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.

Potentially inappropriate prescribing among older patients and associated factors: comparison of two versions of STOPP/START criteria

Abstract The study aimed to estimate and compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) between the STOPP/START original (v1) and updated version (v2) among older patients in various settings, as well as associated factors. The study included 440 patients attending a community pharmacy, 200 outpatients and 140 nursing home users. An increase in the prevalence of STOPP v2 (57.9%) compared to v1 (56.2%) was not statistically significant in the total sample and within each setting (p>0.05). A decrease in the prevalence of START v1 (55.8%) to v2 (41.2%) was statistically significant (p<0.001) in the total sample and within each setting (p<0.05). Drug indication (32.9%) and fall-risk medications (32.2%) were most commonly identified for STOPP v2, while cardiovascular system criteria (30.5%) were the most frequently detected for START v2. The number of medications was the strongest predictor for both STOPP v1 and v2, with odds ratio values of 1.35 and 1.34, respectively. Patients' characteristics associated with the occurrence of STOPP and START criteria were identified. According to both STOPP/START versions, the results indicate a substantial rate of potentially inappropriate prescribing among elderly patients. The prevalence of PIMs was slightly higher with the updated version, while the prevalence of PPOs was significantly lower

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

ABSTRACT 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 "Niška Banja", Niš, 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.

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.

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.

Hyperparathyroidism as a cause of recurrent acute pancreatitis: A case report.

Introduction: One of the more uncommon etiological factors responsible for the development of acute pancreatitis (AP) is hypercalcemia. Hyperparathyroidism (HPT), as a cause of hypercalcemia, is responsible for 1.5­13% of AP according to a number of studies. A mechanism of the development of AP in hyperparathyroidism is still unclear. Case report: We presented a 47-year-old female patient, who had five episodes of AP in total before the etiological factors were finally determined. The patient had certain comorbidities which were considered to be potential causes of AP. She had chronic renal insufficiency (she was on a regular hemodialysis program), systemic lupus erythematosus and mioma uteri. She used to regularly take an antiepileptic drug (combination of sodium valproate and valproic acid). During the fifth episode of AP, the serum calcium level was for the first time elevated to twice the normal value. Level of parathyroid hormone was several times higher. A static scintigraphy found hyperplasia or hyperfunctional adenoma of the right inferior and superior parathyroid glands. Abdominal multislice computed tomography (MSCT) scan verified the enlargement of the entire pancreas, as well as the presence of heterogeneous structures with diffuse amorphous calcifications. The lytic lesions in the pelvic bones could be seen in both sides. Parathyroidectomy was being postponed by an endocrine surgeon because of the poor overall condition of the patient. In the next period the patient had five more episodes of AP. The condition was significantly contributed by increasingly more frequent and longer episodes of metrorrhagia. Despite all therapeutic measures that were taken, systemic inflammatory response syndrome (SIRS) developed, and fatal outcome occurred. Conclusion: In case of recurrent pancreatitis, hyperparathyroidism is to be considered even if a significant elevation of serum calcium is not present. This is especially the case for patients with chronic renal insufficiency or impaired vitamin D metabolism, who have a higher risk of secondary hyperthyroidism.

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.