Detecting prostate cancer (PCa) using non-invasive diagnostic markers still remains a challenge. The aim of this study was the identification of urine proteins that are sufficiently sensitive and specific to detect PCa in the early stages. Comparative proteomics profiling of urine from patients with PCa, benign prostate hyperplasia, bladder cancer, and renal cancer, coupled with bioinformatics analysis, were performed. Statistically significant difference in abundance showed 20 and 85 proteins in the 2-D DIGE/MS and label-free LC-MS/MS experiments, respectively. In silico analysis indicated activation, binding, and cell movement of subset of immune cells as the top affected cellular functions in PCa, together with the down-regulation of Acute Phase Response Signaling and Liver X Receptor/ Retinoid X Receptor (LXR/RXR) activation pathways. The most promising biomarkers were 35, altered in PCa when compared to more than one group. Half of these have confirmed localization in normal or PCa tissues. Twenty proteins (CD14, AHSG, ENO1, ANXA1, CLU, COL6A1, C3, FGA, FGG, HPX, PTGDS, S100A9, LMAN2, ITIH4, ACTA2, GRN, HBB, PEBP1, CTSB, SPP1) are oncogenes, tumor suppressors, and multifunctional proteins with highly confirmed involvement in PCa, while 9 (AZU1, IGHG1, RNASE2, PZP, REG1A, AMY1A, AMY2A, ACTG2, COL18A1) have been associated with different cancers, but not with PCa so far, and may represent novel findings. LC-MS/MS data are available via ProteomeXchange with identifier PXD008407.

Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt′s group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may respond fully to the treatment with steroids or cyclosporine A. The patients with CUBN may benefit the treatment with vitamin B12. The detection of causative mutations may also be very important for familial genetic counseling and for prenatal diagnosis.

The 4th meeting on rare diseases in South Eastern Europe (SEE) was held in Skopje, at the Macedonian Academy of Sciences and Arts (MASA) on the 14(th) of November 2015. The focuses were metabolic, rare brain diseases as well as the rare dysmorphic syndrome. The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. The talk on an iminosugar-based pharmacological chaperone compound as a drug candidate for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B) was enlightening. To date, there is no treatment available to be offered to patients, but chaperones lead mutated proteins to adopt a native-like conformation and to successfully traffic to their normal cellular destination. DORPHAN is developing an iminosugar-based pharmacological chaperone compound for the treatment of GM1-gangliosidosis and mucopolysaccharidosis IVB. A talk on recent developments in the laboratory diagnosis of mucopolysaccharidoses (MPS) was particularly interesting, covering the laboratory diagnosis of the MPS diseases by a strategy of clinical examination, biochemical analysis of urine samples, enzyme tests and genetic characterization of underlying mutations. New techniques were developed, including analysis of urinary glycosaminoglycans with tandem mass spectrometry, miniaturized enzyme tests or novel synthetic substrates for enzyme assays using mass spectrometry detection of products using dried blood spots. Feasibility and cost-effectiveness of these methods in newborn screening programs have been demonstrated. Neuromuscular RDs, and especially familial amyloid polyneuropathy (FAP) were a topic of the Bulgarian colleagues. Diagnosis, screening and the role of microglia were also topics of particular interest. In summary, this year RD meeting was exciting and productive on a wide range of diseases and on a novel insights on diagnosis and treatment. New methods are expanding our capabilities for a fast and precise diagnosis. Novel knowledge offers better distinction on whom to treat with which medications (e.g. steroid dependent nephrotic syndrome). Novel diseases or variants are published (segmental overgrowth). The authors of the report are particularly keen on stating that one of the main goals of the meeting, namely to help the treatment of patients with rare disease has begun to bear fruits. Namely, the Health Fund of Macedonia for the first time treats the patients with Gaucher's disease. We are hopeful that the number of patients treated for Gaucher's disease and the number of treated patients with other treatable RDs diseases will continue to grow.

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.

Pediatric kidney diseases were in the focus of the World Kidney Day 2016. Macedonian pediatric nephrologists gave their contribution with public appearance in kindergartens, primary and secondary schools, with interactive lectures and discussion with the youngest about the kidney function, healthy life style and simple measures to prevent kidney and urinary tract diseases. Besides promotive appearance in the media, series of lectures were presented in front of the health professionals. The aim was to attract the attention of the professionals for early diagnosis and prevention of kidney disease. The action starts in utero, followed by early postnatal imaging and assessment, conservative treatment and in selected cases surgical treatment. The emphasis is on the multidisciplinary and comprehensive approach to children and adolescents with kidney diseases.