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Background: There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane.Methods: 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate).Findings: At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension).Interpretation: There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes. [ABSTRACT FROM AUTHOR]

Objectives: Incidence of vascular anomalies in donor kidneys varies from 18% to 30% and presents a challenge for a transplant surgeon in kidney transplant. Here we present our personal experience for man - agement of the complicated and unexpected cases., Materials and Methods: A total of 250 kidney transplants (226 living, 24 deceased) were performed in a period of 24 years; mean donor age was 55 years (range, 25-86 years), and mean recipient age was 38.6 years (range, 14-66 years). We analyzed the surgical techniques, complications and outcomes, rejection episodes, kidney function, and graft and patient survival rates., Results: Of 250 nephrectomies, 209 had a single artery (83.6%), 34 had 2 arteries (13.6%), and 7 had 3 arteries (2.8%). Of 34 double arteries, 14 had 2 main arteries, 15 had a main and a polar artery, and 5 had an aortic Carrel patch after deceased donation. According to the size, type, and position, the anastomoses were performed with branches of hypogastric, epigastric inferior, iliac external, and main renal artery, intracorporeally or in bench surgery. Regarding veins, 1 double inferior vena cava, 1 left-side inferior vena cava, 4 retroaortic, 2 circumaortic, 10 large lumbar veins draining into the left renal veins, and 8 cases with 2 or more different size renal veins were managed. In 9 cases with short right renal vein, an extension with vena cava (a "Barry cavoplasty") was performed in deceased donor organs. No serious surgical complications related to vascular anomalies were observed. There were no statistical differences in 1-, 6-, and 12-month graft survival rates between the groups with or without vascular anomalies., Conclusions: Vascular anomalies should no longer be considered a contraindication for transplant, if careful anastomosis is performed in every case to avoid ischemia and further complications. Therefore, management of vascular anomalies could be a graftsaving procedure.

Introduction: The effectiveness of a low protein diet (LPD) to delay the progression of chronic kidney disease (CKD) remains controversial. The questions persist regarding which LPD for which CKD patients? Our study aimed to investigate the role of LPD in selected patients with CKD stage G3a., Methods: Forty-seven selected patients (23 men, mean age 55 ± 12), in stage G3a of CKD (eGFR: 45-59 ml/min) were included in this prospective 12 months study with a recommended dietary protein intake (DPI) of 0.8 g/kg/day. The DPI was estimated from 24 h urinary urea nitrogen excretion (Maroni formula).  All patients were trained by dietitian-nutritionist and had one baseline control and three visits. The clinical data, blood pressure, diet-adherence, eGFR, albumin, cholesterol, hemoglobin, proteinuria, and BMI were analyzed., Results: According to the adherence to LPD, the patients were divided into Adherent group (AG, n =24, 51 %) with DPI of 0.75 ± 0.25 g/kg/day and non-Adherent group (NAG, n =23, 49 %) with DPI of 1.3 ± 0.31 g/kg/day. During the follow up the eGFR decreased from 57.68 ± 4.0 to 56.11 ± 4.8, and from 55.45 ± 7.0 to 52.46 ± 7.2 for AG and NAG, respectively. The real drop of eGFR after 12 months was 1.57 for AG and 2.99 ml/min for NAG. The difference was statistically significant (p <0.01)., Conclusion: Despite the significant percentage of non-adherent patients, our pilot study confirms the beneficial effect of LPD on CKD progression. Adherent patients in G3a stage protect more successfully their GFR compared with non-adherent patients after 12 months. CKD stages with mild reduction of GFR are more challenging for further clinical studies. HIPPOKRATIA 2018, 22(4): 178-182., Competing Interests: Authors declare no conflict of interest., (Copyright 2018, Hippokratio General Hospital of Thessaloniki.)

Introduction: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR)., Aim: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function., Material and Methods: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated "gun" were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used., Results: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a pure antibody-mediated rejection (ABMR-Cat 2) and T-cell Mediated Rejection (TCMR-Cat 4). The remaining 17 samples were classified as a "mixed" rejection: 7 (41%) ABMR + IF/TA, 5 (29%) ABMR + BL + IF/TA, 2 (11%) BL + IF/TA, 1 (5%) ABMR + BL, 1 (5%) ABMR + TCMR and 1 (5%) TCMR + IF/TA. The mean serum creatinine at the time of the biopsy was 126.7 ± 23.4 µmol/L, while GFR-MDRD 63.4 ± 20.7 ml/min, which means that the majority of the findings were subclinical. Among the non-immunological histological findings (Cat 6), 3 cases belonged to CNI toxicity, 1 to BK nephropathy and 1 to recurrence of the primary disease., Conclusion: Our 12-month protocol biopsy study revealed the presence of different forms of mixed subclinical rejection. Use of recent BANFF classification and scoring system enables more precise diagnosis and subsequently different approach to the further treatment of the KTR. More correlative long-term studies including Anti HLA antibodies and Endothelial Cell Activation- Associated Transcripts (ENDAT) are needed.

The fast development of nephrology in the world, especially in the second half of the 20 th century demanded protocol (guidelines) for nephrological activity for all levels of medical care, of doctors and specialists. The International Society of Nephrology, the European Renal Association and other national associations created their own protocol (guidelines) for nephrological activity. The Macedonian Society of Nephrology, Dialysis, Transplantation and Artificial Organs (MSNDTAO) proclaimed the First Protocol for Performing Nephrological Activity in the Republic of Macedonia at the First Congress of the MSNDTAO, held in Ohrid 1993, and it was published in the Macedonian Medical Review, 1994; Supplement 14: 397-406 [1]. The update of the Protocol for Performing Nephrological Activity in the Republic of Macedonia was proclaimed at the Fourth Congress of MSNDTAO, held in Ohrid 2012 and it presented in this text.

Lipid metabolism disorders in patients with end-stage renal disease, particularly in patients with nephrotic syndrome, were described by Dr Bright as long ago as 1827 [1]. It is known that patients with end-stage renal disease (ESRD) display a clinical picture of early accelerated (premature) atherosclerosis with severe cardiovascular and cerebral complications that are very often present even at a relatively early age compared with the general population. Today, it is considered that uraemic dyslipidaemia has persisted for many years before chronic dialysis treatment begins and presents a basic risk factor for an early start of the atherogenesic processes. That is why an analysis of apolipoprotein and lipid abnormalities as well as their etiopathogenetic mechanism in patients diseased with ESRD treated with repeated haemodialysis in the initiation phase of dialysis (the first 6 months), can clearly contribute to taking timely preventive measures (dietetic, healing) by which the frequency of apolipoprotein and lipid abnormalities will be decreased, which, at the same time, will result in reducing the processes of early atherosclerosis with all its complications in ESRD patients [2]. Disorders of apolipoprotein metabolism are considered as one of the most important factors for early atherosclerosis in patients with ESRD [3].

The appearance of soft tissue calcifications in patients with chronic renal failure has been recognised as one of the serious complications of uremia. An elevated serum calcium-phosphate product has almost invariably been detected, although the exact mechanisms of precipitation are still not fully understood. Among the factors responsible for triggering the precipitation process are: hyperphosphatemia, secondary hyperparathyroidism, hypercalcemia, treatment with vitamin D3, etc. Phosphate binders have been used to prevent, among other things, soft tissue calcifications, and parathyroidectomy has most frequently been applied as the therapy of choice, once precipitation of calcium salts has occurred. We present a case of soft tissue calcifications in the gluteal regions of a chronic haemodialysis female patient. The therapy we chose was a combination of biphosphonate and deferoxamine. The patient was treated for two months. The regression of the soft tissue calcifications was very significant, as registered both clinically and radiologically. The exact mechanism by which this reversal was achieved needs further investigation.

Acute renal failure (ARF) is a complex syndrome, frequently reported with mortality in 20-80% of the patients. Infection, as a cause or a complication of the syndrome, is a risk factor which unfavourably determines the outcome. A prospective 4-year study was performed of 112 ARF patients in the intensive care unit (ICU), with an evaluation of 68 clinical and laboratory parameters, as risk factors, at admission to the ICU. The scoring system used was SOFA (Sepsis-related Organ Failure Assessment). The outcome was associated with 27 risk factors among which infection as an acute ARF insult has shown a particularly strong correlation (p<0.0001). There was no association with infection as an intra-hospital complication. When divided according to the outcome (survivors vs. non-survivors), platelets, hematocrit, total protein and mean arterial pressure were significantly higher, while leucocytes and bilirubin significantly lower in the surviving group of patients. The parameters of the SOFA scoring system, such as the coagulation, liver and cardiovascular code, were statistically significant in relation to the outcome, and also the SOFA score taken as an independent variable (p<0.0001). The classification matrix of the analyzed SOFA scoring system was successful in the classification of 91.95% of the surviving and 48.00% of the non-surviving patients with ARF and the odds ratio was 41.0. Mortality rate in patients with ARF is 22.7%. Patients with ARF due to sepsis have a worse prognosis than those with non-septic ARF. Coagulation disorder, liver and cardiovascular dysfunction, as well as the SOFA score itself are independent variable in the outcome prediction. The SOFA score, derived from easily obtained data, is useful for judging survival prognosis in patients with ARF.

Background: As elsewhere, the growing organ shortage is a main problem for organ transplantation. To solve the problem, we started accepting genetically unrelated, but emotionally related living donors., Methods: In the period of 1998-2002, 14 LERT are performed in the University Clinical Centre in Skopje, Republic of Macedonia. As suitable donors are used predominantly spouses, but also mother and brother in law. The immunosuppression included a quadruple protocol with Interleukin-2R antagonists, late cyclosporin A, MMF and steroids. The two-year graft and patients survival of LERT was compared with 22 living genetically related donor transplantation (LRT) performed in the same time., Results: The two years graft survival was 100% in LERT and 92% in LRT. There are not any significant difference among the medical and surgical complications between the two groups of pts. The actual serum creatinin was 101+22 in LERT compared with 142+34 in LRT., Conclusion: The authors recommend the LERT as a valid alternative especially in the countries where the regular cadaver transplantation is not yet established.

Aim: Efforts to increase the donor pool and available organs included some unconventional kidney transplantation. One of these was including elderly donors for both, living and cadaver kidney transplantation. The aim of the study was to review our single centre experience with living donor transplants from elderly advanced age donors., Patients and Methods: During a period of 7 years, 71 living related renal transplantations were performed. Twenty-six of them were over 65 (mean 69+/-4, range 65 to 81), but 10 were over 70 years of age. The survival rate was compared with 45 transplants from younger donors (mean age 51+/-6, range 24 to 59). The cold and warm ischemia time, the preservation procedure and blood vessels anastomosis time were comparable in both donor groups. The immunosuppression included sequental quadruple protocol with ATG, PRED, AZA and CyA replacing ATG after 7 days. The triple drug (AZA, PRED, CyA) maintenance therapy was applied to all recipients., Results: Kaplan-Meier 1-, 3- and 5-year graft survival was 88.0%, 79.2% and 68%, respectively, for advanced donor age group and 90.2%, 82.4% and 74%, respectively, for younger donor group. The difference was slightly statistically significant (p < 0.05). In 6 patients who received graft from elderly donors, a delayed graft function was observed, whereas only in one in the younger donor group., Conclusion: Despite the worse results in the elderly donors' transplants, we consider the advanced age donors as an important source of kidneys contributing to solving the actual organ shortage, especially in our region.

Transplantations using grafts from living donors were performed on 70 patients with chronic kidney failure, 66 of them involved matching recipients-donors and four involved non-matching recipients-donors. Immunological data were analyzed in 56 pairs of recipients and patients. Of these pairs, one was identical, seven had three identical antigens, 46 were haploidentical at A and B loci, one pair was identical in one antigen and one pair was completely incompatible. The survival of transplanted kidneys largely depended on the degree of histocompatibility. In 33 (59%) transplantations kidneys are functioning from more than 36 months. In the group of seven transplanted pairs with three identical antigens kidneys are functioning in six cases, with four of them functioning from more than 72 months. In the remaining patients (41 patients [73%]) kidneys are functioning, with 8 of them functioning from more than 10 years. The existence of HLA antibodies was investigated. Preimmunization was found in 18 (32%) patients and correlated with the number of blood transfusions. Rejection crises were observed in 12 (21%) patients. As the number of blood transfusions per patient increased the number of rejection crises decreased. Rejection crises were also observed in haploidentical pairs, with a relative risk > 30%. They occurred in the first 2 weeks following transplantation.

Efforts to increase the donor pool of available organs have resulted in some unconventional kidney transplantation procedures. One of these is the use of elderly donors for both living and cadaver kidney transplantations. The aim of this study was to review our experience with kidney transplants from living elderly donors. During a period of 10 years, 70 living renal transplantations were performed. In 32 transplants the age of the donor was above 65 years (mean 69 +/- 4 years, range: 65 to 81 years) and in 10 of these 32 transplants the age of the donor was over 70 years. The survival rate was compared with that of 38 transplants from younger donors (mean age 51 +/- 6 years, range: 24 to 59 years). The time to cold and warm ischemia, the preservation procedure and time to anastomosis of blood vessels were comparable in both groups of donors. Immunosuppression included a sequential quadruple protocol, using thymoglobulin (ATG), prednisolone (PRED), azathioprin (AZA) and cyclosporin A (CsA), which replaced ATG/PRED after day seven. A triple drug maintenance therapy (AZA, PRED, CsA) was used in all recipients. Kaplan-Meier survival curves at 1, 3 and 5 years showed that graft survival was 88%, 79% and 64% respectively for grafts from the advanced age donor group and 92%, 82% and 68% respectively for grafts from the younger donor group. The difference was slightly statistically significant (p < 0.05). Functioning of the graft was delayed in six patients who had received grafts from elderly donors and in one patient who had received a graft from a young donor. Despite worse results in transplantation with grafts from elderly donors, we consider this population as an important source of kidneys, which might help solve the present organ shortage, especially in our region.

Despite the remarkable development of kidney transplantation techniques, surgical complications are still a very important factor affecting the final outcome of kidney transplantation. After 92 kidney transplantations (22 from cadaver donors and 70 from living donors) performed at Skopje hospital (Macedonia), we observed the following complications: nine (10%) urinary fistula, five (5%) graft ruptures, seven (8%) lymphoceles, two (2%) urinary calculosis, two (2%) intestinal perforations, four (4%) renal artery stenoses, one (1%) renal artery thrombosis, and seven (8%) early complications following surgical incision. Complications were detected by either ultrasonography, intravenous pyelography, percutaneous nephrostomy with anterograde pyelography, computerized tomography, and intravenous digital angiography. They were subsequently treated by application of modern surgical procedures: use of the ureter (termino-terminal or uretero-pyelic anastomosis) for treatment of urinary fistulas; conservative surgery using tissue glue and external compression with polyglactin 910 (Vicryl) mesh for graft ruptures; drainage and application of sclerosants under ultrasound control and intraperitoneal marsupialization for the clinically relevant lymphoceles; transluminal angioplasty with balloon dilatation in case of significant arterial stenosis; extracorporeal shock wave lithotripsy and surgery for urinary calculi. Intestinal perforations and problems relating to parietal tissue were quickly solved using standard surgical techniques. On total, rejection of the graft occurred in four (4%) cases following surgical complications, while one death was encountered due to septic peritonitis. We consider the percentage of surgical complications acceptable, as this work consists of a pioneering effort in this Balkan region.

Human leukocyte antigens (HLA) at loci A (14 antigens) and loci B (29 antigens) were determined in 2,385 healthy Macedonians, using the microlymphocytotoxicity test. Results were compared with those obtained in Caucasians. The most common HLA antigens in the Macedonian population are: A2 (51.65%), A1 (25.87%), A3 (17.14%) and A24 (20.41%) for loci A and B51 (32.03%), B35 (23.98%), B8 (12.11%), B44 (12.11%), B7 (11.48%) and B18 (10.23%) for loci B. These frequencies are similar to those found in Caucasians. However, antigens B12, B44, B7, B8 and especially B15 are more common in Caucasians, while B51 and B35 antigens are more common in the Macedonian population. The most common haplotypes in the Macedonian population are: A2/B51 (15.68%), A2/B35 (10.35%), A2/B12 (7.79%), A9/B51 (7.50%) and A1/B8 (7.50%). The frequencies of HLA antigens were also determined in 348 patients with chronic renal disease and compared with those observed in the healthy population (2,385 subjects). No significant differences was observed between HLA frequencies depicted in patients and those described in healthy individuals. Results should therefore make easier the finding of compatible kidney transplants in the Macedonian population.

Serum from 115 HIV negative renal transplant recipients having more than 6 months follow-up was tested for the presence of mono- or oligoclonal immunoglobulins (moIg) by immunoelectrophoresis or immunofixation. Mono/oligoclonal gammapathy was detected in 16 patients (13.9%). Eight of these patients had only one monoclonal band, whereas the other eight had two or more bands. Thirteen of the 16 patients (81.3%) were IgG kappa positive, nine (56.3%) were IgG lambda positive, four (25.0%) were IgM lambda positive and only one (6.3%) was IgM kappa positive. Six monoclonal patients (37.5%) were IgG kappa positive and two monoclonal patients (12.5%) were IgG lambda positive. The oligoclonal combination IgG kappa lambda was present in three patients (18.8%), the combination IgG lambda + IgM lambda was present in two patients (12.5%) and IgG lambda + IgM lambda was present in one patient. The triple combination IgM kappa lambda + IgG kappa lambda and IgM lambda + IgG kappa lambda was found in two patients (12.5%). Ninety percent of these moIg did not exceed 2 g/L. MoIg appeared between 1 and 28 months after the kidney transplantation (mean value: 8.5 5.9 months) but were often transient, disappearing within 1 to 19 months in 13 patients (81.3%). Nine of the 16 cases (56.3%) disappeared before the end of the first year after detection. Risk factors for the appearance of these immunoglobulins have been identified as: the patient's age, the duration of haemodialysis, the occurrence of prior (anti-cytomegalovirus [CMV]) infection, and therapy with cyclosporin A (CsA). The persistence of monoclonal gammapathy was associated with acute or reactivated Epstein-Barr virus (EBV) infection and inability to convert IgM to IgG CMV antibodies. Furthermore, no association was established with previous hepatitis B or C infection or the number of rejection episodes. Kaposi's sarcoma was found in one patient (6.3%) but had no correlation with the presence of moIg. We recommend careful follow up of renal transplant patients in whom moIg have been discovered.