Congress, in Skopje, at MASA. The Congress also marked the 80th anniversary of the birth of M. H. Polenakovic. Apart from the participants from R. Macedonia, the congress was attended by renowned nephrologists from Europe and the world. A novelty of the last congresses was the organization of 9 CME (Continuing Medical Education) courses with famous lecturers. CME courses supported by the ERA-EDTA and / or the ISN were as follows: 2005 - Ohrid (BANTAO), 2006 - Skopje (MSNDTAO), 2009 - Skopje (MSNDTAO), 2010 - Skopje (ERA-EDTA - ESAO), 2011 Skopje (ERA-EDTA - EUTox group), 2012 - Ohrid (MSNDTAO), 2014 -Skopje (MSNDTAO), 2016 - Skopje (MSNDTAO), 2018 - Skopje (MSNDTAO - ERA-EDTA & ISN), 2019 - Skopje (BANTAO - ISN & ERA-EDTA). In addition to the congresses, MSNDTAO has held meetings with nephrological associations from the neighboring countries as Croatia, Serbia, Albania and Kosovo. The congresses of MSNDTAO contributed to the introduction and education of doctors in the diagnosis and treatment of kidney patients. They were a strong stimulus for the development of nephrology in R. Macedonia and beyond.

A bone biopsy of the anterior iliac crest is the gold standard for the evaluation of bone disease in chronic kidney disease (CKD). The bone histomorphometric analysis consists of a detailed description of bone histology, including skeletal remodeling, bone mineralization, and bone microarchitecture. Like many histopathological diagnostic classifications (e.g. Banff), bone histomorphometry is based on a semi-quantitative assessment, utilizing both quantitative cutoffs of key parameters and a qualitative interpretation by an experienced physician.

Prof. Dr. Dimitar T. Hrisoho was born on June 11, 1924 in Bitola, R. Macedonia. He died in Struga on September 22, 1986, and was buried in Skopje. He completed primary and secondary education in Bitola. He graduated from the Medical Faculty in Belgrade in 1951 as one of the best students of his generation (average grade of 9.75). In 1953 he was employed at the Internal Clinic of the Medical Faculty in Skopje, where in 1955 he passed the specialist exam in internal medicine. He successfully defended his habilitation “Polyarthritis chronica evolutiva” and his doctoral dissertation “Clinical features of Vitina nephropathy”. The doctoral dissertation indicates that Vitina nephropathy is a new site of the Balkan Endemic Nephropathy entity and that more genetic testing of patients were needed. Based on numerous clinical and scientific researches published in over 200 papers, he was elected a Full Professor of internal medicine at the Medical Faculty of the Ss. Cyril and Methodius University in Skopje in 1971. In 1970, he formed the nephrology section of the Macedonian Medical Association (MMA), which grew into the nephrology Association of MMA. Through the Association, the education of the medical staff from the field of nephrology was performed. He also set up a bio-cybernetics association. He achieved his vision and desire to transfer and apply the achievements of modern nephrology in the diagnosis and treatment of kidney patients in Macedonia at the Clinic of Nephrology of the Medical Faculty in Skopje, which was the first specialized institution established for examination and treatment of kidney patients in the former Yugoslavia and the Balkans. The Clinic educated nephrological staff and examined and treated kidney patients with new methods and drugs that positively affected the development of nephrology as a subspecialty of the internal medicine. D. Hrisoho was actively involved in the introduction of new methods for examination of kidney patients, as well as in the treatment of patients with acute and chronic renal insufficiency with dialysis since 1965. He also participated in the first two kidney transplantations from living donors performed in 1977. He wrote a chapter on “kidney examination”, printed in the book of Prof. A. J. Ignjatovski “Fundamentals of Internal Propedeutics” Part III, published by “Prosvetno delo”, 1963, in Skopje. This is the first text to investigate a patient with kidney disease published in a textbook in R. Macedonia. In 1984 he published the textbook “Clinical Nephrology” printed by the University of the Ss. Cyril and Methodius University in Skopje. Prof. D. Hrisoho organized the First Scientific Meeting of Yugoslav Nephrologists with international participation, from 26 to 28 September 1977, in Struga, R. Macedonia. The meeting was attended by prominent nephrologists from the former Yugoslavia, the Balkans, Europe and the United States, among them: J.S. Cameron from UK, J.L. Funck-Brentano from France, M. Burg and P. Ivanovich from the USA, R. Kluthe from Germany and A. Puchlev from Bulgaria. The scientific meeting was the largest nephrology event until then organized in the former Yugoslavia. The meeting provided an exchange of experiences with world-renowned nephrologists. D. Hrisoho presented the paper Artificial intelligence in nephrology. The author tried to apply bio-cybernetics in nephrology. Prof. D. Hrisoho was Vice Dean of the Medical Faculty in Skopje in the period 1963-1965 and Vice Rector of the University of the Ss. Cyril and Methodius University in Skopje in the period 1974-1975. Prof. Hrisoho was also active in socio-political organizations. For his medical, educational and scientific activities he received several awards and recognitions in the country and abroad. Thus, the work of Prof. D. Hrisoho was permanently embedded in the nephrology of R. Macedonia.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has recently emerged in the world. There are limited data describing the clinical progression of COVID-19 in transplanted patients. In the general population, clinical presentation ranges from asymptomatic infection to severe pneumonia and may also develop renal failure. In kidney transplant (KT) patients, management of these patients was mainly based on anecdotal experience. CASE REPORT: We report our first experience of KT patients with COVID-19. A 49-year-old male with KT in 2017 presented on March 20, 2020, with fever, weakness, smell loss, chest pain, and caught. On chest X-ray, he presented ground-glass opacities and bilateral pneumonia. There was a slight progression to acute hypoxic respiratory failure. We reduced immunosuppression therapy and since we suspected seasonal flu, we applied available antiviral oseltamivir till confirmation of RNA sequence of the SARS-CoV-2 virus. Moreover, we applied azithromycin and broad spectrum of antibiotics as well as an anticoagulant therapy. Graft function remained stable during 14 days of hospitalization. The patient clinically improved with decreasing oxygen requirements and manifested clinical recovery. After two negative PCR test, he was discharged and immunosuppression therapy was returned to previous. CONCLUSION: This case highlights the importance of earlier outpatient hospitalization and testing which may improve COVID-19 outcomes among transplanted patients.

Introduction: Asymptomatic hypoglycaemia has been reported in both diabetic and non-diabetic patients on haemodialysis. Uremic symptoms as inadequate appetite, nausea and vomiting worsen the risk of hypoglycaemia at dialysis initiation. As a standard therapeutic approach for decreasing this risk and dis-equilibrium syndrome at our dialysis unit, a continuous venous 5% glucose solution is applied during the glucose-free dialysate (GFD) dialysis. In this interventional study we sought to assess the glycaemic control during standard initiating dialysis protocol versus novel approach with glucose-rich dialysis fluid (GRD). Material and methods: Twenty-one dialysis patients with chronic renal failure were dialyzed alternatively using GRD (5.6 mmol/l) and GFD fluid. They were not taking any hypoglycaemic medication prior and food during dialysis session. Blood was sampled at regular intervals during dialysis. The dialysis prescription consisted of ultrafiltration (UF) of up to 1 L, membrane surface (MS) up to 1.4 square meters and duration time of 2-2.5 hours. Intra-patient glycaemic variability was defined by Coefficient of variation (CV). In paired analysis t-test was used to determine the glucose control differences in both therapeutic approaches in each patient. For the whole group t-test was used to assess the glucose variability as CV. Results: The mean age of study participants was 62.95±11.73 years; 7 (33%) had diabetes. The two dialysis approaches did not differ in respect of initial blood pressure, UF and MS. Only two episodes of hypoglycaemia occurred in both types of dialysis. The mean glucose level was higher during GRD (8.15±1.89 vs. 6.29±1.33, p=0.001), respectively. The glucose CV was lower in GRD dialysis when pared t-test was applied, without significant difference (16.97± 8.86 vs. 21.05±11.99, p=0.151). When only diabetic patients were analysed, there was no significant glucose CV difference as well (p=0.151). For the whole cohort glucose variability was significantly higher in glucose-free dialysate dialysis (p=0.0001). Conclusion: The GRD approach for initiating dialysis sessions is non-inferior to standard GFD care. Dialysate rich in glucose obtains better glucose control during dialysis compared to glucose-free dialysate.

The Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was established in Ohrid, Republic of Macedonia on October 9, 1993 during the First Congress of the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO). The idea of the founders was that such Society would have a clear impact on several aspects of practice and research in nephrology and artificial organs in the Balkans, firstly, by increasing its international visibility and potential collaborative work, and recognition by international organizations. Secondly, such a society would facilitate the exchange of experience and knowledge between experts in our area. In addition, it would be a very positive symbolic act showing that collaborative work for the betterment of life is possible and desirable in our area and that coming together will bear better fruits at the human and cultural levels. It will also send a very clear signal to the outside world that the Balkans can be a place of collaboration and mutual understanding. Several international bodies such as the International Society of Artificial Organs and the International Faculty of Artificial Organs have signaled their interest in and support for the creation of such a society. Despite the turbulent times in the Balkan Peninsula, the First BANTAO Congress was held in Varna from September 22 to 24, 1995, which was an impressive event. F. Valderrabano, Chairman of the EDTA–ERA registry reported on that event with a lot of sympathy in the paper entitled “Nephrologists of the Balkan countries meet across political frontiers and war fronts – an example to politicians. The foundation of and the Second Congress of BANTAO were also well accepted by the colleagues nephrologists from Russia. The Second Congress was held on September 6-10, 1997 in Struga, the Third BANTAO Congress was held on September 18-20, 1998 in Belgrade, the Fourth Congress of BANTAO was held in Izmir on November 14-16, 1999, the Fifth Congress of BANTAO was held in Thessaloniki on September 30 – October 3, 2001, the 6th BANTAO Congress was held in Varna, on October 6-9, 2003, the 7th BANTAO Congress was held in Ohrid, on September 8-11, 2005, the 8th BANTAO Congress was held in Belgrade, on September 16-19, 2007, the 9th BANTAO Congress was held in Antalya, November 18-22, 2009, the 10th BANTAO Congress was held in Chalkidiki, October 13-15, 2011, the 11th BANTAO Congress was held from 26 to 29 September 2013 in Timisoara on the 20th Anniversary of the foundation of BANTAO, the 12th BANTAO Congress was held on October 15-18, 2015 in Opatija, the 13th BANTAO Congress was held on 4-8 October, 2017 in Sarajevo, the 14th BANTAO Congress was held on September 20-23, 2018, in Budva and the 15th BANTAO Congress was held in Skopje, 26-29 September 2019. Another milestone in the life of BANTAO was the appearance of the BANTAO journal in 2003, which has been published biannually since then. In the past 17 years there have been 33 editions of the journal and seven supplements reporting BANTAO congresses. The editors of the journal past and present are: 2003–2005 (Dimitar Nenov); 2005–2009 (Ali Basci); 2009–(Goce Spasovski). Up to date, more than 400 papers have been published. The BANTAO journal is registered on EBSCO, DOAJ, SCOPUS, and has become a strong ‘glue’ among nephrologists from the Balkan cities. The BANTAO congresses and the BANTAO journal have succeeded in elevating nephrology knowledge and thus increased the standards of nephrology patient care throughout the Balkans. Standing above the divisive forces of politics, language and war, BANTAO gives a living example that collaboration and humility are feasible in times of maddening destruction, and are transformative.

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut-brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system. Funding Agencies|COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT)

BACKGROUND: COVID-19 prediction models based on clinical characteristics, routine biochemistry and imaging, have been developed, but little is known on proteomic markers reflecting the molecular pathophysiology of disease progression. METHODS: The multicentre (six European study sites) Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection Study (Crit-COV-U) is recruiting consecutive patients (≥ 18 years) with PCR-confirmed SARS-CoV-2 infection. A urinary proteomic biomarker (COV50) developed by capillary-electrophoresis-mass spectrometry (CE-MS) technology, comprising 50 sequenced peptides and identifying the parental proteins, was evaluated in 228 patients (derivation cohort) with replication in 99 patients (validation cohort). Death and progression along the World Health Organization (WHO) Clinical Progression Scale were assessed up to 21 days after the initial PCR test. Statistical methods included logistic regression, receiver operating curve (ROC) analysis and comparison of the area under the curve (AUC). FINDINGS: In the derivation cohort, 23 patients died, and 48 developed worse WHO scores. The odds ratios (OR) for death per 1 standard deviation (SD) increment in COV50 were 3·52 (95% CI, 2·02-6·13, p

Background Kidney transplantation is the best treatment option for end-stage kidney disease but is still associated with long-term graft failure. In this study, we evaluated the application of urinary proteomics to identify grafts with high failure risk before initial decline of estimated glomerular filtration rate (eGFR) with irreversible graft changes. Methods Fifty-two living donor kidney transplant recipients (KTR) with 8-year follow-up were enrolled. All patients underwent clinical examination and had a routine laboratory screening at 3, 6, 12, 24, 36, 48 and 96 months post-transplantation, including creatinine, urea, albumin and 24-h proteinuria. Graft function was estimated according to Nankivell. Urine samples at Month 24 were analysed by capillary electrophoresis coupled mass spectrometry followed by classification with the chronic kidney disease classifier CKD273. Results CKD273 showed significant correlation with serum creatinine at every time point and moderate inverse correlation for the slope in glomerular filtration rates by Nankivell (r = −0.29, P = 0.05). Receiver operating characteristics analysis for graft loss and death within the next 6 years after proteomic analysis resulted in an area under curve value of 0.89 for CKD273 being superior to 0.67 for Nankivell eGFR. Stratification into CKD273-positive and -negative patient groups revealed a hazard ratio of 16.5 for prevalence of graft loss in case of CKD273 positivity. Conclusions Using a representative KTR cohort with 8-year follow-up, we could demonstrate significant value of CKD273 for risk stratification of graft loss. This study provides the conceptual basis for further evaluation of CKD273 as a prognostic tool for long-term graft function risk stratification by large prospective clinical trials.

Fibroblast growth factor-23 (FGF23) appears to be one of the most promising biomarkers and predictors of cardiovascular risk in patients with heart disease and normal kidney function, but moreover in those with chronic kidney disease (CKD). This review summarizes the current knowledge of FGF23 mechanisms of action in the myocardium in the physiological and pathophysiological state of CKD, as well as its cross-talk to other important signaling pathways in cardiomyocytes. In this regard, current therapeutic possibilities and future perspectives are also discussed.

The aim of the study is to review recent studies on the management of acute and chronic hyponatremia.In acute symptomatic hyponatremia, bolus infusion of hypertonic saline improves hyponatremia and neurological status more quickly than continuous infusion. In chronic hyponatremia, newly identified predictors of nonresponse to fluid restriction include a high urine osmolality (500 mOsm/kg) and high urine sodium (133 mmol/l). Vasopressin-receptor antagonists effectively raise the serum sodium concentration in patients with euvolemic or hypervolemic hyponatremia but have a risk of overcorrection, even at low doses. Several observational studies now support the use of urea for a more gradual correction of hyponatremia without a risk of overcorrection. Recently identified risk factors for overcorrection include lower serum sodium at presentation, polydipsia, hypovolemia, and early urine output during treatment. Specific treatments with potential efficacy are the use of intravenous albumin for hyponatremia because of liver cirrhosis, and fludrocortisone for hyponatremia in tuberculous meningitis.The recent data will help to further optimize and personalize the management of patients with acute and chronic hyponatremia. However, most data are still observational and retrospective. Therefore, the field is in need of prospective studies comparing interventions for chronic hyponatremia and focusing on patient-relevant outcomes.

World Kidney Day (WKD) is a global campaign to raise awareness of the importance of our kidneys to overall health and to reduce the frequency and impact of kidney disease and associated health problems worldwide. Kidney disease is a non-communicable disease (NCD) and currently affects around 850 million people worldwide. One in ten adults has chronic kidney disease (CKD). The global burden of CKD is increasing, and is projected to become the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume 2–3% of the annual healthcare budget in high-income countries. Crucially, kidney disease can be prevented and progression to end-stage kidney disease can be delayed with appropriate access to basic diagnostics and early treatment. This year World Kidney Day continues to raise awareness of the increasing burden of kidney diseases worldwide and to strive for kidney health for everyone, everywhere. During the pandemic with COVID 19 patients kidneys are also damaged, apart from the respiratory tract and other organs. It can lead to an increase in acute renal failure and consequent chronic kidney insufficiency, as well as number of deaths. Therefore, it is important to evaluate the renal function in each patient with COVID 19 virus. In the Republic of North Macedonia from 2006 to present day nephrologists and other medical personnel devoted to the early diagnosis, prevention and treatment of renal disease have participated in the activities of the World Kidney Day. These activities were supported by the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs, the Department of Nephrology at the Medical Faculty, the Macedonian Academy of Sciences and Arts, the Government of the Republic of North Macedonia, non-governmental nephrology organizations (NEFRON) and the media. There were lectures and presentation devoted to the various theme of the WKD, publications in journals, as well as activities for examination of the renal function of patients in the medical centers. The activities during the WKD contributed to the improvement of the nephrological protection of the citizens of the Republic of N. Macedonia.

Tuberous sclerosis complex (TSC) is an autosomal-dominant multi system disorder. The genetic basis of the disorder is mutations in the TSC1 or TSC2 gene, which leads to over activation of the mammalian target of rapamycin (mTOR) protein complex and results in development of benign tumors in different body systems such as brain, skin, lungs and kidney. The mTOR inhibitors are presently the main treatment option for patients with TSC. We here report a 21-year female patient with large bilateral angiomyolipoma (AML) in both kidneys with longest diameter more than 12.3 cm and subependymal giant cell astrocytoma (SEGA). Treatment with everolimus (EVE) was initiated at a dose of 10.0 mg/day and continued during the following 3 years. Magnetic resonance imaging (MRI) was performed before treatment with everolimus was initiated, and consequently at 12 and 36 months for follow-up of the efficacy of the treatment. After 3 years, the total size of largest AML decreased by ~24.0% in the longest diameter. A reduction of the total size of SEGA was also observed. The most common adverse effect of treatment was stomatitis grades 3 to 4 and one febrile episode associated with skin rash that required a reduced dose of EVE. In conclusion, the everolimus treatment improved even such a large renal AML and the effect persisted during the long-term administration with a small number of adverse effects. A positive effect was observed on the brain tumor as well.

In patients with critical or mild COVID19 (WHO stages 6-8 [n=53] and stages 1-3 [n=66]), 593 urinary peptides significantly affected by disease severity were identified, reflecting the molecular pathophysiology associated with the course of the infection. The peptide profiles were similar compared with those observed in kidney disease, a prototype of target organ damage with major microvascular involvement, thereby confirming the observation that endothelial damage is a hallmark of COVID19. The clinical corollary is that COVID19 is an indication for anti-oxidative, anti-inflammatory and immunosuppressive treatment modalities protecting the endothelial lining.

Chronic renal failure; Dialysis; Kidney transplantation Insuficiència renal crònica; Diàlisi; Trasplantament de ronyó Insuficiencia renal crónica; Diálisis; Trasplante de riñón Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3–5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease–related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs. The treatment of kidney failure is costly, therefore financial support from governments is essential to ensure that all patients receive appropriate treatment. This imposes a major burden on the economy. According to the World Bank, only 74% of governments in Eastern and Central Europe provide full support for KRT [7]. Funding of treatment in earlier stages of CKD is even more problematic because of the high number of patients and because the diagnosis may not be made in a timely manner. Although no objective data are available, it is very likely that public funding at earlier stages of CKD is less common or, at least, less comprehensive than reimbursement of KRT.

BACKGROUND: Excess mortality is defined as mortality above what would be expected based on the non-crisis mortality rate in the population of interest. AIM: In this study, we aimed to access weather the coronavirus disease (COVID)-19 pandemic had impact on the in-hospital mortality during the first 6 months of the year and compare it with the data from the previous years. METHODS: A retroprospective study was conducted at the University Clinic of Nephrology Skopje, Republic of Macedonia. In-hospital mortality rates were calculated for the first half of the year (01.01–30.06) from 2015 until 2020, as monthly number of dead patients divided by the number of non-elective hospitalized patents in the same period. The excess mortality rate (p-score) was calculated as ratio or percentage of excess deaths relative to expected average deaths: (Observed mortality rate–expected average death rate)/expected average death rate *100%. RESULTS: The expected (average) overall death mortality rate for the period 2015–2019 was 8.9% and for 2020 was 15.3%. The calculated overall excess mortality in 2020 was 72% (pscore 0.72). CONCLUSION: In this pragmatic study, we have provided clear evidence of high excess mortality at our nephrology clinic during the 1st months of the COVID-19 pandemic. The delayed referral of patients due to the patient and health care system-related factors might partially explain the excess mortality during pandemic crises. Further analysis is needed to estimate unrecognized probable COVID-19 deaths.

An arteriovenous fistula (AVF) remains the best choice of vascular access (VA) for hemodialysis (HD). The aim of the study was to determine the factors associated with the achievement of adequate blood flow (BF) of AVFs at the 4th week after creation. Created AVFs in 63 patients with chronic kidney disease (CKD) stage 4/5 and CKD stage 5 on hemodialysis (CKD5D) were analyzed in a prospective study. Doppler ultrasound (DUS) was used for measuring the diameter of the radial artery, the brachial artery and the cephalic vein before AVF creation. The BF of AVF was calculated by DUS at the 4th week after creation and adequate BF was defined as ≥ 600 mL/min. The average age of patients was 61.31 ± 12.9 years. An adequate BF of AVF at the 4th week after creation was achieved in 43.54% of patients. The BF of AVF measured in male patients was significantly higher compared to the BF of AVF obtained in females (576.03 mL/min vs 375.12 mL/min, P = 0.004). The diameter of the blood vessels with achieved adequate BF was significantly larger compared to the diameter of the blood vessels without adequate BF (radial artery: 2.45 mm vs 2.03 mm, P = 0.000; brachial artery: 4.78 mm vs 4.06 mm, P = 0.001 and cephalic vein: 3.12 mm vs 2.83 mm P = 0.018). The gender and the diameter of the blood vessels before AVF creation were significantly associated with achievement of adequate BF of AVF at the 4th week of creation.

Background and Aims HLA compatibility between donor and recipient is an important factor that influences graft outcomes after kidney transplantation. Increasing number of class I (HLA-AB) and class II (HLA-DR) mismatches are associated with an increased risk of acute rejection and graft loss. Recent developments have increased our understanding of the structural basis of HLA antigenicity and may allow accurate evaluation of the immunogenic potential of broad antigen HLA mismatches. The immunogenicity of HLA antigens is determined by continuous and discontinuous short sequences of amino acids that form the antibody-accessible regions within each HLA allele known as epitopes. HLAMatchmaker, a computer algorithm that calculates the number of epitope mismatches between donors and recipients by considering each HLA allele as a combination of distinct epitopes known as triplets (continuous amino acid sequences) or eplets (closely located contiguous amino acid sequences). Method A total number of 55 adult patients with LDKT were included in the study. The inclusion criteria: first transplantation of one organ - kidney, use of living donor related or unrelated, emotionally related (spouses) donor. Data concerning donor - sex, age of the donor, type of donation (related or unrelated donor), and data concerning the recipients: sex, age, hemodialysis vintage, underlying disease, type of immunosuppressive therapy, were analyzed. The number of eplet HLA mismatches for each recipient and donor pair at HLA class I (HLA-AB) and class II (HLA-DR) loci was calculated using HLAMatchmaker (Version 1.2) Results In our study we have included 55 patients. 44 patients have related and 11 have unrelated donors. From the group of related donors 31 patients were haploidentycal, with 3 HLA miss match, in the group of unrelated donors-recipients 5 of them have 6 miss match. According HLA MM triplets Class 1 + 2 < or> 20 we have devided 2 groups, but no statistical difference on the graft function was observed in the follow up period. Three acute rejections were reported in the group of patients with HLA miss match triplets Class 1 + 2> 20. Conclusion An increasing number of epitope HLA mismatches is associated with an increased risk of acute rejection. Triplet HLA mismatches may provide better risk stratification for acute rejection and graft survival among those who are otherwise classified as low immunological risk at the broad antigen level.

Background and Aims An arteriovenous fistula (AVF) remains the best choice of vascular access (VA) for hemodialysis (HD). The aim of our study was determination of factors associated with achieved adequate blood flow (BF) of AVF during 4-th week after creation Method : Created AVF in 63 patients with chronic kidney disease (CKD) stage 4, 5 and 5-HD were analyzed in the prospective single center study, from January 2019 to October 2019. Preoperative mapping of blood vessels by Doppler ultrasound (DUS) on the forearm was performed in all patients. All patients were undergoing surgical creation of new forearm AVF (radio-cephalic) by one doctor. The DUS was used for measuring the diameter size of artery radialis, artery brachialis and vein cephalica before creation of AVF and again on 1-st day, 2-nd and 4-th week after AVF creation. In addition the BF of AVF was also measured by DUS on 1-st day, 2-nd and 4-th week after AVF creation. The adequate BF of AVF for hemodialysis treatment was defined as ≥ 600 ml/min. Patient gender and age, hemodialysis vintage, diameter size of artery radialis, artery brachialis and vein cephalica before creation of AVF were analyzed as factors that were affecting the achieved BF of AVF during 4-th week after creation. Results : The average age of patients was 61.31 ± 12.9 years. From all patients, 60.31% (38/63) were men. The adequate BF of AVF (≥600 ml/min) during 4-th week after creation was achieved in 43.54% (27/63) of created AVFs. The blood flow of AVF measured in male gender was significantly higher compared to the blood flow of AVF measured in female gender (576.03 ml/min vs 375.12 ml/min, p=0.004). The age of the patients and hemodialysis vintage were not significantly associated with achieved adequate BF of AVF during 4-th week after creation of AVF. The adequate BF of AVF was achieved in blood vessels with bigger diameter size. The diameter size of the blood vessels with achieved adequate BF was significantly higher compared to the diameter size of the blood vessels without adequate BF (artery radialis : 2.45 mm vs 2.03 mm, p=0.000; artery brachialis: 4.78 mm vs 4.06 mm, p=0.001 and vein cephalica: 3.12 mm vs 2.83 mm, p=0.018). Conclusion The gender and the diameter size of artery radialis, artery brachialis and vein cephalica before creation of AVF were significantly associated with achieved adequate BF of AVF (≥600 ml/min) during 4-th week after creation of AVF.

Background and Aims The life expectancy in dialysis patients depends on patients’ age and comorbidities. Frailty in elderly patients is a state of impaired homeostasis with loss of physiologic reserve and a consequent impaired responses to dialysis burden. In this study we assessed the impact of age, comorbidities and frailty on dialysis patients’ survival. Method The study enrolled 162 prevalent patients on chronic hemodialysis with mean dialysis vintage of 100 months, 55% were women and 21 % had diabetes. Patients were divided into three groups by the Khan Comorbidity index score, highest score was considered worse. Frailty was assessed by presence of 3 or more symptoms (unintentional weight loss, feeling exhausted, weak grip strength, slow walking speed and low physical activity) and expressed as absolute number. Estimates of five years life expectancy were assessed by Kaplan Meier survival log-rank test and Cox regression hazard model. Results There were 26 (16%) with lowest score, 85 (52%) with medium score and worst highest score in 51 (31%). During the 5 years of follow up 69(43%) patients died of all-cause mortality. There were no deaths in the group with lowest score and mortality rates in the intermediate and worse score group increased by double (0; 30%; 69%, respectively). Significantly higher mean life expectancy was found in lower Khan Score groups: 60mo; 48.40 ± 18.51; 32.44 ± 22.06, log-rank: p < 0.012. Patients that scored worse had four folds higher risk for death HR 4.2 (95% CI: 2.72 – 6.36), p=0.0001. In the multivariate model Khan Score was a more powerful predictor of mortality than frailty in elderly, with HR 3.2 (95% CI: 2.88 – 5.41), p=0.0001. Conclusion Comorbidities and age outperforms frailty burden as a predictor of mortality in dialysis patients.

Background and Aims After the first year following kidney transplantation approximately 3-5% of grafts fail each consecutive year. Many factors have impact on the graft function and only a few may be modifiable. Monitoring of the graft function by serum creatinine concentrations and estimated glomerular filtration rate (eGFR) are recommended methods for evaluation. The aim of the study was to assess the decline of graft function defined by change in the annual eGFR slope and factors that might affect it. Method A total number of 55 adult patients with living donor kidney transplant (LDKT) were included in the study. The inclusion criteria were: first transplantation of one organ - kidney, use of living donor related or unrelated (emotionally related - spouses) donor. Clinical and biochemical variables, serum creatinine, BUN, protein status, 24 hours proteinuria and body weight were analyzed at 12, 24, 36 and 48 months after transplantation. The Nankivell equation for estimating glomerular filtration rate was used to calculate the slope of renal function over time (1 to 4 years post-transplantayion) by linear regression analysis. Results Out of 55 kidney transplant recipients 18 (33.3%) were female. The majority of transplants had good function (eGFRNankivell ≥ 60 ml/min) at 1 year. The average GFR at 12 months was 67.81±16.7 mL/min/1.73 m2 with majority of patients at stage 2 of chronic kidney disease classification. Thirty eight patients had eGFR slope 5ml/min/year). Only 5 patients (∼ 9%) have graft failure during the period of follow up of 48 months. The average slope decline calculated with linear regression analysis was -3.42 ± 3.2 mL/min/year (range -12.38 – 3.29 ) (slope ± standard error). Proteinuria was predictive for worsening of the graft function. Rapid progressors have been associated with a higher proteinuria at 24 and 48 months: 0.35 ± 0.39 g/24h, median 0.24 (range 0.11 – 0.43 g/24h) and 0.49 ± 0.59 g/24h, median 0.31 (range 0.14 – 0.48 g/24h), (p=0.044 and p=0.021, respectively). Younger patients have more rapid eGFR slope decline (slope (-7.81 ± 2.12 vs. -2.40 ± 1.3, mL/min/year, p=0,0001). The mean recipient age in the group with stabile eGFR slope was 37.59± 8.7, and in the group with rapid progression was 29.1 ± 8.6 years (p=0.0046). Conclusion Proteinuria after kidney transplantation has been identified as a risk factor associated with poor graft survival. Younger renal transplant recipients are associated with more rapid decline of the graft function that could be partially explained with their more potent immune response

Background and Aims Kidney size has been found to be correlated with anthropometric features and is different among different ethnicities. In this study, we used ultrasonography for measurement of kidney volumes in healthy individuals and evaluated the relationships with body height, age and gender. Method We conducted a cross-sectional observational study and evaluated 108 healthy individuals whose serum creatinine level was within reference range. Patients’ medical clinical and laboratory records were reviewed. Age, gender and height were recorded. Pearson correlation coefficients were used to evaluate the strength of association between ultrasonographic parameters with each other and with other parameters, and were expressed as r2. Variations in left and right renal dimensions between various age groups were compared using a one-way analysis of variance, followed by a post-hoc Tukey's test. Results Subjects’ age ranged from 16 to 84 years and the mean age was over 50 years. There was an equal distribution among genders. Strong and positive correlations were seen for the measured length, parenchyma thickness and also for both total and parenchymal volumes with subjects’ height for both kidneys. The strongest correlations were observed for the left and right kidney length and also for the right kidney parenchymal volume (r=0.536, p=0.001; r=0.469, p=0.001; r=0.44, p=0.001). On the opposite, most of the relations with age were negative, but week and insignificant. When we divided the study subjects into three age groups and compared them for the height, there was no significant difference among them. Regarding the parenchymal and total kidney volumes of both kidneys, the different age groups showed similar findings in the ultrasonographic measurements. The mean calculated volumes were slightly declining with age and showed the largest values in the first group of patients under 30 years and lowest values in patients over 70 years old. Ultrasonographic measurements were also compared among the two genders. Both (men and women) showed similar age (53.55 ± 18.22 vs. 50.79 ± 18.13 p= 0.430, respectively). As for the height, men were significantly taller than women (1.734 ± 0.007 vs.1.637 ± 0.005, p= 0.001). The kidney length, volume and parenchymal volumes of both kidneys were significantly larger in men. Conclusion Renal length and volume are strongly correlated with body height. This relation must be considered in clinical decisions on further investigations regarding kidney disease progression.

Background and Aims Non-compliant dialysis patients are at increased risk of mortality. Compliance depends on patient demographics, educational level and income. Family support and marital status might also influence the patients compliance, as well as the quality of life. Missed/shortened dialysis sessions, adherence to prescribed medications, excessive phosphate serum values and interdialytic weigh gain, smoking and adherence to medical investigations provide indicators of non-compliance. Aim: To assess the impact of family support on different compliance indicators in the dialysis patients. Method In this observational study 134 dialysis patients were scored for different indicators of compliance from 0-2 and summary scores of compliance were assessed. Clinical and laboratory data were obtained from the previous two years. Patients with mean IDWGs >4.5% of body weight (BW) and/or phosphorous level above 1.6 mmol/L were scored with 1, patients with IDWG/BW more than 5.7% and/or 2.0 for mean phosphorous level were scored with 2. Summary scores of non-compliance were also assessed. Patients were scored for quality of life with SF-36 questionnaire. Patients non-adherence was analysed for predictors in multivariate analysis. Results Estimated rates of noncompliance varied: Medical investigations 63%, phosphorous 33, IDWG 22, therapy 14%, HD treatment 9%. When the complete dietary fluid, medications and treatment regimen were studied noncompliance rate was 73%, and when adherence to medical investigations was added the rate rose up to 87%. Patients with family support above median level (≥25) were significantly more often men (0.049), with diabetes (p=0.014), lower socioeconomic status (0.001) and married (0.003). The quality of life scores were significantly worse in the low family supported patients (56.73±26.15 vs 39.23±24.05, p=0.0001). They also scored worse in overall non-compliance scores 2.04±1.71 vs 2.97±2.06, p= 0.007). In the multivariate analysis the non-compliance was predicted most powerfully in patients with younger age, low social status and lower family support (β=-0.202, p=0.023, β=0.220, p=0.036, β=-0.175, p=0.019, respectively). Conclusion Family support is crucial for dialysis patients adherence to treatment and Quality of life. Efforts should be done to recognize the patients real needs and adequately help those confronting dialysis burden and improve their quality of life.

Chronic kidney disease is defined as a decrease in renal function or evidence of kidney injury for >3 months. This represents an oversimplification that may confuse physicians. Thus kidney function is equated to glomerular filtration rate, which represents one of multiple kidney functions. Some potentially more important renal functions are lost earlier, such as the production for the anti-ageing factor Klotho. Overall, these changes modify the emergent properties of the body, altering the relationships between different organs and systems, in a manner that is difficult to predict the response to interventions based on normal physiology concepts, as there is a novel steady state of interorgan relations. In this regard we now discuss the impact of CKD on heart failure; osteomuscular and joint pain and bone fragility and fractures; and osteosarcopaenia as seen by a cardiologist, a rheumatologist and a geriatrician. ispartof: CLINICAL KIDNEY JOURNAL vol:14 issue:4 pages:1077-1087 ispartof: location:England status: published

Background: \ud Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone.\ud \ud Methods: \ud In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed.\ud \ud Findings: \ud Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0–3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80–3·42; p

In the period from 26th until 29th of September 2019, the 15th BANTAO Congress (Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs) in conjunction with the 6th Congress of the Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) was held in Skopje, Republic of North Macedonia, hosted by the Macedonian Academy of Sciences and Arts (MASA). MSNDTAO was created in 1992 and the First Congress of the MSNDTAO was held on 9th October 1993 in Ohrid when, also, the Balkan Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was established, as the only professional association of this kind in the Balkans and Southern Europe. Since then, MSNDTAO has been very active in education and collaboration with BANTAO, the European Renal Association (ERA-EDTA) and the International Society of Nephrology (ISN). The 15th BANTAO and the 6th MSNDTAO Congress were highly professional events in honor of the 80th anniversary of Academician Momir Polenakovic from the Republic of North Macedonia, one of the founders of BANTAO and MSNDTAO, who was unselfishly dedicated to the education and guidance for many generations of young doctors in this region. This year’s Congress was endorsed by the ERA-EDTA, and supported by the ISN. On the first day of the Congress, a European Renal Best Practice (ERBP) session was held, in which the Chair of the ERBP Working Group, Prof. Dr. Jonathan Fox gave a comprehensive insight of the purpose and aims of ERBP, the methods used for their achievement, and an overview of the recently produced and guidelines in development. The second day was organized in four sessions: Clinical nephrology and renal registries; CKD Diagnosis, comorbidities and treatment; Kidney transplantation and Acute and chronic renal failure management. On the third congress day, the ISN CME Course with ERA-EDTA endorsement was held. The course was entitled “Possibility of diagnosis and treatment of the CKD progression and complications/Possibility of diagnosis and treatment of the CKD progression – current perspective” and was chaired by Prof. Dr. Caskey Fergus and Prof. Dr. Serhan Tuglular. On the last Congress day, before the official closure and the best wishes from the President of the Congress, Prof. Dr. Goce Spasovski, a session about CKD and the renal replacement therapy complications was held. This event was of an exceptional importance for the region, considering the charred international achievements and the most up-to-date methods used in the Nephrology field, bringing out continuous quality improvement in the treatment of patients with renal diseases.

Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As a non-atheromatous process, it could be partially explained why standard CV disease-modifying drugs do not provide such an impact on CV mortality in CKD as observed in the general population. We summarize the potential association of CV comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers.

Aim: \ud To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273.\ud \ud Methods: \ud We conducted a prospective, randomized, double‐blind, placebo‐controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high‐ or low‐risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis.\ud \ud Results: \ud A total of 1777 participants from 15 centres were included, with 12.3% of these having a high‐risk proteomic pattern. Participants in the high‐risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low‐risk group (n=1559, P

Secondary hyperparathyroidism (SHPT) is common among patients with end-stage renal disease (ESRD). SHPT is associated with high-turnover bone disease, interstitial and vascular calcifications, cardiovascular morbidity and mortality. The pharmacological management of SHPT has progressed in recent years. The introduction of targeted therapies, such as selective vitamin D receptors activators and calcium-sensing receptor modulators, offers an increased opportunity to adequately control elevated parathyroid hormone (PTH), especially in patients with chronic kidney disease under dialysis treatment. Calcimimetic medications such as cinacalcet negatively feedback on the parathyroid glands and do not have the consequences of calcium augmentation. However, there are no randomised, prospective data that demonstrate improved quality of life, improvement in anemia, reduction in phosphate binders, reduction in use of vitamin D analogs, or reduction in mortality. Literature supports cinacalcet therapy to improve patient outcomes, especially with regard to vascular calcifications and presumably the very lethal condition of calciphylaxis. However, cinacalcet is administered orally and has been associated with gastrointestinal intolerance along with hypocalcemia. In addition, poor adherence has been observed among dialysis patients self-administering oral cinacalcet. On the other hand, successful surgical parathyroidectomy (sPTX) can yield a dramatic reduction in PTH level and clinical symptoms. The advanced pharmacological treatments of SHPT often obviate parathyroidectomy; however, some researchers have reported that sPTX may be more cost-effective than cinacalcet in some patients with ESRD and suffering uncontrolled SHPT.

Background. Kidney transplantation (TR) is the best treatment of chronic kidney disease. Chronic cellular and antibody mediated rejections have still major impact on graft survival. Single antigen bead technology enabled detection of donor specific (DSA) and non-donor specific (Non-DSA) anti HLA antibodies (HLA-Ab). Our study investigates the impact of de novo HLA-Ab on graft function (GF) 12 months after TR. Material and methods. 50 pts with living (42) and deceased donor (8) transplantation were included in a 12-month prospective study. HLA-Ab were analyzed using LABScreen mixed kit in the 1st and 12th month after TR. According to the presence of HLA-Ab, pts were divided in group 1 (HLA+) and group 2 (HLA -). Both groups did not differ regarding gender, age, living or deceased donor, immunosuppression, underlying renal disease, rejection episodes, HLA mismatch, cold and warm ischemia time. Serum creatinine (SCr), GFR (Cockroft Gault) and proteinuria (Pr) were analyzed 1st and 12th month after TR. Results. HLA-Ab were detected in 17 pts (34%), 5 with DSA (10%) and 12 with Non-DSA (24%). Group 1 has a significant worsening of GFR (SCr increased from 112.1 to 141.5 ( p

Identification of significant changes in urinary peptides may enable improved understanding of molecular disease mechanisms. We aimed towards identifying urinary peptides associated with critical course of COVID-19 to yield hypotheses on molecular pathophysiological mechanisms in disease development. In this multicentre prospective study urine samples of PCR-confirmed COVID-19 patients were collected in different centres across Europe. The urinary peptidome of 53 patients at WHO stages 6-8 and 66 at WHO stages 1-3 COVID-19 disease was analysed using capillary electrophoresis coupled to mass spectrometry. 593 peptides were identified significantly affected by disease severity. These peptides were compared with changes associated with kidney disease or heart failure. Similarities with kidney disease were observed, indicating comparable molecular mechanisms. In contrast, convincing similarity to heart failure could not be detected. The data for the first time showed deregulation of CD99 and polymeric immunoglobulin receptor peptides and of known peptides associated with kidney disease, including collagen and alpha-1-antitrypsin. Peptidomic findings were in line with the pathophysiology of COVID-19. The clinical corollary is that COVID-19 induces specific inflammation of numerous tissues including endothelial lining. Restoring these changes, especially in CD99, PIGR and alpha-1-antitripsin, may represent a valid and effective therapeutic approach in COVID-19, targeting improvement of endothelial integrity. ispartof: PROTEOMICS vol:21 issue:20 ispartof: location:Germany status: published