Risk Factors for Potential Drug-Drug Interactions in Patients on Chronic Peritoneal Dialysis.

INTRODUCTION: The prevalence of potential drug-drug interactions (pDDIs) is becoming a major safety concern, as it has been previously linked to a significant number of adverse drug events and could have serious consequences for patients, including death. This is especially relevant for patients with chronic renal failure, as they are particularly vulnerable to drug-drug interactions. The aim of this study was to evaluate the prevalence and associated factors of pDDIs in patients receiving chronic peritoneal dialysis. METHODS: An observational, cross-sectional study was conducted on consecutive peritoneal dialysis patients attending four tertiary care hospitals for regular monthly examination. The primary outcome was the number of pDDIs identified using Lexicomp. Potential predictors were determined using multiple linear regression. RESULTS: Total number of patients included in the study was 140. The results showed that pDDIs were highly prevalent, especially in patients who use antiarrhythmics (p = 0.001), have diabetes mellitus (p = 0.001), recently started peritoneal dialysis (p = 0.003), or have higher number of prescribed drugs (p < 0.001). Number of prescribed drugs (p < 0.001) remained a significant predictor of high-risk pDDIs in addition to the female gender (p = 0.043). CONCLUSION: Clinicians should be particularly cautious when prescribing multiple medications to high-risk patients, such as peritoneal dialysis patients, to mitigate the risk of drug-drug interactions and associated adverse health outcomes.

Presence of Non-Diabetic Kidney Diseases in Biopsy Specimens of Diabetic Patients' Single Center Experience.

The complications of type 2 diabetes mellitus (T2DM) are well known and one of them is diabetic chronic kidney disease (DCKD). Over time, it has become clear that patients with T2DM can have nondiabetic chronic kidney diseases (NDCKD), especially those that affect the glomeruli. Clinical indicators for identifying DCKD from NDCKD with high sensitivity and specificity have not yet been identified. Therefore, kidney biopsy remains the golden standard for DCKD diagnosis in patients with T2DM. Despite some indications for kidney biopsy, criteria for a biopsy differ between countries, regions, and doctors. The aim of the study was to analyze the biopsy findings in our T2DM population and the justification of the biopsy according to widely accepted criteria. This single center retrospective study analyzed data from 74 patients with T2DM who underwent kidney biopsy from January 2014 to January 2021. According to the biopsy data, we categorized31 patients in the DN group, patients with typical diabetic glomerulopathy, 11 patients in the mixed group, patients who had pathohistological elements for both DN and non-DN glomerulopathy, and 32 patients in the non-DN group, patients with primary glomerulopathy not linked with DM. In the non-DN and mixed groups, the most frequent glomerulopathy was mesangioproliferative glomerulonephritis, including IgA and non-IgA forms, found in 10 patients, and membranous nephropathy (MN) in 10 patients. We analyzed several parameters and only the amount of proteinuria was found to be significantly linked to biopsy findings related to DN. With the existing criteria for kidney biopsy, we managed to detect changes in the kidneys in about half of our patients with T2DM. These patients required specific treatment, different from that which we use for DCKD patients.

Factors Associated with Potentially Inappropriate Prescribing in Patients on Peritoneal Dialysis.

INTRODUCTION: Inappropriate prescribing is common in patients with end-stage kidney disease, especially in those over 65 years of age. Our study aimed to reveal potentially inappropriate drug prescribing in patients on peritoneal dialysis (PD) and explore factors associated with this phenomenon. METHODS: The research was designed as an observational, cross-sectional study on a convenient sample of 145 consecutive patients with PD who attended the four tertiary-care hospitals in Serbia. The main outcome was the extent of inappropriate prescribing, as assessed by the medication appropriateness index, and potential predictors were tested by multiple linear regression. RESULTS: Inappropriate prescribing was a widespread phenomenon among patients on PD. The main factors that promote inappropriate prescribing in this subgroup of patients on kidney replacement therapy are comorbidities (p = 0.000), increased body weight (p = 0.022), a number of prescribed drugs (p = 0.000), and arterial hypertension on examination (p = 0.030). On the other hand, drinking alcohol and higher systolic blood pressure were associated with a lower inappropriate prescribing. CONCLUSION: In order to prevent the occurrence of inappropriate prescribing and its severe health or economic consequences, clinicians should pay special attention when prescribing new drugs to high-risk patients.

First case of drug-induced liver injury associated with the use of tocilizumab in a patient with COVID-19.

BACKGROUND AND AIMS: Tocilizumab (TCZ; interleukine-6 receptor antagonist) has been proposed to treat severe forms of Coronavirus disease-19 (COVID-19) because interleukine-6 plays an important role in COVID-19-induced cytokine storm. Several clinical studies have shown very good effects of TCZ in patients with COVID-19, with a few minor side effects reported. Only eight serious liver injuries caused by TCZ were reported before being used in the treatment of patients with COVID-19. Considering the significantly increased use of TCZ for the treatment of COVID-19, we would like to warn of its rare but possible serious hepatotoxicity, especially when used together with other hepatotoxic drugs. METHODS: We describe a patient with COVID-19-induced cytokine storm who developed drug-induced liver injury associated with the use of TCZ. RESULTS: One day after TCZ administration, serum transaminase levels increased 40-fold. Nevertheless, TCZ had a positive effect on clinical and laboratory parameters in cytokine storm, with transaminases values normalizing in 10 days. CONCLUSIONS: This is the first reported case of DILI caused by TCZ in a COVID-19 patient. Intensive liver function monitoring is imperative in COVID-19 patients, because of frequent polypharmacy with potentially hepatotoxic drugs.

Vitamin E-Bonded Membranes Do Not Influence Markers of Oxidative Stress in Hemodialysis Patients with Homozygous Glutathione Transferase M1 Gene Deletion.

BACKGROUND: Increased oxidative stress is a hallmark of end-stage renal disease. Hemodialysis (HD) patients lacking glutathione transferase M1 (GSTM1) enzyme activity exhibit enhanced oxidative DNA damage and higher mortality rate than those with active GSTM1 enzyme. To our knowledge, this is the first study to use the vitamin E-bonded membranes (VEM) in patients with homozygous GSTM1 gene deletion, and we aimed to determine the effect of VEM on oxidative and inflammatory status in HD patients with homozygous GSTM1 gene deletion. METHODS: GSTM1 genotypes were determined by polymerase chain reaction (PCR) in 170 chronic HD patients. Those with GSTM1-null genotype were randomized and 80 were included in the study. Forty of them were dialyzed for three months with VEM, while the other forty were dialyzed with high-flux same-surface polysulfone dialyzers. Markers of protein and lipid oxidative damage and inflammation (thiol groups, malondialdehyde (MDA), Interleukin-6 (IL-6)), together with plasma antioxidant activity (glutathione peroxidase (GPX), superoxide dismutase (SOD)) were determined. RESULTS: Seventy-five patients finished the study. There were no differences at baseline in markers of protein and lipid oxidative damage, inflammation and plasma antioxidant activity. After three months of therapy, GPX, MDA, and thiol groups increased significantly in both groups, but without statistical significance between groups. SOD and C reactive protein (CRP) did not change significantly during the three-month period. IL-6 increased in the control group, and at the same time, decreased in the VEM group, but without statistical significance. Hemoglobin (Hb) value, red blood cells, erythropoiesis resistance index (ERI), serum ferritin and iron did not change significantly within or between groups. Regarding other laboratory parameters, proteins, albumins, triglycerides, serum phosphorus, serum bicarbonate and Kt/V showed significant improvements within groups but with no significant difference between groups. CONCLUSIONS: Our data shows that therapy with VEM over three months had no benefit over standard polysulfone membrane in decreasing by-products of oxidative stress and inflammation in dialysis patients lacking GSTM1 enzyme activity.

Impact of Angiotensin-converting Enzyme and Matrix Metalloproteinase-3 Gene Polymorphisms on Risk for Developing Vascular Access Failure in Hemodialysis Patients - A Pilot Study.

For adequate hemodialysis, functional vascular access is obligatory. Neointimal hyperplasia (NIH) has a central role in stenosis and thrombosis development, which represent the most frequent causes of vascular access failure. Polymorphism of different genes that have a significant role in endothelial function may have an impact on NIH development. Therefore, the aim of our study is to determine the effect of angiotensin-converting enzyme (ACE) I/D and matrix metalloproteinase-3 (MMP3) 5A/6A polymorphism on risk for developing vascular access failure in hemodialysis patients. The study included 200 patients on regular hemodialysis at Nephrology Department, University Medical Center Zvezdara. Retrospective analysis included a collection of general and vascular access data from medical records. Genetic analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Patients were divided into two groups: Group 1-patients who have never experienced vascular access failure and Group 2-patients who have at least one spontaneous vascular access failure. There was no difference in age, gender, hemodialysis vintage, main diagnosis, presence of hypertension, and diabetes mellitus between the two groups. There were no statistically significant differences in the frequencies of ACE and MMP3 genotypes between the two groups. Without statistical significance, it was found that homozygotes for I allele had two times higher risk for developing vascular access failure than homozygotes for D allele (OR 2.00; 95%CI: 0.727-5.503; P = 0.180). In addition, patients with 5A allele have 1.7 times higher risk for developing vascular access failure compared with patients without this allele (OR 1.745; 95% CI: 0.868-3.507; P = 0.118). Patients with vascular access failure do not have different genotype distribution regarding ACE gene and MMP3 gene polymorphism as compared with patients without vascular access failure. Still, homozygotes for I allele and homozygotes for 5A allele have higher risk for developing vascular access failure compared with other patients.

The 5A Allele of the MMP3-Gene Promoter Polymorphism Is a Risk Factor for Poor Outcome of Hemodialysis Patients.

Cardiovascular morbidity is the leading cause of death in dialysis patients and many risk factors have been involved in its pathogenesis. Genetic susceptibility may be of importance including polymorphism for matrix metalloproteinase 3 (MMP3), which is an enzyme that catalyzes the degradation of collagen, proteoglycans, fibronectin, laminine and elastin. The MMP3 gene promoter contains an insertion/deletion polymorphism characterised by an array of 5 or 6 adenosine residues (5A/6A) at -1612 position. Literature data show that the 5A or 6A allele of the MMP3 gene shows different risk for cardiovascular and overall outcome in general population. The aim was to analyze the -1612 5A/6A promoter polymorphism in a group of hemodialysis patients and to correlate the findings with cardiovascular morbidity and 7-year all-cause and cardiovascular mortality. This study included 196 patients on hemodialysis for longer than six months at University Medical Center Zvezdara. The leading causes of end stage renal disease were hypertension and diabetes mellitus. Venous blood was collected on midweek dialysis session and genotype analysis was performed by using polymerase chain reaction-restriction fragment length polymorphism method. Among the 198 hemodialysis patients, there were 142 (72%) 5A/6A heterozygotes, 12 (6%) 5A/5A homozygotes, and 44 (22%) 6A/6A homozygotes. These data are consistent with Hardy-Weinberg equilibrium. After 7-year follow-up, the 5A homozygotes showed the lowest all-cause and cardiovascular survival, while the 6A homozygotes showed the highest cardiovascular survival. The 5A allele of the MMP3-gene promoter polymorphism is a potential risk factor in the poor outcome of hemodialysis patients.

Onset of Microscopic Polyangiitis in Binephrectomied Patient on Chronic Hemodialysis-Case Report.

INTRODUCTION: Microscopic polyangiitis (MPA) is one of the causes of the pulmonary-renal syndrome associated with elevated non-specific markers of inflammation and antineutrophil cytoplasmic autoantibody (ANCA) positivity in 50-75%. De novo occurrence of the disease in patients on chronic hemodialysis (HD) has not been described. CASE PRESENTATION: We presented patient who developed MPO-ANCA-associated MPA with lung and musculoskeletal involvement after 4 years on regular HD due to bilateral nephrectomy. After excluding the other causes of MPO-ANCA positivity, diagnosis was confirmed even without renal biopsy. Patient received standard immunosuppression therapy and he is still in remission after 27 months. CONCLUSION: The onset of immune-mediated disease could be observed even after introduction of renal replacement therapy, which may be a diagnostic problem. Early recognition and traditional immunosuppressive regiment may provide successful outcome.

Calcification in arteriovenous fistula blood vessels may predict arteriovenous fistula failure: a 5-year follow-up study.

PURPOSE: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The impact of vascular calcification process on AVF survival remains unclear and results of several studies about this issue are controversial. In the light of the new knowledge about the different susceptibility for calcification process in different blood vessels, the aim of our study was to analyze whether the calcification of AVF-blood vessels may have an impact on AVF longevity. METHODS: The study included 90 patients, 49 males and 41 females, all of them Caucasians, with a mean age 62 ± 11 years, on regular hemodialysis for more than 1 year with patent primary AVFs. Vascular calcification in AVF-blood vessels or in the anastomotic region was detected using X-ray examination. RESULTS: Calcification in AVF-blood vessels was found in 62% of patients. Binary logistic regression analysis demonstrated that male gender, presence of diabetes mellitus and longer duration of AVF before calcification determination were associated with calcification of AVF-blood vessels. Using a Cox proportional hazard model adjusted for these standardized predicted values revealed that patients with present AVF-blood vessels calcification had increased risk to develop AVF failure with a hazard rate of 3.42 (95% confidence interval 1.00-11.67; P = 0.049). CONCLUSIONS: Calcifications of AVF-blood vessels are found frequently among dialysis patients and may jeopardize the survival of native AVF. We suggested the local X-ray as simple and valid method for detection of patients that are at risk for AVFs failure which should be monitored more closely.

Survival Benefit of Hemodiafiltration Compared With Prolonged High-flux Hemodialysis.

INTRODUCTION:  Patients on dialysis have a high rate of death, mainly of cardiovascular cause. Nephrologists are actively looking for ways to improve patients' outcomes, and alternative dialysis strategies, such as long conventional hemodialysis and hemodiafiltration, are currently being investigated. The aim of this study was to compare anemia, nutrition, inflammation, mineral metabolism, and 3-year survival rates between patients treated with hemodiafiltration and prolonged high-flux hemodialysis (HFH). MATERIALS AND METHODS:  A total of 58 dialysis patients were divided into 2 groups to undergo hemodiafiltration 3 times weekly, 12 hours in total per week, or prolonged duration of HFH (≥ 15 h/w). One-year biochemical parameters were collected retrospectively, together with 36 months patients' survival (prospectively). RESULTS: Patients in the HFH group had longer dialysis vintage; significantly higher levels of hemoglobin (despite less frequent use of erythropoietin-stimulating agents), serum albumin, serum calcium, and serum bicarbonate; and a lower in-tact parathyroid hormone level. Survival rates were comparable between the two groups. The Cox proportional hazard model showed that patients treated with longer HFH had a 32% relative risk reduction of mortality compared to patients treated with hemodiafiltration, but without statistical significance (hazard ratio, 0.68; 95% confidence interval, 0.21 to 2.20; adjusted for diabetes mellitus). CONCLUSIONS: Longer duration of hemodialysis with high-flux membranes had beneficial effects on anemia indexes, mineral metabolism, nutrition parameters, and acidosis in comparison with hemodiafiltration. However, hemodiafiltration did not offer a 36-months survival benefit over prolonged HFH.