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Introduction/Objective. Heart failure (HF) is the main cause of morbidity and mortality of hemodialysis (HD) patients. The aim of this cross-sectional single-center study was to examine the following: 1. frequency and characteristics of HF phenotypes in prevalent HD patients, 2. association of HF with traditional and non-traditional risk factors for cardiovascular diseases. Methods. We included all 96 maintenance HD patients from Special Hospital for Internal Diseases, Lazarevac, Serbia, and determined the prevalence of HF with preserved ejection fraction (HFpEF) (per the 2016 criteria of the European Society of Cardiology) and HF with reduced and moderately reduced EF ? HFrEF + HFmrEF ? together in a group HFrEF (EF < 50%) using standardized post-HD transthoracic echocardiography. Clinical, routine laboratory and volume status parameters (by bioimpedance spectroscopy) was assessed. Results. Sixty-three out of 96 examined patients (65.6%) had HF, among them 42 had HFpEF (66.7%), and 21 had HFrEF (33.3%). HFrEF was more common in older males, with diabetic nephropathy as underlying kidney disease, with a longer dialysis vintage and in those with a previous history of ischemic heart disease. HFpEF was more common in males, with lower HD quality (kT/V) and higher pre-dialytic systolic blood pressure. In multivariable regression analysis, HFrEF was associated with diabetic nephropathy, hypervolemia (positively) and triglycerides (negatively), while HFpEF was associated negatively with hemoglobin, iron, and triglycerides. Conclusion. In order to control patients on maintenance HD with HF, in addition to appropriate drug therapy, it is advice to control of volemia and maintaining triglyceride, hemoglobin, and iron concentration approximately within normal limits.

Contrast-induced nephropathy (CIN) is the impairment of kidney function defined as a serum creatinine increase of 25% or 44 µmol/L compared with baseline, usually occurring 24 to 48 hours after the use of intravenous contrast. Important risk factors for CIN include female sex, advanced age (>65 years), type 2 diabetes (T2D), kidney disease, advanced heart failure, and intravascular volume depletion. We herein present a male patient with T2D, moderately reduced renal function, no albuminuria, and a positive echocardiography stress test. He underwent percutaneous coronary intervention (PCI), and two drug-eluting stents (in the left anterior descending coronary artery) and three bare-metal stents (in the right coronary artery) were implanted. Despite adequate rehydration (0.9% intravenous NaCl with 8.4% sodium bicarbonate) before and after the procedures, he developed irreversible kidney injury after coronary angiography and PCI. This case report demonstrates the unpredictable clinical course of CIN. Patients with T2D are at high risk for the occurrence of CIN, so careful clinical assessment is recommended with global renal functional reserve evaluation.

Cardiac surgery-associated acute kidney injury (CSA-AKI) frequently occurs in patients assessed as low-risk for developing CSA-AKI. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1) and lactate are promising biomarkers of CSA-AKI but have not yet been explored in low-risk patients.To evaluate urinary NGAL (uNGAL), KIM-1 and lactate as biomarkers of CSA-AKI in patients with low-risk for developing CSA-AKI.This prospective, observational study included 100 adult elective cardiac surgery patients assessed as low-risk for developing CSA-AKI. UNGAL, KIM-1 and lactate were measured preoperatively, at the end of cardiopulmonary bypass (CPB) and 3, 12, 24 and 48 h later.Fifteen patients developed CSA-AKI. Patients with CSA-AKI had significantly higher lactate but similar uNGAL and KIM-1 levels compared to patients without CSA-AKI. Unlike uNGAL and KIM-1, postoperative lactate was good biomarker of CSA-AKI with the highest odds ratio (OR) 2.7 [1.4-4.9] 24 h after CPB. Peak lactate concentration ≥ 4 mmol/L carried dramatically higher risk for developing CSA-AKI (OR 6.3 [1.9-20.5]).Unlike uNGAL and KIM-1, postoperative lactate was significant independent predictor of CSA-AKI with the highest odds ratio 24 h after CPB.Akutno oštećenje bubrega nakon kardiohirurških procedura (KH-AOB) nastaje često i kod bolesnika koji su ocenjeni kao niskorizični za nastanak KH-AOB. Neutrofilna želatinaza udružena sa lipokalinom (NGAL), bubrežni štetni molekul-1 (KIM-1) i laktat su novi biomarkeri KH-AOB ali do sada nisu ispitivani kod niskorizičnih bolesnika.Ispitati urinarni NGAL (uNGAL), KIM-1 i laktat kao biomarkere KH-AOB kod bolesnika koji su ocenjeni kao niskorizični za nastanak KH-AOB.Ovom prospektivnom opservacionom studijom obuhvaćeno je 100 odraslih elektivnih kardiohirurških bolesnika koji su ocenjeni kao niskorizični za razvoj KH-AOB. UNGAL, KIM-1 i laktat su određivani preoperativno, na kraju kardiopulmonalnog bajpasa (KPB) kao i 3, 12, 24 i 48 sati kasnije.KH-AOB se razvilo kod 15 bolesnika. Bolesnici sa KH-AOB su imali značajno više vrednosti lakatata ali slične vrednosti uNGAL i KIM-1 u poređenju sa bolesnicima bez KH-AOB. Za razliku od uNGAL i KIM-1, vrednost lakatata posle operacije se pokazala kao pouzdan biomarker KH-AOB sa najvišim OR 2.7 [1,4–4,9] 24 sata nakon završetka KPB. Vrednosti lakatata ≥ 4 mmol/L su bile povezane sa dramatično povišenim rizikom za nastanak KH-AOB (OR 6,3 [1,9–20,5]).Za razliku od uNGAL i KIM-1, vrednosti lakata posle operacije su bile značajan nezavisni prediktor razvoja KH-AOB sa najboljom prediktivnom vrednošću 24 sata nakon završetka KPB.

Background and Objectives: Abnormal arterial stiffness (AS) is a major complication in end-stage kidney disease (ESKD) patients treated by dialysis. Our study aimed to determine the significance of AS for survival of prevalent dialysis patients, as well as its association with cardiovascular parameters or vascular calcification promoters/inhibitors or both and AS. Materials and Methods: The study involved 80 adult hemodialysis patients. Besides standard laboratory analyses, we also determined promoters and inhibitors of vascular calcification (bone biomarkers): serum levels of fibroblast growth factor 23 (FGF23), soluble Klotho, intact parathormone (iPTH), 1,25-dihydroxyvitamin D3, osteoprotegerin, sclerostin, AS measured as ankle carotid pulse wave velocity (acPWV), Ankle Brachial Index (ABI), and vascular calcification (VC) score. Patients were monitored for up to 28 months. According to the median acPWV value, we divided patients into a group with acPWV &le, 8.8 m/s, and a group with acPWV &gt, 8.8 m/s, and the two groups were compared. Results: Values for bone biomarkers were similar in both groups. Mean arterial blood pressure (MAP), central systolic and diastolic brachial blood pressure, heart rate, and pulse pressure were higher in the group with acPWV &gt, 8.8 m/s than in the group with acPWV &le, 8.8 m/s. The mortality was higher for patients with acPWV &gt, 8.8 m/s at any given time over 28 months of follow-up. In multivariable analysis, predictors of higher acPWV were age &gt, 60.5, higher pulse rate, and higher central systolic or brachial diastolic blood pressure. Conclusions: According to our results, we advise the measurement of acPWV preferentially in younger dialysis patients for prognosis, as well as intervention planning before the development of irreversible changes in blood vessels. In addition, measuring central systolic blood pressure seems to be useful for monitoring AS in prevalent hemodialysis patients.

Background. The incidence of renal replacement therapy (RRT) in the general population >= 75 years of age varies considerably between countries and regions in Europe. Our aim was to study characteristics and survival of elderly RRT patients and to find explanations for differences in RRT incidence. Methods. Patients >= 75 years of age at the onset of RRT in 2010-2013 from 29 national or regional registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry were included. Chi-square and Mann-Whitney U tests were used to assess variation in patient characteristics and linear regression was used to study the association between RRT incidence and various factors. Kaplan-Meier curves and Cox regression were employed for survival analyses. Results. The mean annual incidence of RRT in the age group >= 75 years of age ranged from 157 to 924 per million age-related population. The median age at the start of RRT was higher and comorbidities were less common in areas with higher RRT incidence, but overall the association between patient characteristics and RRT incidence was weak. The unadjusted survival was lower in high-incidence areas due to an older age at onset of RRT, but the adjusted survival was similar [relative risk 1.00 (95% confidence interval, 0.97-1.03)] in patients from low- and high-incidence areas. Conclusions. Variation in the incidence of RRT among the elderly across European countries and regions is remarkable and could not be explained by the available data. However, the survival of patients in low-and high-incidence areas was remarkably similar.

Introduction. Pulmonary embolism (PE) is a serious complication of deep venous thrombosis, with a significant morbidity and mortality. More often, PE complicates the course of the nephrotic syndrome (NS), in particular when the disease is active, but it may occur as the first sign of illness when the diagnosis of the NS is being delayed as a result. Membranous nephropathy is, generally speaking, the most commonly reported glomerulonephritis associated with the increased risk of thrombosis. Case outline. This report summarizes our experience with three young male patients (a 26-year-old, a 22-year-old, and a 45-year-old), in which PE was the first presenting feature of the NS. All of them were admitted to the hospital experiencing chest pains, dry cough, and shortness of breath. One of them had high temperature and the other two swelling of the lower parts of legs. Computed tomography of the thorax showed pulmonary artery thrombosis in all three patients. Diagnosis of the NS was confirmed by laboratory analysis, while renal biopsy showed membranous nephropathy. The treatment was based on the pulse of methylprednisolone (1.5 g over a period of three days), with alternating therapy of oral corticosteroids and cyclophosphamide on a monthly basis during six months. After six months, two patients reached incomplete remission, while the third one still has the NS and normal renal function. Conclusion. Not so rare occurrence of thromboembolic events in the NS suggests that one should always suspect the NS in all patients with deep venous thrombosis or PE.

Background: In 2009, Belgrade nephrologists and general practitioners from thirteen health centers carried out screening for chronic kidney disease (CKD). Three years later, medical records of patients from four health centers participating in the screening study were retrospectively analyzed in order to check whether general practitioners had continued to control patients at risk for CKD in accordance with the recommendations provided. Methods: The study included 460 patients who visited their doctor at least once in the three-year period. Data on blood pressure, ACEI use, estimated glomerular filtration rate (eGFR) and comorbidities were taken from patients’ medical records. Results: Blood pressure was not recorded in any of the three years in 42.8% and eGFR in 36.7% of the patients, but blood pressure was registered every year in 7.8% and eGFR in 4.3% of them. Over the three years, the relative number of patients with recorded blood pressure decreased from 41.7% to 17.8%, and with recorded eGFR from 41.7% to 21.5%. Multivariate linear regression found that Health Center, systolic and diastolic blood pressure and presence of hypertension were negatively associated with number of years with recorded blood pressure. Health Center, systolic blood pressure and sum of years with recorded eGFR below 60 ml/min/1.73m2 were associated with number of years with recorded eGFR. Conclusions: Under-recording of blood pressure and eGFR in primary care health centers suggests lack of adherence to current guidelines and insufficient care of CKD patients. This implies the necessity for continuous education of physicians.

Background: This article summarizes the European Renal Association - European Dialysis and Transplant Association Registry's 2014 annual report. It describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2014 within 35 countries. Methods: In 2016, the ERA-EDTA Registry received data on patients who in 2014 where undergoing RRT for ESRD, from 51 national or regional renal registries. Thirty-two registries provided individual patient level data and 19 provided aggregated patient level data. The incidence, prevalence and survival probabilities of these patients were determined. Results: In 2014, 70 953 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 133 per million population (pmp). The incidence ranged by 10-fold; from 23 pmp in the Ukraine to 237 pmp in Portugal. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. By day 91 of commencing RRT, 81% of patients were receiving haemodialysis. On 31 December 2014, 490 743 individuals were receiving RRT for ESRD, equating to an unadjusted prevalence of 924 pmp. This ranged throughout Europe by more than 10-fold, from 157 pmp in the Ukraine to 1794 pmp in Portugal. In 2014, 19 406 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 36 pmp. Again this varied considerably throughout Europe. For patients commencing RRT during 2005-09, the 5-year-adjusted patient survival probabilities on all RRT modalities was 63.3% (95% confidence interval 63.0-63.6). The expected remaining lifetime of a 20- to 24-year-old patient with ESRD receiving dialysis or living with a kidney transplant was 21.9 and 44.0 years, respectively. This was substantially lower than the 61.8 years of expected remaining lifetime of a 20-year-old patient without ESRD., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

Serum cystatin C (Cys C) was evaluated as a predictor of kidney graft failure progression, and its predictive ability was compared to other markers of graft function.The following kidney graft markers were determined in 91 patients who came for regular checkups of kidney graft function to our outpatient service in February 2008: Cys C, serum creatinine (sCr), 24-h proteinuria and 24-h urinary creatinine clearance (CCr). Glomerular filtration rate (eGFR) was estimated using sCr-based and Cys C formula. Patients were regularly monitored until February 2013 or to graft failure.During follow-up, graft failure occurred in 21 recipients. The Cys C ≥2.65 mg/l discriminated patients with and without graft failure (sensitivity of 80.95% and specificity of 92.86%). According to c statistic, the highest performance was achieved for Cys C (0.874). In addition, Cys C area under the curve (AUC) was significantly better than CCr AUC (p = 0.007), 24-h proteinuria AUC (p = 0.03), eGFR estimated by the chronic kidney disease epidemiology collaboration (EPI) AUC (p = 0.05), but not better than sCr or eGFR AUCs calculated by other formulas. In the multivariable model, sCr, CCr, Cys C and eGFRs were predictors of graft failure. Combination of Cys C, sCr and logarithm of 24 h proteinuria (0.883) or Cys C, CCr and logarithm of 24-h proteinuria (0.884) had the highest AUC for predicting graft outcome that exceed insignificantly Cys C or sCr areas.The most reliable predictors of graft outcome were Cys C, sCr and proteinuria. Because Cys C is unavailable in many transplant centers, from the practical point of view, sCr remains the most sensitive predictor of graft outcome.

Because no consensus exists regarding the most accurate calculation to estimate glomerular filtration rate (GFR) based on serum creatinine concentrations (sCr) after kidney transplantation, this study sought to assess the potential role of tubular dysfunction on GFR estimates using various equations as well as the effect of pharmacologic blockades on tubular secretion of creatinine on creatinine clearance (ClCr).Iohexol GFR (mGFR) was performed in 17 stable kidney transplant recipients(R) at24 months post-transplantation. Their mean age was 48.3 ± 11.3 years. All R were treated with a calcineurin inhibitor (CNI). At the time of study we measured sCr, 24 hour-ClCr, cystatin C, 24-hour proteinuria, microalbuminuria, FE Na, alfa1-microglobulinuria (alfa1-MG), and CNI concentrations. To block tubular secretion of Cr, recipients were prescribed cimetidine (2400 mg) 2 days before the sCr measurement. Additionally, to exclude dietary influences on sCr, R did not eat meat for 2 days before testing. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockroft-Gault (CG), and Cystatin C (Cyst C) GFR equations. Mean kidney graft function over the previous 6 months was used as the control. Pearson correlation was determined between the differences between mGFR and estimatedGFR: Iohexol minus MDRD, EPI, Cyst C or CG GFR for paired estimates. The diagnostic accuracy of the eGFRs to detect an mGFR of 60 mL/min/1.73 m(2) was examined by receiver operating characteristic curves.Mean mGFR was 75.2 ± 35.8 mL/min/1.73 m(2). The sCr increased but the 24-hour ClCr, MDRD, EPI, and CG decreased after vs before cimetidine. The difference was significant for sCr (F = 12.933; P = .002) and MDRD GFR (F = 15.750; P = .001). mGFR was not significantly higher than all pair values of eGFRs, and not significantly lower than 24-hour ClCr before and after cimetidine. However, in comparison to all eGFRs, ClCr after cimetidine most approached mGFR. A significant positive correlation was observed between alfa1-MG and the difference between mGFR and MDRD (before, r = .543 [P = .045]; after cimetidine, 0.568 [P = .034]), EPI (before, r = 0.516 [P = .050]; after cimetidine, r = 0.562 [P = .036]), and ClCr (r = 0.633; P = .016), CG (P = .581; P = .029) before cimetidine. Accuracy of eGFRs to detect mGFR of 60 mL/min/1.73 m(2) showed EPI GFR before cimetidine to show diagnostic accuracy for patients with GFR60 mL/min/1.73 m(2) with a sensitivity of 81.8% and a specificity of 71.4%.Because mGFR is unavailable in many transplant centers, determination of ClCr after cimetidine may help to achieve a more accurate diagnosis of CKD among transplant patients.

Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury.

Albuminuria is an early and sensitive marker of kidney damage in diabetic patients, a good predictor of kidney outcome and cardiovascular disease. Screening for albuminuria is important to identify individuals at risk for renal outcome, i.e., developing end-stage renal disease, acute kidney injury, and progressive chronic kidney disease as well as cardiovascular disease and all-cause mortality in both general and high-risk population (diabetes, cardiovascular disease, hypertension, and older patients). Also, it is the most widely used clinical marker of diabetic nephropathy. The terminology of “early diabetic nephropathy” indicated diabetic subjects with albuminuria. In this early phase of diabetic V. Lezaic (*) Faculty of medicine, University of Belgrade, Belgrade, Serbia e-mail: mf.bg@med.bg.ac.rs; visnjalezaic@gmail.com # Springer Science+Business Media Dordrecht 2015 V.B. Patel, V.R. Preedy (eds.), Biomarkers in Kidney Disease, DOI 10.1007/978-94-007-7743-9_31-1 1 nephropathy, the glomerular filtration rate is usually well preserved. In patients with several cardiovascular risks, albuminuria is predicting outcome, even below the level to be taken as normal. It seems that the pathophysiologic mechanisms linking albuminuria to cardiovascular and renal risk are generalized loss of vascular endothelial function in organs. Furthermore, albuminuria can be used as a target for treatment for primary and secondary prevention of renal and cardiovascular disease development. ACE inhibition in subjects with nondiabetic albuminuria may prevent future cardiovascular events. Measurement of albuminuria can help to determine whether or not the patient with hypertension should be treated, how aggressively they should be treated, and what medications we should treat them with.

Background: This article provides a summary of the 2013 European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry Annual Report (available at http://www.era- edta-reg.org), with a focus on patients with diabetes mellitus (DM) as the cause of end-stage renal disease (ESRD). Methods: In 2015, the ERA-EDTA Registry received data on renal replacement therapy (RRT) for ESRD from 49 national or regional renal registries in 34 countries in Europe and bordering the Mediterranean Sea. Individual patient data were provided by 31 registries, while 18 registries provided aggregated data. The total population covered by the participating registries comprised 650 million people. Results: In total, 72 933 patients started RRT for ESRD within the countries and regions reporting to the ERA-EDTA Registry, resulting in an overall incidence of 112 per million population (pmp). The overall prevalence on 31 December 2013 was 738 pmp (n = 478 990). Patients with DM as the cause of ESRD comprised 24% of the incident RRT patients (26 pmp) and 17% of the prevalent RRT patients (122 pmp). When compared with the USA, the incidence of patients starting RRT pmp secondary to DM in Europe was five times lower and the incidence of RRT due to other causes of ESRD was two times lower. Overall, 19 426 kidney transplants were performed (30 pmp). The 5-year adjusted survival for all RRT patients was 60.9% [95% confidence interval (CI) 60.5-61.3] and 50.6% (95% CI 49.9- 51.2) for patients with DM as the cause of ESRD.

The best treatment for end stage renal disease (ESRD) patients is kidney transplantation, but the renal transplant recipients still have a higher incidence of cardiovascular events compared with general population. Cardiovascular risk factors were imposed long before ESRD, as the majority of patients starting dialysis or kidney transplantation already have signs of advanced atherosclerosis. Artery calcification is an organized, regulated process similar to bone formation. Coronary artery calcification (CAC) is found frequently in advanced atherosclerotic lesions and could be a useful marker of them. We evaluated the prevalence of CAC in 49 stable renal transplant recipients and in 48 age- and gender-matched patients with chronic kidney disease (CKD) in stages 2-5 not requiring dialysis to assess risk factors associated with CAC. Computed tomography was used for CAC detection and quantification (CAC score). The prevalence of CAC was 43.8% in transplant recipients and 16.7% in CKD patients (p0.001). Transplant recipients with CAC were significantly older and had longer duration of CKD and/or dialysis than recipients without CAC. In contrast, the serum levels of fetuin A (an inhibitor of vascular calcification) and albumin were significantly lower in CKD patients with CAC than those without CAC. During the observation period (30 months), 30 patients, including 23 CKD patients, began dialysis, and 4 transplant recipients and 2 CKD patients died. Independent predictors of mortality were age, serum amyloid A and the CAC score. In conclusion, the examination and prevention of risk factors associated with atherosclerosis should be started at the beginning of renal failure.

Background and Aims: The frequency of chronic kidney disease (CKD) markers was assessed in two groups of patients over 60 years – one without and the other with hypertension. Methods: The cross-sectional study involved 585 asymptomatic elderly patients (227 males), 93 without and 492 with hypertension. Data on patients were obtained by interview, analysis of medical records and physical examinations. Serum and urine creatinine, proteinuria, microalbuminuria (MAU, turbidimetry), and urinary sediment were analyzed. Results: Among the 585 patients, there were 54.5% with a positive family history for hypertension and 14% for kidney diseases. MAU was significantly more frequent (30 vs. 11%) and the mean estimated glomerular filtration rate (eGFR) higher (71 ± 14 vs. 64 ± 14 ml/min/1.73 m) in patients without hypertension than in those with hypertension. The majority of patients with stage 3 CKD had eGFR >45 ml/min/1.73 m2 with normal urinary findings. Multivariate logistic regression analysis found age and treatment with angiotensin-converting enzyme inhibitors to be associated with reduced eGFR, MAU and proteinuria. In addition, smoking was associated with eGFR, but a family history for kidney disease and belonging to the group without hypertension were associated with MAU. Conclusion: The high prevalence of markers for CKD in symptomless elderly without hypertension confirmed that the elderly, as a high-risk population, should be screened based on increased age alone.

Assessment of the first febrile urinary tract infection (UTI) in children has been the subject of debate for many years. Diagnosis of acute pyelonephritis (APN) is usually based on clinical and biological data. The clinical usefulness of early Tc-99m DMSA scintigraphy remains controversial, although it may influence the type and duration of treatment. The aim of this study was to assess the role of initial cortical scintigraphy in the detection of early renal parenchymal damage in children highly suspected of having APN and to compare the scintigraphic findings with selected clinical/laboratory parameters and ultrasonography.A prospective study was conducted in 34 infants and young children (18 boys, 16 girls), aged 1.5-36 months (mean 9.8 ± 8.7 months), hospitalized with a first episode of clinically suspected APN. Within the first 5 days after admission, Tc-99m DMSA renal scintigraphy, ultrasonography (US), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell count (WBC) and urine analyses were performed.DMSA scintigraphy showed changes consistent with APN in 27/34 (79%) patients, with a mean age of 10.9 months, including 12 males (44%) and 15 (56%) females. Out of 9 febrile children with negative urine culture and supportive evidence of UTI, scintigraphy showed parenchymal involvement in 8 children (24% in the whole group, 30% in scintigraphically documented APN). There were no statistically significant correlations between the frequency or size of the initial scintigraphic abnormalities and age, sex, body temperature, CRP levels or ESR. A CRP level of54 mg/L and a WBC of13,300/mm³ had sensitivities of 56 and 59% and specificities of 86 and 71%, respectively. US showed changes consistent with APN in 7/34 (21%) in the whole group and in 7/27 (26%) patients with positive cortical scan (p0.05).Initial DMSA renal scintigraphy is a sensitive method for the early diagnosis of APN in young children and is useful in the assessment of the severity of kidney injury even in patients with negative urine culture. Clinical, biological and ultrasound parameters do not identify children with renal damage. Normal DMSA study, excluding parenchymal involvement and late sequelae, could minimize the use of scintigraphy in the follow-up and reduce the redundancy of cystography.

SUMMARY Background: A cross-sectional study was carried out in Velika Hoca and Orahovac, two rural communities in Kosovo and Metohia, with the aim of assessing the prevalence of chronic diseases and associated risk factors. Methods: The study involved 423 (180 male) adult inhabitants aged 51±16 years and included an interview, medical documentation, physical, ultrasound, laboratory examinations and ECG. Results: Hyperlipidemia was the most frequent (70%) risk factor followed by alcohol consumption (47%), hypertension (42%), smoking (36%) and obesity (32%). Ischemic heart disease was diagnosed in 25 patients, hypertensive cardiomyopathy in 17, other cardiomyopathies in 5 and arrhythmia in 20 patients. Nine persons had chronic obstructive pulmonary disease. Previously diagnosed liver cirrhosis occurred in 5 and chronic hepatitis in 8 subjects, while liver steatosis with elevated serum transaminases (22 persons), elevated transaminases with normal ultrasound (20 persons), tumor or suspected tumor (7 persons) were detected in the survey. Gastrointestinal symptoms were the most prevalent but peptic ulcer and gastritis had been previously diagnosed in 64 and 47 patients. Kidney and urinary tract diseases were known for 52 patients (12 with chronic renal failure and 4 on hemodialysis) and 46 more were detected in the study. Among them in 22 patients with markers of kidney disease and unclear diagnosis 12 had a positive family history, 8 low-grade proteinuria, 14 tubular dysfunctions and 7 eGFR (estimated glomerular filtration rate) below 60 ml/min/1.73 m 2 . Conclusion: In the Serbian enclave of Velika Hoca and Orahovac the prevalence of cardiovascular diseases was similar to that of gastrointestinal, liver and kidney diseases. This differs from other parts of Serbia where cardiovascular disorders are the leading cause of disease burden.

Background A number of studies have reported lower mortality of overweight hemodialysis patients. This post hoc analysis of an observational prospective single-center study was aimed at elucidating whether both being overweight and surviving longer could result from changes in the hemodialysis modality. Methods The study included a cohort of 242 patients who were gradually switched from cuprophane membrane and acetate dialysis to polysulfone (including high-flux) membranes and bicarbonate dialysis. The analysis involved 12 months of baseline data obtained during the first calendar year after the patients entered the study (1994–2001) and repeated measurements for up to 132 months of follow-up (until 2004). Anthropometric measurements were made during the winter season and the percentage of body fat (%fat) was calculated from triceps, biceps, subscapular, and suprailiac skinfolds (K/DOQI guidelines). Kt/V, normalized protein catabolic rate, and cardiovascular comorbidity were also determined and laboratory analyses undertaken. Results Significant correlations were found between %fat and bicarbonate dialysate as well as polysulfone membrane and high-flux membrane. The linear mixed model showed dependence of %fat on polysulfone and high-flux membrane (pConclusion Changes in hemodialysis modality were followed by both higher body fat percentage and patient survival. The reverse epidemiology of overweight patients might be at least partially the result of the influence of nonnutritional factors, such as a change in hemodialysis modality (introducing biocompatible high-flux and low-flux membranes and bicarbonate dialysis).

Introduction. Results of epidemiological analysis show that one third of patients with diabetes mellitus develop diabetic nephropathy (DN). Strategies used until now to slow down the progression of DN were initiated when the symptoms of DN were already present. Objective. Our objective was to analyze the prevalence and characteristics of DN and to determine the factors leading to DN. Methods. Fifty-two patients with diabetes mellitus (DM) - 32 with type 1 aged 32 years and 20 with type 2 aged 59 years - were referred from the Institute of Endocrinology, Diabetes and Metabolic Diseases to the Department of Nephrology for kidney function evaluation. Apart from routine laboratory analyses, glomerular filtration rate was calculated using the MDRD formula (modification of diet in renal disease), the size of the kidney was measured by ultrasound, and kidney volume was calculated using the ellipsoid formula. Results Thirty percent of the patients revealed normal (eight patients with DM type 1) or satisfactory kidney function (eight patients with DM type 1) with physiological proteinuria. Micro-albuminuria (MAU) or pathological proteinuria (PRT) were found in 10 and 9 patients, respectively, with DM type 1, while decreased kidney function was found in one patient without proteinuria. MAU or PRT were found in four and eight patients, respectively, with DM type 2 and decreased kidney function in four patients without proteinuria. Kidney function was significantly lower in patients with DM type 2 in comparison to DM type 1, while the patients with decreased kidney function had a higher PRT. Compared to DM type 2, in DM type 1 patients, the kidney was longer, and parenchymal artery resistance index was lower in DM type 1 patients compared to DM type 2. Factors associated with DN were patient's age, duration of diabetes, systolic blood pressure, HbA1c and kidney volume. Conclusion. The prevalence of DN among the studied patients was 70%. Treatable factors associated with the development of DN are strict control of blood pressure and glycaemia control.

INTRODUCTION. Two types of hereditary nephritis, nonprogressive and progressive, clinically present as asymptomatic haematuria, sometimes combined with proteinuria. At the onset, in both types, light microscopic changes are minimal, immunofluorescence findings are negative, and diagnosis can be made only upon electron microscopic findings that are considered to be specific. OBJECTIVE. The aim of this study was to determine the significance of Goodpasture antigen detection in diagnosis of progressive and nonprogressive hereditary nephritis in its early phase. METHOD. Analysis of renal biopsy specimens was done in patients with hereditary nephritis that were followed from 1990 to 2005. Progression of renal disease was examined in 14 patients with Alport’s syndrome, 10 patients with thin basement membrane disease, and 6 patients with unclassified hereditary nephritis diagnosed. For all these cases, indirect immunofluorescence study with serum from a patient with high titer of Goodpasture autoantibodies that recognize the antigenic determinants in human glomerular and tubular basement membrane was performed. RESULTS. In 11 out of 14 cases diagnosed as Alport’s syndrome, there was negative staining with Goodpasture serum, and in 3 additional cases with Alport’s syndrome, expression of Goodpasture antigen in glomerular basement membrane and thin basement membrane was highly reduced. In all 10 patients with thin basement membrane disease, immunofluorescence showed intensive, bright linear staining with Goodpasture serum along glomerular and tubular basement membrane. In 2 out of 6 patients with unclassified hereditary nephritis, Goodpasture antigen expression was very strong, in one patient it was very reduced, and in 3 patients it was negative. CONCLUSION. The results of our study show that Goodpasture antigen detection plays a very important role in differential diagnosis of progressive and nonpregressive hereditary nephritis, particularly in early phases of the disease.

A comparison of the outcome of hepatitis virus-positive and -negative kidney transplant and hemodialysis patients was the aim of this investigation.The study involved 384 kidney transplant patients (67 HBsAg positive, 39 anti-HCV positive, 278 hepatitis negative), transplanted between 1987 and 2001, and 403 hemodialysis patients (128 HBsAg positive, 83 anti-HCV positive, 192 hepatitis negative) who had started hemodialysis and were referred to the kidney transplant waiting list during the same period.Hemodialysis patients were older than transplant patients. Comparison of the groups' survival rates, adjusted for patient age, showed that all kidney transplant patients survived longer than hemodialysis patients (p0.001). HBV infection had a negative impact on patient survival, especially in hemodialysis patients. HCV infection did not have a significant influence on patient survival. Cardiovascular disease was the main cause of death of all hemodialysis- and hepatitis-negative transplant patients. Liver failure was one of the leading causes of death in HBV-positive transplant patients. Mortality risk was higher for older patients, HBV-positive and -negative hemodialysis patients.Kidney transplantation offers longer survival for hepatitis-positive and -negative hemodialysis patients. HBV but not HCV infection had a negative impact on ESRD patient survival.

The aims of this investigation were to compare changes of function of adult living kidney grafts transplanted into adult and child recipients and to analyze factors associated with graft function during the first post-transplant year. The study involved 53 adult and 23 pediatric recipients with immediate graft function and without complications that could influence graft function. In comparison to children, adult recipients and their donors were older, and having been longer on hemodialysis they had received more transfusions. Although similar baseline graft function--GFR(0) was transplanted in both groups, absolute and relative GFR in adults rose and maintained stable, while in children absolute GFR decreased and remained similar to the GFR(0) until the end of the study. Significant predictors of kidney function in both adult and child recipients were donor age, ratio between GFR(0) and recipient BSA, induction immunosuppression, and systolic hypertension. In conclusion, the function of adult live kidney grafts changed differently in children and adults because of different functional requirements of recipients but donor age, induction immunosuppression and hypertension are significant predictor of graft function in both adults and children.

This prospective study was conducted with the aim of examining the efficacy of lowering dialysate calcium (dCa) in order to: (i) stimulate bone turnover in hemodialysis patients with biochemical signs of adynamic bone disease (ABD) (hypercalcemia, normal alkaline phosphatase and intact parathyroid hormone (iPTH)150 pg/mL); and (ii) diminish hypercalcemia in patients with secondary hyperparathyroidism (sHPT) (hypercalcemia, high alkaline phosphatase and iPTH400 pg/mL), thus permitting the use of calcium-containing phosphorus binders and vitamin D metabolites. Patients were divided into: an ABD-treated group (24 patients), a sHPT-treated group (18 patients), an ABD-control group (12 patients) and a sHPT-control group (11 patients). For the ABD- and sHPT-treated patients, hemodialysis was conducted with dCa 1.5 mmol/L for three months and then with dCa 1.25 mmol/L for an additional three months, while in the control groups hemodialysis was conducted with dCa 1.75 mmol/L during the entire study. Reduction of dCa in patients with ABD caused a slight but insignificant decrease of Ca, but a significant and permanent increase of bone-specific alkaline phosphatase and intact parathyroid hormone level serum levels. Reduction of dCa in patients with sHPT slightly but insignificantly decreased Ca and intact parathyroid hormone level values. Nevertheless, this enabled the calcium-based phosphate binder dose to be raised and vitamin D3 metabolites to be introduced. Logistic regression analysis indicated that milder bone disease (both ABD and sHPT) was associated with more the favorable effect of dCa reduction. Thus, low dCa stimulated parathyroid glands and increased bone turnover in ABD patients, and enabled better control of mineral metabolism in sHPT patients.

Recent studies show that clinically stable renal transplant recipients have an increased prevalence of hyperhomocysteinemia (hyperHcy), but the mechanism of this disorder has not yet been elucidated. The aim of the present study was to evaluate the factors associated with hyperHcy after a successful renal transplantation. In 106 stable renal transplant recipients, total serum Hcy level (tHcy), folate, total protein, serum creatinine concentration, creatinine clearance, lipid status, body weight (BW), body mass index (BMI), and body fat (BF) were determined. The mean doses of cyclosporine, prednisolone, and azathioprine (mg/kg/day) were recorded. The mean serum tHcy level was significantly higher in renal transplant patients than in healthy controls (22.02 +/- 8.02 versus 13.0 +/- 3.3 micromol/ L; p0.001), and the incidence of patients with hyperHcy was 82%. Comparison of the group of 20 patients with tHcy level15 micromol/L and the group of 86 patients with tHcy level15 micromol/L revealed that the latter was significantly older, heavier, had been longer on dialysis before renal transplantation, and had older donors and poorer renal graft function. Significant correlation was found between tHcy level and recipient age, dialysis duration, BW, creatinine clearance, serum creatinine, and folate concentration. However, multivariate analysis indicated that creatinine clearance (p = 0.025) and BW (p = 0.03) were the only determinants of elevated total Hcy level in renal transplant recipients. HyperHcy persists after successful kidney transplantation in the majority of renal transplant recipients, and its appearance is primarily associated with creatinine clearance and body weight.

This study aimed to estimate the relationship between the single kidney glomerular filtration rate (SKGFR) of a planned kidney transplant and the subsequent graft function and survival of living related kidney recipients (LKRs). Of 180 LKRs with the graft functioning for more than a year, 70 patients without delayed graft function (DGF) or acute rejection (AR) were selected for the study. According to SKGFR, assessed by 99mTcDTPA, the patients were allocated into Group 1, receiving kidney with SKGFR50 mL/min (32 patients), and Group 2, with SKGFR50 mL/min (38 patients). The database included donor, recipient and transplant variables. No significant difference was found between the patient and graft survival rate, creatinine clearance (CCr) and the rate of CCr change between the groups. Additional evaluation revealed no significant influence of the ratio of SKGFR and the recipient's body weight/size on patient and graft outcome. The analysis of factors of influence on patient and graft survival and function revealed the major influence of nonimmunological factors but not of SKGFR of the transplanted kidney. Our study did not confirm the influence of SKGFR on graft function and survival in the LKRs without DGF and AR but the limited number of patients must not be disregarded.

Acute renal failure (ARF) requiring hemodialysis (HD) treatment is related to high mortality. The aim of this study was to analyze the influence of age, disease severity, and catabolism intensity on ARF outcome in patients requiring HD treatment during a 15-year period (1987-2001).The retrospective, single-center study included 583 patients, 428 male, 155 female, age 49+/-15 years, treated by intermittent HD using cuprophane membranes with surface area of 1.3 m2. Liano's Acute Tubular Necrosis Individual Severity Score (ATNISS) score and Hypercatabolism Depuration Score (HDS) score were calculated to estimate disease severity and catabolism intensity in ARF patients.Average age of patients significantly increased during the 15-year period for more than one decade (44 to 55 years; p=0.0359), especially during the last five-year period (47+/-14.5 vs. 53+/-14.7, p=0.00015). Disease severity showed significant increase comparing periods 1992-1996 and 1997-2001 (ATNISS 0.385+/-0.197 vs. 0.437+/-0.208; p=0.00137), while catabolism intensity during these periods was similar (HDS 0.569+/-0.145 vs. 0.582+/-0.127; p=0.357). Despite the older and more severely ill population of ARF patients, mortality showed a sustained decrease during the 15-year period. Mortality in the period from 1987 to 1991 (49/83; 59%) was similar with the period 1992-1996 (chi2=0.44, p=0.5081), but significantly higher than in the period 1997-2001 (114/250; 45.6%; chi2=3.98, p = 0.0471).The results showed an improvement in the outcome of patients with ARF requiring HD treatment, despite increasing age, disease severity, and use of bioincompatible membranes.

Donor specific transfusion (DST) is proclaimed to improve graft survival in living related kidney transplantation (LRTx). The aim of the present study was to estimate the influence of DST on LRTx graft function, acute rejection rate (AR) and survival in the early and late post transplant period. Fifty-five LRTx patients (grafted in the same year, and matched for recipients' and donor's age, sex) were included into the study. Ninety pts received DST: 4 patients were excluded from further evaluation (3 developed positive cross match reaction and one patients received cadaver graft) and 15 patients subsequently underwent LRTx from their respective blood donors (group 1). Their outcome was compared with 15 patients who had never been transfused before (group 2) and 25 random transfused patients (group 3). Besides similar patients' and donors' sex and age, kidney transplantations were performed in the same period. Graft functions were followed-up 6-60 months after LRTx. DST protocol consists of 3x150 ml potentially related donor's fresh whole blood at 2-week intervals (DST1, DST2, DST3) with 3 days azathioprine administration (2 mg/kg bw, one day before to one day after DST administration). Donor specific citotoxic antibodies were determined before DST1, at the day of DST2, DST3 and 14 and 28 days after DST3. All patients were grafted at least one month after the DST3. Immunosuppressive protocol consisted of three drugs. There is no difference in HLA mismatches, MLC answer, and pretransplant panel reactive antibodies level between groups. One patient from group 2 lost their graft in the first postTx month (acute tubular necrosis). A better graft function was preserved in patients from groups 1 and 3 than group 2 in the observed periods. Number of patients with acute rejection was unsignificantly different: 5/15 from group 1,12/25 from group 3 but 8/10 patients from group 2. However, the acute rejection rate was lower in patients from group 1. One and five-year graft survival was 100% for grafts from groups 1 and 3, while it is gradually decreased for group 2 grafts: 84.5% and 57%. Our results confirmed the beneficial effect of blood transfusion on LRTx renal graft function and survival and DST on the incidence of acute rejection.

Lack of cadaveric organs for transplantation resulted in increased number of living related kidney donors examinations and consequent transplantations in our Department. Donor procedure, selection, drop-outs and final results for living related donors (LRD) were retrospectively analyzed in this paper. Between 1987 and 1994 202 potential LRD were examined. Most of them were females (59%) and about 30% were older than 60 years. The family relation between LRD and recipients were: parents (95%), siblings (3%), grandmother grandfather (1.5%) and uncle (0.5%). Potential LRD were informed on risks advantages and procedure of living donor transplantation. After primary information 26% of potential LRD gave up further examinations. Following immunological and clinical evaluations 48% of LRD actually donated a kidney. The other 26% were excluded during the selection procedure. High immunological risks including ABO incompatibility, HLA mismatches and positive cross match test were the reasons for drop outs of 35 potential LRD (17%). Five more donors were excluded for medical reasons: one because of low creatinine clearance and four because of neoplasms, discovered during examination (kidney, laryngeal, lung). Fourteen transplantation were not realized due to different recipient reasons: 5 of them had clinical contraindications, two died and in 7 cadaveric kidney transplantations were performed. Mild hypertension, coronary disease and diabetes mellitus type 2 were presented in 5 LRD accepted for transplantation. Five more had to be operated before donation (abdominal or urological operation). Early complications after donor nephrectomy were acute renal failure, stress ulcus, pleuropneumonia in three and thromboflebitis in two donors. In conclusion, although kidney transplantation from LRD is highly successful careful examination during selection procedure is indispensable.

Despite improvement in graft survival, infection continues to be an important cause of morbidity and mortality after kidney transplantation. We analyzed the clinical courses and outcomes of 16 transplanted patients with positive cultures for mycobacterium tuberculosis. In the course of a 20 year period, there were 13 cases of tuberculosis registered that developed in 456 patients who underwent kidney transplantation in our department, and in three refugees transplanted in other centers (a prevalence of 3.13%). Five of them developed tuberculous infections during 1997. Five patients had residual tuberculosis in preoperative chest X-ray, and specific pyelonephritis as an underlying kidney disease in two of them. All patients with treated with triple immunosuppressives. Before tuberculosis onset, 14 patients experienced one or more episodes of acute rejection and were treated with steroid pulses, ALG or OKT3. Tuberculosis was diagnosed after a period of 1.5 months to 10 years after transplantation. At the time of an infection, the graft function was normal in eight patients and chronic graft failure was evident in eight patients (sCr 210-700 micromol/L). The infection was pulmonary in 12 patients; urinary in two; disseminated in two; pulmonary and urinary, pulmonary and intestinal, and pancytopenia in one patient. All patients were treated with rifampicin and isoniazid in addition to ethambutol for the first two-month period. Treatment lasted from 1-22 months. With 14 patients favorable microbiological responses were registered. Two patients died within the first six months (both with disseminated disease), and the mortality rate was 14.3%. Throughout the followup period, the graft function remained stable and normal in eight patients who had normal graft function at the time of infection onset. Although six patients recovered, progressive graft failure developed and hemodialysis was restarted in one patient two months after antituberculous therapy introduction, and in two patients three years later. Four patients died 2-14 months after AT therapy withdrawal. The causes of death were severe liver failure, cerebrovascular insult and CMV.

An increased degree of oxidative stress (OS) in chronic renal failure (CRF) and a possible role of free radicals in CRF have already been described. However, data on OS after renal transplantation are scarce. The aim of the present study was to estimate the degree of OS in renal transplant patients. The study included four groups: 1) 15 haemodialysis patients (HD group), 2) 11 renal transplant patients with stable function (SF group), 3) 12 renal transplant patients with chronic biopsy-proven rejection (CR group), and 4) 10 healthy controls (C group). Markers of OS (malondialdehyde and thiol group levels) and antioxidant activity (glutathione peroxidase and Cu,Zn-superoxide dismutase) were determined in plasma and in red blood cells of all examined individuals. After successful renal transplantation a significant improvement, but not normalization, of antioxidant enzyme activities accompanied by significantly reduced lipid peroxidation were found. In the CR group the degree of OS was increased, and our results suggest that OS may be a relevant pathophysiological factor for CR development.

Introduction. One of the criteria for chronic kidney disease detection is determination of microalbuminuria. Objective. This analysis was performed to evaluate accuracy of three useful methods for microalbuminuria detection in 24h urine collection and in the morning urine specimen calculated from urine albumin creatinine ratio, or with a dipstick in patients with different kidney diseases or kidney function. Methods. Microalbuminuria was detected in 74 patients referred to the Outpatient Nephrology Department for kidney function determination or regular nephrology checking. Albumin concentration determined using immunonephelometry was lower than 300 mg/day. Discriminates cutoff values for spot urine test strip and albumin creatinin ratio in predicting 24 h protein ?threshold? excretion were determined using ROC analysis. Results. Mean value of 24 h microalbuminuria was 80.3 mg/24 h, and value >30 mg/24 h was present in 71.8% of patient. Correlation coefficients between dipstick microalbuminuria or albumin/creatinine ratio in a spot urine specimen and 24 h microalbuminuria were 0.709 and 0.598 (p30 mg/24 h, the coresponding dipstick microalbuminuria value was ?20 mg/L (AUC 0.849, specificity 95%, positive predictive value 97.3%), and ?3.55 mg albumin/mmol creatinine ratio (AUC 0.914, specificity 90% and positive predictive value 95.5%). No difference was found between dipstick mikroalbuminuria and albumin/creatinine ratio value. In addition, albumin/creatinine ratio value from 24 h urine was similar to the value obtained from the spot urine sample. Conclusion. Obtained results indicated that albuminuria could be determined accurately in spot urine either with the Micral test strip or with albumin creatinine ratio.

Background: Bone alkaline phosphatase (BALP) is a direct and independent indicator of impaired bone turnover. We intended to find out whether there are any significant changes in BALP and iPTH levels, in comparison to total Ca, total Mg, inorganic P, total alkaline phosphatase (ALP), and tartrate resistant acid phosphatase (TRAP) in predialysis and dialysis patients. Methods: Out of 266 patients investigated, 114 were on continuous ambulatory peritoneal dialysis, 112 were on maintenance haemodialysis, while 40 predialysis patients had end stage renal disease. The parameters were analysed according to the manufacturers' instructions. Results: Correlations were established for the bone marker concentrations analysed among the studied groups. The largest ranges were determined for BALP and iPTH. Predialysis and dialysis patients showed very low levels of BALP. Dialysis patients had lower levels of iPTH (p lt 0.001), while in predialysis patients the levels were significantly higher (p lt 0.05) than recommended for low bone turnover, according to K/DOQI. Conclusions: The observations made in this study identify BALP as a good indicator of decreased bone turnover in predialysis and dialysis patients. However, in order to reveal a difference between bone activity and the level of parathyroid activity and its effect on bone turnover, it is always necessary to observe both BALP and iPTH levels. (Clin. Lab. 2012;58:747-753. DOI: 10.7754/Clin.Lab.2011.110816)

To the Editor: Recently, Perkins et al.1 reported that in patients with type 1 diabetes (DM1) and new-onset of microalbuminuria (MAU) glomerular filtration rate (eGFR-MDRD) began to decline even before the development of proteinuria.

Idiopathic membranous nephropathy (IMN) is one of the most frequent causes of the nephrotic syndrome in adults and one of the most common cause of chronic renal failure among primary glomerular diseases. The aim of this study was to develop artificial neural networks (ANN) to investigate factors of poor outcome for IMN and to evaluate the efficacy of different therapeutic protocols. Data were collected retrospectively for 124 patients with IMN (82 males, mean based on the received therapy patients were divided into three groups: corticosteroids only (group 1), cyclophsophamide with corticosteroids (group 2), and so called Ponticelli protocol (group 3). After achieving satisfactory truthfulness of the transcription function of ANN through clustering, we have applied the efficacy analysis to all patients and then compared them to each group separately, and evaluated the influence of initial characteristics on disease outcome as well as the therapy efficacy. The greatest therapy inefficiency was recorded for isolated corticosteroid therapy (29.41%) and the smallest inefficiency for Ponticelli protocol, for which the greatest accuracy of prognosis was recorded (82.09%). The greatest negative prognostic influence had kidney insufficiency (22%), quantitative proteinuria (15%) and index of interstitial infiltration (14%). Based on our results, we can recommend that patients diagnosed with IMN with renal insufficiency, nephrotic syndrome or a high degree of interstitial infiltration at the time of diagnosis should be treated concomitantly with cytotoxic drugs and corticosteroids, particularly with the Ponticelli protocol.

BACKGROUND AND AIMS Chronic kidney disease mineral- and bone disorder (CKD-MBD) has been studied more often in dialysis than in predialysis CKD patients. The association between efficacy of hyperphosphatemia control and chronic renal failure (CRF) progression, prevalence of bone disease and cardiovascular calcification was the objective of the present investigation. MATERIAL AND METHODS 42 patients with CKD in Stage 5, regularly monitored for 5 years, were divided into Group 1 of 20 patients with normal serum phosphate (sPO4) levels and Group 2 of 22 patients with hyperphosphatemia registered at the majority of checks. Serum urea, creatinine, calcium (sCa) and sPO4 levels were regularly determined in the retrospective 5-year period. At the end of this period iPTH, bone alkaline phosphatase-BAP and inflammation markers (CRP, fetuin-A) were measured, valvular and arterial calcifications were detected by B mode echocardiogram and soft-tissue native radiograms of the pelvis and the wrist. RESULTS Progression of CRF (1/sCr over time) was faster in Group 2 than in Group 1 (b = -0.0577 vs. -0.0288, p = 0.003) during the study period. Average BAP and iPTH values were similar in both groups and 23/42 patients had PTH > 300 pg/ml. Arterial and valvular calcifications were found in 5/23 patients from Group 1 and 14/22 patients from Group 2 (p = 0.011). Linear regression analysis revealed sPO4 as a predictor for total calcification number, inflammatory diseases as a predictor for valvular calcifications, while sPO4 and iPTH were predictors for arterial calcifications. CONCLUSIONS More than half the patients with Stage 5 CKD not yet on dialysis exhibited elevated PTH. Faster CRF progression and frequent arterial and valvular calcifications were seen in patients with poor phosphate control and sPO4 was selected as an independent predictor of total calcification score.

The purpose of the study was to evaluate the impact of conversion from azathioprine (AZA) to mycophenolate mofetil (MMF) on graft function in 35 renal transplant recipients with chronic allograft nephropathy (CAN). The immunosuppressive regimen originally consisted of AZA, cyclosporine (CsA), and prednisone (Pr). At the onset of the study (mean period = 39 posttransplant months), a graft biopsy was performed on all patients who were randomly divided into group 1 (n = 17) in whom MMF was introduced instead of AZA. The remaining 18 subjects (group 2) were maintained on the previous regimen. Two periods were analyzed: period I: 12 months before, and period II: 12 months after biopsy and therapy conversion. Graft function was assessed monthly by measurements of the 24-hour creatinine clearance (CCr). Analysis of variance (ANOVA) was used to compare the differences in CCr and proteinuria between the two groups. No difference was observed in the baseline characteristics, in the incidence of delayed graft function and acute rejection, or in the mean CsA dose. Pathohistological analysis revealed advanced CAN in the majority of patients in both groups. The morphological changes negatively correlated with graft function. The graft function showed parallel deterioration in the two groups; no significant difference was observed in the mean CCr values in the periods studied. Proteinuria was similar for both groups throughout the study. Conversion of AZA to MMF in recipients with CAN, albeit safe, was without significant benefit on the progression of chronic graft failure over the period of a year.

The lack of available cadaveric organs for transplantation has resulted in an increased number of kidney transplants from living donors. During a period of 6 years, 149 kidney transplantations were performed from living related donors in our institute, 33.5% of whom were older than 60 years of age. In this study we examined the survival of patients and grafts as well as the graft function in 50 patients with transplants from donors over 60 years (mean age 65 years) as compared with those of 99 patients with transplants from donors younger than 60 years (mean age 47 years). There were no significant differences in the course of donor nephrectomy, postoperative complications, or remnant kidney function. However, delayed graft function occurred more frequently in recipients of transplants from older donors. Improvement in graft function was also slower in recipients of kidneys from older donors, with significant differences in serum creatinine levels observed during the first 12 months after transplantation. More frequent acute complications and more progressive chronic graft failure, irrespective of the causes, occurred during the 1st post-transplant year in recipients with grafts from older donors. Five-year patient survival (77% vs 92%) and kidney graft survival differed significantly for the same period with worse results for patients receiving grafts from older donors. It may be concluded that kidney grafts from donors older than 60 years -- and especially those older than 70 years -- may be used for living related kidney transplantation, but with precautions.

The rHuEpo effect on anemia in eight renal transplant patients (group A) with severe anemia (Hb 6.0-7.5 g/dL) and chronic graft failure (CGF) (sCr 281-794 mumol/L) was compared to the rHuEpo effect on anemia in predialysis (20 patients-group B) and hemodialysis patients (17 patients-group C) in order to examine the rHuEpo effect on anemia and graft failure progression, and to find out whether the response to therapy in these three patient groups differed. Although renal function impairment was similar in patients from group A and B, anemia was more severe in patients from group A. Serum immunoreactive erythropoietin levels were within normal limits for nonanemic persons, that is, inadequate for the level of anemia in all patients before therapy. Maintenance immunosuppression given after renal transplantation consisted of cyclosporine, azathioprine, and prednisone in standard doses. The startig rHuEpo dose of 150 U/kg/wk increased by 25 U/kg if the target Hb of 10.0 g/dL was not achieved at the end of a 4-week period. When target Hb was achieved, the rHuEpo dose was regularly adjusted to maintain Hb of 10.0 g/dL. Most patients from group A and group C were polytransfused before rHuEpo therapy and consequently with iron overload so that only some patients from these groups and all predialysis patients needed iron supplementation given orally. Anemia improved in all patients with 2 to 10 weeks of treatment. Mean rHuEpo doses for the first 2 months were similar in three studied groups, but the patients with the lowest initial hemoglobin values responded better to rHuEpo therapy. The rate of Hb increase during the initial phase of therapy was significantly higher in patients from group A and B comparing to patients from group C, indicating the importance of residual renal function for rHuEpo effect on anemia. Progression of CGF expressed by the slope of l/sCr vs. time did not change in either patients from group A or in predialysis patients. It could be concluded that rHuEpo therapy improved anemia in transplant patients as in predialysis and hemodialysis patients. Anemia improvement by rHuEpo did not accelerate the progression of graft function.