Branka Mitic

Oxidative stress parameters as possible urine markers in patients with diabetic nephropathy

OBJECTIVE Reactive oxygen species play a crucial role in the pathogenesis of diabetic nephropathy (DN). The present study was performed to assess oxidative stress parameters-thiobarbituric acid reactive substances (TBARS), reactive carbonyl derivates (RCDs), and total sulfhydryl groups (TSHGs)-in serum and urine of patients with DN. METHODS All parameters were determined in patients with type 2 and type 1 diabetes mellitus and microalbuminuria (DMT2-MIA, DMT1-MIA, respectively) and patients with type 2 diabetes mellitus and macroalbuminuria (DMT2-MAA) compared to healthy controls. RESULTS Serum and urine TBARS levels were higher in all patients with DN and microalbiminuria compared to the control group. RCD levels significantly increased in serum of patients with DMT2 relative to the controls as well as in urine of patients with DMT2-MAA and DMT1-MIA. In all groups of patients, TSHGs decreased in serum but not in urine of patients with DMT2-MAA. CONCLUSION Urine TBARS, RCDs, and TSHGs could be proposed as possible markers for oxidative damage of kidney in DN.

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.

Immunosuppressive medication adherence in kidney transplant patients.

Objectives: To assess the degree of immunosuppressive medication adherence in kidney transplant patients (KTPs) and to determine if there is a difference in the rate of adherence to tacrolimus (Tac), cyclosporine (CsA) and sirolimus (Sir). Subjects and Methods: From a total of 63 KTPs treated at the Clinic of Nephrology, Clinical Centre Niš, Serbia, 60 participated in the study by responding to questionnaires. They were divided into the adherence group (n = 43) and the nonadherence group (n = 17) according to their degree of adherence which was measured using a validated survey form, the simplified medication adherence questionnaire. The KTP adherence to the different immunosuppressive regimens (Tac, CsA and Sir) was compared. Statistical analysis was performed using the Student t test. Results: Adherence was observed in 43 (71.7%) patients, and only 17 (28.3%) did not follow the prescribed therapy. The estimated glomerular filtration rate was significantly lower in the nonadherence group (38.52 ± 18.22 ml/min) than in the adherence group (52.43 ± 16.91 ml/min, p < 0.05). With regard to the Tac level, a significant difference was also found between the adherers and the nonadherers (6.30 ± 2.06 vs. 5.0 ± 1.52 ng/ml, p < 0.05). Conclusion: The KTPs in this study demonstrated a high level of adherence. Nonadherence was associated with worse graft function and a lower Tac level. Knowledge about the degree of adherence could help the early identification of nonadherent patients and the development of strategies to improve this.

Monocyte chemoattractant protein-1 as a marker of systemic lupus erythematosus: an observational study

There is a pivotal need for new markers to be tested in every day clinical practice for systemic lupus erythematosus (SLE) and lupus nephritis (LN). The levels of monocyte chemoattractant protein-1 (MCP-1) in the serum and urine of 72 SLE patients (27 with LN and 45 without LN involvement) and 30 healthy individuals were studied to establish their clinical significance. The SLE Disease Activity Index (SLEDAI) was used to establish the disease activity. Urine and serum MCP-1 was determined using the sandwich enzyme immunosorbent assay. Urinary, but not serum MCP-1, positively correlated with proteinuria (r = 0.839; p < 0.001) and negatively correlated with glomerular filtration, evaluated using the modification of diet in renal disease (MDRD) formula (r = − 0.293; p < 0.05), and with C3 complement component in active LN patients (r = − 0.519, p = 0.019). Both serum and urinary MCP-1 demonstrated a positive correlation with SLEDAI (r = 0.318; p < 0.01 and r = 0.431; p < 0.001). We also demonstrated that the levels of serum and urinary MCP-1 were significantly higher in patients with SLE compared to healthy controls, regardless of the disease activity and renal involvement. We recommend MCP-1 measurement in the routine laboratory follow-up of the SLE patients.

Acute renal failure after licorice ingestion: A case report

A 39-year-old female presented to the nephrology clinic emergency department with a complaint of muscle weakness and stomach pain. A detailed personal history revealed ingestion of 50–100 g herbal products which contained licorice, every day for 8 weeks to treat sterility. The herbal product was studied and determined to contain ‘licorice’ containing glycyrrhizic acid. Licorice (a plant which contains glycyrrhizic acid) induced hypokalemia which usually has a mild progression. However, it may cause critical failure in physical action by means of weakness followed by paralysis and may cause rhabdomyolysis, acute renal failure and hyperaldosteronism. This report presents the first case with acute renal failure due to licorice consumption from Serbia. In addition, the report aims to emphasize the importance of obtaining the detailed personal history of a patient for precise diagnosis.

Biomarkers of early kidney cells dysfunction in patients with membranous nephropathy

Online first: March 14, 2017 SUMMARY Introduction/Objective An unfavorable prognosis of membranous nephropathy (MN) is determined by the presence of persistent proteinuria and extensive tubulointerstitial lesions at initial biopsy. Our study investigated the value of markers of renal cell dysfunction (glomerular filtration rate, urinary excretion of protein, ectoenzyme proximal tubular epithelial cells, and oxidative stress) in patients with MN, and points to the use of these markers in a possible therapeutic modification. Methods The study included 28 patients with MN and 30 healthy individuals as control. In addition to the basic laboratory studies, enzyme [aminopeptidase N (APN), plasma cell glycoprotein-1 (PC-1), N-acetylβ-D-glucosaminidase (NAGA), and dipeptidyl peptidase-4] activity was determined in serum and urine, as well as parameters of oxidative damage [thiobarbituric acid concentration of substance-responders (TBARS), malondialdehyde, and the concentration of the total sulfhydryl (SH) group]. Results In patients with MN, serum activity of PC-1 and APN and urinary excretion of NAGA were significantly higher than in the control group. Also, significant correlation between daily proteinuria and serum PC-1 activity and urinary excretion of NAGA was found in patients with MN. Serum and urine levels of TBARS as well as total SH group levels were significantly lower in patients with MN than in healthy controls. Conclusion Kidney damage in MN is accompanied by the release of several tubular enzymes, with potential diagnostic and prognostic significance. The study suggests a possible role of oxidative stress in pathogenesis of MN and the use of antioxidants in preventing impairment as part of future therapy.

Aristolochic Acids as Persistent Soil Pollutants: Determination of Risk for Human Exposure and Nephropathy from Plant Uptake

Exposure to aristolochic acids (AAs) from Aristolochia plants is one of the major global causes of nephropathy, including Balkan endemic nephropathy (BEN); renal failure; and urothelial cancer. The high incidence of BEN on the Balkan Peninsula is assumed to result from consumption of Aristolochia clematitis L. seeds coharvested with crops. Here, we show that AAs are long-lived soil contaminants that enter wheat and maize plants by root uptake with strong pH dependence. Soil and crops from Serbian farms in areas endemic for A. clematitis were found to be extensively contaminated with AAs, with contamination strongly correlated with local incidence of BEN. The persistence of AAs as soil contaminants suggests that weed control for A. clematitis plants is needed to reduce the incidence of BEN and aristolochic acid nephropathy, systematic surveys of soil and crop AA levels would identify high-risk regions, and it is imperative to research soil-remediation methods.

Metronidazole- and levofloxacin-induced psychotic disorders in chronic kidney patient

We present a case which reports the occurrence of psychotic disorders after metronidazole and levofloxacin therapy in a chronic kidney patient while being treated for enterocolitis and urinary infection. A 48-year-old female was admitted to a hospital for the placement of a peritoneal dialysis catheter due to indicated peritoneal dialysis. During admission, symptoms of enterocolitis and urinary infection had occurred, so metronidazole and levofloxacin were introduced into therapy, respectively. After 4 days of metronidazole and 3 days of levofloxacin therapy, the patient became confused, disoriented, with signs of delirium. Since the diagnosis of psychoorganic disorder was made, the therapy with lorazepam and haloperidol was initiated, while metronidazole and levofloxacin were discontinued. Complete recovery 4 days after discontinuation indicates that the patient has experienced antibiotics-induced neurotoxicity. This is the first report of expressed neurotoxicity after the combination of metronidazole and levofloxacin in chronic kidney patients.

Antihipertenzivna terapija u trudnoći

Postoji opsta saglasnost o neophodnosti hitnog lecenja trudnica sa teskomhipertenzijom, u cilju smanjenja rizika za razvoj akutnih cerebrovaskularnihkomplikacija, eklampsije i smrti. U kontroli teskih oblika hipertenzije, intravenskiprimenjen labetalol ili peroralno dat nifedipin su podjednako efikasnii udruženi sa manjim brojem neželjenih reakcija u odnosu na intravenskiaplikovan hidralazin. Jos uvek ne postoji definisan stav o terapiji blage doumerene hipertenzije u trudnoci, s obzirom da ne postoji jasan odnos potencijalnihkoristi/rizika uzrokovanih primenom antihipertenzivne terapije utrudnoci. Metildopa, labetalol i dugodelujuci nifedipin su najcesce koriscenilekovi za regulaciju krvnog pritiska kod trudnica sa hipertenzijom, s obziromna njihovu bezbednu primenu u trudnoci. Atenolol, kardioselektivni betablokator, treba izbegavati u trudnoci jer dovodi do sniženja telesne težinena rođenju i smanjenja fetalnog rasta. Kontraindikovana je