History Of Acute Kidney Injury Research Articles

Association of a history of acute kidney injury with major adverse cardiovascular events in chronic kidney disease patients

Abstract Background/introduction Acute kidney injury (AKI) is strongly associated with major adverse cardiovascular events (MACE), particularly heart failure, in both general and critically ill populations. A recent study questioned whether this association holds true only for patients without chronic kidney disease (CKD). Purpose To evaluate the association of a history of AKI with MACE in a large real-world CKD population defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective cohort study was conducted using Merative® Explorys electronic health records (>54 million patients) from Jan 2010 to Dec 2019. Six cohorts of CKD patients (diagnosed or not) were created, one for each stage (1-5). Patients were required to have two consecutive abnormal eGFR, uACR/uPCR results within 3-18 months to determine CKD stage, to have at least a 12-months lookback period, and no history of end-stage kidney disease. CKD classification was not mutually exclusive (individual patients could contribute to multiple stages). Index date was the date of the second abnormal test. History of AKI was defined using ICD diagnosis codes, not through biological changes. We followed each patient until the occurrence of a composite of MACE including death, coronary events [acute coronary syndrome + coronary revascularization], any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. We used multivariable Cox proportional hazards regression to estimate associations between the history of AKI and the risk of MACE during follow-up, adjusted for the following confounders: age, sex, ethnicity, systolic blood pressure, eGFR, BMI, CV history, diabetes, and any CKD diagnosis at baseline. Results Most of the 969,394 patients included in at least one CKD stage cohort were in stage 3a (see table) and Caucasian. Mean ages were 57-75y and 42%-64% were females across the 5 CKD stages. The prevalence of pre-existing CV disease increased from 24% in stage 1 to 57% in stage 4. The proportion of patients with a history of AKI increased from 4% in stage 1 to 36% in stage 4, as well as, the proportion of patients with a ICD code for CKD diagnosis at baseline (3% to 44%). The 5-year incidence of the composite of MACE increased from 25.1% in stage 1 to 65.8% in stage 5. Death was the most frequent event across all stages. In multivariable analysis, a history of AKI was associated with increased risk of MACE (hazard ratios, HR 1.19 to 1.32), all-cause death (HR 1.12 to 1.86), and hospitalization for Heart Failure (HR 1.59 to 1.98) for all CKD stages, and coronary events for stage 2 to 5 (HR 1.14 to 1.22), but not stroke. Conclusion Patients with CKD and a history of AKI are at higher risk of adverse CV outcomes, especially hospitalization for heart failure. This study suggest that these patients should receive cardio -protective intervention.

A-106 Determination of Urinary NGAL Reference Intervals from Specimens of Healthy Adult and Pediatric Individuals

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is a 25kDa protein implicated in multiple biological processes, including attenuation of apoptosis and differentiation of renal tubule epithelial cells and nephrons. NGAL is also produced and secreted by injured kidney tubule epithelial cells. As such, NGAL can serve as an early urinary biomarker for acute kidney injury (AKI). This multi-site, cross-sectional study aimed to establish reference intervals for urinary NGAL (uNGAL) in healthy pediatric and adult populations using a particle-enhanced turbidimetric assay. Methods Apparently healthy individuals, aged ≥ 3 months, were eligible for this study. Subjects with an active urinary tract infection (UTI) on the day of sample collection, acute kidney injury (AKI) or a history of AKI, stage 4 or 5 chronic kidney disease (CKD), known congenital anomalies of the kidney and urinary tract, known urothelial, urological, or kidney malignancies were excluded from the study. Subjects with uncorrected congenital heart disease, having undergone solid organ or bone marrow transplantation, receiving renal replacement therapy, and having undergone surgery (urologic, nephrectomy, or correction of congenital heart disease) were also excluded. A total of 688 subjects were screened, 677 were eligible, and 629 (91.4%) were considered evaluable per the protocol. The 59 excluded subjects were ineligible due to missing/incorrect information in the informed consent form, or not evaluable due to meeting exclusion criteria, mostly a positive UTI test. Urine samples were tested for NGAL on a Roche cobas® c501 analyzer in single determinations. Results Tables 1 and 2 describe the NGAL summary statistics and central 95% reference intervals by age and gender. Conclusions These data demonstrate the normal urine NGAL values in an apparently healthy pediatric and adult populations.

#2379 Acute kidney injury as a key predictor of major adverse cardiovascular events in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) significantly raises cardiovascular event risks. The influence of acute-on-chronic kidney incidents is less understood. This study examines the link between acute kidney injury (AKI) episodes and subsequent Major Adverse Cardiovascular Events (MACE) in CKD patients. Method From 2013 to 2016, the CKD-REIN cohort enrolled 3033 adults with CKD stages 3-5 (average age 67; 66% male; mean eGFR 33 mL/min/1.73m²) from 40 French outpatient nephrology clinics, reflecting national geographic and legal diversity. During a 5-year follow-up, all AKI episodes, whether inpatient or outpatient, were identified, confirmed, and categorized per KDIGO-AKI standards by an expert panel. Cardiovascular events were evaluated using clinical trial Cardiovascular and Stroke Endpoint Definitions. MACE cumulative incidences (myocardial infarction, stroke, heart failure hospitalization, cardiovascular death) post-AKI were calculated using Aalen-Johansen methods, accounting for kidney failure and death risks. The impact of the first AKI episode on MACE risk was analyzed using a multivariable Cox model, treating AKI as a time-variable and stratifying by characteristics (in/outpatient status, AKI stage, pre-renal causes, renal recovery at discharge). Factors like demographics, cardiovascular risks, CKD severity, and treatments were considered. Interaction and sensitivity analyses were performed, excluding those with prior AKI or cardiovascular disease. Results During a median follow-up of 5.2 years, 530 patients experienced an incident AKI episode. The cumulative incidence of MACE at 1 year following this initial episode of AKI was 8.1% [95% confidence interval, 6.1; 10.8], with a median time to occurrence of 6.7 months after AKI. After adjustment for multiple confounders, we observed a substantial increased hazard of MACE associated with a first episode of AKI (HR = 5.99 [4.63; 7.76], p < 0.001), and this association remained significant for each MACE component (Fig. 1A). A dose-response relationship was observed, with higher risks in more severe AKI cases (KDIGO grades 2-3) and among hospitalized versus non-hospitalized patients (Fig. 1B). This association was also observed across all subgroups, without any interaction with age, sex, nor major comorbidities (diabetes, history of AKI, or cardiovascular events), as well as in various sensitivity analyses. Overall, we estimated an attributable risk fraction of 18.1% [13.6; 22.4] for MACE associated with AKI episodes within this population. Conclusion Our study highlights a strong dose-response relationship between incident AKI events and the risk of subsequent major cardiovascular events in CKD patients. These findings suggest that AKI may not only be a marker of increased cardiovascular risk but also a potential mediator of this risk. From a clinical perspective, these results underscore the importance of close monitoring and management of AKI in CKD patients to reduce the risk of MACE. This study improves our understanding of the interplay between renal and cardiovascular health, emphasizing the need for integrated care approaches in this high-risk population.

#2333 Risk of NDI and CKD in individuals treated with lithium

Abstract Background and Aims Nephrogenic diabetes insipidus (NDI) is a known side effect of lithium treatment. Lithium has also been associated with the development of chronic kidney disease (CKD). The aims of this study were to examine the risk factors for NDI among persons on lithium treatment and the association of NDI and other risk factors with the development of chronic kidney disease (CKD). Method This was a retrospective cohort study of all persons in Iceland using lithium in the years 2003-2018. Lithium exposure was defined as at least one lithium prescription or at least one serum lithium measurement with a detectable lithium level. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. NDI was defined as concomitant serum sodium (SNa) >144 mmol/L and urine specific gravity (SG) <1.005; individuals with no SNa measurement after 2003 were excluded from the analysis. CKD stages 3-5 were defined according to the KDIGO guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated from serum creatinine (SCr) using the CKD-EPI equation. The analysis of incident CKD was limited to the period when standardized SCr measurements had become available, in 2008-2018. Individuals with <2 SCr measurements after 2008 and those with CKD stages 3-5 before 2008 were excluded. In addition, this analysis specifically examined the relationship between the mean serum lithium concentration and the development of CKD, comparing those not exposed to lithium to 3 groups of lithium users with a mean serum lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid conditions were defined based on ICD-9 and ICD-10 diagnosis codes. Multivariable Cox regression with time-dependent covariables was used for risk assessment. Results In the analysis of the development of NDI, the group exposed to lithium consisted of 2252 individuals, of whom 58 (2.6%) met the criteria for NDI compared with 13 (1.0%) of the 1272 controls. When compared with those without lithium exposure. the risk of NDI was lithium concentration dependent, with a hazard ratio (HR) of 1.22 (95% CI, 0.50–2.98), 5.52 (95% CI, 2.81–10.85) and 10.03 (95% CI, 4.51–22.27) for groups with a mean lithium concentration of 0.3–0.59, 0.6–0.79 and 0.8–0.99 mmol/L, respectively. A previous diagnosis of CKD was also a significant risk factor (HR 3.00 [95% CI, 1.50–6.12]). In the CKD analysis, the group of lithium users comprised 1401 individuals. Of those, 192 (13.7%) developed CKD, compared with 39 (2.8%) of the 1406 controls. Analysis adjusted for initial eGFR showed that NDI was a significant risk factor for CKD (HR 1.90 [95% CI, 1.03-3.54]). Other significant risk factors were mean lithium concentration with HR of 1.25 (95% CI, 0.82–1.91), 2.84 (95% CI, 1.94–4.15) and 5.11 (95% CI, 3.22–8.07) for the groups with a mean lithium concentration of 0.6–0.79 and 0.8–0.99 mmol/L, respectively. Other significant risk factors were age per year (HR 1.03 [95% CI, 1.02–1.05]), diabetes (HR 1.62 (95% CI, 1.08–2.46]) and history of AKI (HR 1.92 [95% CI, 1.33–2.77]). Conclusion Lithium use is associated with NDI in a concentration-dependent manner. Long-term lithium treatment is associated with a risk of CKD, which also is concentration dependent, in patients with bipolar and unipolar mood disorders. NDI may be an important risk factor for CKD.

Acute kidney injury causes subclinical renal and endothelial injury in female rats which predisposes to adverse outcomes of pregnancy

Clinical data report a 3-5-fold increase in adverse pregnancy outcomes, including preeclampsia and small for gestational age neonates, among women with a history of acute kidney injury (AKI) despite clinical recovery of renal function. We developed a rat model of pregnancy post-AKI: Sprague-Dawley (SD) rats undergo a bilateral renal-ischemia reperfusion and fully recover renal function as measured by creatinine clearance 30 days post-AKI. Rats are then mated and during pregnancy recovered AKI rats exhibit decreased creatinine clearance, increased uterine artery resistance, reduced plasma volume expansion, and decreased fetal growth compared to pregnant rats that received sham surgery. Healthy pregnancy demands robust renal and vascular adaptations. Whether subclinical renal and vascular injury persists following AKI in females, and whether this is exacerbated in pregnancy to drive the adverse pregnancy outcomes remains unknown. We tested the hypothesis that AKI results in subclinical renal and vascular injury that lingers into pregnancy. Female SD rats were randomized to 45-minute warm bilateral renal ischemia reperfusion or sham (N=6-8/grp) and renal and vascular injury assessments were made 30 days post-AKI/Sham (pre-pregnancy) or during pregnancy on gestational day 20 (GD20). Pre-pregnancy urine volume measured via metabolic cage was greater in post-AKI rats compared to sham (10±1 vs 21±2 ml/daily urine, p<0.05). Urinary kidney injury marker-1 (KIM-1) measured via ELISA 30 days post-AKI/Sham was greater in pre-pregnant AKI rats compared to sham (9685±871 vs. 6399±198 pg/24 hrs urine, p<0.05). Vascular function, measured via wire myography on 3rd order mesenteric arteries 30 days post-AKI/Sham, revealed decreased endothelial-dependent relaxation to acetylcholine (ACh) (concentration-response, 1 nM-10 μM, 2-way ANOVA, RM, *p<0.05). GD20 urine volume (31±5 vs 19±2 ml/daily urine, p<0.05) and KIM-1 levels (9125±673 vs 6380±297 pg/daily urine, p<0.05) were elevated in post-AKI pregnant rats compared to sham pregnant rats. Mason Trichrome renal staining revealed greater glomerular fibrosis (0.93±0.08 vs 0.04±0.04, *p<0.05) and tubular fibrosis (1.7±0.19 vs 0.0±0.0, *p<0.05) in post-AKI pregnant rats vs. sham pregnant. Ultrastructural changes to the kidneys were evaluated via electron microscopy and further revealed extensive brush border loss, loss of mitochondrial structure and mitochondrial swelling in post-AKI pregnant rats compared to sham pregnant. Endothelial-dependent relaxation to ACh was also lower (2-way ANOVA, *p<0.05), suggesting enhanced endothelial dysfunction in post-AKI pregnant rats vs. sham pregnant. Taken together, these data suggest that with a history of AKI, subclinical renal and vascular injury is present despite “recovery” of renal function using clinical definitions and may predispose to adverse pregnancy outcomes in pregnant women with a history of AKI. 1R01HL169576 4R00HL146948 1RO1DK134695 AHA967662. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Serum Lithium Concentration and the Risk of Chronic Kidney Disease

IntroductionLithium is an important treatment option for individuals with mood disorders, but its use has been linked to the development of chronic kidney disease (CKD). Existing studies on this association have reported conflicting results.ObjectivesThe aim of this study was to examine the risk of developing CKD with lithium use adjusting for common comorbidities.MethodsThis was a retrospective cohort study that included all individuals in Iceland receiving lithium therapy between 2008 and 2018. Lithium use was defined as at least one dispensed prescription for Lithium or at least one serum lithium concentration above the detection limit. Patients with affective disorders (ICD-10 codes F30-F39) attending the outpatient clinics of Landspitali–The National University Hospital Mental Health Services in 2014-2016, without lithium exposure, served as controls. CKD stages 3-5 were defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines for CKD as estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the serum creatinine (SCr) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Acute kidney injury (AKI) was defined according to the SCr component of the KDIGO criteria for AKI, and other comorbid diseases were defined based on ICD-9 and ICD-10 codes. Individuals with fewer than 2 SCr measurements during the study period and those with CKD stages 3-5 prior to 2008 were excluded. Cox regression analysis with time dependent variables was performed to assess the risk of CKD.ResultsThe study included 2046 individuals exposed to lithium, of whom 221 (10.9%) developed CKD in the study period. Among the 1220 control subjects, 39 (3.2%) developed CKD. Lithium use was associated with CKD (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.37–2.74) after adjusting for sex, age, and comorbid diseases. Other significant risk factors were age (per year, HR 1.03, 95% CI 1.02–1.04), initial eGFR (per mL/min/1.73 m2, HR 0.92-0.96, 95% CI 0.90–0.99), presence of diabetes (HR 1.73, 95% CI 1.15–2.48) and history of AKI (HR 1.89, 95% CI 1.32–2.70). When compared to the control group not exposed to lithium, the risk (HR) of CKD was 1.24 (95% CI 0.81–1.89), 2.88 (95% CI 1.97–4.20) and 5.23 (95% CI 3.31-8.26) for groups with a mean lithium concentration of 0.3-0.59, 0.6-0.79 and 0.8-0.99 mmol/L, respectively.ConclusionsLong-term lithium therapy seems to increase the risk of CKD in a concentration-dependent manner in individuals with bipolar and unipolar mood disorders. To mitigate this risk, it is essential to monitor blood levels carefully and use doses of lithium as low as possible for adequate mood stabilization and treatment.Disclosure of InterestNone Declared

Predictors of Acute Kidney Injury (AKI) among COVID-19 Patients at the US Department of Veterans Affairs: The Important Role of COVID-19 Vaccinations.

There are knowledge gaps about factors associated with acute kidney injury (AKI) among COVID-19 patients. To examine AKI predictors among COVID-19 patients, a retrospective longitudinal cohort study was conducted between January 2020 and December 2022. Logistic regression models were used to examine predictors of AKI, and survival analysis was performed to examine mortality in COVID-19 patients. A total of 742,799 veterans diagnosed with COVID-19 were included and 95,573 were hospitalized within 60 days following COVID-19 diagnosis. A total of 45,754 developed AKI and 28,573 AKI patients were hospitalized. Use of vasopressors (OR = 14.73; 95% CL 13.96-15.53), history of AKI (OR = 2.22; CL 2.15-2.29), male gender (OR = 1.90; CL 1.75-2.05), Black race (OR = 1.62; CL 1.57-1.65), and age 65+ (OR = 1.57; CL 1.50-1.63) were associated with AKI. Patients who were vaccinated twice and boosted were least likely to develop AKI (OR = 0.51; CL 0.49-0.53) compared to unvaccinated COVID-19 patients. Patients receiving two doses (OR = 0.77; CL = 0.72-0.81), or a single dose (OR = 0.88; CL = 0.81-0.95) were also less likely to develop AKI compared to the unvaccinated. AKI patients exhibited four times higher mortality compared to those without AKI (HR = 4.35; CL 4.23-4.50). Vaccinated and boosted patients had the lowest mortality risk compared to the unvaccinated (HR = 0.30; CL 0.28-0.31). Use of vasopressors, being unvaccinated, older age, male gender, and Black race were associated with post COVID-19 AKI. Whether COVID-19 vaccination, including boosters, decreases the risk of developing AKI warrants additional studies.

Soluble suppression of tumorigenicity 2 is a potential predictor of post-liver transplant renal outcomes.

Acute kidney injury is considered an independent prognostic factor for mortality in patients with liver cirrhosis. Non-treated acute kidney injury can progress to hepatorenal syndrome with a poor prognosis. As suppression of tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor family that aggravates inflammation and fibrotic changes in multiple organs, we measured soluble ST2 (sST2) level in the serum and urine of liver-transplant recipients at the time of transplantation. The serum sST2 level significantly increased in liver-transplant recipients with suppressed kidney function compared with that in recipients with normal function. In recipients with severely decreased liver function (model for end-stage liver disease score ≥ 30), the serum sST2 level was higher than that in recipients with preserved liver function (model for end-stage liver disease score ≤ 20, P = 0.028). The serum sST2 level in recipients with hepatorenal syndrome was higher than that in liver-transplant recipients without hepatorenal syndrome (P = 0.003). The serum sST2 level in patients with hepatorenal syndrome was higher than that in recipients without a history of acute kidney injury (P = 0.004). Recipients with hepatorenal syndrome and recovered kidney function showed higher sST2 levels than those who did not recover (P = 0.034). Collectively, an increase in the serum sST2 level reflects a decrease in both kidney and liver functions. Thus, measuring sST2 level at the time of liver transplantation can help predict renal outcomes.

Exploring the connection between types of acute kidney injury and chronic kidney disease

Acute kidney injury (AKI) is a common clinical condition characterized by a rapid decline in renal function. AKI is associated with significant morbidity and mortality, and many patients with AKI develop chronic kidney disease (CKD). Previous studies have examined the association between AKI and CKD; however, the relationship between AKI types and CKD development has not been thoroughly investigated. Therefore, a multi-center prospective observational study is required to investigate this relationship thoroughly. These findings may have significant implications for the early identification, prevention, and management of CKD in patients with a history of AKI.

ТЕЧЕНИЕ IgA-НЕФРОПАТИИ У ДЕТЕЙ И ОГРАНИЧЕННЫЕ ВОЗМОЖНОСТИ ИММУНОСУПРЕССИВНОЙ ТЕРАПИИ

It is believed that IgA nephropathy (IgAN) in childhood is predominantly manifested by hematuria with episodes of macrohematuria and has a relatively favorable course. The purpose of this research was to analyze the frequency of the use of mycophenolate mofetil (MMF) in children with IgAN in the Nephrology Department of the National Medical Research Center for Children’s Health (Moscow, Russia) and to evaluate the results of treatment in terms of the severity of proteinuria and the presence of a decrease in renal function by glomerular filtration. Materials and methods used: to assess the clinical course, histological features and kidney function during therapy, Authors analyzed the results of 737 biopsies performed in 2018-2022. Results: 126 biopsy specimens with predominant IgA deposition and mesangial proliferation and/or crescents were identified, 20 of them were excluded from further analysis due to the clinical picture of IgA vasculitis. 17 (16% of the remaining 106) patients had nephrotic-level of proteinuria prior to the biopsy, 11 had a history of acute kidney injury and 9 had a persistent decrease in glomerular filtration renal function. Steroid therapy with prednisolone at a dose of 0.5 to 1 mg/kg was carried out in 21 children, 14 (66.7%; CI 45.4-84.1%) of them had relapse or resistance. MMF therapy was started in 16 (11 boys and 5 girls) patients, median age of the therapy initiation was 13.4 [7.9; 15.3] y/o, 6 had a decrease in glomerular filtration rate (GFR) in the range of 64 to 85 ml/min. Kidney biopsy specimens were ere scored according to the Oxford classification MEST-C criteria. During the follow-up period (median 27.6 [20.0; 49.4] months), 14 (88% CI; 66-98) of 16 achieved complete (10) or partial remission, 2 patients had proteinuria of more than 1 g/l. Of 56 patients (median age 13.3 [9.6; 14.9] months) with a follow-up period of more than 6 months, a decrease in GFR was recorded in 5 (31.3%; CI 12.5-55.5) patients on MMF therapy and 4 (22.2%; CI 7.5-44.3) patients who received only a course of steroids and a single one (4.5%; CI 0.3-18.5) who received ACE inhibitor only. Analysis of biopsy results showed an increased risk of reduced GFR in patients with tubular atrophy. Conclusion: MMF therapy may have limited efficacy for proteinuria in IgAN though it does not prevent the GFR decline.

Acute kidney injury in children with haematological malignancy: a territory-wide study.

In onco-nephrology, data on acute kidney injury (AKI) among children with haematological malignancies are scarce. A retrospective cohort study of all patients in Hong Kong diagnosed with haematological malignancies from 2019 to 2021 before 18years of age, was conducted to investigate the epidemiology, risk factors and clinical outcomes of AKI during the first year of treatment. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We included 130 children with haematological malignancy at median age of 9.4years (IQR, 3.9-14.1). Of these patients, 55.4% were acute lymphoblastic leukemia (ALL), 26.9% were lymphoma and 17.7% were acute myeloid leukemia (AML). Thirty-five patients (26.9%) developed 41 AKI episodes during the first year of diagnosis, corresponding to 32 episodes per 100-patient-year. A total of 56.1% and 29.2% of the AKI episodes occurred during induction and consolidation chemotherapy respectively. Septic shock (n = 12, 29.2%) was the leading cause of AKI; 21 episodes (51.2%) were stage 3 AKI; 12 episodes (29.3%) were stage 2 AKI; and 6 patients required continuous kidney replacement therapies. Tumor lysis syndrome and impaired baseline kidney function were significantly associated with AKI on multivariate analysis (P = 0.01). History of AKI was associated with chemotherapy postponement (37.1% vs. 16.8%, P = 0.01), worse 12-month patient survival (77.1% vs. 94.7%, log rank P = 0.002) and lower disease remission rate at 12-month (68.6% vs. 88.4%, P = 0.007), compared to patients without AKI. AKI is a common complication during treatment of haematological malignancies which is associated with worse treatment outcomes. A regular and dedicated surveillance program for at-risk patients should be studied in children with haematological malignancies for prevention and early detection of AKI. A higher resolution version of the Graphical abstract is available as Supplementary information.

595 - Female rats with history of acute kidney injury develop adverse maternal and fetal events during pregnancy

595 - Female rats with history of acute kidney injury develop adverse maternal and fetal events during pregnancy

Recent advances in molecular mechanisms of acute kidney injury in patients with diabetes mellitus.

Several insults can lead to acute kidney injury (AKI) in native kidney and transplant patients, with diabetes critically contributing as pivotal risk factor. High glucose per se can disrupt several signaling pathways within the kidney that, if not restored, can favor the instauration of mechanisms of maladaptive repair, altering kidney homeostasis and proper function. Diabetic kidneys frequently show reduced oxygenation, vascular damage and enhanced inflammatory response, features that increase the kidney vulnerability to hypoxia. Importantly, epidemiologic data shows that previous episodes of AKI increase susceptibility to diabetic kidney disease (DKD), and that patients with DKD and history of AKI have a generally worse prognosis compared to DKD patients without AKI; it is therefore crucial to monitor diabetic patients for AKI. In the present review, we will describe the causes that contribute to increased susceptibility to AKI in diabetes, with focus on the molecular mechanisms that occur during hyperglycemia and how these mechanisms expose the different types of resident renal cells to be more vulnerable to maladaptive repair during AKI (contrast- and drug-induced AKI). Finally, we will review the list of the existing candidate biomarkers of diagnosis and prognosis of AKI in patients with diabetes.

Assessment of Kidney Involvement in COVID-19 Patient.

Background and aim: Physicians need to be aware of the difficulties that SARS-CoV-2 infection brings to other regions of the body, such as the kidneys, even though the key emphasis is on pulmonary characteristics. The most frequent kidney complication among COVID-19 hospitalized patients is considered acute kidney injury (AKI). This study aimed to describe overall different aspects of acute kidney injury (AKI) in COVID-19 patients admitted to JLNMCH during the COVID-19 pandemic and to determine the prevalence of AKI among COVID-19 hospitalized patients.Methods and materials: All adult patients (over the age of 18 years) who screened positive for COVID-19 in a swab specimen from areas of nasopharyngeal by reverse transcriptase polymerase chain reaction and then hospitalized were included in the study. Information was gathered on the patient's demographics, general medical history, and drugs prescribed. From past medical information, associated comorbidities and home pharmaceuticals were identified. We gathered hospitalization information, such as duration of stay in ICU, details about the application of mechanical ventilation, information regarding extracorporeal membrane aeration, details of the use of vasopressor administration, and baseline results of laboratory test along with baseline clinical information during 48 hours of hospitalization.Results: The percentage of patients with no history of AKI requiring traumatic mechanical ventilation was 79.4%, while the percentage of patients with no history of AKI not requiring traumatic mechanical ventilation was 11.5%. The difference was relevant statistically (p<0.001). The percentage of patients with AKI of any stage requiring traumatic mechanical ventilation was 22.8%, while the percentage of patients with no history of AKI not requiring traumatic mechanical ventilation was 76.8%. The difference was relevant statistically (p<0.022).Conclusion: We discovered that AKI was a rather typical finding among hospitalized COVID-19 patients. Patients hospitalized for COVID-19 had a poor prognosis if they developed AKI.

Abstract 123: Female Rats With History Of Acute Kidney Injury Develop Endothelial Dysfunction, Increased Renal Inflammation And Decreased Aldosterone During Pregnancy

Clinical data report a 3-5 fold increase in adverse pregnancy outcomes among women with prior acute kidney injury (AKI), despite clinical recovery of renal function (creatinine clearance) before pregnancy. We showed that female Sprague-Dawley (SD) rats with recovered renal function from bilateral renal ischemia-reperfusion (AKI) develop decreased creatinine clearance, increased uterine artery resistance and decreased fetal growth in pregnancy via mechanisms unknown. We tested the hypothesis that AKI prior to pregnancy induces endothelial dysfunction, renal inflammation and dysregulated renin-angiotensin aldosterone system (RAAS) activation. Female SD rats received either 45-minute AKI or sham surgery and mated after 30 days (N=9 Sham, N=10 AKI). Gestation day 1 (GD1) was identified through vaginal smear and on GD19, rats were placed in metabolic cages before sacrificed on GD20 for plasma and tissue collection. Vascular function was assessed via wire myography on 3 rd order mesenteric arteries while renal inflammation was quantified via flow cytometry. Pre-pregnancy AKI reduced endothelial-dependent relaxation to acetylcholine (ACh) compared to sham (concentration-response, 1nM-10uM range, 2-way ANOVA, RM, *P&lt;0.05), indicating endothelial dysfunction. LNAME incubation ablated ACh-mediated relaxation equivocally in post-AKI and sham rats, indicating AKI induces a non-NO mediated endothelial dysfunction. Renal CD3+ T cells increased (4.4±0.23 vs 2.4±0.14%Total Renal Cells, *P&lt;0.05) while renal IL-10 decreased (3.0±0.8 vs 12.4±2.2%CD3+ T cells) in post-AKI pregnant rats compared to sham. Urinary volume/day (29.6±5 vs 18.6±2 ml/day, *P&lt;0.05), water intake (54.7±5 vs 40.6±1 ml/day*P&lt;0.05) and kidney weight (2.777±0.3/mg/g vs 2.4245±0.3) increased in post-AKI pregnant rats compared to sham. In addition, urinary aldosterone levels measured by ELISA decreased in post-AKI pregnant rats compared to sham (188±34 vs 312±35 pg/ml/day, *P&lt;0.05), suggesting disruption of fluid homeostasis and RAAS by pre-pregnancy AKI. Collectively, these data indicate that AKI prior to conception induces endothelial dysfunction, increases renal inflammation and decreases RAAS activation in pregnancy.

Fasting during Ramadan and acute kidney injury (AKI): a retrospective, propensity matched cohort study

BackgroundDuring the month of Ramadan, Muslims abstain from daytime consumption of fluids and foods, although some high-risk individuals are exempt. Because fasting's effects on the risk of acute kidney injury (AKI) have not been established, this study assesses the relationship between fasting and risk of AKI and identifies patients at high risk.MethodsA single-center, retrospective, propensity-score matched, cohort study was conducted with data collected from adult patients admitted to the emergency room during Ramadan and the following month over two consecutive years (2016 and 2017). AKI was diagnosed based on the 2012 definition from the Kidney Disease: Improving Global Outcomes clinical practice guideline. Multivariable logistic regression analyses were used to examine the correlation and measure the effect of fasting on the incidence of AKI, and assess the effect of different variables on the incidence of AKI between the matching cohorts.ResultsA total of 1199 patients were included; after matching, each cohort had 499 patients. In the fasting cohort, the incidence of AKI and the risk of developing AKI were significantly lower (adjusted odds ratio (AOR) 0.65;95% confidence interval (CI) 0.44–0.98). The most indicative risk factors for AKI were hypertension (AOR 2.17; 95% CI 1.48–3.18), history of AKI (AOR 5.05; 95% CI 3.46–7.39), and liver cirrhosis (AOR 3.01; 95% CI 1.04–8.70). Patients with these factors or most other comorbidities in the fasting cohort had a lower risk of AKI as compared with their nonfasting counterparts.ConclusionThe data show a strong reduction in the risk of developing AKI as a benefit of fasting, particularly in patients with comorbid conditions. Therefore, most patients with comorbid conditions are not harmed from fasting during Ramadan. However, larger prospective studies are needed to investigate the benefit of fasting in reducing the risk of developing AKI.

Children with Diabetic Ketoacidosis Treated with Restricted Fluid Regime in Intensive Care: Risk of Acute Kidney Injury is not Increased and Resolves

Background: Children admitted to intensive care with diabetic ketoacidosis are at risk of acute kidney injury. Recent UK guidelines recommends against restricted fluid provision due to a theoretical risk of kidney injury. To date no data has been published that documents this risk in an intensive care cohort. Aims: To describe the natural history of acute kidney injury in patients admitted with diabetic ketoacidosis in whom a restrictive fluid regime was provided. Methods: Retrospective analysis, within a UK Pediatric Intensive Care Unit. Between January 2011 and December 2020 219 patients were referred to the South Thames Retrieval Service with Diabetic Ketoacidosis, of whom 52 were admitted to Evelina PIC. 49 of these records were complete and used for analysis of acute kidney injury stage using Kidney Disease: Improving Global Outcomes criteria measured by serial creatinine. Clinical outcome at discharge from Pediatric Intensive Care was also recorded. Results: 19 out of 49 (38%) patients had acute kidney injury (17 present on admission to pediatric intensive care). Three patients required renal replacement therapy though all of them went on to re-establish their baseline renal function. This compares favourably to published data documenting an acute kidney injury incidence of 43-64% in general paediatric and pediatric intensive care cohorts. Conclusion: In the context of diabetic ketoacidosis, use of a restrictive fluid regime was not associated with higher levels of acute kidney injury than other studies and renal function recovery was observed in all patients followed up.

Serum catalytic iron and progression of chronic kidney disease: findings from the ICKD study.

The non-transferrin bound catalytic iron moiety catalyses production of toxic reactive oxygen species and is associated with adverse outcomes. We hypothesized that serum catalytic iron (SCI) is associated with progression of chronic kidney disease (CKD). Baseline samples of the Indian Chronic Kidney Disease participants with at least one follow up visit were tested for total iron, iron binding capacity, transferrin saturation, SCI, ferritin and hepcidin. SCI was measured using the bleomycin-detectable iron assay that detects biologically active iron. Association with the incidence of major kidney endpoints, (MAKE, a composite of kidney death, kidney failure or > 40% loss of eGFR) was examined using Cox proportional hazards model adjusted for sex and age. 2002 subjects (49.9 ± 11.6 years, 68.1% males, baseline eGFR 41.01 ml/min/1.73m2) were enrolled. After a median follow up of 12.6 (12.2, 16.7) months, the composite MAKE occurred in 280 (14%). After adjusting for age and sex, increase from 25th to 75th percentile in SCI, transferrin saturation, ferritin and hepcidin were associated with 78% (43-122%), 34% (10-62%), 57% (24-100%) and 74% (35-124%) increase in hazard of MAKE, respectively. SCI was associated with MAKE and kidney failure after adjustment for occupational exposure, hypertension, diabetes, tobacco, alcohol use, history of AKI, baseline eGFR, uACR, and allowing baseline hazard to vary by centre. SCI is strongly and independently associated with composite MAKE in patients with mild to moderate CKD. Confirmation in other studies will allow consideration of SCI as a risk marker and treatment target.

The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics.

ABSTRACTBackgroundChronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low–middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD.MethodsICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15–60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants.ResultsA total of 4056 patients have been enrolled up to 31 March 2020. The mean ± SD age was 50.3 ± 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73 m2. About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants.ConclusionsThe ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.

782-P: Machine Learning to Identify Diabetes Patients Initiating SGLT2i at High-Risk of Acute Kidney Injury

One of the main safety concerns associated with SGLT2 inhibitors (SGLT2i) is the increased risk of acute kidney injury (AKI), likely attributed to their diuretic effect and the induced hypovolemia. Yet, little is known about what patients are at highest risk of developing AKI when using SGLT2is. We applied machine learning techniques to predict AKI in type 2 diabetes (T2D) patients treated with SGLT2i and identify risk factors associated with AKI. Using a 5% random sample of Medicare claim data, we identified 17,694 T2D patients who filled ≥1 prescription for canagliflozin, dapagliflozin or empagliflozin prescriptions between 04/01/2013 and 12/31/2016. The cohort was split randomly and equally into training and testing sets. We measured 65 predictor candidates using claims data from the year prior to SGLT2i initiation and applied 3 machine learning models, i.e., random forests (RF), elastic net, least absolute shrinkage and selection operator (LASSO). The incidence rate of AKI was 1.1 % over a median 1.5-year follow up. Among 3 machine learning methods applied, RF produced the best prediction (C- statistic =0.72 ,95% CI 0.68, 0.76), followed by LASSO (C-statistic=0.69 95% CI 0.65,0.73). Among individuals classified in the top 10% of the RF risk score (i.e., high risk group), the actual incidence rate of AKI was as high as 3.7%. RF and LASSO selected similarly sets of important predictors, such as age, Medicaid eligibility, and loop diuretics use. In the logistic regression including 14 predictors selected by LASSO, use of loop diuretics [adjusted OR: 3.72 (2.44, 5.76)] and history of AKI [adjusted OR: 2.78 (1.06,7.3)] had the strongest associations with incidence of AKI. Our machine learning model efficiently identified patients who are at high risk of AKI after SGLT2i initiation. Strikingly, we identified an almost four-fold increased risk of AKI associated with background loop diuretic use among SGLT2i users. Disclosure L. Yang: None. N. Gabriel: None. I. Hernandez: Consultant; Self; Bristol-Myers Squibb Company, Pfizer Inc. A. G. Winterstein: Research Support; Self; Merck Sharp &amp; Dohme Corp. S. Kimmel: Consultant; Self; GE Healthcare, GlaxoSmithKline plc. J. Guo: None.