20 years since the establishment of the BANTAO association (Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs).

The Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was born in Ohrid on October 9, 1993. The war in former Yugoslavia negatively affected the development of nephrology and also the connections among the nephrologists from the Balkans. However, there was willingness for further mutual collaboration between the nephrologists from the Balkans. The war in Yugoslavia created hate among people, between the newly established countries, and there were problems with the recognition of the names of the new countries, and so, the nephrologists decided to apply the ancient principle of using the names of the cities, instead of the countries, as the founders of the Association. The main goal of BANTAO is to promote scientific and technical cooperation in the fields of renal disease and artificial organs between the regions on the Balkan Peninsula and the world, to give an opportunity for exchange of experience and knowledge among the experts in the area and to engage in collaborative projects in order to demonstrate that cooperation is possible even on the turbulent Balkan Peninsula. The I BANTAO congress was held in Varna from September 22 to 24th, 1995 (President--D. Nenov, Varna). The II congress of BANTAO was held from September 6th to 10th, 1997 in Struga, (President--M. Polenakovic, Skopje). The III BANTAO congress was held in Belgrade from September 18th to 20th, 1998 (President--Lj. Djukanovic, Belgrade). The IV congress of BANTAO was held in Izmir from 14th to 16th November 1999 (President--A. Akcicek, Izmir). The V Congress of BANTAO was held in Thessaloniki from September 30th to October 3rd, 2001 (President--P. Stathakis, Athens). The VI Congress of BANTAO was held for the second time in Varna from 6th to 9th October 2003 (President--D. Nenov, Varna). The VII congress of BANTAO was held from September 8th to 11th, 2005 in Ohrid, (President--M. Polenakovic, Skopje). The VIII BANTAO congress was held in Belgrade, 16-19 September 2007 (President--V. Nesic, Belgrade). The IX BANTAO congress was held in Antalya, 18-22 November 2009 (President--A. Basci, Izmir). The X BANTAO congress was held from 13 to 15 October 2011 in Chalkidiki (President--D. Tsakiris, Thessaloniki). The XI BANTAO congress is being held on 26-29 September 2013 in Timisoara (President--A. Schiller, Timisoara). At the VII BANTAO Congress for the first time a CME Course was organized by ERA/EDTA and ISN/COMGAN entitled "Frontiers in Nephrology" with seven distinguished speakers. Very important event in the existence of BANTAO is the appearance of the BANTAO journal in 2003. The BANTAO journal has been published biannually since 2003. In the past 10 years, 20 regular issues; 2 supplements (Antalia and Chalkidiki congresses) have been published. Editors of the journal were as follows: 2003-2005--D. Nenov, Editor; 2005-2009--A. Basci, Editor; 2009--Goce Spasovski, Editor. Until now 332 papers have been published. The BANTAO journal is on EBSCO, DOAJ, SCOPUS. After the First Congress of BANTAO, F. Valderrábano, chairman of the EDTA--ERA Registry, at that time, wrote in Nephrology Dialysis Transplantation (1996) 11:740: "Nephrologists of the Balkan countries meet across political frontiers and war fronts--an example to politicians! BANTAO: a new European Medical Association overcomes Political obstacles." Despite the difficulties imposed by major events, such as devastating wars and catastrophic earthquakes in many countries of the Balkan Peninsula BANTAO has made considerable progress. The BANTAO Congress was established as the major scientific and institutional forum for Balkan nephrologists, with its own journal, indicating our will to communicate, to collaborate, to get to know each other and to share our difficulties. Now, we expect further successful work of BANTAO.

Should dialysis modalities be designed to remove specific uremic toxins?

The definition of optimal dialysis therapy remains elusive. Randomized clinical trials have neither supported using urea as a surrogate marker for uremic toxicity nor provided clear cut evidence in favor of larger solutes. Thus, where to focus resources in the development of new membranes, and therapies remains unclear. Three basic questions remain unanswered: (i) what solute(s) should be used as a marker for optimal dialysis; (ii) should dialytic therapies be designed to remove a specific solute; and (iii) how can current therapies be modified to provide better control of uremic toxicity? Identification of a single, well-defined uremic toxin appears to be unlikely as new analytical tools reveal an increasingly complex uremic milieu. As a result, it is probable that membranes and therapies should be designed for the nonspecific removal of a wide variety of solutes retained in uremia. Removal of the widest range of solutes can best be achieved using existing therapies that incorporate convection in conjunction with longer treatment times and more frequent treatments. Membranes capable of removing solutes over an expanded effective molecular size range can already be fabricated; however, their use will require novel approaches to conserve proteins, such as albumin.

Salt, the neglected silent killer.

A diet high in salt (sodium chloride) is considered to promote a series of pathological sequelae. Despite increasing scientific evidence, which supports the notion that reducing salt intake has positive long-term effects, citizens from the Western Hemisphere consume more, not less salt. Changes in lifestyle of modern societies associated with an increased consumption of "fast food" contribute to this development leading to the "disease of the good life" which involves hypertension, cardiovascular events, and even inflammatory effects. By contrast, consuming diets with reduced salt content are associated with a smaller shift of body fluids from the interstitial into the intravascular space, less antihypertensive medication, a reduced asymmetric dimethylarginine (ADMA) production and, after the generation TGFbeta-mRNA, to a lower mitogen-activated protein kinases (MAPK) activation. Therefore, the recommendation of the clinical practice guidelines for dialysis [Depner et al. (14)] (as well as numerous other guidelines) to reduce salt intake is not a surprise.

Health is wealth! Is wealth health?

Current demographic analyses of the world population show a considerable increase in life expectancy of the general population in nearly all regions of the world. Consequently, "Health Economy", defined as "Provision and marketing of goods and services in order to support the maintenance and restoration of health", has become the megatrend of the millenium. This holds true not only for national economies and GDPs, but also - in qualitative terms - for the elderly generation. Guestimates on the purchasing power of the elderly generation show a threefold higher figure compared to the actual working population, at least in the Western hemisphere. A globally organized wellness industry will profit from this situation. However, the increased morbidity of the elderly generation requires enormous financial endeavours to provide resources not only for healthcare programmes, such as disease prevention, healthcare education and improvement in quality-of-life pattern, but also for the development of sophisticated medical devices and therapies which are closely adapted to the needs of the elderly. The notion "Wealth is health" is valid indeed and so is "Health is wealth". Wellness, not just sickness, will determine the lifestyle of coming elderly generations.

Testing biomaterials for application in artificial organs: impact of procedures, donor and patient properties.

Many factors can affect the characterisation of biomaterials during testing. These include drugs administered prior to testing and shear stress on blood cells induced by different blood flows and specific blood donor conditions. Some of the misconceptions in testing are described here and serve to indicate that a systems approach, and not only individual test parameters, is best when testing for biocompatibility. "Methodology is everything and the devil is in the details", remarked Paul Simmons, the current president of the International Society for Stemcell Research, in an article in Nature magazine [1]. The article refers to current problems related to the reproducibility of data in stem cell research. Reproducibility in in vitro testing is also mandatory when selecting polymers for medical device applications. Many mechanical and physical engineers are surprised when they realise the enormous standard deviations (sometimes between 50 and 100%) of data found in biological or physiological investigations of biomaterials. The reasons for this are the complexity of physiological parameters such as the nature of blood originating from a variety of donors and hour-to-hour and day-to-day physiological differences. As a consequence, standardisation is a condition sine qua non in biomaterial testing, and knowledge of possible pitfalls is absolutely necessary. Therefore ISO 10993-4, Biological Evaluation of Medical Devices, Selection of Tests for Interaction With Blood, [2] provides a practical tool, including a decision tree for use in the selection of appropriate polymers for biomaterial applications. However, the interested reader finds in Section 3.1 of ISO 10993-4 the definition of blood-device interaction: "Any interaction between blood or any component of blood and a device, resulting in effects on blood, or on any organ or tissue, or on the device". A note added to this definition further clarifies: "Such effects may or may not have clinically significant or undesirable consequences." This prompts one to ask if effects leading to undesirable consequences that are not clinically significant would be helpful to the polymer chemist. This article provides some observations and examples of the misconceptions and pitfalls that exist in testing biomaterials for biocompatibility.

How can liver toxins be removed? Filtration and adsorption with the Prometheus system.

The application of extracorporeal blood circuits in liver failure therapy has its roots in the two functions of the liver, first as a detoxifying and second as a synthetizing organ. In contrast to hydrophilic uremic toxins, most liver toxins are hydrophobic and bind preferentially to blood proteins. Consequently, the majority of these compounds cannot be removed by hemodialysis or similar dialytic procedures. Current systems use albumin as a transport vehicle for hydrophobic compounds across high flux membranes (e.g. albumin-dialysis, molecular adsorbent recirculating system (MARS)). In contrast to these devices, the Prometheus system (Fresenius Medical Care, Bad Homburg, Germany) applies filtration across highly permeable membranes with a molecular weight cut-off of >300.000. These membranes facilitate a direct filtration of most of the toxin-bearing proteins. In a secondary circuit these toxins are then removed by adsorber beads assembled in specially designed cartridges. The protein-containing toxin-free solution returns to the primary circuit. Clinical testing of the Prometheus system's safety and efficacy parameters showed that cell counts and coagulation factors were not significantly affected. Total bilirubin-, bile acid- and plasma ammonia-levels were reduced in vivo by -21%, -43% and -40%, respectively. First successful therapeutic results have been obtained for patients treated for drug abuse and for patients waiting for transplantation. Thus, a combination of plasma fractionation with highly permeable membranes followed by a secondary circuit with adsorber cartridges proves to be the most effective method of removing toxic waste in liver failure. Further investigations will follow in order to extend the application of the Prometheus system to larger cohorts of patients.

Peritoneal dialysis in refractory end-stage congestive heart failure: a challenge facing a no-win situation.

BACKGROUND: Current medical therapeutic strategies for refractory congestive heart failure (CHF) in the population of 65 years and older with contraindications for heart transplantation are limited. Peritoneal dialysis applied to CHF patients with or without renal impairment showed clinical functional improvement. METHODS: A single centre, prospective but non-randomized study in 20 patients with severe congestive heart failure refractory to optimal pharmacological therapy [New York Heart Association (NYHA), class IV] was performed between 2000 and 2003. The mean age was 65.71+/-7.66 years. The patients had a baseline glomerular filtration rate of 14.84+/-3.8 ml/min. Fifteen patients were diabetics (type I, 10; type II, five). For all patients, the baseline ejection fraction was <35% (31.2+/-4.7%). The mean Charlson's co-morbidity index was 7.8+/-1.8. Patients were treated initially by 2-5 sessions of continuous veno-venous haemofiltration (CVVH) or sequential haemofiltration (SHF). Automated peritoneal dialysis (APD) was started after implantation of a Tenckhoff catheter. Three APD sessions/week (8 h each), with 15-20 l of dialysis fluid (PDF) per session (10.35+/-3.05 l of 1.5% lactated glucose and 8.95 +/-2.95 l of 4.25% glucose PDF), were performed. Total follow-up ranged between 7 and 35 months (mean 19.80+/-7.37). RESULTS: After 1 year of follow-up, all patients showed haemodynamic improvement: significant improvement of left cardiac work index (2.33+/-0.69 to 2.59+/-0.47 kg min/m(2)), reduction of the systolic times ratio (61.14+/-12.57 to 39.18+/-13.44%), lower thoracic fluid contents (0.04+/-0.005 to 0.003+/-0.0001 Omega) as well as a regression from NYHA class IV to class I. Need for hospitalization for CHF decreased from 157 to 13 days. CONCLUSIONS: Peritoneal dialysis appears to be a promising therapeutic tool for patients affected by refractory CHF. Clinical improvement of cardiac function may be related to clearing blood from middle molecular weight myocardial depressant substances, including atrial natriuretic peptide. Prospective multicentre trials are needed to confirm these encouraging results.

Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy.

BACKGROUND: The goal of the current study was to examine the potential value of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes in the process of human kidney aging in vivo, and in the development of chronic allograft nephropathy (CAN). METHODS: Expression of p16(INK4a) and p27(Kip1) CDKI genes was evaluated and compared in 20 normal human kidney tissues of different ages (range, 21 to 80 years) and in 9 chronically rejected kidney grafts. Age dependency of marker expression was analyzed by the Pearson correlation and linear regression. RESULTS: Expression of p16 in cortical tubular (CTS) and interstitial (CIS) cells of normal kidney was age dependent (correlation coefficients: 0.608 and 0.726, 95% confidence interval [CI]: 0.227 to 0.828 and 0.417 to 0.884, respectively). Cortical tubular expression of p27 was also correlated with increasing age (0.672, 95% CI: 0.327 to 0.859). Linear regression analyses confirmed the linearity of marker relationship with age (coefficient of determination R(2):0.370, 0.452, and 0.527 for CIS p16, CTS p27, and CTS p16, respectively). The mean chronological and predicted graft ages (53 +/- 21 and 76 +/- 8.9 years, respectively) were significantly different (P = 0.0126). The glomeruli, tubules, and interstitial cells of rejected grafts expressed significantly higher levels of p16 and p27 than normal kidneys. Expression of p16 in glomerular and cortical interstitial cells was higher in grade 3 of CAN than in grade 2 (P = 0.013 and 0.004, respectively). CONCLUSION: The results of the current study show that expression of p16(INK4a) and p27(Kip1) CDKI genes is increased in cortical cells of the aging human kidney and in chronic allograft rejection, supporting the senescence theory of CAN.

Increased expression of p21 (WAF1/CIP1) cyclin-dependent kinase (CDK) inhibitor gene in chronic allograft nephropathy correlates with the number of acute rejection episodes.

The p21 (WAF1/CIP1) cyclin-dependent kinase (CDK) inhibitor gene is considered to be the senescence marker in some recent publications. Expression of the gene was evaluated in 14 normal human kidney tissues of different ages and in nine chronically rejected renal allografts. All normal kidneys were negative for p21 expression. Glomerular, tubular and interstitial expression of the marker was detected in 88.9% ( P<0.0001) and vascular expression in 66.7% of chronically rejected grafts ( P<0.001). No correlation was found between the intensity of p21 expression and recipient age, donor age or number of human leukocyte antigen (HLA) mismatches. The marker was expressed more in grade 3 of chronic allograft nephropathy (CAN) than in grade 2 ( P=0.059 for glomerular score). Tubular expression of p21 was correlated with the number of acute rejections: P<0.05 for three vs one and two, and P=0.0046 for three vs no previous acute rejection episodes.

Quo vadis dialysis membrane?

The development of dialysis membranes is closely related to the development of dialysis as a routine therapy for patients with kidney failure. Without having membranes and dialyzers available as commodity products, the treatment of more than 1 million uremic patients worldwide would be impossible. Several transition periods can be identified: a change in membrane geometry from flat sheet to capillaries, a shift in market appreciation from cellulose to synthetic polymers, and from low-flux to high-flux dialyzers. This shift is supported by the notion that convective therapies using high-flux membranes allow the removal of large-molecular-weight solutes. From a historical background, three eras of perception can be identified for both membrane and dialysis development. First, the period of survival when nephrologists had to focus on techniques for blood access and availability of membranes. Second, the period of issues dedicated to rather specific features of membranes and dialysis therapy such as dose of dialysis, reuse, sterilization, and membrane biocompatibility. And third, the period of quality tops this sequence with a complicated approach: the principal area of interest from the medical community has switched to issues such as quality of life, morbidity, mortality, therapy standards, and cost-effectiveness. New membrane developments should focus on this situation.

Acetate-free biofiltration versus on-line hemodiafiltration: A prospective, cross-over study / 中华肾脏病杂志

Objective To compare the therapeutic efficacy between on-line hemodiafiltration (On-line HDF) and acetate-free biofiltration(AFB) in prospective, randomized cross-over way. Methods Twelve stable dialysis patients, aged (49. 7?11. 3) years old and on dialysis for (83. 5?6.7)months, were prospectively, randomizedly treated by AFB, pre-dilution HDF(Pre-HDF), and post-dilution HDF (Post-HDF) for total 36 weeks using F60S high-flux dialyzers. Routine blood biochemical tests, bone metabolism parameters and clearance for both small and larger molecular weight substances were measured at defined intervals. Meanwhile, inter-and intra-dialysis symptoms, hypotension episodes and intra-dialysis arterial blood gas were recorded during the research period. Results Both AFB and on-line HDF were well accepted by the overwhelming majority of patients and dialysis staff. Pre-treatment sodium, total and ionized calcium, chloride, bicarbonate, and urea did not differ within or between three treatment groups, while potassium increased slightly in HDF patients, and phosphate, ?z-microglobulin(?2-m) decreased in all groups. After dialysis, AFB patients exhibited significantly higher bicarbonate concentration and lower potassium level when identical potassium level in dialysate was used. Patients receiving AFB manifested less intra-dialysis PO2 drop and PCO2 rise than those on HDF treatments. HDF treatments could afford higher single-pool and double-pool Kt/V, higher effective urea and ?z-m clearance, and lower total inter-dialysis symptom scores than AFB method. While bone metabolism parameters did not differ between three dialysis modalities, some parameters, such as deoxypyridinoline in HDF and osteocalcin, pyridinoline, deoxypyridinoline in AFB, deteriorated at the end of cross-over. Aluminum concentration decreased progressively to about one-third of pre-study values at the end of study with all three treatments. AFB was associated with a lower pre-dialysis MAP, a smaller drop in MAP during treatment, and similar hypotension episodes compared with two HDF treatments. Albumin concentration showed a trend to decrease during the first 2 months of research period, followed by a slight increase thereafter, but still significantly lower than initial value at the end of cross-over. Conclusions Both on-line HDF and AFB share most of the features of optimal renal replacement therapy. On-line HDF is superior to AFB in such aspects as increased dialysis dose both for small and larger molecular weight toxins and less inter-dialysis symptoms. On the other hand, AFB is associated with smaller effect on arterial blood gas and improved intra-dialysis hemodynamic tolerance. Some dialysis-related symptoms and complications in the case of our AFB practice could be attributable, at least in part, to low dialysate calcium level.