Milena Rajić

Diagnostic Value of the Aminopeptidase N, N-Acetyl-β-D-Glucosaminidase and Dipeptidylpeptidase IV in Evaluating Tubular Dysfunction in Patients with Glomerulopathies

Aim. The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-β-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. Subjects and Methods. PC-1, APN, NAGA, and DPP IV activities were determined in serum, urine, and lymphocytes of 178 subjects, including 10 patients with membranous nephropathy, 38 with IgA nephropathy, 29 with lupus nephritis, 51 with diabetic nephropathy, and 50 control subjects. Results. Urinary PC-1 excretion in IgA nephropathy group was significantly higher (p < 0.05) than in controls. Urinary NAGA excretion was markedly (p < 0.01) higher in membranous nephropathy group, and APN excretion in diabetic nephropathy group was significantly higher (p < 0.01) than in healthy controls. Urinary APN activity was significantly (p < 0.01) higher in both type 1 and type 2 diabetic patients with microalbuminuria, as well as urinary NAGA and DPP IV activities in type 2 diabetics with microalbuminuria (p < 0.01 and p < 0.05, respectively) compared to controls. Serum PC-1 and APN activities were significantly higher than the control level in membranous nephropathy group, as well as serum PC-1 and DPP IV activities in IgA nephropathy patients (p < 0.05). However, significantly lower serum DPP IV and APN activity was observed in type 2 diabetics with microalbuminuria compared to controls (p < 0.05). Conclusion. Damage of tubules in primary glomerulonephritis, lupus nephritis, and diabetic nephropathy is accompanied by a release of several tubular enzymes, with possible diagnostic and prognostic significance. Increased serum PC-1, APN, and DPP IV activities could be also of diagnostic significance.

THE PREDICTIVE VALUE OF 131I-HIPPURATE CLEARANCE IN THE PROGNOSIS OF ACUTE RENAL FAILURE

The aim of this investigation was to study the validity ofthe radionuclide methods in the estimation of kidney function, for prognosisand follow-up of acute renal failure (ARF). In thirty-one ARF patients, theevaluation of glomerular filtration rate (GFR) by 99mTc-DTPAclearance and effective renal plasma flow (ERPF) by 131I-ortoiodohippurate(131I-OIH) clearance was performed within 7 daysand after 6 months from ARF onset. All patients were divided in three groupsaccording to 131I-OIH clearance values obtainedwithin 7 days: group 1, under 150 mL/min; group 2, 150–250 mL/min; andgroup 3, over 250 mL/min. Seven days clearance values of both radiopharmaceuticalswere found to be very low, however, GFR was found more severely impaired thanERPF. Clearance values obtained after 6 months demonstrated no recovery ofrenal function in the first group, partial recovery in the second and almostcomplete recovery in the third group. Patients with the lowest 131I-OIHclearance values at the ARF onset had no recovery of renal function, whilein the other two groups recovery corresponded to initial 131I-OIHclearance values. In patients with ARF both, 99mTc-DTPAand 131I-OIH clearances were shown suitable forthe follow up of renal function, however, only 131I-OIHclearance had a strong predictive prognostic value for renal function recoveryin ARF.

Tubular marker excretion in children from families with Balkan nephropathy

Balkan nephropathy (BN) has not been described in children; however, some previous studies in children from families with BN have revealed abnormalities of the urinary tract. In this study, urinary excretion of β2-microglobulin, N-acetyl-β-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (GGT) was studied three times a year: spring, autumn, and winter, during a 3-year period, in 703 healthy children, initial age 9–13, from endemic and nonendemic settlements around the South Morava River. Beta-2-microglobulin excretion in urine, in all three seasons, was highest in children from families with BN compared with the excretion in children from the city, nonendemic villages, and those from nonendemic families. Increased urinary GGT excretion in children from endemic villages in October was higher than in children from the city and control villages, being the same in both endemic and nonendemic families. However, in February, it was similar in children from the city, endemic, and control villages. In conclusion, children from families with BN excreted significantly more β2-microglobulin in all three seasons (spring, autumn, winter) of the study, in multivariate analysis significant for family status, gender, and the season (p < 0.001). NAG emerged as a potentially useful marker for seasonal exposure to an environmental nephrotoxin.

Radionuclide Staging of Renal Function in Type 1 Diabetes Mellitus

Aim. The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-β-D-glucosaminidase (NAGA) excretion rates. Patients and methods. Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m (99mTc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m (99mTc-DMSA). Additionally, 99mTc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. Results. 99mTc-DTPA clearance and 99mTc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between 99mTc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with 99mTc-DTPA clearance rate (r = −0.485, p = 0.0004) and 99mTc-DMSA tubular fixation (r = −0.526, p = 0.0002). Conclusions. The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.

99mTc-dimercaptosuccinic Acid Tubular Fixation in Diabetic Nephropathy Patients

Dimercaptosuccinic acid labeled with technetium-99m (99mTc-DMSA) has been reported to be a good agent for quantitative estimation of renal function. Its biodistribution is found to be altered in tubular disorders. The aim of the present study was to assess tubular function in diabetic nephropathy patients by studying 99mTc-DMSA biodistribution and to compare the findings obtained with those of primary glomerulonephritis patients. This study included 18 insulin-dependent patients with overt diabetic nephropathy and 16 glomerulonephritis patients with normal serum creatinine levels and moderately decreased glomerular filtration rate. Renal fixation of 99mTc-DMSA and whole blood activity 2 and 4 h following radiopharmaceutical injection, as well as 4 h cumulative urinary excretion were determined. All values were expressed as per cent of net administered activity. 99mTc-DMSA renal accumulation was significantly decreased (p<0.001), while urinary excretion was increased (p<0.005) in both groups examined, as compared to 15 healthy persons. The reduction in 99mTc-DMSA renal fixation was more marked in diabetic nephropathy than in glomerulonephritis (p<0.05). Whole blood activity was markedly higher in diabetic patients (p<0.05), but nonsignificantly increased in glomerulonephritis patients. Markedly decreased tubular fixation of 99mTc-DMSA associated with high blood activity and increased urinary excretion demonstrated more pronounced tubular dysfunction in diabetic nephropathy than in primary glomerulonephritis at the same level of glomerular filtration rate.

Wood resource management using an endocrine NARX neural network

Planning and forecasting wood resources implies a challenging analysis, which has a direct impact on planning human resources, production timeline, as well as stock management of wooden assortments, which requires a complex data analysis taking into account all inputs that define the yield of wooden material. This paper includes an analysis of monthly time series data from 1991 to 2015 which can be characterized as long time dependence data. In recent years, artificial neural networks have become a popular tool for time dependence data treatment. Therefore, a prediction of monthly requirements of treated wood is performed by developing a new type of neural network in this research. The nonlinear autoregressive model with exogenous inputs (NARX) is used as a foundation of a new network. NARX is a type of recurrent neural network which is a very effective tool for approximation of any nonlinear function, especially ones which could occur during a nonlinear time sequence prediction. The main contribution of this paper is the introduction of an artificial endocrine factor inside the standard NARX structure. The developed ENARX model provides an extra sensitivity of the network to environmental conditions and external disturbances, as well as its improved adaptive capability. The proposed network shows better forecasting performances compared to the default NARX network, thus establishing itself as an excellent prediction tool in the field of wood science, engineering and technology.

Solitary congenital pelvic kidney: An extremely rare developmental aberration

&NA; An ectopic pelvic kidney contralateral to an agenetic one is an extremely rare congenital malformation that is usually discovered incidentally on abdominal ultrasound or computed tomography. The authors describe a 40‐yearold woman with right renal agenesis and a contralateral pelvic kidney who had a history of symptomatic recurrent urinary tract infections. She underwent Tc‐99m DTPA dynamic scintigraphy and clearance measurement to assess renal function and the patency of the urinary tract. She had bacteruria and proteinuria at the time of the study but normal blood urea (4.6 mmol/l) and serum creatinine (91 μmol/l) levels. An ultrasound scan did not show renal pelvis dilatation. Dynamic scintigraphy and the clearance value of Tc‐99m DTPA showed a compensatory elevated glomerular filtration rate and normal urine outflow despite the presence of a urinary tract infection and short ureter, which is commonly associated with an ectopic kidney.

Transperitoneal Removal of Osteocalcin, Calcitonin and Parathyroid Hormone in Patients Treated by CAPD

Dr. Vladisav Stefanovic, Institut za nefrologiju i hemodijalizu, B. Taskovica 48, SER-18000 Nis (Serbia) Dear Sir, Renal osteodystrophy is a major complication of end-stage renal disease (ESRD) [1]. Determinations of Ca and P, as well as hormones regulating kinetics of these minerals provide a reliable index of bone metabolism. CAPD was introduced originally as a procedure with superior clearance of low molecular mass proteins, as compared to hemodial-ysis. Considering the relatively small size of the molecules of parathyroid hormone (PTH), calcitonin (CT) and osteocalcin (OC), a remarkable peritoneal removal of these polypeptides might be expected. In order to estimate peritoneal fluxes of hormones and their impact on the corresponding blood levels, serum and dialysate levels of PTH, CT and OC were determined in 20 patients with ESRD on CAPD treatment for 3-19 months. CAPD was performed by standard technique, with a dialysis fluid containing 1.75 mmol/l calcium and 0.75 mmol/l magnesium. Of the four bag exchanges, generally 3 were with dextrose solution 1.5% and only one with dextrose 4.25%. All patients were on unrestricted diet except for potassium, phosphate and fluid intake. Aluminum-containing phosphate binders were only prescribed when repeated serum phosphate measurements were > 2.0 mmol/l. Immunoreactive CT and C-terminal PTH were determined by commercial RIA kits from Byk-Mallinckrodt, Germany, while OC measurements were performed by a kit from Sorin Biomedica, Italy. Blood samples were drawn at 07:00 h, and peritoneal fluid samples collected at the end of each of four daily exchange periods. Results are expressed as means ± SEM. Statistical significance was estimated by Student’s t test for paired data.

Placental growth factor and placental protein 13 in patients with Balkan endemic nephropathy, a worldwide disease.

Abstract Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial kidney disease occurring in people living in along the tributaries of the Danube River. The aim of the study was to determine serum level and urinary excretion of placental growth factor (PlGF) and placental protein 13 (PP13) in patients with BEN. Methods: Thirty patients with BEN from the South Morava River region of Serbia and 18 controls were studied. Age of patients was 74 yr (53–87) and 73 yr (66–83) in controls. Results: In patients with BEN, serum creatinine was significantly higher than in controls (129.7 vs. 83.2 µmol/L, respectively), but GFR was lower in patients than in controls (40.7 vs. 54.6 mL/min). Serum PlGF was significantly higher in BEN patients than in controls (9.90 vs. 6.80 pg/mL), urinary excretion being significantly lower in patients (0.20 vs. 0.90 pg/mmol creat.). Serum PP13 was significantly lower in BEN patients (208.2 vs. 291.0 pg/mL). Urinary excretion of PP13 was also significantly lower in BEN patients than in controls (32.5 vs. 182.5 pg/mmol creat). In multivariate regression analysis BEN, sex and age were significant determinants of the observed changes in PlGF and PP13. Conclusion: Important changes of PlGF and PP13 in patients with BEN were demonstrated, where kidney disease, female sex, and the age have been significant determinants.

Correlation between clinical prediction tests for coronary heart disease and findings on spect myocardial perfusion scintigraphy and coronary angiography

Sažetak: Uvod i cilj: Klinički predikcioni testovi su značajan dijagnostički alat u odreĎivanju grupa pacijenata koji treba da budu podvrgnuti daljim dijagnostičkim metodama u cilju detekcije koronarne bolesti. Cilj ovog rada je bio utvrĎivanje korelacije izmeĎu verovatnoće za postojanje koronarne bolesti (CHD) dobijene Djukovom kliničkom predikcijom za postojanje koronarne bolesti i rezultata dobijenih SPECT perfuzionom scintigrafijom miokarda i koronarnom angiografijom. Pacijenti i metode: U studiju je bilo uključeno 56 pacijenata, 35 muškaraca i 21 žena, starosti od 32 do 78 godina, sa izraženom simptomima AP. Svim pacijentima izračunavana je verovatnoća za postojanje koronarne bolesti, odnosno potreba za indikovanjem drugih dijagnostičkih metoda preko Djukove kliničke predikcije (DCS). Pacijentima je nakon toga uraĎena SPECT perfuziona scintigrafija miokarda sa testom fizičkog opterećenja (SPECT MPI) i izračunavanjem Djuke trejdmil skora (DTS), odnosno koronarna angiografija (CA). Rezultati su statistički obraĎeni SPSS statističkim alatom, neparametrijskim statističkim testovima. Rezultati: DCS je pokazao nisku verovatnoću za postojanje CHD kod 10 (17,9%), dok je kod 46 (82,1%) pacijenata pokazao umerenu verovatnoću. DTS je kod 8 (14,3%) pacijenata pokazao nisku verovatnoću, a kod 48 (85,7%) visoku verovatnoću za CHD. SPECT MPI je dao 22 (39,3%) normalnih i 34 (60,7%) patoloških rezultata. CA je bila negativna kod 21 (37,5%) pacijenta, dok je kod 35 (62,5%) pokazala postojanje značajne stenoze koronarne arterije. U grupama pacijenata sa niskom DCS i DTS verovatnoćom za postojanje CHD, nisu naĎeni perfuzioni defekti na SPECT MPI, ni stenoze koronarne arterije na CA. Zaključak: Prediktivni klinički testovi, DCS i DTS, kojima se uspostavlja ili odbacuje sumnja na postojanje CHD, predstavljaju značajne dijagnostičke alate kojima se izbegava nepotrebno izlaganje pacijenata daljim dijagnostičkim metodama koje podrazumevaju bilo invazivni dijagnostički pristup, bilo nepotrebnu ekspoziciju pacijenata jonizujućem zračenju. DCS i DTS imaju visoku negativnu prediktivnu vrednost za CHD i pouzdani su u izboru pacijenata sa AP za dalje dijagnostičke modalitete. Ključne reči: Djuke klinički skor, Djuke trejdmil skor, perfuziona scintigrafija miokarda, koronarna angiografija.