Use of elderly living kidney donors: twenty years' experience in the Balkans.

The Balkan region has dramatically changed during the last 20 years. Despite transplantation efforts, dialysis remains the usual way to treat end stage renal diseases. Living donor renal transplantation is still the predominant transplant activity. Seeking to solve the problem, we decided to accept expanded criteria living donors, including elderly, marginal, unrelated, and ABO-incompatible individuals. Herein we have presented our 20 years' experience with 230 living donor renal transplantations using elderly individuals, including 90 older than 65 years (mean age 68 ± 4.5; range = 65-86; ED group). The predominantly haploidentical recipients had a mean age of 45 ± 6 years (range = 18-66). Sequential immunosuppressive protocols were used in all cases including induction with anti-thymocyte-globulin or interleukin-2 receptor antagonists. We analyzed the 5-year Kaplan-Meier graft survival rate, rejection episodes, delayed graft function, and renal function for comparison with these outcomes of 110 kidneys from younger donors (mean age = 53.4 years; range = 25-62; YD group) and haploidethical recipients (mean age = 32.2, range = 16-42), performed within the same period. The 3- and 5-year cumulative graft survival rates in the ED group were 81% and 72% compared with 85% and 81% in the YD group respectively (P > .9; NS). The incidences of acute rejection episodes were also comparable for both groups (19% and 17%, respectively). Delayed graft function occurred in 15% of the ED group but only 8% of the YD group. The serum creatinine value at the end of 60 months' follow-up was 146.04 µmol/L in the ED group versus 123.38 µmol/L in the YD group (P < .001). There were no major surgical complications in either group. We recommend the use of elderly living donors as a valuable source of kidneys, especially in countries wherein deceased donor transplantation is not yet established.

Optimal blood grouping and antibody screening for safe transfusion.

(Full text is available at http://www.manu.edu.mk/prilozi). Introduction. Blood group antigens as integrated parts of the red cell membrane have many essential functions for the cell as well as for the organism, but they are recognized as unique antigens for the purpose of safe blood transfusion. Especially in the case of those with great clinical importance because of their involvement in haemolytic transfusion reactions and hemolytic disease of the newborn, it is very important that they be correctly, and some of them routinely, typed in blood donors as well as in patients. Aim. Evaluation of Rh and Kell blood group antigen frequencies in blood donors as well as the incidence of alloimmunization in transfused patients in the Macedonian population. The need for routine typing of certain blood group antigens in addition to ABO and RhD was also evaluated. Material and method. We evaluated data from 1600 ABO/Rh and Kell typed blood donors (from January 2003 to May 2008), as well as the data from pretransfusion testing (ABO/RhD blood typing, irregular red blood cell antibody screening and compatibility testing) and antibody identification in the period from January 2005 to November 2008. All tests were performed by the DiaMed micro tube gel system. Results. The frequencies of ABO antigens were as follows: A (39.7%), O (38%), B (14.1%), AB (7.4%). The frequencies of Rh antigens were as follows: D pos. (84.2%), D neg. (15.8%), C (58.3%), c (82.4%), E (21.3%), e (97.1%). We found the following frequencies of Kell phenotypes: K+ k- (0.25%), K+ k+ (6.18%), and K- k+ (93.6%) with the total frequency of K antigen of 6.4%. Antibody screening and/or cross-match were positive in the sera from 150 transfused patients. In 75 (50%) sera the following 81 antibodies were identified: anti-K (26), -E (25), -e (1), -C (4), -c (6), -C(w) (2), -k (1), -Fy (a) (3), -Fy(b) (1), -Jk(a) (3), -Lu(b) (1), -Le(b) (2), -Le(a) (1), -M (4), -P1 (1). The most frequent alloantibody was anti-K with 32%, and anti-E with 30.8% of all identified antibodies. Conclusion. Alloimmunization to red cell antigens is still a current problem in our transfusion practice. It is obvious that the additional testing of blood donors for Rh and Kell antigens should be implemented as a routine to prevent as far as possible the incidence of alloimmunization. It would also be cost-effective, bearing in mind the additional laboratory testing necessary to provide compatible blood for alloimmunized patients. Extended blood typing should be implemented for some categories of polytransfused patients as well. This strategy is another step forward to improve the safety of blood transfusion with optimal blood grouping. Key words: Kell phenotypes frequency, alloimmunization, blood grouping, safe transfusion.

De novo malignancies after renal transplantation--a single-center experience in the Balkans.

The occurrence of malignancies is a well-known serious complication after organ transplantation. Despite the fact that many factors may be involved, the pathogenesis is still unclear. The aim of the present study was to examine the incidence and clinical characteristics of de novo malignancies that arise after renal transplantation over a 13-year experience in a single center in the Balkan Peninsula. During this period, 185 renal transplantations (139 living related and 46 cadaveric) were followed in our department. Overall, 19 malignancies (9.78%) were observed in 15 patients (7.8%). The mean age of these patients was 45 years (range, 21-53 years). Ten patients (55%) developed skin cancers: 8 squamous and 2 basal cell. Kaposi's sarcomas were found in 3 patients (16.6%, 1 visceral form). We also detected 1 breast cancer, 1 seminoma, 1 colon cancer, 1 urogenital-transitional cell-like cancer, 1 renal cell carcinoma, 1 plasmacytoma, and 1 retroperitoneal sarcoma after an ABO incompatible transplantation. All cancers were de novo malignancies that presented at a mean time of 21 months (range, 2-52 months) after surgery. In conclusion, the incidence of malignancy in the present series was similar to that reported elsewhere. The predominance of skin cancers was understandable bearing in mind the sunshine. The appearance of skin malignancies in our group of patients was earlier, more severe, and multiple sites. No cases of posttransplantation lymphoproliferative disorders were observed. Careful clinical examination and long-term screening protocols are needed for early detection and treatment of this life-threatening complication among the transplant population.

Living emotionally related renal transplantation (LERT)--single center experience in the Balkans.

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.

Living related renal transplantation--the use of advanced age donors.

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.

[Kidney transplantation in Macedonia]. / Transplantation rénale en Macédoine.

During the last 10 years we performed 92 renal transplantations in our Skopje hospital (Macedonia), using 22 cadaver donors and 70 living donors. We also performed 15 explanations from cadavers and seven kidneys were allocated to former Yugoslavia. Standard surgical procedures were used for both living and cadaver donor explantations and transplantations. For living explantations, donors were matching in 66 cases (94.28%) and in four cases (5.7%) non-matching donors who however were relatives of the patient Explantations and transplantations took place only after all ethical- and legal-related problems had been solved. The minimum acceptable HLA mismatch was 50% with negative present or historical cross-match. A quadruple sequential immunosuppressive treatment was used, including either poly- or monoclonal globulins (thymoglobulin [ATG], lymphoglobulin [ALG], daclizumab, OKT-3) as an induction therapy and prednisolone, azathriopin and cyclosporin A as maintenance therapy. Rejection episodes were treated by pulse MP therapy or OKT-3 and increased doses of MMF if the patients were steroid-resistant. Kaplan-Meier survival curves showed that survival at 12, 36 and 60 month reached 90%, 75% and 60%, respectively. Survival was better after transplantation using a graft from a living donor than after transplantation using a graft from a cadaver donor (survival rates: 92%, 82% and 68% at 12, 36 and 60 months after surgery). Delayed graft functioning (DGF) was observed in 16 patients (17.3%), reaching 46.6% after transplantation of a graft from a cadaver donor and 10% after transplantation of a graft from a living donor. The relatively high percentage of DGF in the living donor program was due to the use of grafts from elderly donors (over 65 years of age). We registered 26 (29%) episodes of acute rejection that were predominantly histologically confirmed and further classified according to the BANFF criteria. Treatment of five steroid-resistant rejections proved to be successful. Neither early nor late surgical and medical complications were different from those reported in the literature. Despite the modest number of kidney transplantations, chronic renal failure has decreased in our region. The authors expect further improvement in this powerful therapeutic procedure thanks to links with regional and European transplant centers allowing better cooperation and organ sharing.

[Kidney transplantation using living donors over age 65]. / Transplantation rénale utilisant des donneurs vivants de plus de 65 ans.

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.

[Epidemiology of the major histocompatibility complex-human leukocyte antigen in the Madeconian population]. / Epidémiologie du complexe majeur d'histocompatibilité "human leucocyte antigens" dans la population macédonienne.

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.

[Living donors: immunologic factors]. / Donneurs vivants: aspects immunologiques.

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.

[Postoperative complications following kidney transplantation]. / Complications chirurgicales après la transplantation rénale.

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.

[Cancer after kidney transplantation and immunosuppression]. / Cancer après transplantation rénale et immunosuppression.

Between 1977-1998 we followed up 115 patients with renal allograft. Seventy patients had received a graft from a living donor, while 45 had received a graft from a cadaver donor. The immunosuppressive therapy included azathioprin (AZA), prednisolone (PRED) and cyclosporin A (CyA) in 90 patients and AZA and PRED in 25 patients. Nine patients showed skin malignancies (7.3%), three of these patients had Kaposi's sarcoma and the other six patients squamous or basal cell carcinoma. All cases were clinically and histologically confirmed. Squamous or basal cell carcinoma occurred mostly on the head and was radiosensitive, though recurrences might be observed. Kaposi's sarcoma was localized on either the lower extremities or the face. The condition of two patients treated by radiotherapy only partially improved. Due to chronic renal allograft rejection immunosuppressive therapy was withdrawn in two patients and dialysis was restarted without any other recurrence of the sarcoma. The rate of cancer occurrence in patients with renal allograft is consistent with the findings of other authors. Reduction or withdrawal of immunosuppressive therapy may have a beneficial effect on malignancy, but incurs the risk of losing the allograft.

[Mono- and oligoclonal immunoglobulin anomalies in kidney transplant patients]. / Les anomalies immunoglobulinémiques mono- et oligoclonales chez les transplantés rénaux.

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.