Recent Advances of Acute Kidney Injury in Hematopoietic Cell Transplantation

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) and is associated with non-relapse mortality (NRM) and quality of life (QOL). Multiple factors may contribute to AKI during allo-HCT and are often present at the same time making it difficult to determine the cause of AKI in each patient. Nephrotoxic drugs, infections, thrombotic microangiopathy (TMA), and sinusoidal obstruction syndrome (SOS) are well described causes of AKI during allo-HCT. Acute graft-versus-host disease (aGVHD) is a major complication of allo-HCT that mainly targets the intestines, liver, and skin. However, recent studies suggest aGVHD may also attack the kidney and contribute to AKI following allo-HCT. For example, severe aGVHD is associated with AKI, suggesting a link between the two. In addition, animal models have shown donor immune cell infiltration and increased expression of inflammatory cytokines in recipient kidneys after allo-HCT. Therefore, aGVHD may also target the kidney and contribute to AKI following allo-HCT. Herein, we describe the etiology, diagnosis, risk factors, pathophysiology, prevention, and treatment of renal injury after allo-HCT. In addition, we highlight emerging evidence that aGVHD may contribute to the development of AKI after allo-HCT.

Trends in Prescribing Patterns and Drug Related Problems of Kidney Disease Patients

Objective: The aim of the study was the evaluation of drug-related problems, including drug-drug interactions, dose error, use of nephrotoxic drugs and polypharmacy with special emphasis on kidney disease patients. Methods: Descriptive cross-sectional study from January to April 2019 was carried out in nephrology ward of Ayub teaching hospital, Abbottabad, Pakistan to review patient’s medication orders for evaluation of drug-related problems. Doses of medicine and drug-drug interactions were evaluated by comparing it with standard protocols given in BNF and Lexicomp software. Prescriptions were also evaluated for polypharmacy and use of nephrotoxic drugs. Results: Out of 131 patients, majority were males 72 (55%). Drug-drug interactions were found in 69 (52.7%) patients among which the highest percentage was of the moderate drug-drug interaction (48.1%) followed by major and minor drug-drug interaction (29.8% and 20.6% respectively). Incidence of polypharmacy (51.9%) and use of nephrotoxic drug (77%) was high while dose error was low up to 10.7%. All the drug-related problems were present with a high percentage in patients with CKD as compare to other kidney diseases. There was significant association of CKD stages with DDIs, polypharmacy, dose error and prescribing drugs. There was significant positive correlation among DDIs-polypharmacy and prescribing drugs was noted in the study. Conclusion: The higher incidence of drug-related problems in our study setting reflects irrational prescribing trends and deficiency of professional staff dealing kidney disease patients. Key Words: kidney disease, drug-drug interactions, polypharmacy, nephrotoxic drugs, dose error. Continuous...

Effect of biochemical and biomechanical factors on vascularization of kidney organoid-on-a-chip

Kidney organoids derived from the human pluripotent stem cells (hPSCs) recapitulating human kidney are the attractive tool for kidney regeneration, disease modeling, and drug screening. However, the kidney organoids cultured by static conditions have the limited vascular networks and immature nephron-like structures unlike human kidney. Here, we developed a kidney organoid-on-a-chip system providing fluidic flow mimicking shear stress with optimized extracellular matrix (ECM) conditions. We demonstrated that the kidney organoids cultured in our microfluidic system showed more matured podocytes and vascular structures as compared to the static culture condition. Additionally, the kidney organoids cultured in microfluidic systems showed higher sensitivity to nephrotoxic drugs as compared with those cultured in static conditions. We also demonstrated that the physiological flow played an important role in maintaining a number of physiological functions of kidney organoids. Therefore, our kidney organoid-on-a-chip system could provide an organoid culture platform for in vitro vascularization in formation of functional three-dimensional (3D) tissues.

Drug-Induced Acute Kidney Injury

Drug-induced nephrotoxicity is the third most common cause of acute kidney injury (AKI). The aim of the study was to analyse and summarise data on the factors and mechanisms responsible for increased risk of drug-induced AKI, to analyse potential methods of its prevention and treatment. At present, the following phenotypes of drug-induced AKI are distinguished: acute vascular disease, acute glomerular disease, acute tubular injury / necrosis, and acute interstitial nephritis. It was discovered that most often these complications occur following the use of antimicrobial drugs, renin-angiotensin-aldosterone system inhibitors, non-steroidal anti-inflammatory drugs, and anticancer drugs, including targeted therapy. Risk factors for drug-induced AKI include age >65, female gender, low body weight, pre-existing chronic kidney disease, hypovolemia, hypoalbuminemia, acute and chronic heart failure, diabetes, malignancies, liver cirrhosis, prolonged use of nephrotoxic drugs, and simultaneous use of two or more nephrotoxic drugs. Discontinuation of the drug which resulted in kidney failure is the first and foremost principle for managing not only drug-induced, but all AKI patients. The use of potentially nephrotoxic drugs should be avoided, especially in high-risk patients, in order to prevent drug-induced AKI. If a patient needs a drug that affects renal hemodynamics, the therapy should begin with a minimum effective dose, and combinations of two and more nephrotoxic drugs should be avoided. Close monitoring of kidney function is crucial for high-risk patients. They should also be informed about the importance of adequate water consumption schedule for prevention of hypovolemia.

Hospital-Acquired Acute Kidney Injury in Older Patients: Clinical Characteristics and Drug Analysis

<b><i>Background:</i></b> Information on older patients with hospital-acquired acute kidney injury (HA-AKI) and use of drugs is limited. <b><i>Aim:</i></b> This study aimed to assess the clinical characteristics, drug uses, and in-hospital outcomes of hospitalized older patients with HA-AKI. <b><i>Methods:</i></b> Patients aged ≥65 years who were hospitalized in medical wards were retrospectively analyzed. The study patients were divided into the HA-AKI and non-AKI groups based on the changes in serum creatinine. Disease incidence, risk factors, drug uses, and in-hospital outcomes were compared between the groups. <b><i>Results:</i></b> Of 26,710 older patients in medical wards, 4,491 (16.8%) developed HA-AKI. Older patients with HA-AKI had higher rates of multiple comorbidities and Charlson Comorbidity Index score than those without AKI (<i>p</i> &#x3c; 0.001). In the HA-AKI group, the proportion of patients with prior use of drugs with possible nephrotoxicity was higher than that of patients with prior use of drugs with identified nephrotoxicity (<i>p</i> &#x3c; 0.05). The proportions of patients with critical illness, use of nephrotoxic drugs, and the requirements of intensive care unit treatment, cardiopulmonary resuscitation, and dialysis as well as in-hospital mortality and hospitalization duration and costs were higher in the HA-AKI than the non-AKI group; these increased with HA-AKI severity (all <i>p</i> for trend &#x3c;0.001). With the increase in the number of patients with continued use of drugs with possible nephrotoxicity after HA-AKI, the clinical outcomes showed a tendency to worsen (<i>p</i> &#x3c; 0.001). Moreover, HA-AKI incidence (adjusted odds ratio [OR], 10.26; 95% confidence interval (CI), 8.27–12.74; <i>p</i> &#x3c; 0.001), and nephrotoxic drugs exposure (adjusted OR, 1.76; 95% CI, 1.63–1.91; <i>p</i> &#x3c; 0.001) had an association with an increased in-hospital mortality risk. <b><i>Conclusion:</i></b> AKI incidence was high among hospitalized older patients. Older patients with HA-AKI had worse in-hospital outcomes and higher resource utilization. Nephrotoxic drug exposure and HA-AKI incidence were associated with an increased in-hospital mortality risk.

Acute Kidney Injury related to intravenous Colistin Use in Lebanese Hospitalized Patients: Incidence and Associated Factors

Introduction: Colistin use has risen because of the emergence of Gram-negative resistant infections. Acute kidney injury (AKI) remains a treatment-limiting factor for widespread colistin clinical use. This study aimed to determine the incidence and the factors associated with the development of colistin-induced AKI. Method: A retrospective observational study was conducted by reviewing files of adult patients, with normal kidneys function between January 2015 to March 2019 at a university hospital located in Beirut city. AKI was defined based on KDIGO criteria. Several variables were tested to determine independent factors that were associated with colistin induced AKI. Results: A total of 113 patients were included in this study. AKI occurred in 53 patients (46.9%). The Charlson Comorbidity Index (CCI) was significantly higher in the AKI group (2.26, P-value = 0.026). In the multivariate analysis, low serum albumen was found as an independent significant predictor for AKI (OR=.065, 95%CI: .013-.337, P-value=0.001). Moreover, the risk for AKI increased by 2 folds (OR=2.019, 95%CI: 1.094-3.728, P-value: 0.025), when two or more nephrotoxic agents were administered simultaneously with colistin. Patient’s age was also found as significant predictor for AKI (OR=1.034, 95% CI:1-1.07), with a cut-off value of 58.5 year-old. Conclusion: This study demonstrated that the use of concomitant use of two or more nephrotoxic drugs, patient’s age of 58.5 or more, and the presence of hypoalbuminemia were independent factors for the development of colistin-induced AKI. These factors should be therefore taken into consideration when prescribing colistin in clinical practice to reduce the risk of AKI.

Risk of acute kidney injury in cancer patients after iodinated contrast medium administration and prophylactic strategies: Summary from the most recent guidelines

Post-contrast acute kidney injury (PC-AKI) is a serious complication that primarily affects people with multiple comorbidities who undergo imaging examination with iodinated contrast medium (CM), worsening their outcome and prognosis. This is particularly true for cancer patients, for whom contrast enhanced computed tomography (CECT) is of considerable value in diagnosis and management of the tumor and who are frequently subjected to dehydration and administration of nephrotoxic drugs. The debate on the real prevalence and severity of acute kidney injury (AKI) due to CM administration is still ongoing and the lack of controlled studies and reliable evidence has generated wide heterogeneity in patient management and prophylaxis. The whole idea of this protocol is to analyze most up-to-date guidelines on preventing AKI due to CM administration trying to provide a practical guide.

MO1035KIDNEY KNOWLEDGE AMONG USERS OF AN ONLINE SELF MANAGEMENT PLATFORM FOR PEOPLE WITH CKD

Background and Aims Renal Tracker is a blended on- and offline self management platform for people with CKD. One of the goals of the program is to increase user’s knowledge about their kidney disease in order to facilitate communication with their health care providers. In the present study we aim to a baseline data for kidney knowledge to which the program could be compared. Method We recruited a cohort of 74 users from the United States of America via social media channels, including Facebook, Pinterest and Google Adwords. The users were offered a 12 week online course program in addition to a 1-on-1 call with a health coach specialized in renal nutrition. Before starting the program users were prompted to complete the Kidney Knowledge Survey (Wright et al AJKD 2011). We compared our results to those in the study by Wright. Pseudonymized data for users was obtained from the RenalTracker analytics server, and analyses were performed using Python 3.8.5 with a JupyterLab 2.2.28 shell. Results The mean overall score for our cohort was 18.8 (SD 4.0) for a 67% (SD 14%) correct. By comparison, Wright reported a mean score of 66% (15%). Users found the question about what medication to avoid hardest (26% correct). In addition, users were only able to identify half of the usual symptoms associated with kidney disease. Likewise, they were able to point out about only half of the functions of the kidney. Conversely, 88% knew their target blood pressure, possible long term consequences of CKD. Conclusion Our results highlight that even among a subgroup of patients actively researching and looking for information, kidney specific health knowledge needs to be improved. In particular limited knowledge about nephrotoxic drugs is worrying.

FC 070USE OF POTENTIALLY NEPHROTOXIC MEDICATIONS IN PERSONS WITH CHRONIC KIDNEY DISEASE: PARALLEL COHORT STUDIES IN SWEDISH AND U.S ROUTINE CARE

Background and Aims Many adverse drug events are preventable, such as those potentially resulting from the prescription of nephrotoxic drugs to persons with chronic kidney disease (CKD). We here quantify the extent of contemporary nephrotoxic medication use in patients with CKD. Method In two observational cohorts of Swedish (Stockholm CREAtinine Measurements [SCREAM] project, Stockholm, Sweden) and U.S. (Geisinger Health System, Pennsylvania) adults with confirmed CKD stages G3-G5 undergoing routine care during 2016-2018, we explored the prescription (in U.S.) and dispensation (in Sweden) of 115 different ambulatory drugs with proven or purported nephrotoxicity during the 12 months following study inclusion. We evaluated the proportion of participants receiving nephrotoxic drugs, ranked main contributors and identified clinical predictors. Results In the Swedish cohort, there were 57880 patients (54.6% women) with median age of 80.00 (inter-quartile range [IQR]: 73.0-86.0) years and eGFR 48.9 ([IQR]: 39.9-55.0) mL/min/1.73 m2. In the U.S. cohort, there were 16255 patients (59% women) with median age of 76 years and eGFR 44 mL/min/1.73 m2. During observation, 20% (Sweden) and 17% (U.S.) of patients received at least one nephrotoxic drug. The top 3 potentially inappropriate nephrotoxic drugs identified were NSAIDs (9% and 11% of participants in U.S. and Sweden received it), antivirals (2.0% and 2.5%) and immunosuppressants (1.5% and 2.7%). Bisphosphonate use was common in Sweden (3.3% of participants), but not in U.S. (0.5%). Conversely, fenofibrates were common in U.S. (3.6%), but not in Sweden (0.13%). In adjusted analyses, patients with young age (&lt;65 years old), women, or with CKD G3 were at higher risk of receiving nephrotoxic medications in both cohorts (P&gt;0.05 for all). Notably, patients aware of their CKD (identified either by issued diagnosis or recent visit to a nephrologist), were at lower risk of nephrotoxic drug use (OR 0.87, 95% CI 0.82-0.92 in Sweden and 0.89, 95% CI 0.81-1.01 in U.S.). Conclusion In two geographically distinct health systems, one in five patients with CKD received potentially inappropriate nephrotoxic medications, mainly NSAIDs. Strategies to increase CKD awareness and physician’s knowledge of drug nephrotoxicity may reduce inappropriate ambulatory prescriptions and prevent iatrogenic kidney injury.