Beneficial short term effect of low protein diet on chronic kidney disease pro-gression in patients with chronic kidney disease stage G3a. A pilot study.

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.

Interviews With Patients Who Traveled From Macedonia/Kosovo, The Netherlands, and Sweden for Paid Kidney Transplantations.

BACKGROUND: Patients travel worldwide for paid kidney transplants. Although transplantations abroad are not always illegal, they are commonly perceived to be illegal and unethical involving risks. AIM: We aimed to describe the motivations and experiences of patients who traveled abroad for paid kidney transplantations and to examine how these transplantations were facilitated. METHODS: We interviewed 22 patients who traveled from Macedonia/Kosovo, the Netherlands, and Sweden for paid kidney transplantations between years 2000 and 2009. RESULTS: Patients traveled because of inadequate transplant activity in their domestic countries and dialysis-related complaints. However, 6 patients underwent preemptive transplantations. Cultural factors such as patients' affinity with destination countries, feelings of being discriminated against by the health-care system, and family ties also help explain why patients travel abroad. Seven of the 22 patients went to their country of origin. They were able to organize their transplantations by arranging help from family and friends abroad who provided contacts of caregivers there and who helped cover the costs of their transplants. The costs varied from €5000 to €45 000 (US$6800-US$61 200). Seven patients paid the hospital, 5 paid their doctor, 4 paid a broker, and 6 paid their donors. CONCLUSION: Research should include interviews with brokers, transplant professionals, and other facilitators to achieve a full picture of illegally performed transplantations.

Could living unrelated renal transplantation ameliorate the actual shortage of organs in the Balkan region?

BACKGROUND: Despite the efforts for more transplants performed with organs from deceased donors, the living renal transplantation is still the predominant transplant activity in the Balkan region. In order to adress the severe organ shortage, we started accepting unrelated (emotionally related) living donors (LURD). Here we present our 10-year experience with living unrelated renal transplantation (LURT). METHODS: Twenty four LURT were performed in our center in the last 10 years. The mean recipients and donors age was 41.7 and 47.2 years, respectively. As LURD spouses (n=17) and extended family members (n=7) were accepted predominantly. All donors went through careful psychological evaluation in order to confirm emotional relationship. The final decision was taken after both the recipient and the donor signed a consent in front of a judge. A quadruple sequential immunosuppressive protocol was used in all recipients. The 5-year Kaplan Meier graft survival rate, HLA mismatch, rejection episodes, delayed graft function, serum creatinine and Glomerular filtration rate-Modification of the diet in renal disease (GFR-MDRD) were analyzed. The results were compared with 30 living related renal transplants (LRT) performed during the same time with mean recipients and donors age of 35.9 and 58.5 years, respectively. RESULTS: The mean follow up for LURT and LRT recipients were 81.4 and 79.6 months, respectively. There was a significant difference regarding recipients and donors age, HLA mismatch (5.07 and 2.9) and rejection episodes (16% vs. 11%) in LURT and LRT recipients. The 5 years graft survival rate was excellent in both groups (83 and 81%, respectively). There was no significant difference in 5 years serum creatinine (129.3 vs 121.1 µmol/lit) and 5 years GFR-MDRD (56.6 and 58.6 ml/min). CONCLUSION: The authors present an excellent 5-year graft survival rate in both LURT and LRT recipients. Therefore, LURT could ameliorate the severe organ shortage in the region and could be recommended as a valuable source of organs in the countries with developed and underdeveloped deceased donor donation.

Acute renal failure in a patient with diffuse large B-cell lymphoma: case report.

INTRODUCTION: Renal parenchymal involvement is common in systemic lymphomas. In almost all cases, renal involvement appears to be a secondary process, either by direct extension from a retroperitoneal mass or via haematogenous spread in the setting of disseminated disease. Secondary renal involvement in systemic lymphomas is generally presented as multiple masses, but also as a solitary nodule. Acute renal failure by a lymphoma infiltration of the kidney is extremely rare. Primary renal non-Hodgkin's lymphoma is even more uncommon and it is a debated issue because of the absence of lymphoid tissue in normal kidneys. CASE PRESENTATION: We report on the case of a 62-year old woman, who had melena, abdominal pain, malaise and fever. She was hospitalized at the Nephrology Clinic due to severe anemia and signs of acute renal failure. The peripheral blood smear showed the presence of dysplastic erythroblasts and hypo-granular neutrophils. Ultra-sound was performed, which showed enlarged kidneys with signs of urinary obstruction of the first degree, with swollen, hypoechogenic parenchyma. After not responding to the conducted treatment, the patient died from heart failure. An autopsy was performed and Non-Hodgkin's, diffuse large B-cell lymphoma infiltrating multiple parenchymal organs was determined as the main cause of death. CONCLUSION: Diffuse large B-cell lymphoma with multiple organ affection and secondary renal involvement, presented as an acute renal failure is a rare case. We report on this case to update the literature concerning this topic and highlight the importance of renal biopsy in the diagnostics.

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.

Clinical importance of insulin resistance after renal transplantation in patients on triple immunosuppressive therapy with cyclosporine, corticosteroids and mycophenolate mofetil.

INTRODUCTION: Post-transplant diabetes mellitus and impaired glucose tolerance are confirmed complications after solid organ transplantation associated with the use of glucocorticoids and calcinuerin inhibitors in maintenance immunosuppression. Insulin resistance (IR) is also an independent factor for cardiovascular morbidity and mortality among renal allograft patients. The aim of our work was to investigate the clinical importance of elevated IR in renal transplant recipients on standard triple-drug immunosuppression in correlation with immunosuppressive therapy and certain independent factors such as body mass index (BMI), time after transplantation, lipid disorders, etc. METHODS: 36 allograft pts with different periods after transplantation without previous glucose disorders were included in the study. An oral glucose tolerance test (OGTT) was made to distinguish pts with or without glucose disorders. The basal values of glucose (G) and insulin (I) were used to calculate indexes of IR and beta-cell function according to the homeostasis equations. Impaired fasting glucose (IFG), impairred glucose tolerance (IGT), impaired post prandial hyperglycemia (IPPH) and diabetes mellitus (DM) were also analysed. RESULTS: The mean value of the IR index was 2.57 +/- 1.20. It was elevated in 31 pts (86%) The IR showed a positive correlation with: I0 (p < 0.01), I2 (p < 0.05), beta cell function (p < 0.05) and CsA (p < 0.01). The fasting I, G, and BMI were shown as independent risk factors for IR (p < 0.01, p < 0.01, and p < 0.05 respectively). There were 12 pts with different glucose disorders (IFG, IGT, DM) and 24 pts without. The pts with glucose disorders showed an elevated IR index (91%) more frequently compared with (41.67%) decreased beta-cell function. CONCLUSION: IR is frequent among renal recipients with and without glucose disorders. IR is an independent risk factor for atherogenesis. Higher CsA trough levels are assotiated with higher Insulin values and indexes of IR. The defect in insulin action is more a prominent mechanism in post-transplant glucose disorders than the impaired insulin secretion.

Do we have to treat subclinical rejections in early protocol renal allograft biopsies?

The aim of the present study was to evaluate whether treatment of subclinical, borderline rejections (SR/BR) or histological findings of chronic allograft nephropathy (CAN) in protocol biopsies in the first month posttransplantation after living related kidney transplantation has a beneficial effect on graft histology and renal function at 6 months. Among the 40 paired biopsies, only 6/80 showed no histological lesions. BR was found in 13/40 and 12/40, and SR in 15/40 and 21/40 of patients on the 1- and 6-month biopsies, respectively. The mean histological index/total sum of scores for acute and chronic changes (HI) increased at 6-month biopsy: 5.3 +/- 2.9 vs 7.8 +/- 3.6 (P < .001). Similarly, the mean sum of histological markers for chronicity (CAN score) of 2.1 +/- 1.5 increased to 4.6 +/- 2.3 (P < .001) on the 6-month biopsy. When divided according to whether there was treatment of BR and SR, the treated BR/SR group on 1-month biopsy had a mean HI score of 7.11 +/- 1.9, which remained almost the same (7.11 +/- 2.32) at 6 months. Among the untreated BR/SR group it increased from 4.95 +/- 1.99 to 8.16 +/- 4.30. However, there was no difference in graft function between the groups from 1 to 6 months. In conclusion, a protocol 1-month biopsy may be valuable to establish the prevalence of BR/SR in stable allografts. The presence of an untreated BR/SR upon a 1-month biopsy showed greater susceptibility for histological deterioration on the 6-month biopsy due to an accelerated CAN process.

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.

Inflammation and anaemia as predictors of cardiovascular mortality in hemodialysis patients.

BACKGROUND: Cardiovascular diseases are the most common causes of death among hemodialysis (HD) patients, yet the risk factors for these events have not been well established. Our study objective was to determine predictors of cardiovascular mortality, considering the non-traditional/disease-related and treatment-related/ cardiovascular risk factor in HD patients. MATERIAL AND METHODS: Disease-related cardiovascular risk factors, such as anaemia, calcium-phosphate disorders, nutrition-inflammation and treatment/dialysis-related cardiovascular risk factors such as HD dose, using the index Kt/V were analyzed in 214 patients on HD. Mortality was monitored prospectively over a two year period. RESULTS: Fifty-three of the 214 HD patients died during the follow-up period and the main cause of death was cardiovascular events (56.6%), followed by infection/sepsis (26.4%). The patients who died were significantly older than those alive, had significantly lower serum levels of hemoglobin (Hb), albumin and Kt/V. Serum levels of calcium, C-reactive protein (CRP) and fibrinogen were significantly higher in patients who died during the follow-up period. Kaplan-Meier analysis showed that the all cause and cardiovascular mortality was considerably higher in patients with Hb<110 g/l, albumin <40 g/l, CRP>8 mg/l and spKt/V<1.2 (log rank, p=0.000/p=0.000, p=0.000/ p=0.001, p=0.000/p=0.000, p=0.000/p=0.000), respectively. No difference in cardiovascular mortality was observed between the fibrinogen <4 g/l> levels. High CRP, low Hb levels and low spKt/V were significant predictors of all-cause mortality, but low albumin and high fibrinogen levels were not in the Cox proportional hazards analysis. When only cardiovascular mortality was entered into the Cox model, high CRP and low Hb levels were the only significant predictors for mortality. CONCLUSIONS: It can be concluded that, inflammation (elevated CRP) and anaemia (decreased Hb), were identified as significant independent non-traditional, disease-related cardiovascular risk factors that predict cardiovascular mortality in HD patients.

Hypertension and progression of nephropathy in diabetic and non-diabetic chronic kidney disease patients.

BACKGROUND: Hypertension is associated with more rapid progression of chronic kidney disease. Several studies have shown that treating hypertension in patients with chronic kidney disease and proteinuria may attenuate the decline in glomerular filtration rate. STUDY OBJECTIVE: The study evaluates the prevalence of hypertension and its association with chronic kidney disease progression in patients without and with diabetic nephropathy. METHODS: Patients with CKD stage 2-4 were followed up by a nephrologist for 12-52 months. A total of 137 patients were included in the study, 70 with non-diabetic CKD and 67 with type 2 diabetes and diabetic nephropathy. Demographic and clinical parameters were recorded at initiation and during follow-up. Glomerular filtration rate was estimated by the Cockroft-Gault formula and progression of CKD by the slope of the estimated GFR decline. RESULTS: Out of 70 patients in the non-diabetic group, 34 were males, (mean age 50.37+/-12.2 years). Out of 67 diabetic patients, 30 were (males, mean age 57.8+/-8.4 years). 77% in the non-diabetic group had SBP above 140 mmHg. The higher SBP was associated with older age, (53.16+/-10.8 vs 40.9+/-12.2 years, p<0.0001). Diastolic blood pressure above 90 was present in 73%. Pulse pressure above 80 had 5.7% and was associated with older age (p<0.02). Progression of chronic kidney disease correlated inversely with age, and positively with diastolic blood pressure and proteinuria (p=0.005, p=0.019 and p=0.02 respectively). Multiple regression analysis showed that only younger age and higher proteinuria were predictive for chronic kidney disease progression (p=0.00002). 6% of pts in the diabetic group had SBP below 140, 19% between 140 and 160, and 75% above 160 mmHg. Diastolic blood pressure below 80 had only 6% of patients, between 80 and 90 had 37% and above 90 mmHg had 57%. Pulse pressure below 80 mmHg had 55% and it was correlated positively with age, p=0.009. Progression of chronic kidney disease in the diabetic group correlated positively with mean arterial pressure, systolic blood pressure and proteinuria, (p=0.017, 0.036 and 0.000000 respectively) and inversely with age (p=0.0003). Multiple regression analysis showed that proteinuria, age and SBP were the only predictors for chronic kidney disease progression in diabetics. CONCLUSION: Isolated systolic hypertension predominates the older age groups, proteinuria and age significantly correlate with GFR decline in both groups, and SBP is associated with more rapid progression of CKD in the diabetic patients.

The evolution of untreated borderline and subclinical rejections at first month kidney allograft biopsy in comparison with histological changes at 6 months protocol biopsies.

Our study sought to identify the possible implications of histological findings of borderline and subclinical rejections as well as histological markers of chronic allograft nephropathy (CAN) in protocol biopsies at 1 and 6 months after living-related kidney transplantation. Twenty-eight paired allograft biopsies were blindly reviewed using Banff '97 criteria, among which only 10.7% (6/56) showed no histopathological lesions. BR was found in 9/28 (32.1%) and 6/28 (21.4%), and SR in 3/28 (10.7%) and 10/28 (35.7%) of the patients, in the 1 and 6 month biopsies, respectively. The mean CAN score (sum of histological markers for chronicity) increased significantly at 6 months biopsy, 1.57 +/- 1.36 vs. 4.36 +/- 2.32 (p < 0.01). When compared according to chronicity index (CI < 5 >), the high CI group had a mean CAN score of 2.36 +/- 1.15 at 1 month, which increased to 5.14 +/- 1.99 at 6 months biopsy (188.9%). The proportion of these changes in low CI group were also increased from 0.79 +/- 1.12 to 3.57 +/- 2.38 (451.9%). In conclusion, a protocol 1 month biopsy may uncover a high prevalence of BR or SR in stable allografts. The presence of an untreated BR or SR in biopsies with low chronicity index showed greater susceptibility to histological deterioration on the 6 month biopsy, associated with rapid impairment of graft function and chronic allograft nephropathy.

Living-unrelated (paid) renal transplantation--ten years later.

Due to the increase of organ shortage and still inadequate development of cadaver transplantation, many end-stage patients from the Balkan region travel mostly to India to buy a kidney. Despite all the ethical dilemmas and discussions, organ sales is present nowdays in Third-World countries. Sixteen patients (13 from Macedonia and 3 from Kosovo, SCG) were observed clinically during a period of 10 years. Recipients of mean age 36.5 years (range 10 to 58) displayed the following underlying diseases: chronic glomerulonephritis (n = 5), urethral valves with reflux (n = 2), ADPKD (n = 1), hypertensive nephropathy (n = 4), lithiasis (n = 1), and unknown cause of ESRD (n = 3). The donor population was young (22 to 29 years). Most patient records did not include data on HLA, cross-match, MLC, kind of surgery, or usual pretransplant workup. The immunosuppressive protocol included CyA, PRED, and AZA or MMF. All transplanted patients were followed on an outpatient basis in our department; patients with complications were hospitalized. The 1, 3, 5, and 10 year Kaplan Meier graft survival rates were 78.6%, 50.2%, 33.3%, and 18.8%, respectively. Seven patients were lost (43.7%), two during the first month after transplantation, two at the end of the first year, and three at 5, 6, and 8 years thereafter. The main reasons for death were severe pulmonary infections with sepsis, hepatitis B with liver cirrhosis, Kala Azar, CMV, and cancer of the colon. Five grafts were lost due to repeated rejection episodes and chronic graft nephropathy. The last three cases remained with good renal function and actual serum creatinine values of 135 +/- 9. In view of this experience, the authors cannot recommend this type of transplantation, not only from the ethical point of view, but also from frequent medical and surgical complications which are sometimes life threatening.

Protocol biopsies in kidney transplant recipients: histologic findings as prognostic markers for graft function and outcome.

The aim of the present study was to identify subclinical and borderline rejections as well as histological markers of chronic allograft nephropathy (CAN) among protocol biopsies performed at 1 and 6 months after living related kidney transplantation to assess their possible implications for graft function. Twenty paired allograft biopsies performed at 1 and 6 months were reviewed according to the Banff scoring scheme. The mean ages of donors and recipients were 59.6 +/- 13.8 and 34.4 +/- 8.7 years, respectively. Among all biopsies only 10% (4/40) showed no histopathological lesions. At the first month borderline rejection was shown in 35% and subclinical rejection in 10% of patients. At 6 months the proportion of findings was even higher, namely, 40% and 30%, respectively. When divided according to donor age, donors above 55 years showed a mean CAN score of 2.33 +/- 1.56 which increased to 5.0 +/- 2.26 on the 6 month biopsy (214.3%). Unexpectedly, the proportion of these changes in the younger donor group also increased by 173.3%, which might have been explained by the greater number of borderline and subclinical rejections in the younger donor group at the 1 month biopsy. In conclusion, 1 month biopsy may be valuable to determine borderline and subclinical rejection and to prognosticate the outcome of renal allograft function. Our findings suggest a greater susceptibility of histological deterioration among the older donor population. However, the presence of an untreated rejection in the younger donor pool leads to a rapid impairment of the graft function accelerating the process of chronic allograft nephropathy.

Recurrent glomerulonephritis in living kidney transplantation.

Glomerulonephritis (GN) is one of the most frequent causes of end-stage renal disease. Recurrent GN can occur very early after transplantation in up to 20% of renal-allograft recipients and should be considered with late graft dysfunction in 2-5%. Importantly, diagnosis of a clinically silent recurrence of the disease will pass undetected unless transplant centers have a policy of protocol biopsies. In addition, the classification of the type of recurrent GN should be done with data on electron microscopy and immunofluorescence, in order to promote prompt treatment and a strategy for long-term graft survival. The aim of our paper was to present a few typical cases of recurrent GN, showing the actuality of the problem in living related kidney transplant recipients and to ascertain the importance of precise and timely diagnosis by protocol biopsy. Recurrent focal segmental glomerular sclerosis (FSGS) in childhood is associated with the highest number of graft loss. The treatment of recurrent FSGN is difficult, so prophylactic plasmapheresis prior to transplantation appeared to be more effective in preventing recurrence than plasmapheresis after transplantation, especially in population of children. Mesangio proliferative GN type II is the second most frequent recurrent GN, followed by type I. Here, it is of paramount importance to classify the type of the disease. The family of the patient at risk for recurrent GN, a candidate for living related kidney transplantation, should be informed for the expected outcome and their voluntary decision whether to proceed with transplantation should be awaited.

Chronic allograft nephropathy (CAN) in early renal protocol biopsies: does treatment of borderline and subclinical acute rejections prevent development and progression of CAN?

Histological markers of chronic allograft nephropathy (CAN) in early protocol biopsies may ultimately result in deterioration of graft function. The aim of our study was to evaluate risk factors of early CAN histology and to determine whether treatment of borderline and subclinical acute rejections (BR/SAR) at 1-month posttransplant, prevents development and/or progression of CAN at 6-month biopsy. Thirty-five paired kidney allograft biopsies at 1 and 6 months after transplantation were blindly reviewed using Banff'97 criteria. The mean CAN score (sum of histological markers for chronicity) increased significantly at 6-month biopsy (1.83 +/- 1.46 vs 4.66 +/- 2.35; p < 0.01). No CAN was present in 27/70 biopsies (38.6%), 71.4% showed progression and 28.6% were with stable CAN at 6-month biopsy. When compared according to the progression, mean histological index (HI) score (sum of acute/chronic changes) in progressed CAN group (pCAN) increased significantly at 6-month biopsy (5.0 +/- 3.0 vs 9.5 +/- 2.8; p < 0.001). At 1-month biopsy, BR/SAR were found in 68% and 70%, in the pCAN and stable (sCAN) groups, respectively. The percentage of treated BR/SAR in sCAN group was significantly higher (57.1 vs 23.5%; p < 0.05), and the score of acute histological lesions lower (1.08 +/- 0.95 vs 0.35 +/- 0.66; p < 0.01) at 6-month biopsy. In conclusion, 1-month protocol biopsy may be valuable to uncover BR/SAR and the presence of early CAN in stable renal allografts. Progression of CAN at 6-month biopsy in our study was found to be associated with a greater number of untreated BR/SAR at 1-month biopsy. This observation may have important implications in the design of clinical trials aimed to prevent the progression of CAN.

Short-term effect of folic acid supplementation in renal transplant recipients and chronic kidney disease patients with comparable renal function impairment.

Recent evidence suggested that the efficacy of folic acid supplementation in reducing plasma total homocysteine (Hcy) concentration might be similar in renal transplant recipients (RTR) and chronic kidney disease (CKD) patients with a comparable degree of reduction of renal function. However, a direct comparison of the response to high dose folic acid supplementation between renal transplant recipients and CKD patients has never been made. Therefore, the goal of this study was to evaluate the response to folic acid (5 mg/day) supplementation in 15 stable renal transplant recipients with evidence of chronic allograft nephropathy, and in 15 CKD (stage 3) patients matched for age, sex and renal function living in the area of Skopje, Macedonia. After 12 weeks of folic acid supplementation, plasma total Hcy concentrations were significantly reduced in the two groups. Percent reduction of plasma total Hcy levels was nearly identical in the two groups (25.7% vs 24.5%, p = NS). These results confirm previous findings regarding the efficacy of folic acid therapy given separately to either renal transplant recipients or CKD patients, and extend them to a direct confirmation of identical efficacy.

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.