Vascular access in hemodialyis patients - registry data.

BACKGROUND: The use of arteriovenous fistula over a central venous catheter in hemodialysis patients is recommended whenever possible. It has become the gold standard among all the available permanent vascular accesses for hemodialysis as it is associated with less complications. The aim of our study was to analyze the type of vascular access in hemodialysis patients in our country, FYR of Macedonia and to see its association with other variables recorded by the National Renal Registry in 2009. MATERIAL AND METHODS: Data were collected by 18 hemodialysis centers in the country. A total of 1,457 patients were analyzed. One hundred and ninety one patients were incident, and 164 out of 1,457 died during the year. Except for 9 patients, all the others had data on type of vascular access, as well as data on any vascular access intervention performed during the year. RESULTS: The overall mean age was 58.8 ± 13.1 years. Eighty-nine percent of the non-incident patients (prevalent plus those who died during the year) had arteriovenous fistula, 10.6% central venous catheter and 0.2% vascular graft. When incident to non-incident patients were compared, incident patients were significantly older, had significantly higher mortality and significantly lower percentage of arteriovenous fistula. Patients with arteriovenous fistula had significantly longer dialysis vintage and significantly less deaths compared to those with central venous catheters. CONCLUSIONS: The study showed that the number of non-incident hemodialysis patients with arteriovenous fistula in the country was high. The incident hemodialysis patients have high number of central venous catheters as vascular access for hemodialysis and significantly higher mortality compared to non-incident patients. Hippokratia 2014; 18 (3): 209-211.

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.

Brain natriuretic peptide between traditional and nontraditional risk factors in hemodialysis patients: analysis of cardiovascular mortality in a two-year follow-up.

BACKGROUND: The ability of brain natriuretic peptide (BNP) together with other traditional and nontraditional risk factors to predict cardiovascular (CV) mortality in hemodialysis (HD) patients has not been well established. The aim of this prospective study was to determine the predictive cutoff values of baseline measurement of BNP along with the known CV disease risk factors to predict all-cause and CV mortality in HD patients. METHODS: BNP concentration before HD was measured in 125 prevalent HD patients (age 53.0 ± 13.5 years, HD vintage 75.2 ± 61.0 months). In addition, several traditional CV risk factors (blood pressure, dyslipidemia, diabetes mellitus, body mass index, left ventricular hypertrophy) and uremia/dialysis-related CV risk factors (anemia, calcium and phosphate impairment, malnutrition, inflammation, ultrafiltration, HD duration, Kt/V) were examined. RESULTS: During the 2-year follow-up, we lost 28 out of 125 patients (22.5%), with CV disease (65.7%) being the main cause of mortality. The cutoff point for BNP, as predictor of the clinical outcome, according to the ROC curve was 1,194 pg/ml for CV mortality with sensitivity and specificity of 63 and 65%, respectively (AUC 0.61 and confidence interval (CI) 95% 0.47-0.75). Kaplan-Meier analysis showed that all-cause (log-rank, p = 0.002) and CV mortality (log-rank, p = 0.001) were the cause of a significantly lower survival in patients with a mean BNP >1,200 pg/ml. The univariate Cox regression analysis found the following factors to be predictors of all-cause mortality: hemoglobin (<110 g/l), phosphorus (>1.78 mmol/l), albumin (<40 g/l), C-reactive protein (CRP ≥ 10 mg/l), BNP (>1,200 pg/ml) and cardiac ejection fraction (≤ 55%). The multivariate Cox regression analyses demonstrated that only CRP ≥ 10 mg/l with a hazard ratio (HR) 6.82 (CI 95% 1.86-24.9, p = 0.004) and BNP >1,200 pg/ml with HR 5.79 (CI 95% 1.58-21.3, p = 0.004) were predictors of all-cause mortality. BNP >1,200 pg/ml with HR 13.52 (CI 95% 1.68-108.9, p = 0.014) was found to be an even stronger predictor of CV mortality than CRP ≥ 10 mg/l with HR 6.53 (CI 95% 1.35-31.6, p = 0.020). CONCLUSIONS: Our study pointed out that BNP >1,200 pg/ml as a marker of cardiac dysfunction and CRP ≥ 10 mg/l as a marker of inflammation identify HD patients at increased risk of CV mortality.

Slow progression of chronic kidney disease and what it is associated with.

INTRODUCTION: The risk factors for CKD include diabetes, hypertension, smoking, systemic inflammation, obesity, proteinuria, dislipidaemia and anaemia, as well as gender, age, ethnic minority status and positive family history. By screening and adequate treatment of modifiable risk factors we are able to prevent or delay the progression of the disease. AIM: The aim of the study was to assess the risk factors associated with rapid progression of CKD and to see what factors are protective of slow progression. METHODS: The study is retrospective. The medical charts of 116 patients with CKD who had been followed up for several years at the Outpatient Department of the Nephrology Clinic in Skopje were analysed. Patient age ranged from 19 to 78 years. The patients were divided into two groups: fast progressors - group I (n = 82; GFR decline > 0.1 ml/min/month) and slow progressors - group II (n = 34; GFR decline = or < 0.1 ml/min/month) with an average follow-up time of 55 months. Patients with diabetic nephropathy were excluded from the study because they are known to be fast progressors. The following variables were analysed: underlying cause of CKD, gender, age, time of follow-up, initial GFR (calculated creatinine clearance according to the Cockroft and Gault formula), final GFR, systolic and diastolic blood pressure, mean and pulse blood pressure, haemoglobin, cholesterol and 24h protein excretion rate. Progression of CKD was assessed by linear regression analysis of the mean monthly decrease of calculated creatinine clearance (delta CCcr). RESULTS: There was no statistically significant difference between fast and slow progressors regarding their systolic, diastolic, mean and pulse arterial blood pressure. With regard to the other risk factors, it appeared that progressors are significantly younger (50.50 vs 59.20; p = 0.001, more anaemic Hb-116.68 g/l vs 123.27; p = 0.0036), more proteinuric (1.46 g/d vs 0.76; p = 0.003) and have higher diastolic blood pressure (92.25 mmHg vs 84.75 mmHg; p = 0.005) compared to non-progressors. There was no statistical difference between the groups in terms of gender (p = 0.451). Regarding renal diagnosis, there was a statistically significant difference in progression among the four diagnostic groups, p = 0.00208. Chronic glomerulonephritis (GN) was associated with significantly faster progression (delta KKK = -0.5525 ml/min/mo) compared to interstitial nephritis/nephrosclerosis (IN/NS) (delta KKK = -0.2542 ml/min/mo), p = 0.03918, and compared to unknown renal disease (Unkn) (delta KKK = -0.1487 ml/min/mo), p = 0.0245. Polycystic kidney disease (PKD) had faster progression (delta KKK = -0.5704 ml/min/mo) compared to IN/NS, p = 0.04340 and compared to Unkn, p = 0.0251. CONCLUSION: Timely recognition of risk factors for CKD progression and their treatment by correction of high blood pressure, reduction of proteinuria, correction of anaemia and dyslipidaemia (to lower cardiovascular risk) may retard progression of CKD to end-stage renal disease, thus delaying the need for renal replacement therapy.

Dialysis and aphaeresis in the Republic of Macedonia "a success story".

The first haemodialysis (HD) in the Republic of Macedonia (RM) was performed in 1959 in a patient with acute renal failure (ARF) using Kolff-Brigham rotating drum artificial kidney at the Blood Transfusion Institute in Skopje. In 1965 the Renal Unit at the Dept. of Medicine, Medical Faculty, Skopje obtained a modern, new artificial "Websinger" kidney with sigma motor pump and possibilities for use of disposable Kolff "twin coil" dialyser. Between 1959 and 1971, HD was performed only in patients with ARF. In May 1971 at the Renal Unit, a Unit for chronic HD was founded and the program of maintenance haemodialysis (MHD) was started with five Stuttgart Fresenius machines and 12 patients dialysed on twin coil dialyzers. 1173 patients were treated in 18 HDC in the RM in 2007. 320 machines were used; 299 (93%) for bicarbonate HD and 21 (7%) for acetate HD. In all centers the water for HD was processsed by reverse osmosis. There was no reuse of dialysers. All patients received the same treatment. The patients received epoetin (recombinant human erythropoetin - alpha and beta) to maintain hemoglobin between 100 and 120 g/L. Our patients received epoetin between 62% and 100 % in HDC according the individual need. The Cimino - Brescia arterial-venous fistula was typically used as permanent vascular access. Prevalence of the HBV in patients on MHD varied between 6-28% in different centers. Prevalence of HCV in patients on MHD was between 37-78% in some centers. Nosocomial infection is probably one of causes of the so high prevalence of HCV in our patients. We do not have HIV infection in patients on MHD. The survival rate of our patients treated with MHD was 60% at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. PD was started in 1995 in children and in 1996 in adults. Now, there are 24 adult patients treated with PD. Since 1985 membrane PE has been in regular use. Most therapeutic procedures were performed on patients from the Dept. of Neurology. 1216 patients were on RRT in 2005. On HD were 1077 (89%), with transplanted kidney 121 (10%) and on PD - 18 (1%). 601, 4 patients were on RRT per million of population. The activity of the Macedonian nephrology societies helped a lot in the development of the nephrology and dialysis inviting distinguished nephrologists from Europe and the world and transferring the achievement of the world in our practice. Having in mind that CKD, ESRD and RRT are a great burden for the health budget, we need early diagnosis and treatment of CKD, i.e. prevention of kidney disease.

Association between haemoglobin level and all-cause mortality in haemodialysis patients: the link with inflammation and malnutrition.

Although anaemia management has improved in haemodialysis (HD) patients in recent years, many of them still have haemoglobin (Hb) levels below the current recommendations. The consequent anaemia could be one of the links between malnutrition and inflammation, and higher mortality in HD patients. The study objective was to determine the relationship between Hb levels and outcome in patients undergoing HD, accounting for inflammation and malnutrition. We retrospectively analysed a total of 236 patients on HD between January 2003 and December 2005, classified by absence or presence of inflammation and malnutrition (defined as serum albumin levels < 40 g/L and CRP > 8mg/l). Serum levels of Hb, ferritin, creatinine, cholesterol, triglycerides, HDL (high-density lipoprotein cholesterol), LDL (low-density lipoprotein cholesterol), albumin and CRP were measured monthly, fibrinogen was measured every third month. Over the period of three years, 73 out of 236 patients (30%) had died, most from cardiovascular diseases (62%). Presence of inflammation and malnutrition (in 44% of patients) was associated with older age (60.69 -/+ 12.46 vs. 54.52 -/+ 12.37, p = 0.0002), lower levels of Hb (99.53 -/+ 14.97 vs. 111.86 -/+ 10.38 g/l, p = 0.0000), creatinine (835.88 -/+ 179.84 vs. 1069.98 -/+ 821.23-/+mol/l, p = 0.0047), albumin (36.58 -/+ 3.41 vs.40.32 -/+ 2.82 g/l, p = 0.0000), cholesterol (4.32 -/+ 1.04 vs. 4.75 -/+ 1.09 mmol/l, p = 0.0025) and higher levels of fibrinogen (4.94 -/+ 1.18 vs. 4.29-/+0.91g/l, p=0.0000) and CRP (30.42-/+29.47 vs. 5.24-/+4.89 mg/l, p=0.0000). The Kaplan-Meier analysis showed that, irrespective of the absence or presence of inflammation and malnutrition, the all-cause mortality was higher in patients with Hb <110g/l (Log-Rank, p=0.00147; p=0.00222). On the other hand, Kaplan-Meier showed that, irrespective of the absence or presence of anaemia (Hb > 110g/l and Hb < 110g/l), the all-cause mortality was higher in patients with the presence of inflammation and malnutrition (Log-Rank, p=0.00222; p=0.00263). The Cox proportional hazard analysis, adjusting for age, showed that only lower serum levels of Hb and higher CRP were associated with all-cause mortality (chi-square=110,306, p=0.0000). Our findings confirm the association of Hb levels < 110g/L with higher mortality among maintenance HD patients, especially in patients with the presence of inflammation and malnutrition. Further investigation of the relationships among anaemia, inflammation and malnutrition and survival is warranted.

Effect of nephrology referral on the initiation of haemodyalisis and mortality in ESRD patients.

Late nephrology referral of patients with chronic kidney disease (CKD) has been suggested as increasing mortality after the initiation of dialysis. The aim of this study was to assess the impact of nephrology referral on the initiation of haemodyalisis (HD) and mortality during HD treatment in end-stage renal disease (ESRD) patients who have died in our institution over a five-year period. We studied data from all 117 patients on HD treatment in our institution who died (after 90 days of HD treatment) in the period between 01.01. 2002 and 31.12. 2006. Early (ER) and late referral (LR) were defined by the time of follow-up by a nephrologist greater than or less than 6 months, respectively, before the initiation of haemodialysis. Out of a total of 117 patients, 37.6% (44 patients) started HD in the ER group and 62.4% (73 patients) in the LR group. At the start of HD, LR patients were older, had a higher proportion of temporary catheters and had a significantly lower levels of haemoglobin and diuresis. Creatinine clearance was less in the LR (7.67 +/- 3.86 ml/min/1.73 m2) vs. the ER group (8.70 +/- 3.62 ml/min/1.73 m2), but not significantly different. Cardiovascular disease (CVD), defined by a history of myocardial infarction, cerebral vascular disease, peripheral arteriopathy, and/or heart failure, was also significantly more common among LR patients compared to ER (56%; 27%, p = 0.002). During the haemodyalisis treatment, the LR group had significantly lower levels of haemoglobin and haematocrit. CVD accounted for about 64% of deaths observed in the LR group. According to echocardiography data, there were no significant differences in the left ventricular mass index (LVMI) between the LR and ER groups at the time of dialysis initiation, but during haemodialysis treatment the LR group had significantly greater LVMI than the ER group (232,96 +/- 92,48 g/m2 vs.184,09 +/- 51,74 g/m2; p = 0,031). The time until death in months during dialysis treatment was significantly different between the LR and ER group, (69.51 +/- 64.03 vs.113.27 +/- 89.03, p = 0.0025). LR patients experienced a greater degree of anaemia and a high prevalence of CVD at the time of dialysis initiation. Our data suggest that the anaemia, CV damage and progression of left ventricular hypertrophy (LVH) in the LR patients during haemodialysis treatment are associated with poor survival on haemodialysis.

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.

Inflammation predicts all-cause and cardiovascular mortality in haemodialysis patients.

Among non-traditional cardiovascular risk factors both malnutrition and inflammation appear to be strong predictors of mortality and morbidity in haemodialysis (HD) patients. Our study objective was to determine predictors of all-cause and cardiovascular mortality, considering the nutritional and immunologic parameters, in a cohort of HD patients treated in a single haemodialysis centre. 216 patients on HD were analyzed for clinical, nutritional-serum albumen and BMI, immunologic-serum CRP (C-reactive protein) and fibrinogen and dialysis parameters -- ultrafiltration, length of dialysis in hours, HD dose (using spKt/V and eKt/V). Mortality was monitored prospectively over a two-year period. Fifty-five of the 216 HD patients died during the follow-up period and the main cause of death was cardiovascular disease (CVD) -- 33 patients out of 55 (60%), followed by infection/sepsis (13 pts, 24%). The patients who died were significantly older, had a significantly shorter duration of HD in hours, ultrafiltration was significantly less, HD doses were significantly lower, as were serum levels of albumin (36.06 +/- 4.17 vs. 39.74 +/- 3.31; p=0.000) and Hg (93.14 +/- 15.43 vs. 109,16 +/- 12,08; p=0.000), but they had significantly higher serum levels of CRP (40.26 +/- 34.75 vs. 8.71 +/- 7.68, p=0.000) and fibrinogen (5.28 +/- 1.28 vs. 4.42 +/- 0.97, p=0.000). Kaplan-Meier survival estimates showed that the group with the lowest levels of albumin (< 3.5 g/L), and with the greatest levels of CRP (>20 mg/l) and fibrinogen (>5 g/L) had the lowest survival (log-rank test p=0.0008, p=0.00000, p=0.0000). However, in the Cox proportional hazards model, a high CRP and low Hg level (chi-square=96.467, p=0.0000) were predictors of all-cause mortality, whereas serum level of albumin did not show to be predictive. When only cardiovascular mortality is entered into the Cox model, CRP and Hg levels are still more important in predicting mortality (chi-square=70.055, p=0.0000) and only if CRP is not taken into account in the multivariate analysis, serum albumin level remains, after Hg, the strongest predictor for both overall and cardiovascular mortality (chi-square=76,564, p=0.0000; chi-square 50.619 p=0.0000). It can be concluded that inflammation predicted all-cause and cardiovascular mortality in our study group, because high CRP, as a marker of inflammation and low haemoglobin, as a result of inflammation, remained powerful predictors of both overall and cardiovascular death.

Early mortality rate in end-stage renal disease patients initiating hemodialysis.

Early referral of patients with chronic renal failure (CRF) to a nephrologist improves morbidity and delays mortality after start of renal replacement therapy (RRT). Late referral is associated with increased cardiovascular morbidity and short-term mortality. The aim of this study was to assess the factors associated with early mortality rate in ESRD patients, during the first month after initiating hemodialysis. One hundred and eighty nine 189 patients hospitalized at the Department of Nephrology in Skopje after starting RRT and followed up during the first month were included in this study. Early referrals were considered those who had been referred to a nephrologist for more than 3 months before initiating RRT. Female to male ratio was 93 to 96 (49/51%). Out of them, 110 were late referrals, and 79 early ones (58/42%). Out of 189, 20 patients died during the first month of follow up (10.6%). 85% of the patients who died were late referrals, not having time and opportunity to be treated for renal anemia, for malnutrition and prevention of cardiovascular and uraemic complications, and all of them lacked permanent vascular access. Early mortality was also associated with older age, renal anemia and malnutrition. Late referrals were also older, predominantly male and had higher serum potassium levels. The main causes of death were related to uraemic intoxication, malnutrition and inflammation as well as lack of permanent vascular access, all of it leading to sepsis, and cardiovascular complications.

Differences in renal registries between the Balkans and Western Europe.

The epidemiology data of renal replacement therapy are collected by national renal registries and extended to international registries as the European Renal Association Renal Registry. The extent and accuracy of data vary widely among countries. The aim of this study was to compare combined data from the national renal registries of Balkan countries contributing the ERA-EDTA Registry or from other sources, with combined data from renal registries of the Western and Northern European Countries and regions contributing the ERA-EDTA Registry. Data regarding incident and prevalent patients in 2003, mean age of incident and prevalent patients, incidence and prevalence by cause of renal failure and prevalence by established therapy were compared between the countries of the Balkan region and the countries of Western and Northern Europe contributing to the ERA-EDTA Registry. Data were obtained by the Annual Report 2003 of the ERA-EDTA Registry, and for Romania by the study of G. Mirescu published in NDT 2004. Some data were obtained by the questionarries sent to people responsible for the national registries. The results showed the following: the incident number of patients per million population (pmp) at day 1 of RRT, as well as at day 91, adjusted for age and gender, did not statistically differ between the Balkans and Western Europe: 119.2 +/-25.1 vs. 123.3 +/- 25.9 and 110.9 +/- 34.7 vs. 106.5 +/- 18.3, respectively. The mean age of incident patients at day 91 of RRT significantly differed between the Balkans and Western Europe, 57.7 +/- 4.49 vs. 63.3 +/- 2.2, p < 0.005. The percentage of incident patients by cause of renal failure at day 91 of RRT did not significantly differ between the Balkans and Europe. The mean incidence of the percentage of DM as a cause of renal failure between the Balkans and Western Europe did not differ, 23.05+/- 4.5 vs. 20.3 +/- 7.2. When adjusted for age and gender, the significant difference in prevalent number of ESRD patients between the Balkans and Western Europe disappeared. The mean age of prevalent patients between the Balkans and Europe did not significantly differ, 54.3 +/- 4.2 vs. 58.2 +/- 2.8. The percentage of primary renal disease in prevalent patients did not significantly differ, except for policystic kidney disease which is significantly more frequent in Western Europe compared to the Balkans, 9.2 +/- 1.9 vs. 6.8 +/- 1.8, p < 0.01. Diabetes mellitus and hypertensive nephropathy are much more frequent in incident patients compared to prevalent ones. Transplantation is significantly more frequent in Western Europe, predominantly cadaveric, whereas dialysis is more frequent in the Balkans. It can be concluded that no difference exists between the incidence and prevalence of diabetes mellitus as a primary renal disease in ESRD patients between the Balkan and European countries, indicating that the epidemic of diabetes is already present in the Balkans and imposing, perhaps, efforts to be undertaken for planning prevention strategies; kidney transplantation is significantly less represented as RRT in Balkan countries compared to Western and Northern Europe, and efforts should be made for its increase, particularly the cadaveric one, and moreover, because the population on RRT is significantly younger in the Balkans.

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.

[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.

Elevated basal levels of cytosolic calcium of thymocytes in chronic renal failure.

The basal levels of cytosolic calcium ([Ca2+]i) in rats and/or humans with chronic renal failure (CRF) are elevated in many cells including brain synaptosomes, pancreatic islets, polymorphonuclear leukocytes, platelets and B and T cells. This rise in [Ca2+]i has been attributed to the state of secondary hyperparathyroidism of CRF. These observations have led to the proposition that CRF is a state of cellular calcium intoxication mediated by excess parathyroid hormone (PTH). The documentation of a high basal level of [Ca2+]i in other cells is needed to provide further support for this postulate. The present study evaluated the basal levels of [Ca2+]i of thymocyte, which are targets for PTH action, in normal, CRF, and CRF parathyroidectomized (CRF-PTX) rats. We also examined whether CRF affects the phenotype expression (Thy-1, CD4 and CD8) in thymocytes. The results showed that the basal levels of [Ca2+]i in thymocytes from CRF rats (81 +/- 3.7 nM) are significantly (p < 0.01) higher than those in normal animals (60 +/- 2.9 nM). PTX of CRF animals prevented the elevation in the basal levels of [Ca2+]i of thymocytes; in these animals, the levels were 59 +/- 2.8 nM. Neither CRF nor the elevation in [Ca2+]i of thymocytes affected their phenotype expression.

Parathyroid hormone increases cytosolic calcium of thymocytes.

Parathyroid hormone (PTH) has been implicated in the genesis of the abnormalities of the immune system in uremia. This action was attributed to the ability of PTH to augment entry of calcium and hence sustain an elevation of the basal level of cytosolic calcium ([Ca2+]i) in the cells of the immune system. However, direct evidence for such an action of the hormone on these cells is lacking. We examined whether PTH affects [Ca2+]i of rat thymocytes and the potential mechanisms of such an effect. 1-84 PTH (0.5, 1.0, 2.0 x 10(-7) M) increased [Ca2+]i in a dose-dependent manner by 31 +/- 2.6, 73 +/- 3.8, and 128 +/- 10.8 nM, respectively. 1-34 PTH had no effect. The various doses of PTH antagonist ([Tyr-34] bPTH (7-34)NH2) blocked the PTH-induced rise in [Ca2+]i by 41-67%. Dibutyryl adenosine 3',5'-cyclic phosphatase (cAMP), forskolin and phorbol ester 12-0-tetradecanoyl-phorbol 13-acetate (TPA) also produced a significant rise in [Ca2+]i of thymocytes. Verapamil blocked the PTH action by 44% but had no effect on the dibutyryl-cAMP-, forskolin- or TPA-induced rise in [Ca2+]i. Absence of calcium in the media abolished the PTH-induced increase in [Ca2+]i and significantly reduced that of dibutyryl cAMP. Staurosporine completely prevented the TPA-induced rise in [Ca2+]i but had no effect on that produced by PTH. 1-84 PTH in the presence of calcium in the medium produced a significant rise in thymocyte cAMP but had no effect in the absence of calcium in the media.(ABSTRACT TRUNCATED AT 250 WORDS)

Verapamil reverses glucose intolerance in preexisting chronic renal failure: studies on mechanisms.

Glucose-induced insulin secretion is impaired in chronic renal failure (CRF), and this abnormality is due to the elevation of cytosolic calcium [Ca2+]i and other derangements in pancreatic islet metabolism. Verapamil given to rats from day 1 of CRF prevented the rise in [Ca2+]i of islets and the impairment in insulin secretion. However, it is not known whether verapamil can reverse the abnormalities of islet function and metabolism in animals with preexisting renal failure. Such a documentation has important clinical implications for the treatment of carbohydrate intolerance in patients with CRF. The present study examined this question. After 6 weeks of CRF, rats were randomized into two subgroups and maintained for additional 6 weeks. One subgroup received intraperitoneal injections of verapamil (0.1 micrograms/kg body weight twice daily) and the other received vehicle only. At the time of randomization, there were no significant differences between the two subgroups in their body weight, plasma levels of calcium, phosphorus and creatinine, serum parathyroid hormone and creatinine clearance. Similarly, at the time of sacrifice (12 weeks), there were no significant differences in these parameters except for a modestly lower plasma level of creatinine and modestly higher creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic nervous system dysfunction and volume nonresponsive hypotension in hemodialysis patients.

Studies were conducted in 9 dialysis patients with volume-nonresponsive hypotension, 6 dialysis patients with volume-responsive hypotension and in 10 normal subjects in an effort to evaluate the role of dysfunction of the autonomic nervous system (ANS) in the genesis of volume-nonresponsive hypotension. ANS function was evaluated by the Valsalva maneuver, handgrip exercise, and by the response of heart rate and blood pressure to change of posture from a supine to a standing position. Patients with volume-nonresponsive hypotension displayed significant derangements in the function of ANS as compared to normal subjects and to patients with volume-responsive hypotension. Data show that dysfunction of ANS plays an important role in the genesis of volume-nonresponsive hypotension in dialysis patients.