Assessment of Retinal Microangiopathy in Patients with Balkan Endemic Nephropathy Using Optical Coherence Tomography Angiography-A Pilot Study.

Background and Objectives: It is well known that alterations in microvascular structure and function contribute to the development of ocular, renal, and cardiovascular diseases. Accordingly, the presence of fundus vascular changes in patients suffering from chronic kidney disease (CKD) and Balkan endemic nephropathy (BEN) may provide information of prognostic value regarding the progression of renal disease. This study aimed to examine the associations between clinical characteristics and retinal optical coherence tomography angiography (OCTA) parameters in patients with BEN and compare them with those in CKD. Materials and Methods: This pilot study, conducted from March 2021 to April 2022, included 63 patients who were divided into two groups: the first group consisted of 29 patients suffering from BEN, and the second was a control group of 34 patients with CKD. Demographic, laboratory, clinical, and medication data were noted for all the patients included in this study. Each eye underwent OCT angiography, and the results were interpreted in accordance with the practical guide for the interpretation of OCTA findings. Results: Statistically significantly higher levels of total serum protein and triglycerides were recorded in the BEN group than in the CKD group, while the level of HDL cholesterol was lower. Based on the performed urinalysis, statistically significantly higher values of total protein and creatinine were detected in patients with CKD compared to the BEN group. It was demonstrated that the OCTA vascular plexus density of certain parts of the retina was in significant association with systolic and diastolic blood pressure, creatinine clearance, urinary creatinine, total cholesterol, diabetes mellitus type 2, age, body mass index, total serum and urinary protein, sCRP, and diuretic and antihypertensive treatment. Conclusions: In comparison with CKD, BEN leads to more significant disturbances in retinal vasculature density.

Trend of Galectin-3 Levels in Patients with Non-ST-Elevation and ST-Elevation Myocardial Infarction.

Background and Objectives: Given the fact that galectin-3 has a predictive significance on the development of myocardial dysfunction after acute myocardial infarction, the aim of our study was to examine potential factors that could be important for the dynamics of the concentration of this biomarker in the early postinfarction period. Materials and Methods: This study included 89 patients with a diagnosis of stable angina pectoris (SAP) or the first non-ST elevation (NSTEMI) or ST-elevation (STEMI) myocardial infarction, who underwent percutaneous coronary intervention (PCI). The study group included 23 patients with the first NSTEMI and 42 patients with STEMI, while the control group consisted of 24 patients with SAP hospitalized for elective PCI without a previous MI. All patients had preserved left ventricular ejection fraction. Galectin-3 levels were determined on days 1, 5, and 30 after PCI. The significance of various independent variables as predictors of galectin-3 concentration was analyzed after a series of univariate linear regression modeling in a multivariate linear regression model. Results: The average patients' age was 63.99 ± 9.13 years. Statistically significantly higher values of C-reactive protein were established in STEMI compared to SAP (p < 0.01) or NSTEMI (p < 0.001), whereas WBC count was significantly lower in SAP than in STEMI (p < 0.001) and NSTEMI (p < 0.01) group. Although there were no statistically significant differences in measured galectin-3 concentrations between the examined groups on days 1, 5, and 30 after PCI, HTA, triglyceride level, LA size, treatment with trimetazidine and long-acting nitrates, as well as percentage of LM stenosis and E/A ratio were identified as independent predictors of galectin-3 concentration. Conclusions: In the post-MI period, very early values of galectin-3 correlate mostly with atherosclerosis factors, while on day 30 this biomarker correlates with diastolic dysfunction and "announces" left ventricular remodeling.

Assessment of pharmacokinetic mycophenolic acid clearance models using Monte Carlo numerical analysis.

Previously, we performed population pharmacokinetic analysis and indicated age, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) daily dose, and presence of nifedipine in patient therapy as significant predictors of MPA apparent clearance (CL/F) variability. This study aimed to determine the reliability of previously published population pharmacokinetic models derived from similar studies. Furthermore, this study investigated correspondence between chosen population models from the literature.By means of the Monte Carlo simulation method, pharmacokinetic models from different studies are simulated and analysed in the range of standard deviations of measured system parameters as well as the range of observed model parameters taken from the comparison studies.The 1000 numerical simulations were performed for every analysed model in order to calculate the most possible MPA CL/F values according to the expected values from the performed experiment. Fitting our results with other models showed how the presence of nifedipine makes difference in MPA CL/F values.By testing the data from selected studies into our model, a similar range of expected CL/F values was obtained, which may confirm the validity of our model. The results of our population pharmacokinetic study are partially applicable in models by other researchers.

Elevated Serum Ferritin Levels Are Predictive of Renal Function Recovery among Patients with Acute Kidney Injury.

Oxidative stress (OS) frequently contributes to the development of acute kidney injury (AKI). Iron can promote oxidative stress and tissue injury by catalyzing free reactive oxygen species (ROS) generation and increasing the steady-state concentration of these potent oxidants. The anticipated role of ferritin is to protect from OS by sequestering iron and limiting its involvement in reactions that generate ROS. In this prospective study, we aimed to investigate the association between serum ferritin levels and kidney function recovery among patients with AKI. Renal recovery was determined as a return of serum creatinine to less than 1.25 times the baseline value after 90 days of follow-up. One hundred twelve patients (72 males and 40 females, 63.68 ± 10.6 years old) were included in the final analysis. They were divided into AKI recovery (n = 76) and non-recovery groups (n = 36). Ferritin levels on admission were higher in AKI recovery group [284 (IQR 153-525) ng/mL] compared with the non-recovery group [127.4 (IQR 30-243) ng/mL], p < 0.001. Serum ferritin levels and the renal recovery significantly positively correlated (r = 0.72, p < 0.001). In multiple linear regression analysis, higher serum ferritin was associated with renal function recovery (OR 3.68, CI 2.02-3.97, p < 0.001). The optimal cut-off point of 240.5 ng/mL was determined for serum ferritin, which showed a sensitivity of 75.8% and a positive predictive value of 90%. In conclusion, serum ferritin levels on admission may be used as a prognostic marker for predicting renal recovery in AKI patients.

Associations of Cardiovascular and All-Cause Mortality with Metabolic Syndrome in Hemodialysis Patients: A Prospective Single-Center Study.

Background and objectives: Metabolic syndrome (MetS) is a cluster of risk factors, such as abdominal obesity, insulin resistance, dyslipidemia and hypertension, that together increase the risk of cardiovascular disease. Chronic hemodialysis (HD) patients have multiple comorbidities and many metabolic disorders, causing the frequent occurrence of metabolic syndrome. The goal of this study was to assess the prevalence of MetS in HD patients, and its association with all-cause and cardiovascular (CV) mortality. Patients and methods: A total of 138 HD patients were included in this prospective study. We analyzed demographic, anthropometric and biochemical data. Outcome measures were all-cause and CV mortality during the three-year follow-up. Results: MetS was diagnosed in 57.24% of enrolled patients. During the 36 months of follow-up, 33 patients died. MetS patients showed a significantly higher mortality rate than non-MetS (30.4% versus 16.36%, p < 0.001). The association of different MetS components with cardiovascular mortality reached significance when a minimum of three components were present (1.81 (95% confidence interval CI = 1.21-2.33)), with a grouped increase in effect size for subjects with four or five MetS components. Subjects with MetS exhibited nearly twice as high risk for all-cause (hazard ratio HR = 1.99 (95%CI) = 1.42-2.97) and 2.5 times for CV (HR = 2.51 (95%CI) = 1.25-3.83) mortality compared with those without MetS, after adjustment for age, gender, and cardiovascular disease. Conclusions: The study demonstrates that MetS is widespread in HD patients. In future, the focus must be on an active screening approach, and treatment of cardiometabolic risk factors, aiming to reduce mortality.

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.

Gender-dependent predictable pharmacokinetic method for tacrolimus exposure monitoring in kidney transplant patients.

Tacrolimus (Tac) is an immunosuppressive drug with a narrow therapeutic width and highly variable pharmacokinetics. Therefore, monitoring of Tac blood concentrations is of utmost importance in the management of renal transplant recipients. The occurrence and intensity of adverse effects depend on blood concentration and total exposure of the organism to this drug. This implies finding a new gender-dependent predictable method for Tac exposure monitoring based on determination of the area under the time concentration curve (AUC). The primary aim of this study was to investigate gender differences in systemic body exposure to Tac in renal transplant patients after the first oral dose and in a steady state by determining 12-h AUC (AUC(0-12)). The secondary objective was to find the best sampling time in which measured Tac concentration best predicts AUC value with respect to gender. Tac pharmacokinetic study was conducted in 20 kidney transplant recipients (10 men/10 women) on quaternary immunosuppressive therapy. The first oral Tac dose (0.05 mg/kg) was given on the fifth day post-transplant. After reaching steady state, regimen stabilized and dosage was adjusted in accordance with the level of Tac. Blood concentrations were measured by microparticle enzyme immunoassay method. AUC(0-12) for each patient was calculated after the first oral Tac dose and in the steady state from a plot of Tac concentration versus time from 0 to 12 h using the trapezoid rule. Associations between each sampling time point of concentrations within 12 h after the administration and AUC(0-12) were evaluated by Pearson correlation coefficients. Abbreviated sampling equations were derived by multiple stepwise regression analyses. Statistically significant difference was found in AUC(0-12) between male and female patients after the first oral dose (p < 0.01), but this difference was lost in a steady state. In female recipients C(2) seemed to be good indicator of total body exposure to Tac after the first oral dose and this was also confirmed in a steady state. The three-point sampling method was required for calculating AUC after the first oral dose in male patients, whereas in the steady state, concentration of C(8) seemed to be a good indicator of abbreviated AUC for a Tac monitoring strategy in male patients. Non-compartment Tac pharmacokinetic and regression analysis showed gender difference in total Tac exposure and determined the best predictable Tac concentrations after the first oral dose. Our study confirmed gender-dependent pharmacokinetics in a steady state in terms of best sampling time in which measured Tac concentration best predicts AUC value.

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 Nis, 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.

Utility of salivary mycophenolic acid concentration monitoring: Modeling and Monte Carlo validation approach.

The results of the previous studies demonstrated an association between mycophenolic acid (MPA) exposure, serum albumin level (ALB), and adverse effects in kidney transplant patients. The aim was the identification of mathematical correlation and association between both, total and unbound MPA concentration in relation to ALB, body mass (BM), age and estimated glomerular filtration rate (eGFR) in stable kidney transplant recipients. Furthermore, investigation was conducted with the aim to clarify the role of salivary concentration (CSAL ) of MPA in adverse effect profile. In order to analyze the association between total and salivary concentration of MPA in relation to ALB, BM, age and eGFR, a least squares method for determining the correlation between these parameters was performed. In addition, derived mathematical model based on experimental data can also be performed and simulated through the Monte Carlo (MC) approach. Adverse effects were grouped according to the nature of symptoms and scored by a previously published validated system. Numerically calculated values of CSAL from the models [CSAL  = f(ALB, BM, age, eGFR, CP ) = a00 + a10 *(ALB, BM, age, eGFR) + a01 *CP ] were then compared with those from validation set of patients, where the best fitting model was for ALB [CSAL  = 54.96-1.64*ALB +13.4*CP ]. Adverse effects estimation showed the difference in esthetic score, positively correlated with CSAL in the lower ALB group (145.41 ± 219.02 vs. 354.08 ± 262.19; with statistical significance p = .014) and almost significant for gastrointestinal score (167.69 ± 174.79 vs. 347.55 ± 320.95; p = .247). The study showed that CSAL MPA may contribute to management of adverse effects, but these findings require confirmation of clinical utility.

Platelet thrombus formation in patients with end-stage renal disease before and after hemodialysis as measured by the total thrombus-formation analysis system.

BACKGROUND: Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) often experience bleeding. However, mechanisms behind this bleeding tendency are incompletely understood but may involve platelet dysfunction. We, therefore, studied platelet-dependent thrombus formation in flowing whole blood inside a microchip coated with collagen, and its association with circulating von Willebrand factor (VWF). METHODS: Blood samples were obtained in 22 patients before and after HD. The area under the 10 min flow pressure curve in a microchip (AUC10) reflecting total platelet thrombogenicity was measured, using the Total Thrombus-formation Analysis System (T-TAS01). AUC10 < 260 indicates platelet dysfunction. VWF activity and antigen in plasma were also assayed. RESULTS: VWF levels were moderately elevated and increased further after HD (P < 0.01 or lower). In contrast, AUC10 before and after HD was < 260 in 17/22 patients and < 130 in 15/22 patients, with no statistically significant difference in pre- vs post-HD measurements, indicating reduced platelet thrombogenicity, but with some variability as 5/22 patients showed normal platelet responsiveness. AUC10 and VWF activity or antigen levels in plasma were not correlated, either before or after HD. CONCLUSIONS: Most ESRD patients display moderate-to-severe platelet dysfunction as assessed by shear-induced platelet-dependent thrombus formation with T-TAS01. HD does not influence platelet function despite HD-induced elevations in VWF. T-TAS01 should be further evaluated as a tool in the assessment of bleeding risk in patients on HD.

Gender-specific differences in hemodialysis patients: a multicenter longitudinal study from Serbia.

PURPOSE: The study was undertaken with the aim to determine gender-specific differences in incident hemodialysis (HD) patient and their changes over time. METHODS: The retrospective longitudinal closed cohort study involved 441 incident patients starting HD in 2014 and followed for 1-59 (median 43, IQR 40) months. Demographic, clinical data, treatment characteristics, laboratory findings and outcome were abstracted from the patients' medical records. RESULTS: The relative number of males on HD was about twice that of females throughout the five years investigated. At the beginning of the study, no significant differences were found in the main demographic and clinical characteristics except that diabetes was more often the underlying disease in men than in women. Systolic blood pressure decreased over time significantly more in females than in males. Throughout the study spKt/V was significantly higher in females than in males, but it increased in patients of both genders. There were no gender differences for comorbidities, vascular access and the majority of laboratory findings except for higher serum levels of creatinine and CRP in men than in women. Relatively more females were treated with erythropoiesis stimulating agents and phosphate binders than males. Age and malignancy were selected as significant predictors of mortality for both genders, and, in addition, polycystic kidney disease, serum level of albumin and CRP for men, but spKt/V for women. CONCLUSION: Some significant gender differences were observed throughout, while others appeared during the study but none of them were due to gender inequalities in the applied treatment.

Risk factors for urosepsis in chronic kidney disease patients with urinary tract infections.

Occurrence of urosepsis is not uncommon following urinary tract infections (UTI). However, there is a lack of evidence explaining the risk factors predisposing to urosepsis in patients with chronic kidney disease (CKD). This retrospective study was undertaken to evaluate the incidence and possible risk factors for urosepsis among patients hospitalized with UTI in a cohort of CKD patients. Patients were divided into the urosepsis group and the non-urosepsis group. Of 489 hospitalized patients with UTI, 70 (14.3%) acquired urosepsis. Stepwise multivariate logistic regression demonstrated that diabetes, urinary catheter and length of hospital stay (p < 0.001 for all) were significant independent predictive risk factors for urosepsis in CKD patients with UTI in addition to age, glomerular filtration rate, hydronephrosis, acute kidney injury and E. coli infection (p < 0.05 for all). Finally, Klebsiella spp. cases were associated with significantly higher odds for urosepsis than E. coli cases (OR: 3.5, 95% CI: 2.86-7.23, p < 0.001 vs. OR: 1.38, 95% CI: 1.19-3.69, p = 0.038). Diabetes, presence of an indwelling urinary catheter, length of hospitalization, and infection with Klebsiella spp were independent risk factors for urosepsis in CKD patients with UTI.

Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach.

Background: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. Aim: This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C0/D) over 6-12 months on reduced estimated glomerular filtration rate (eGFR) values in the late period after kidney transplantation (Tx), applying Monte Carlo (MC) simulation. Methods: The previously published linear regression was the basis for MC simulation, performed to determine how variations in significant predictors affect the distribution of eGFR from 13 to 36 months post-transplantation. The input C0/D values were derived from CYP3A5 genotype subgroups. Results: Patients characterized by high Tac IPV and low mean C0/D over 6-12 months could have been at greater risk of lower eGFR values in a three-year period following Tx compared to the other patient groups. This effect was more pronounced in patients with a lower eGFR at the 6th month and a history of acute rejection. The proven contribution of CYP3A5 expresser genotype to low C0/D values may suggest its indirect effect on long-term graft function. Conclusion: The findings indicate that simultaneous assessment of Tac IPV, C0/D, and CYP3A5 genotype may identify patients at risk of deterioration of graft function in the long-term post-transplantation period.

Treatment of lupus nephritis by mycophenolate mofetil.

BACKGROUND/AIMS: Mycophenolate mofetil (MMF) has been increasingly used for the treatment of lupus nephritis (LN). The aim of this study was to examine the efficacy and safety of MMF used with low doses of corticosteroids as maintenance therapy in patients with LN. METHODS: The study covered 35 patients, most of them with proliferative types of LN (5 WHO class III, 26 class IV), while 1 had class V and 3 class VI nephritis. MMF was administered in the dose of 1.5-2 g/24 h and prednisone at 10-20 mg/day. The treatment effects were followed over a 12-month period. RESULTS: After 3 months of therapy significant reduction in proteinuria was achieved (2.1 +/- 2.4 g/24 h vs. 1.0 +/- 1.0 g/24 h, p < 0.01) and maintained to the end of the study. In parallel, a significant rise in serum albumin, a fall of cholesterol and a significant increase in mean glomerular filtration rate were noted. Complete remission was achieved in 16 patients (45.7%), including all patients in class III and V plus 10 patients in class IV. Not a single adverse effect was observed. CONCLUSION: MMF combined with low doses of steroids is an effective and safe treatment for the maintenance of stable remission of LN.

Combined Effect of Inter- and Intrapatient Variability in Tacrolimus Exposure on Graft Impairment Within a 3-Year Period Following Kidney Transplantation: A Single-Center Experience.

BACKGROUND AND OBJECTIVE: Tacrolimus is a cornerstone of the most immunosuppressive protocols after kidney transplantation, but its use is complicated by notable interpatient and intrapatient variability (IPV). The goal of this study was to evaluate whether or not tacrolimus IPV, or average dose-adjusted trough concentration (C0/D), during 6-12 months post-transplantation might have contributed to graft function decline in a 3-year period following kidney transplantation. After primary evaluation of individual effects of tacrolimus IPV and C0/D, the study aimed to estimate the combined effect of tacrolimus IPV and C0/D on composite endpoint (consisting of graft failure, chronic allograft dysfunction, chronic rejection, and doubling of serum creatinine concentration) in the period between 13 and 36 months after kidney transplantation. In addition, the goal was to analyze the impact of genetics on interpatient variability in tacrolimus exposure in the early and late post-transplantation periods. METHODS: The study enrolled 104 Caucasian patients and included 2541 patient examinations up to 36 months after kidney transplantation. All patients were genotyped on CYP3A5 6986A>G and ABCB1 3435C>T gene polymorphism. Patients were divided into groups based on the tacrolimus IPV tertiles and the median value of average C0/D during 6-12 months post-transplantation. RESULTS: The results showed a more pronounced decline in estimated glomerular filtration rate values within the high IPV tertile group (p = 0.018), as well as within the low C0/D group (p = 0.013) in a 3-year period after kidney transplantation. The carriers of CYP3A5*1/*3 genotype had lower C0/D compared to the CYP3A5*3/*3 carriers during the entire study period, while the results for ABCB1 were inconsistent when considering tacrolimus C0/D. Patients with high IPV/low C0/D had significantly reduced graft survival compared to the other tacrolimus IPV/C0/D combination groups (i.e., high IPV/high C0/D, low IPV/low C0/D, low IPV/high C0/D) with the hazard ratio of 3.14 in Cox analysis for reaching the composite endpoint. CONCLUSION: The findings of this study suggest that combined assessment of tacrolimus IPV and tacrolimus C0/D may categorize patients towards risk of graft deterioration in the long-term post-transplantation period.

Mycophenolate mofetil in high-risk patients with primary glomerulonephritis: results of a 1-year prospective study.

BACKGROUND/AIMS: Glucocorticoids and classic immunosuppressive drugs can improve disease activity in primary glomerulonephritis (GN). However, these drugs have serious toxicity and patients frequently experience inadequate response or relapse, so there is a need for alternative agents. This multicenter uncontrolled study analyzed the efficacy and safety of mycophenolate mofetil (MMF) in high-risk patients with primary GN. METHODS: A total of 51 patients with biopsy-proven membranous (n = 12), membranoproliferative (n = 15), mesangioproliferative (n = 10), focal segmental glomerulosclerosis (n = 13) and minimal change disease (n = 1) received MMF with low-dose corticosteroids for 1 year. The primary outcome included the number of patients with complete/partial remission. RESULTS: Proteinuria significantly decreased, from its median value of 4.9 g/day (IQR 2.9-8.4) to 1.28 g/day (IQR 0.5-2.9), p < 0.001. The urine protein/creatinine ratio significantly improved, from a median of 3.72 (IQR 2.13-6.48) to 0.84 (IQR 0.42-2.01), p < 0.001. The mean area under the curve for proteinuria significantly decreased, from 4.99 +/- 3.46 to 2.16 +/- 2.46, between the first (visits 1-2) and last (vists 4-5) treatment periods (p < 0.001). The change was similar for every type of GN, without difference between groups. eGFR slightly increased (62.1 +/- 31.8 to 65.3 +/- 31.8 ml/min, p = n.s.) and ESR, total proteins, albumins, total- and HDL-cholesterol parameters improved significantly. Systolic, diastolic and mean blood pressure decreased (p < 0.02 for systolic blood pressure). The age of patients was the only independent predictor of complete or partial remission. CONCLUSION: MMF proved to be efficient in 70% of high-risk patients with primary GN, who reached either complete or partial remission without safety concern after 12 months of treatment. Favorable effects of MMF therapy have to be confirmed in the long term and particularly after discontinuation of the drug.

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.

Analysis on the risk factors for organ damage in patients with systemic lupus erythematosus: a cross-sectional single-center experience.

BACKGROUND: Organ damage in patients with systemic lupus erythematosus (SLE) occurs as a consequence of the disease itself, the therapy applied and the accompanying conditions and complications. Organ damage predicts further organ damage and is associated with an increased risk of death. OBJECTIVE: This study aimed to assess the degree of irreversible organ changes in SLE patients, using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI); to establish correlations between organ damage and disease activity, quality of life, intensity of fatigue and serological factors; and to ascertain the risk factors for organ damage. DESIGN AND SETTING: Cross-sectional single-center study conducted at the Institute for Treatment and Rehabilitation "Niska Banja", Nis, Serbia. METHODS: 83 patients with SLE were enrolled: 58 patients formed the group with organ damage (SDI ≥ 1), and 25 patients without organ damage served as controls (SDI = 0). RESULTS: Organ damage correlated with age (P = 0.002), disease duration (P = 0.015), disease activity (grade 1, P = 0.014; and grade 2, P = 0.007), poor quality of life, severe fatigue (P = 0.047) and treatment with azathioprine (P = 0.037). The following factors were protective: use of hydroxychloroquine (P = 0.048) and higher scores obtained for the physical (P = 0.011), mental (P = 0.022) and general health (P = 0.008) domains. CONCLUSION: It is very important to evaluate risk factors for organ damage in the body, including physicians' overall assessment, to try to positively influence better treatment outcomes.

The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients.

PURPOSE: Cardiovascular events are the major reasons for mortality in haemodialysis patients. Fibroblast growth factor 23 (FGF23), Klotho protein and G-395A Klotho gene polymorphism have been associated with effects on the cardiovascular system. Our study investigates the interrelationship between Klotho protein gene variations, mineral-bone metabolism and left ventricular hypertrophy in patients undergoing chronic haemodialysis programme. MATERIALS AND METHODS: Patients (n = 142) were genotyped for G-395A Klotho gene. Components of mineral-bone metabolism, classical and non-classical (FGF23, Klotho and vitamin D) as well as echocardiographic examination were determined. Predictive models were designed to determine the significance of Klotho gene variations and mineral-bone metabolism components for left ventricle hypertrophy (LVH). RESULTS: A-allele carriers were longer on haemodialysis (p = 0.033), and had higher phosphorus levels (p = 0.016) while the level of Klotho protein was significantly lower (p = 0.001) compared to non-A-allele carriers. The best gains were achieved upon addition of allele A, and all three new markers; the AUC made significant improvement from 0.596 to 0.806 (p < 0.001), and improved net reclassification for 82.1% (95% CI 42.9-121.3%). CONCLUSIONS: The genetic background of A-allele carriers of the G-395A Klotho gene polymorphism increases the susceptibility patients to haemodialysis. A-allele carriers are at a higher risk for the development of cardiovascular complications. The addition of non-classical to classical mineral metabolism components improves prediction power to LVH.

Diagnostic value of the aminopeptidase N, N-acetyl-beta-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-beta-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.