M Kostić

University of Belgrade, Beograd, Central Serbia, Serbia

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Publications (70)141.02 Total impact

  • D. Mekahli, K. Van Straelen, K. Jager, F. Schaefer, J. Groothoff, M. H. Assadi, D. Landau, Y. Chen, R. Rabkin, J. Medrano, [...], R. Attini, A. Piga, M. Postorino, A. Pani, G. Cabiddu, G. B. Piccoli, B. Spasojevic-Dimitrijeva, G. Milosevski-Lomic, M. Cvetkovic, D. Kruscic
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    ABSTRACT: Introduction and Aims: Autosomal recessive polycystic kidney disease (ARPKD) occurs in 1:20,000 live births and is the most common cystic kidney disease in childhood. Since kidney and liver manifestations progress differently in ARPKD, the decision of the right type of transplantation may be challenging. Most often kidney-alone transplantation (KT) is performed first, followed by liver transplantation (LT) or directly combined liver kidney transplantation (CLKT). The choice for CLKT is more and more discussed because (1) 64-80% of the mortality occurring in ARPKD with KT patients is attributed to cholangitis/sepsis related to liver disease; (2) liver allograft is immunologically protective of the kidney graft and (3) CLKT from the same donor probably provides better long-term. However, there is no consensus yet and long-term outcome data are scarce. In the present study, we aimed to analyse the characteristics and outcomes of children with ARPKD of the ESPN/ERA-EDTA registry and compare the outcome of the different transplantation strategies. Methods: 239 incident ARPKD patients were identified from the ESPN/ERA-EDTA registry who started RRT since 1995. Data included date of birth, gender, age at RRT, treatment modality of RRT, type of transplantation (KT or CLKT), changes in RRT modality during follow-up, survival and cause of death. Results: Mean age at start of RRT was 12.8 and 11.4 years in males and females respectively. Five year patient survival on RRT was 88.1%. Patients starting RRT before the age of 1 had a 20% lower 5-year survival (72.9%). Twenty nine patients died and the causes of death were infection (28%), cardiovascular disease (16%), hemorrhage (6.9%), and unknown (31%). There were 197 transplantations among 179 incident patients. Median age at time of the first transplantation was 9.3 years (IQR 3.9 to 13.6), which took place after a median of 0.4 years on dialysis (IQR 0.0-1.3). Twenty three patients (13%) received a CLKT, while 123 (69%) received a KT and in 33 (18%) the type of transplantation was unknown. There was a significant difference in 5-year patient survival according to the type of transplantation (78.6% for CLKT vs. 96.2% for KT) (p=0.03). Five year death censored renal graft survival was 74.3% (71.5% and 77.0% for CLKT and KT respectively p=0.83). There were 18 patients with at least 2 transplantations (1 patients received 3). Renal graft survival tended to be worse for the second as compared to the first renal allograft (HR 1.56 95%CI 0.71 to 3.43). Conclusions: The need for RRT in the first year of life for ARPKD adversely impacts survival. CLKT is a significant risk factor for mortality on short-term, and is not associated with better 5-year graft survival. Long term follow-up data are needed to better delineate the best transplantation strategy.
    Nephrology Dialysis Transplantation 05/2014; 29(suppl 3):iii567-iii580. DOI:10.1093/ndt/gfu181 · 3.49 Impact Factor
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    ABSTRACT: Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of progressive chronic kidney disease that may lead to end-stage renal disease and renal replacement therapy in childhood. Altered expression or activity of matrix metalloproteinases (MMPs) have been found in CAKUT. The MMP-1, -3, and -8 polymorphisms studied here are located in the gene promoters and alter expression. Our aim was to investigate associations of MMP polymorphisms, solely and in haplotypes, with CAKUT in children. A case-control study with 101 pediatric patients and 281 controls was performed. The MMP-1 (-1607 1G/2G), -3 (5A/6A), and -8 (-799 C/T) genotypes were determined by PCR-restriction fragment length polymorphism. We found statistically significant associations of MMP-3 5A/6A polymorphism (p < 0.0001) and 1G-1607-6A haplotype, with no preferences for MMP-8 -799C or T alleles, with CAKUT (OR = 2.93, 95 % CI 1.43-5.98, adjusted for gender, p = 0.003) and with obstructive uropathies in a subgroup of patients (OR = 4.57, 95 % CI 2.74-7.61, adjusted for gender, p < 0.0001). MMP-3 genotypes and MMP-3 and -1 haplotypes encompassing either MMP-8 -799C or T alleles were associated with CAKUT and obstructive uropathies in pediatric patients. Still, functional and association studies are needed to elucidate evident roles of MMPs in CAKUT.
    Pediatric Nephrology 01/2014; 29(5). DOI:10.1007/s00467-013-2699-x · 2.88 Impact Factor
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    ABSTRACT: Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of diseases, characterized by abnormal lymphoid proliferation following transplantation. It is a disease of the immunosuppressed state, and its occurrence is mostly associated with the use of T-cell depleting agents, and also intensification of immunosuppressive regimens. In the majority of cases, PTLD is a consequence of Epstein-Barr virus (EBV) infection and is a B-cell hyperplasia with CD-20 positive lymphocytes. The 2008 World Health Organization classification for lymphoid malignancies divides PTLD into four major categories: early lesions, polymorphic PTLD, monomorphic PTLD and Hodgkin PTLD. The treatment and prognosis depend on histology. The cornerstone of PTLD therapy includes reduction/withdrawal of immunosuppression, monoclonal anti CD-20 antibody (rituximab) and chemotherapy. We reported here our experiences with three patients, two girls aged 7.5 and 15 and a 16-year old boy. They had different organ involvement: brain, combined spleen-liver and intestines, respectively. Even though EBV was a trigger of lymphoid proliferation as it was confirmed by histopathology or in cerebrospinal fluid, qualitative EBV-PCR was positive only in one patient at disease presentation. Reduction of immunosuppression therapy was applied in treatment of all three patients, while two of them received rituximab and ganciclovir. They had an excellent outcome besides many difficulties in diagnosis and management of disease. Qualitative EBV-PCR is not useful marker in pediatric transplant recipients. Our suggestion is that patients with the risk factors like T-cell depleting agents, immunosuppressant protocol or increasing immunosuppressive therapy and EBV miss-match with donor must be more accurately monitored with quantitative EBV PCR.
    Srpski arhiv za celokupno lekarstvo 01/2014; 142(1-2):83-8. DOI:10.2298/SARH1402083S · 0.17 Impact Factor
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    ABSTRACT: We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA-EDTA and ERA-EDTA registries. Thirty-two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0-13.5) per million children (pmc). A median proportion of 17% (interquartile range 2-29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10-52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.
    American Journal of Transplantation 05/2013; 13(8). DOI:10.1111/ajt.12288 · 6.19 Impact Factor
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    ABSTRACT: BACKGROUND: The roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis. METHODS: Fifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS). RESULTS: Children with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, μmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS. CONCLUSIONS: Early atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.
    Pediatric Nephrology 11/2012; DOI:10.1007/s00467-012-2323-5 · 2.88 Impact Factor
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    ABSTRACT: Background Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level.Methods From the European Society for Paediatric Nephrology (ESPN)/European Renal Association-European Dialysis Transplant Association (ERA-EDTA) registry, data were available on 2351 children between 1 month and 18 years of age, totalling 5546 measurements from 19 countries.ResultsThe mean Hb level was 10.8 g/dL (5th-95th percentiles, 7.4-13.9). Among those above 2 years of age, the mean Hb level was 10.9 g/dL (11.4% below 8.5 g/dL), while it was 10.3 g/dL among those below 2 years (11.2% below 8.0 g/dL). A total of 91.2% of the patients were on an erythropoiesis-stimulating agent (ESA). Hb levels increased with age and were higher in peritoneal dialysis compared with haemodialysis patients. Patients with congenital anomalies of the kidney and urinary tract showed the highest Hb levels, and those with cystic kidney diseases or metabolic disorders the lowest ones. Ferritin levels between 25 and 50 ng/mL were associated with the highest Hb levels. We found a weak inverse association between parathyroid hormone (PTH) and Hb. Whereas standardized blood pressure (BP) was not elevated in patients with above-target Hb, elevated systolic BP z-score was noted in those with sub-target Hb levels.Conclusions Sub-target Hb levels remain common in children on dialysis, in spite of virtually all children being treated with ESA; although we cannot exclude under-dosing. Optimal ferritin levels seemed to be slightly lower in children (25-50 ng/mL) than those in adults. Other risk factors for sub-target Hb are dialysis modality and a high PTH level.
    Nephrology Dialysis Transplantation 06/2012; DOI:10.1093/ndt/gfs178 · 3.49 Impact Factor
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    ABSTRACT: The authors present the case of a girl with Frasier syndrome that was diagnosed at the age of 4 years. At 3.5 years, she was diagnosed a steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis. The girl presented with female phenotype and male genotype (46XY) as well with gonadal dysgenesis. Genetic analysis confirmed the +2T>C mutation in the intron 9 of the WT1 gene. She developed end-stage renal disease at 14 years, culminating in renal transplantation. The liver biopsy revealed a post-transplantation lymph-proliferative disease.
    Central European Journal of Medicine 04/2012; 7(2). DOI:10.2478/s11536-011-0135-9 · 0.21 Impact Factor
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    ABSTRACT: Urinary tract infection is common in childhood. Depending on the localization of the infection, severity of its clinical presentation and possible acute and long-term complications, it may be described as either acute cystitis or acute pyelonephritis. The aim of this study was to assess the resistance patterns of uropathogens during the last 5 years in newborns and young children with acute pyelonephritis. Uropathogens resistance to commonly usable anti-microbial agents (ampicillin, a combination of sulphamethoxasole and trimethoprim, cephalexin, ceftriaxone, cefotaxime, ceftazidime, gentamycin, amikacin, ciprofloxacin, imipenem and nalidixic acid) was retrospectively studied in newborns and young children treated during early (2005-2007) and late (2008-2009) study periods. Anti-bacterial susceptibility testing of the urine isolates was performed by the standard disc diffusion method. 117 newborns and 294 children aged 9.3 +/- 0.7 months were treated during early (n=136) or late (n=275) study period due to the first episode of acute pyelonephritis. Escherichia coli was the most common bacterial pathogen (85.5%). Compared to children older than one month, newborns had higher degree of antibacterial resistance to 2nd and 3rd generation cephalosporins, aminoglycosides, and nalidixic acid during early, and to ceftazidime, aminoglycosides and nalidixic acid during late study period. Also, multidrug resistance was more common in newborns during the early study period. Newborns had higher rate of antibacterial resistance than young children.The progressive increase of anti-microbial resistance in children with acute pyelonephritis is of great concern.
    Srpski arhiv za celokupno lekarstvo 03/2012; 140(3-4):179-83. DOI:10.2298/SARH1204179P · 0.17 Impact Factor
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    ABSTRACT: Background: This study was conducted to retrospectively investigate the indications for renal biopsy in native kidneys and to analyze pathological findings in the last 10 years in a single tertiary pediatric hospital in Serbia. Methods: All patients who underwent renal biopsy at our hospital between 2001 and 2010 were included in the present study. Renal biopsy was performed under fluoroscopy with a biopsy gun. All renal biopsies were studied under light and immunofluorescent microscopy, while electron microscopy was rarely performed. Results: The study group included 150 patients (56% female) who underwent 158 percutaneous native kidney biopsies. Median age was 11.5 years (range 0.2-20 years). The most frequent indications for renal biopsy were nephrotic syndrome (32.9%), asymptomatic hematuria (23.4%), urinary abnormalities in systemic diseases (15.8%) and proteinuria (11.4%). Primary glomerulonephritis (GN) was the most common finding (57.4%), followed by secondary GN (15.5%) and tubulointerstitial diseases (4.5%). According to histopathological diagnosis, the most common causes of primary GN were focal segmental glomerulosclerosis (20.9%), mesangioproliferative GN (14.6%), IgA nephropathy (8.9%) and minimal change disease (13%). Lupus nephritis (6%) and Henoch-Schönlein nephritis (4%) were the most common secondary glomerular diseases. Conclusions: The epidemiology of glomerular disease in our single-center report is similar to that in data from adjacent Croatia and Greece. Focal segmental glomerulosclerosis was the dominant histopathological finding, followed by mesangioproliferative GN and IgA nephropathy.
    Journal of nephrology 02/2012; 25(6). DOI:10.5301/jn.5000095 · 2.00 Impact Factor
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    ABSTRACT: The objective of this study was to assess the frequency of microalbuminuria and the relationship with other risk factors for the development of diabetic nephropathy. Our cross-section study involved a group of 60 adolescence of both sexes, mean age 15.3 ±2.43 years with mean duration of diabetes 7.74 ±3.44 years. Albumin excretion rate was measured on 2-3 samples of the first morning urine in the period below 6 months and persistent microalbuminuria was defined if its increased in two out of three urine specimens. Ambulatory blood pressure was monitored (ABPM, SpaceLabs 90207). Microalbuminuria developed in 13.3% of adolescents with mostly completed sexual development, statistically significantly poorer metabolic control (9.79% vs. 8.7%) and higher BMI (23.59 kg/m(2) vs. 20.85 kg/m(2)) than in the patients with normoalbuminuria. The mean night-time systolic blood pressure (SBP) was statistically significantly higher in microalbuminuric patients than in normoalbuminurics. The nocturnal dip was reduced in 41.7% of our patients; 38.5% of nondippers were in normoalbuminuric and 62.5% in microalbuminuric patients. Diabetic adolescents require particular attention in order to minimize the factors such as high HbA(1c), elevated body mass index and night-time SBP in the development of incipient nephropathy.
    12/2011; 7(6):1037-41. DOI:10.5114/aoms.2011.26617
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    ABSTRACT: Renal transplant recipients often suffer from dyslipidemia which is one of the principal risk factors for cardiovascular disease. This study sought to determine characteristics of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles and their associations with carotid intima-media thickness (cIMT) in a group of pediatric renal transplant recipients. We also examined the influence of immunosuppressive therapy on measured LDL and HDL particle characteristics. HDL size and subclass distribution were determined using gradient gel electrophoresis, while concentrations of small, dense LDL (sdLDL)-cholesterol (sdLDL-C) and sdLDL-apolipoprotein B (sdLDL-apoB) using heparin-magnesium precipitation method in 21 renal transplant recipients and 32 controls. Renal transplant recipients had less HDL 2b (P < 0.001), but more HDL 3a (P < 0.01) and 3b (P < 0.001) subclasses. They also had increased sdLDL-C (P < 0.01) and sdLDL-apoB (P < 0.05) levels. The proportion of the HDL 3b subclasses was a significant predictor of increased cIMT (P < 0.05). Patients treated with cyclosporine had significantly higher sdLDL-C and sdLDL-apoB concentrations (P < 0.05) when compared with those on tacrolimus therapy. Pediatric renal transplant recipients have impaired distribution of HDL and LDL particles. Changes in the proportion of small-sized HDL particles are significantly associated with cIMT. Advanced lipid testing might be useful in evaluating the effects of immunosuppressive therapy.
    Transplant International 08/2011; 24(11):1094-102. DOI:10.1111/j.1432-2277.2011.01313.x · 3.16 Impact Factor
  • Atherosclerosis Supplements 06/2011; 12(1):22-22. DOI:10.1016/S1567-5688(11)70094-0 · 9.67 Impact Factor
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    ABSTRACT: Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. It is characterized by symptoms including nonthrombocytopenic purpura, abdominal pain, haematuria/proteinuria, and arthralgia/arthritis. The pleiomorphism of clinical signs in HSP could be confused with other conditions or other vasculitis forms. Evaluation of HSP clinical presentation, the onset and severity of renal manifestation in affected children and their outcome. A retrospective study of 49 patients diagnosed with HSP was conducted from September 1999 to September 2009. Children with severe renal manifestations (nephrotic range proteinuria, with or without nephrotic or nephritic syndrome) have undergone kidney biopsy. Twenty-five patients developed renal manifestations after onset of the disease. In our study child's older age was a risk factor for association with HSP nephritis. Six of the patients required kidney biopsy. They were successfully treated with various immunosuppressive protocols, as well as three of nine patients with nephrotic range proteinuria. Two patients developed most severe form of HSP nephritis, nephrotic-nephritic syndrome with histology grade IIIb/IVb. During the study period (average followup 6 years), all patients had a normal global renal function with mild proteinuria in only two cases. The prognosis of renal involvement was better than reports from other patient series. Long-term morbidity of HSP is predominantly attributed to renal involvement. During the study period, no patient had renal insufficiency or end stage renal disease after various combinations of immunosuppressive treatment. It is recommended that patients with HSP nephritis are followed for longer periods of time with a regular measurement of renal function and proteinuria.
    Srpski arhiv za celokupno lekarstvo 01/2011; 139(3-4):174-8. DOI:10.2298/SARH1104174S · 0.17 Impact Factor
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    ABSTRACT: Urinary tract infections (UTI) are common in infants and children and may result in serious complications, such as renal scarring, hypertension, and renal failure. Identification of the new markers in relation to acute pyelonephritis (APN) and its treatment is essential for designing interventions that would minimize tissue damage. This prospective study investigated the first UTI infection in 71 children (age range: 1-24 months) in respect to interleukin-6 (IL-6) -174G/C polymorphism and renal scarring. The patients were divided into an APN group and a lower UTI group according to dimercaptosuccinic acid (DMSA). The IL-6 -174G/C genotypes were determined by tetra-primer ARMSPCR. Serum IL-6 was significantly higher in the APN group than in the group with lower UTI (p<0.05). In both groups, the -174G/C genotype and allele frequencies did not differ significantly from the control group. The highest white blood cell (WBC) count was observed in the CC genotype (p<0.05). A non-significant trend toward higher serum IL-6 was observed in children with CC genotype. On follow-up DMSA imaging performed 6 months later, renal scarring was detected in 36.9% of APN children. We did not find the significant association of IL-6 -174G/C polymorphism with APN and/or postinfectious renal scarring. These results indicate that serum IL-6 concentrations were significantly higher in children with APN than in patients with lower UTI.
    Pediatric Nephrology 10/2010; 25(10):2099-106. DOI:10.1007/s00467-010-1587-x · 2.88 Impact Factor
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    ABSTRACT: Arterial hypertension is a risk factor affecting graft function in pediatric kidney transplants. Recent pediatric studies reported a high prevalence of hypertension, especially nocturnal hypertension in this population. Data regarding the prevalence of masked hypertension in pediatric patients with kidney transplants are still scarce. The aim of this cross-sectional study was to assess the prevalence of masked and hidden uncontrolled hypertension after renal transplantation. A total of 41 patients (25 males) with stable functioning renal graft were included in the study. Their median age was 14.5 years with the median interval since transplantation of 2.5 years (range 0.3 to 20.6). Spacelabs 90207 was used to measure ambulatory blood pressure (BP) during a 24-h period. Ambulatory hypertension was defined as mean systolic and/or diastolic BP index at day-time or nighttime >or=1. Masked hypertension was defined as normal office BP but daytime ambulatory hypertension in patients without antihypertensive medications. Hidden uncontrolled hypertension was defined as daytime ambulatory hypertension undetected by office BP measurements in treated patients. Antihypertensive medications were prescribed to 58%. Prevalence of nocturnal hypertension was 68%. On the basis of combination of office and ABPM masked hypertension and hidden uncontrolled hypertension was detected in 24% and 21% of the study population, respectively. Regular use of ambulatory blood pressure monitoring in transplanted patients enables detection of masked and hidden uncontrolled hypertension.
    Pediatric Nephrology 05/2010; 25(9):1719-24. DOI:10.1007/s00467-010-1552-8 · 2.88 Impact Factor
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    ABSTRACT: Introduction. Growth retardation is a hallmark of chronic illnesses such as chronic kidney disease in children, and it is associated with increased morbidity and mortality. The growth hormone (GH) resistance observed in uraemia can be overcome by supraphysiological doses of exogenous GH. Objective. We would like to present our first results of recombinant human growth hormone (rhGH) treatment, mainly in children on haemodialysis. Methods. Sixteen children, aged 4.5-17.1 years (mean age 11.25±3.57) with height below -2.0 standard deviation score (SDS) for age or height velocity below -2.0 SDS for age, were selected to receive rhGH therapy at our Nephrology and Haemodialysis Department. Most of them were on haemodialysis (14 children) with mean spent time 2.88±2.68 years (0-9 years) before the initiation of rhGH therapy. One half of patients were prepubertal (8 children) and the second half were in early puberty (testicular volume between 4 and 8 ml for boys and breast development B2 or B3 in girls). All patients received 28-30IU/m² rhGH per week by daily subcutaneous injection. The year before rhGH therapy served as a control period. Results. During the first year of treatment, mean height velocity in haemodialysis patients increased from 2.25 cm/year to 6.59 cm/year (p<0.0001) and in the second year it was 5.25 cm/ year (p=0.004). The mean height SDS in haemodialysis children did not improve significantly during the first year of rhGH treatment (from -3.01 SDS to -2.77 SDS, p=0.063). Neither weight nor the body mass index varied compared with the pretreatment period. Two patients developed worsened secondary hyperparathyroidism and were excluded from the study, but the relationship with rhGH remains uncertain. Conclusion. Mean height velocity significantly improved during rhGH therapy in haemodialysis patients. No significant side-effects were observed in children during three-year treatment with GH.
    Srpski arhiv za celokupno lekarstvo 03/2010; 138(3-4). DOI:10.2298/SARH1004197S · 0.17 Impact Factor
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    ABSTRACT: Multicriteria optimization methodology was applied for development of isocratic reversed-phased HPLC method for simultaneous determination of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) in human urine and plasma. In the first stage of method development, pH value of the water phase, percentage of acetonitrile, temperature of the column and flow rate of the mobile phase were investigated using fractional factorial design.Afterwards, the optimal conditions were found employing central composite design and Derringer's desirability function. Two goals were considered, the retention factor of the MPAG to be in the range, between 0.8 and 1.118 which allowed well separation of MPAG from the urine and plasma peaks, and the shortest possible total analysis run time. Then, the obtained sigmoid functions were used to transform the optimization criteria into the desirability values.The satisfactory chromatographic conditions were obtained with mobile phase consisted of acetonitrile–phosphate buffer (pH 2.4; 0.04 M KH2PO4) (28:72, v/v). The separation was performed on C18 Chromolith column (100 mm × 4.6 mm) with flow rate of 5 mL/min, the temperature of the column was 25 °C and the chosen wavelength for simultaneous determination of MPA and MPAG was 215 nm. The MPAG eluted at 0.552 min and the duration of run was 3.092 min.Afterwards, the method was subjected to validation. Linearity was observed over the concentration range of 1–50 μg/mL for MPA and 1–500 μg/mL for MPAG in urine and 1–60 μg/mL for MPA and 1–70 μg/mL for MPAG in plasma matrix. The method showed intra-day and inter-day precision with relative standard deviation lower then 5% and accuracy as recovery (%) between 100 ± 5%.
    Journal of pharmaceutical and biomedical analysis 11/2009; DOI:10.1016/j.jpba.2008.09.052 · 2.83 Impact Factor
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    ABSTRACT: Congenital anomalies of the kidney and urinary tract (CAKUT) are common causes of chronic renal failure in children. The angiotensin II receptor type 2 (AT2R) is one of proposed candidate genes for CAKUT, but the expression was never explored in humans. The aim was to establish the AT2R gene expression in human CAKUT concerning -1332A/G polymorphism, which might affect alternative splicing. Forty-eight patients with CAKUT constitute the basis of this study. Genotyping for -1332A/G, RT-PCR for AT2R gene expression and confirmation sequencing were performed. The expression of Ex 1/2/3 and Ex 1/3 transcript splice variants of the AT2R mRNA were detected in human CAKUT tissue. The pattern was observed independently of A to G transition. The expression of AT2R mRNA in human CAKUT was established for the first time and was not affected by -1332A/G polymorphism in children with CAKUT.
    Clinical biochemistry 09/2009; 43(1-2):71-5. DOI:10.1016/j.clinbiochem.2009.09.009 · 2.23 Impact Factor
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    ABSTRACT: The aim of this study was to develop and optimize a solid phase extraction (SPE) procedure for purification of mycophenolic acid (MPA) and its metabolite mycophenolic acid glucuronide (MPAG) in biological samples. During optimization process chemometric approach was applied. First, in screening experiments fractional factorial design (FFD) was used for selecting the variables which affected the extraction procedure. The ionic strength of the phosphate buffer in the washing step and the percentage of acetonitrile in the elution step were statistically significant for the recovery of MPAG while the percentage of acetonitrile and pH of the washing solution were statistically significant for that of MPA. Afterwards, the significant variables were optimized using central composite design (CCD). The developed SPE method included phosphate buffer (pH 2.4; 0.056 M) in the washing step, and the mixture of acetonitrile and phosphate buffer of which pH was adjusted to 2.4 (70:30, v/v) in the elution step. The investigation was applied to both urine and plasma and the nature of biological matrix appeared to be of no importance. The extraction from both matrixes showed good repeatability with relative standard deviations up to 6% for MPAG and 8% for MPA, and recovery around 100% for both substances. Furthermore, new SPE-RP-HPLC method for determination of MPA and MPAG in both humane urine and plasma has been validated. The great advantage of this method is the chromatographic run of only 3 min.
    Journal of Pharmaceutical and Biomedical Analysis 08/2008; 47(3):575-85. DOI:10.1016/j.jpba.2008.01.046 · 2.83 Impact Factor
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    ABSTRACT: 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.
    Pediatric Transplantation 01/2008; 11(8):906-13. DOI:10.1111/j.1399-3046.2007.00817.x · 1.63 Impact Factor