Rajko Hrvacevic

Epidemiology of end‐stage renal disease and hemodialysis treatment in Serbia at the turn of the millennium

The study presents the epidemiological features of patients treated with renal replacement therapy (RRT) in Serbia from 1997 to 2009 and compares the results of hemodialysis treatment in 1999 and 2009. Epidemiological data were obtained from the National Registry of RRT patients and data on hemodialysis treatment from special surveys conducted in 1999 and 2009. Within the period 1997–2009 the incidence of patients on RRT increased from 108 to 179 per million population (pmp), prevalence rose from 435 to 699 pmp, while mortality rate fell from 20.7% to 16.7%. The frequency of patients with glomerulonephritis decreased, while that of patients with diabetes and hypertensive nephropathy increased. In late 2009 there were 5208 patients receiving RRT in Serbia. Within the examined period new hemodialysis and reverse osmosis equipment were purchased, high‐flux dialyzers with synthetic membranes were increasingly used and the number of patients receiving hemodiafiltration increased to 17.6%. Kt/V greater than 1.2 was recorded in 16% of the patients in 1999 but 52% in 2009. Options for correction of anemia and mineral disorders have also improved. The percentage of patients with HbsAg (13.8% vs. 4.8%) as well as anti‐hepatitis C virus antibodies positive patients (23.2% vs. 12.7%) was significantly lower in 2009 than in 1999. Both the incidence and prevalence of RRT patients in Serbia are rising continuously, while the mortality rate is falling. More favorable conditions for dialysis treatment have brought about significant improvement in the results over the last 10 years.

Urinary Cystatin C as a Marker of Tubular Dysfunction

Urinary Cystatin C as a Marker of Tubular Dysfunction Cystatin C (CysC) is a nonglycosylated 13 KD protein that belongs to the type II cystatin gene family. It is a strong inhibitor of cysteine proteinases, freely filtered by the kidney glomerulus and reabsorbed by the tubulus, where it is almost totally catabolized. Remainder of the nonmetabolized CysC is eliminated in urine and may represent a useful marker of tubular dysfunction. The aim of the study was to confirm the clinical importance of the quantitative determination of CysC by an automated immunonephelometric method (DADE Behring). Two groups of patients were examined: one with glomerular (GD, n=36) and one with tubular dysfunction (TD, n=31), and compared with the control group (CG, n=31) of healthy males and females from laboratory personnel (n=11) and patients on routine systematic examination (n=20), from 25 to 58 years old. The patient groups were categorised according to the urine analysis of total proteins, creatinine and adequate proteins electrophoretic panel. CysC concentration in CG was in the range of 0.02-0.15 mg/L; 0.01-0.48 mg/L and 0.25-18 mg/L in GD and TD groups respectively. Values of means ± SD for patient groups (GD=0.11 ± 0.14; TD=3.92 ± 3.75 mg/L) showed statistical significance (p<0.001) in the TD group in relation to GD and CG groups. It confirms that quantitative determination of CysC in one urine portion, with a fast laboratory method, might be a useful marker of tubular dysfunction, especially in emergency situations, taking into account that there is no interference of circadian variation on its concentration. Cistatin C U Urinu Kao Pokazatelj Tubulskog Oštećenja Cistatin C (CysC) je neglikozirajući protein molekulske mase od 13 KD koji pripada tipu II genske familije cistatina. Ima funkciju inhibitora cistein proteinaze koji se potpuno filtrira u glomerulima a zatim reapsorbuje i kataboliše u proksimalnim tubulima. Preostali i nerazgrađen CysC biva eliminisan urinom pa zato može da bude koristan marker tubulskih oštećenja. Cilj ispitivanja bio je da se utvrdi klinički značaj kvantitativnog određivanja CysC automatizovanom imunonefelometrijskom metodom (DADE Behring). Ispitane su dve grupe bolesnika: sa tubulskom (TI) i glomerulskom (GI) insuficijencijom, i upoređene sa kontrolnom grupom (KG) koju su činile zdrave osobe oba pola (n=31), laboratorijski personal (n=11) i pacijenti na sistematskom pregledu (n = 20), starosne dobi od 25 do 58 godina. Kategorizacija grupa sa GI (n=36) i TI (n=31) ustanovljena je na osnovu koncentracije ukupnih proteina, kreatinina i adekvatnih elektroforetskih denzitometrijskih varijanti karakterističnih za obe grupe. Koncentracija CysC u KG bila je u opsegu 0,02-0,15 mg/L, u grupi sa GI 0,01-0,48 mg/L, a u grupi sa TI 0,25-18 mg/L. Rezultati vrednosti (medijana±SD) za grupu sa GI (0,11 ± 0,14 mg/L) i grupu sa TI (3,92 ± 3,75 mg/L) pokazali su statistički značajnu razliku (p< 0,0001) između grupe sa TI i grupa sa GI i KG. Pokazano je da određivanje CysC u jednom uzorku urina brzim laboratorijskim postupkom može biti koristan test za diferencijalnu dijagnostiku tubulskih u odnosu na glomerulska oštećenja, posebno u urgentnim stanjima, s obzirom na činjenicu da na njegovu koncentraciju nema uticaja cirkadijalnih ritmova.

[Mycophenolate mofetil combined with steroids: new experiences in the treatment of idiopathic retroperitoneal fibrosis].

BACKGROUND/AIM [corrected] Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease characterized by a retroperitoneal fibrotic tissue that often involve the ureters, leading to the obstructive nephropathy and variable impairment of renal function. Findings strongly suggest an autoimmune etiology. Surgery, medical treatment with immunosuppressive drugs, or a combination of both are proposed. The optimal treatment has not been established yet. The aim of this study was to present our experience with combined immunosuppressive therapy of IRF, steroids (S) and mycophenolate mofetil (MMF). METHODS We prospectively followed four patients with IRF from January 2004 to December 2006. Three patients had an active disease with bilateral hydronephrosis. In the two of them acute renal failure was presented, and ureteral catheters were inserted in one in order to manage ureteral obstruction. One patient has came to our unit with a relapse of IRF and incipient chronic renal failure after the prior therapy with ureterolysis and immunosuppressive drugs (azathioprine and tamoxifen). All patients received steroids and MMF. Two patients were treated with intravenous methylprednisolone pulses (250 mg each), for three consecutive days, followed by oral prednisone 0.5 mg/kg/day. The other two patients received oral prednisone at the same dose. Prednisone was gradually tappered to a maintenance dose of 10 mg/kg/day. Simultaneously, all patients received MMF, initially 1 g/day with the increase to 2 g/day. RESULTS After four weeks of the therapy all symptoms disappeared, as well as a hydronephrosis with a decrease of erythrocyte sedimentation rate and Creactive protein (CRP) to normal level in all patients. Three patents remain in remission untill the end of the follow up. One patient had a relapse because of stopping taking the therapy after six months. He was treated by oral prednisone 0.5 mg/kg/day, which was gradually decreased. After twelve weeks hydronephrosis disappeared and CRP returns to the normal level. CONCLUSION The combination of steroids and mycophenolate mofetil led to the remission of IRF with a strong and quick immunosuppressive effect. It also provided avoiding the long-term use of high steroid dose and surgical procedures.

Angiotensin II type 1 receptor gene polymorphism could influence renoprotective response to losartan treatment in type 1 diabetic patients with high urinary albumin excretion rate

BACKGROUND/AIM Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. The aim of this study was to examine if renoprotective response to a short-term losartan therapy depends on 1166 A/C gene polymorphism for its target receptor. METHOD The study included 35 patients with diabetes mellitus type 1 and persistently high urinary albumin excretion rate (UAE: > 30 mg/24 h), genotyped for the 1166 A/C gene polymorphism for the angiotensin II type 1 receptor (AT1R). The participants were segregated into 3 genotype groups according to combinations of A or C allele: AA (16%), AC (15%) and CC (11%). The patients received losartan 50 mg daily for 4 weeks, following 100 mg daily for another 8 weeks. At baseline and after 12 weeks of the treatment period UAE, blood pressure, GFR and filtration fraction (FF) were determined. RESULTS After 12 weeks of the treatment with losartan, albuminuria was reduced from baseline by 9% [95% confidence interval (CI): 1-17, p = 0.039] in the AA genotype, and by 11% (95% CI: 6-17, p = 0.0001) in the AC genotype. Losartan treatment reduced albuminuria in the CC group by 5% (95% CI: -13-22, p = 0.47). Glomerular filtration rate remained unchanged in all genotype groups. Filtration fraction was significantly reduced from baseline by 0.018 +/- 0.024 (p = 0.012) only in the AC genotype. In the AA genotype, FF was reduced from baseline by 0.017 +/- 0.03 (p = 0.052), and in the CC genotype by 0.01 +/- 0.008 (p = 0.092). In the AA group, systolic blood pressure declined from 136 +/- 24 mmHg at baseline, to an average of 121 +/- 18 mmHg at the end of the study (p = 0.001). The AC group achived reduction from 131 +/- 10 mmHg at baseline to 115 +/- 7 mmHg (p = 0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86 +/- 13 mmHg at baseline to 78 +/- 8 mmHg (p = 0.004), and in the AC genotype from 88 +/- 5 mmHg at baseline to 11.7 +/- 5.6 mmHg during the investigation period (p = 0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (p = 0.066). CONCLUSION The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.

Brown tumor of the maxilla in patient with secondary hyperparathyroidism

Brown tumor or parathyroid osteopathy is a kind of bony lesion caused by hyperparathyroidism. It appears as an expansive osteolytic lesion mostly in mandible, ribs, pelvis and femur, but rarely in the upper jaw. Bone resorption is the result of osteoclastic activity due to an increased activity of parathyroid hormone. A 25-years-old male patient was operated on due to clinicaly and radiographicaly obvious maxillary tumor and increased values of parathyroid hormon (PTH-1 050 ng/l). The level of calcium in blood was normal (Ca 2.34 mEq/L). The patient was dialyzed for years because of the chronic renal failure. Histopathologic analysis confirmed brown tumor, that appeared as bony lesion of secondary hyperparathyroidism due to the chronic renal failure. The operation of the upper jaw had been performed before parathyroidectomy, due to an excessive growth of tumor followed by heavy epistaxes. The subsequent parathyroidectomy was followed by the regression of remaining bony lesions.

Predijalizna transplantacija bubrega

Predijalizna transplantacija bubrega je sa medicinskog i socioekonomskog aspekta metoda izbora u lecenju terminalne bubrežne insuficijencije kod bolesnika koji imaju živog davaoca bubrega. Nase pocetno iskustvo sa ovom metodom lecenja vrlo je afirmativno. Predijalizna transplantacija bubrega je posebno prihvatljiva kod dece, dijabeticara i bolesnika sa losim pristupom za dijalizu. U nasoj zemlji postoje dodatni medicinski (los kvalitet dijalize, visok rizik od infekcije virusima hepatitisa, visok rizik od senzibilizacije na tkivne antigene transfuzijama krvi) i paramedicinski razlozi (prepunjenost dijaliznih centara, ograniceni zdravstveni ekonomski resursi) koji namecu potrebu daljeg razvijanja programa predijalizne transplantacije.