Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor

People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics

Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease

The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood–brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain–gut–kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain–gut–kidney axis

antibacterial agents in patients with chronic kidney disease

Funding Information: The authors would like to thank Prof. Giovambattista Capasso, acting chair of Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT) Action and members of COST Action for their support. This article is published as financially supported by the Horizon EU COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT). Publisher Copyright: © The Author(s) 2024.The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood–brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain–gut–kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain–gut–kidney axis.publishersversionpublishe

Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor

People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood–brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics

Molecular characterization and seroprevalence of hepatitis E virus in inflammatory bowel disease patients and solid organ transplant recipients

16 p.-3 fig.-5 tab.Seroprevalence rates and molecular characterization of hepatitis E virus (HEV) prevalent in the Lithuanian human population has not yet been evaluated. Immunosuppressed individuals have been recognized as a risk group for chronic hepatitis due to HEV genotype 3 (HEV-3) infections. The objectives of the present study were to determine prevalence rates of anti-HEV antibodies among inflammatory bowel disease (IBD) patients and solid organ transplant (SOT) recipients, to isolate and characterize HEV strain present in the Lithuanian human population, and to investigate its capacity to infect non-human primate (MARC-145 and Vero), swine (PK-15) and murine (Neuro-2a) cells in vitro. In the present study, the significant difference of anti-HEV IgG prevalence between healthy (3.0% (95% CI 0–6.3)) and immunosuppressed individuals (12.0% [95% CI 8.1–15.9]) was described. Moreover, our findings showed that anti-HEV IgG seropositivity can be significantly predicted by increasing age (OR = 1.032, p < 0.01), diagnosis of IBD (OR = 4.541, p < 0.01) and reception of SOT (OR = 4.042, <0.05). Locally isolated HEV strain clustered within genotype 3i subtype of genotype 3 and was capable of infecting MARC-145 cells. This study demonstrates higher HEV seroprevalence in the risk group compared to healthy control individuals without confidence interval overlap. The high level of genetic homology between human and animal strains in Lithuania and the capacity of locally isolated strains to infect cells of non-human origin suggests its potential for zoonotic transmission.This research was partly funded by the Lithuanian University of Health Sciences Science Foundation (LSMUSF), grant number 119-05 and COST Action CA15116 ASF-STOP, supported by COST (European Cooperation in Science and Technology).Peer reviewe

Cognitive disorders in patients with chronic kidney disease: specificities of clinical assessment

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Renal Anemia Control in Lithuania: Influence of Local Conditions and Local Guidelines

Erythropoietin stimulating agents had a long haul in Lithuania—we had no epoetin till 1994 and there was no intravenous iron in 2001–2004. The aim of this study was to assess the changes of renal anemia control in hemodialysis patients from early independence of Lithuania till nowadays and to evaluate the link of anemia with hospitalization rates and survival and hemoglobin variability in association with mortality. In December of each year since 1996 all hemodialysis centers have been visited and data has been collected using special questionnaires. The history of renal anemia control in Lithuania was complicated; however, a significant improvement was achieved: 54.7% of hemodialysis patients reached the target hemoglobin; all patients have a possibility of treatment with epoetin and intravenous iron. The involuntary experiment with an intravenous iron occurred in Lithuania because of economic reasons and confirmed the significant role of intravenous iron in the management of renal anemia. Hemoglobin below 100 g/L was associated with a 2.5-fold increase in relative risk of death and 1.7-fold increase in relative risk of hospitalization in Lithuanian hemodialysis patients. Although hemoglobin variability was common in Lithuanian hemodialysis patients, we did not find the association between hemoglobin variability and all-cause mortality in our study

The Role of Pre- and Post-Transplant Hydration Status in Kidney Graft Recovery and One-Year Function

Background and Objectives: Early improvements to graft function are crucial for good outcomes in kidney transplantation (kTx). Various factors can influence early graft function. This study aimed to evaluate the pre- and post-transplant hydration statuses of kTx recipients using bioimpedance analysis (BIA) and lung ultrasonography (LUS) and to investigate the hydration status’ relationship with the function of the transplanted kidney during the first year after transplantation. Materials and Methods: This observational prospective cohort study included deceased kidney recipients transplanted in the Hospital of the Lithuanian University of Health Sciences between September 2016 and January 2023. BIA and LUS were performed before transplantation, on days 3 and 7, and at discharge. Data on recipient and donor clinical characteristics were collected. Graft function was evaluated according to the serum creatinine reduction ratio and the need for dialysis. Hydration status was evaluated by calculating B-lines (BL) on LUS and the ratio of extracellular/total body water on BIA. Results: Ninety-eight kTx recipients were included in the study. Patients with immediate graft function (IGF) were compared to those with slow or delayed graft function (SGF + DGF). Recipients in the SGF + DGF group had a higher sum of BL on LUS before transplantation. After transplantation in early postoperative follow-up, both groups showed hyperhydration as determined by BIA and LUS. After one year, recipients with no BL before transplantation had better graft function than those with BL. Logistic regression analysis showed that having more than one BL in LUS was associated with a 2.5 times higher risk of SGF or DGF after transplantation. Conclusions: This study found that lung congestion detected by LUS before kTx was associated with slower graft recovery and worse kidney function after 1 year. Meanwhile, the hyperhydration status detected by BIA analysis did not correlate with the function of the transplanted kidney

The Influence of Tacrolimus Exposure and Metabolism on the Outcomes of Kidney Transplants

Tacrolimus (TAC) has a narrow therapeutic window and patient-specific pharmacokinetic variability. In our study, we analyzed the association between TAC exposure, metabolism, and kidney graft outcomes (function, rejection, and histological lesions). TAC trough (C0), coefficient of variation (TAC CV), concentration/dose ratio (C/D), and biomarkers related to kidney injury molecule-1 (KIM-1) and neutrophil gelatinase lipocalin (NGAL) were analyzed. We examined 174 patients who were subjected to a triple immunosuppressive regimen and underwent kidney transplantation between 2017 and 2022. Surveillance biopsies were performed at the time of kidney implantation and at three and twelve months after transplantation. We classified patients based on their Tac C/D ratios, classifying them as fast (C/D ratio 0 at six months were associated with rejection during the first year after transplantation. A fast TAC metabolism at six months was associated with reduced kidney graft function one year (OR: 2.141, 95% CI: 1.044–4.389, p = 0.038) and two years after transplantation (OR: 4.654, 95% CI: 1.197–18.097, p = 0.026), and TAC CV was associated with reduced eGFR at three years. uNGAL correlated with IF/TA and chronicity scores at three months and negatively correlated with TAC C0 and C/D at three months and one year. Conclusion: Calculating the C/D ratio at three and six months after transplantation may help to identify patients at risk of suffering acute rejection and deterioration of graft function

Immune Response after SARS-CoV-2 Vaccination in Kidney Transplant Patients

Background and Objectives: The prospective study was conducted to evaluate humoral and cellular immune responses after two doses of BNT162b2 (Pfizer-BioNTech) vaccine and possible relation with other factors (medication, etc.) in kidney transplant patients. Materials and Methods: Out of 167 vaccinated patients, 136 agreed to a follow-up visit three to six weeks after vaccination. Results: Only 39 patients (29%) developed antibody response against SARS-CoV-2 (&ge;35.2 binding antibody units (BAU)/mL) after full vaccination. Multivariate binary logistic regression analysis showed that predictive factors for good antibody response to the COVID-19 vaccine were better kidney function, higher hemoglobin level, and no use of mycophenolate mofetil for immunosuppression. For seropositive kidney transplant patients there was a significant negative correlation between anti-SARS-CoV-2 antibody titer and CD4/CD8 ratio (Spearman&rsquo;s correlation coefficient &minus;0.4, p = 0.02), percentage of CD19+ cells (r = &minus;0.37, p = 0.02), and a positive correlation with percentage of CD8+ cells (r = 0.4, p = 0.01). There was an increase of total leucocyte count after vaccination in the total studied population, and in the group of responders. Conclusions: Only one third of kidney transplant patients develop sufficient antibody responses after full COVID-19 vaccination with Pfizer-BioNTech. Better kidney function, higher hemoglobin level, and no use of mycophenolate mofetil for immunosuppression increases the adequacy of response. The antibody titers correlated positively with relative number of CD8+ cells and negatively with CD4/CD8 ratio in responders