Etiology Of Acute Kidney Injury Research Articles

Malaria is the leading cause of acute kidney injury among a Zambian paediatric renal service cohort retrospectively evaluated for aetiologies, predictors of the need for dialysis, and outcomes.

Whilst malaria is a prominent aetiology associated with acute kidney injury (AKI) in many parts of Africa, a shift in the traditional AKI aetiologies has been witnessed in sections of the continent. Additionally, limited access to dialysis worsens patient outcomes in these low-resource settings. This retrospective cross-sectional study aimed to determine the associated aetiologies, predictors of need for dialysis and malaria-associated AKI (MAKI), and outcomes of AKI and dialysis among children evaluated by the renal service in Lusaka, Zambia. The study sampled all children aged 16 years or below, diagnosed with AKI between 2017 and 2021, by the renal unit at the University Teaching Hospitals- Children's Hospital (UTH-CH), and retrospectively abstracted their records for exposures and outcomes. AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Frequency and percentage distributions were used to describe the occurrence of AKI aetiologies and treatment outcomes. Predictors of the need for dialysis, MAKI, and poor treatment outcome were identified by using multivariable logistic regression models. A total of 126 children diagnosed with AKI were included in this study. Malaria was the most frequent aetiology of AKI(61.1% (77/126, 95% Confidence Interval (CI): 52.0%-69.7%)). Of the 126 children with AKI, 74.6% (94) underwent dialysis. Predictors of the need for dialysis were oliguria (p = 0.0024; Odds ratio (OR) = 7.5, 95% CI: 2.1-27.7) and anuria (p = 0.0211; OR = 6.4, 95% CI = 1.3, 30.7). A fifth (18.3%, 23/126) of the children developed chronic kidney disease (CKD), 5.6% (7/126) died and, a year later, 77% (97/126) were lost to follow-up. At UTH-CH, malaria is the most frequent aetiology among children with AKI undergoing dialysis and children from low-medium malaria incidence areas are at risk; a considerable proportion of children with AKI need dialysis and Tenchoff catheter use in AKI is advocated.

Pre-existing chronic kidney disease, aetiology of acute kidney injury and infection do not affect renal outcome and mortality

BackgroundWe aimed to study the role of aetiology, pre-existing chronic kidney disease (CKD) and infections in acute kidney injury (AKI) on renal outcome and mortality.MethodsThis retrospective study analysed patients with AKI admitted to a university nephrology department from January 1st, 2020 through December 31st, 2020. Aetiology of AKI, underlying renal disease in case of pre-existing CKD and presence of infections were assessed. Development of renal function and risk of death were studied with follow-up until January 31st, 2023.ResultsOf 1402 patients screened, 432 patients (30.8%, 67.9 ± 15.4 years) fulfilled the inclusion criteria, half of the population presented with advanced CKD. Even though CKD patients were more often in need of chronic dialysis at time of discharge (6.9% vs 4.5%, p < .001), duration of hospital stay was shorter and in-hospital mortality tended to be lower when compared to AKI without prior renal disease. Neither aetiology of AKI nor pre-existing CKD had an impact on the combined endpoint of end-stage kidney disease and mortality (log rank 0.433 and 0.909). Overall, septic patients showed the highest in-hospital mortality (23.5%) and longest hospital stay (30.0 ± 22.8 days, p < .001), while patients with urosepsis had the shortest hospitalisation time (9.7 days) with lowest risk for dialysis (4.4%). Of note, outcome did not differ in patients with AKI when considering the infectious status.ConclusionsOverall renal outcome and mortality in AKI patients were not affected by the cause of AKI, pre-existent CKD or infectious status. Only severity of AKI had a negative impact on outcome.Graphical abstract

Sex as a biological variable in acute kidney injury.

The purpose of this review is to provide an overview of the preclinical and clinical studies investigating sex as a biological variable, as well as the impact of gender, on the development of and progression of acute kidney injury (AKI). Despite a matched degree of ischemia-reperfusion AKI based on measured glomerular filtration rates, male and female mice demonstrated important sex biases in cardiorenal outcomes (1). Although the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI reported that female sex is associated with increased rates of hospital acquired AKI, subsequent meta-analyses do not show increased risk of AKI in women. Recent large scale, multicenter epidemiologic studies suggest males have higher rates of hospital acquired AKI. However, women have been consistently shown to have worse renal outcomes after AKI. There may be also be gender-based differences in presentation to care and management. Sex is an important biological variable in animal models of acute kidney injury. The impact of sex on AKI likely varies based on the etiology of AKI. Preclinical studies demonstrate the nuances of sex chromosomes, sex hormones and epigenetic factors on AKI, however these have not been well studied in humans. Gender may also impact processes of care, treatment and clinical outcomes related to AKI. The scientific rigor and reproducibility of translational studies benefit from the consideration of sex and gender.

Correlation of urinary neutrophil gelatinase-associated lipocalin levels as an early diagnostic marker for acute kidney injury in patients with sepsis

Background. The exact association between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and acute kidney injury (AKI) is unknown in a critical care setting, in which the population is heterogeneous and the aetiology of AKI is unclear. Aim of this study is to clarify if uNGAL level is an early diagnostic marker for AKI in patients with sepsis. Materials and methods. The current study was conducted on 86 sepsis patients. The prevalence of AKI was identified among them. The role of uNGAL in predicting AKI development, mortality rate and length of the intensive care unit (ICU) stay were analyzed. Sensitivity and specificity were calculated, and the area under the receiver operating characteristic curve was considered as the optimal uNGAL cut-off level for detecting all classifications of AKI. Results. Most patients belonged to the age group of 51–60 years and their mean age was 54.6 years. Most patients (65.11 %) were males. 26.75 % had both type 2 diabetes mellitus and hypertension. AKI was detected in 89 % of subjects in the current study, as per KDIGO definition. 15.12 % of patients had stage 1 CKD, 15.12 % had stage 2 CKD, and stage 3 CKD was diagnosed in 4.65 % of cases. Mortality rate was 11 %, and 89 % of patients were discharged. The mean ICU length of stay among patients with AKI is 8.9 days. There is significant association between the mean ICU length of stay and AKI presence (p = 0.03). 17.4 % (n = 15) of patients required renal replacement therapy. There is a very significant difference in mean baseline uNGAL in patients with and without AKI: 149.9 and 73.2 ng/ml, respectively (p = 0.0006). This indicated that baseline uNGAL levels predict AKI. The mean uNGAL in people with AKI was 356 ng/ml and in those without AKI, it was 95 ng/ml. There is a very significant difference in mean uNGAL 48 hours after in patients with and without AKI (p &lt; 0.0001). At a cut-off value of 120, there were 69 true positive cases, 9 true negative cases, 0 false positive cases, and 8 false negative cases. Based on these, the sensitivity of uNGAL at baseline in detecting AKI is 89.61 %, specificity is 100 %, and accuracy is 90.70 %. At a cut-off point of 120, there were 77 true positive cases, 8 true negative cases, 1 false positive case, and 0 false negative cases. Based on these, the sensitivity of uNGAL 48 hours after was 100 %, specificity 88.89 %, and accuracy was 98.84 %. There is a significant association between uNGAL levels and the ICU length of stay (p = 0.00). Conclusions. Sensitivity analysis was done in cut-off value of 120 for urinary NGAL in predicting AKI. From these results we conclude that urinary NGAL at the time of ICU admission is a reliable marker of renal function in sepsis patients. There is a significant correlation between AKI presence and urinary NGAL, and the ICU length of stay. We recommend not to use uNGAL alone in predicting AKI. It should be combined with glomerular filtration rate to reliably detect AKI development. Study findings indicate that sepsis patients with elevated uNGAL require proper management with close monitoring of blood pressure, urine output and appropriate doses of diuretics to avoid the development of AKI.

Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US

Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p= 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Acute kidney injury in the critical care setting.

Acute kidney injury is a sudden reduction in renal function which impairs the kidneys' ability to maintain fluid, electrolyte and acid-base balance. The syndrome often develops secondary to severe illness and is associated with a significant increase in morbidity and mortality rate in critically ill patients. This article gives an overview of the pathophysiology and aetiology of acute kidney injury, as well as the associated complications and clinical diagnostic signs. The authors also describe some common causes of the syndrome in critically ill patients, specifically sepsis, liver failure and cardiac failure, and discuss patient management in the critical care setting, with a focus on haemodynamic support and continuous renal replacement therapy.

Evaluation of simple diagnostic parameters in acute kidney injury in hospitalized patients—diagnostic recommendations for non-nephrologists

Acute kidney injury (AKI) is very common in hospitalized patients, affecting patient’s mortality and morbidity. Major causes are prerenal AKI and acute tubular necrosis (ATN). Even though a variety of parameters/indices exist, their reliability and practicability are controversial: in fact, there is a need for a simple diagnostic approach for AKI in in-patients with parameters easily obtained in any hospital. The objective of the study was: (1) to assess reliability of simple laboratory parameters/indices to differentiate pre-/intrarenal AKI; (2) to evaluate the most reliable and feasible parameters/indices; and (3) to identify the possible impact of confounding factors. Retrospectively, in-patients with AKI hospitalized in 2020 in a university nephrology department were included. Spot urine and 24-h collection urine was analyzed with urine sodium (UNa), urine specific gravity (USG), fractional excretion of sodium (FENa), fractional excretion of urea (FEUrea), urine osmolality (UOsm), urine to plasma creatinine ratio (UCr/PCr) and renal failure index (RFI). Overall, 431 patients were included. UNa, UOsm, USG and RFI showed high specificity > 85% for prerenal AKI, UNa and RFI provided good specificity for ATN. Loop diuretics, ACE inhibitors/AT1 blockers or pre-existing chronic kidney disease had no impact. In patients with AKI, UNa, USG and RFI: (1) proved to be very specific for prerenal AKI and showed high sensitivity for ATN; (2) can be easily determined using serum and spot urine; and (3) are not confounded by medication or comorbidities. These parameters/indices are helpful to identify the aetiology of AKI and to guide therapy, thereby improving patients’ safety and outcome.

#5535 CALCIUM EXCRETION FRACTION AS AN EMERGING PARAMETER FOR AN ACCURATE DIFFERENTIAL DIAGNOSIS OF ACUTE KIDNEY INJURY

Abstract Background and Aims Urinary parameter determination is an essential tool for differentiating acute kidney injury (AKI) etiology. The most used ion in clinical practice is sodium (and its excretion fraction, NaEF), followed by urea (UreaEF) (that is useful in certain circumstances such as diuretic treatment). However, tubular transport includes other anions and cations that have not been widely studied. In the present study, we aim to evaluate the relation between AKI etiology (i.e. functional vs acute tubular necrosis) and calcium excretion fraction (CaEF). Method This is a transversal study including consecutive patients with diagnosis of AKI. Patients with suspicion of non-functional or ATN etiology (such as those with proteinuria, hematuria) were excluded. At admission, we collected epidemiological data, comorbidities and active treatments. AKI etiology was determined based on urinary parameters (sodium, urea) and recovery pattern of kidney function after treatment instauration. We compared CaEF in patients with ATN and functional AKI in the whole sample and among patients with and without previous CKD and diuretic prescription. Results We included 94 AKI episodes (55% female, 76±15 years). Forty-five (48%) patients had chronic kidney disease (CKD) at baseline and 56 (60%) were receiving treatment with diuretics. Of the 94 AKI, 78 (83%) presented a functional etiology and 16 (17%) were catalogued as ATN. Median CaEF was 1.09 (0.63-2.58) %. CaEF was associated to the etiology of AKI. In patients with functional AKI, median of CaEF was 0.95 (0.60-1.84) % in contrast to ATN (2.33 [1.22-7.27] %)(p&amp;lt;0.001). CaEF presented a positive and significant correlation to NaEF (ρ 0.574, p&amp;lt;0.001) and UreaEF (ρ 0.409, p&amp;lt;0.001). An adjusted regression model including the presence of CKD at baseline and diuretic treatment showed that CaEF independently predicted ATN (OR per 1% increase 1.42, 95%CI [1.16-1.75), p&amp;lt;0.001]. In patients without CKD, CaEF predicted ATN (OR 1.61, 95%CI [1.13-2.28], p = 0.008), in contrast to the cohort with CKD where only a trend was demonstrated (OR 1.29, 95%CI [0.99-1.69], p = 0.057) (Figure 1). CaEF also predicted ATN irrespective of the diuretic prescription at baseline (OR 1.35, 95%CI [1.05-1.74], p = 0.018 for diuretic users and OR 1.57, 95%CI [1.06-2.32], p = 0.025 for non-diuretic users) (Figure 1). Receiving operator curves (ROC) demonstrated a 0,712 area under the curve (AUC) of CaEF &amp;gt;1.6% for ATN, that was the best value for diagnosis in terms of sensitivity and specificity. CaEF&amp;gt;1,6% predicted ATN (OR 8.09, 95%CI [2.32-28.2], p = 0.001) after adjusting for the presence of CKD at baseline and diuretic treatment. Conclusion CaEF could help in the identification of the AKI etiology as higher values (i.e. &amp;gt;1.6%) are independently associated with ATN.

#5618 IMPACT OF THE PATHOPHYSIOLOGY OF ACUTE KIDNEY INJURY IN PATIENTS AFFECTED BY COVID-19 ON CLINICAL OUTCOMES DIALYSIS AND DEATH

Abstract Background and Aims The Coronavirus Disease-19, COVID-19 caused by the Sars-Cov-2 virus has been associated with either asymptomatic and mild conditions or severe acute respiratory syndrome with generalized organ dysfunction and death. One of the most important is Acute Kidney Injury (AKI). It is acknowledged that AKI is multifactorial, as the most relevant factors for its development are the cytokine storm, metabolic stress, medication use, rhabdomyolysis, renal viral tropism, and multiple organ dysfunction. However, little is known about the impact of AKI's pathophysiology on its clinical outcome. Method Retrospective cohort study that evaluated the medical records of patients diagnosed with COVID-19 admitted to a Tertiary Public Hospital, from 06/01/2020 to 07/31/2021 from their admission until the outcome. The evaluation of renal function occurred through the variation of urinary output and serum creatinine measurement, and the diagnosis of AKI followed the 2012 KDIGO criteria. The occurrence of AKI was an inclusion criterion in the study. The nephrotoxic drug usage and the leak of clinical and laboratory data were exclusion criteria in the study. In addition to urine output and serum creatinine, the creatine phosphokinase, type 1 urine test concerning proteinuria and haematuria, cardiocirculatory and ventilatory parameters, and vasoactive, diuretic, antihypertensive and corticoid drugs usage were analysed. Univariate analysis was performed to identify whether the pathophysiological mechanisms of AKI (ischemic, cytokine storm- CS, rhabdomyolysis, renal viral tropism, or multiple organ failure- MOF) are associated with death. Results Until now, we have included 283 patients. There was a predominance of males (55.5%), Caucasian ethnicity (80.6%); median age was 64 years. Most patients were admitted to the ICU (85.1%). The predominant AKI was KDIGO 3 (56.9%). Regarding the different etiologies of AKI, Renal Viral Tropism was the most frequent (21.5%), followed by MOF (19.1%), Septic (16.6%), Mixed Renal Viral Tropism (16.2%), Ischemic (15.5%) and CS (10,9%). Regarding the CS, patients were more often admitted to the ICU (100%; p&amp;lt;0.001) made the least use of corticosteroids (51.6%; p&amp;gt;0.001) and diuretics (12.9%; p = 0.016), they made the most use of mechanical ventilation (100%), vasoactive drugs (100%) and dialysis (74.2%; p&amp;lt;0.001). Paradoxically, they were the most obese (67.74% p = 0.011), but had less hypertension (48.4%; p = 0.025), less previous cardiovascular disease (6.45% p = 0.01), and less dyslipidemia (9.68%; p = 0.012). In general, the mixed etiology markedly comes closest to the CS etiology, followed by the MOF. Patients who least needed dialysis were those with septic etiology (18.18%; p&amp;lt;0.001). Preliminary tests show an impressive mortality of 69.61%, which is associated with the AKI pathophysiological mechanisms (p&amp;lt;0.0001). CS (87.1%), MOF (87.0%), and Mixed Etiologies (89.1%) are the pathophysiological mechanisms associated with poor prognosis; and Viral Renal Tropism (54.3%), Sepsis (48.3%), and Ischemic Injury (34.1%) are the pathophysiological mechanisms related to the best outcomes. Conclusion AKI related to COVID-19 patients are mostly elderly, admitted to ICU, classified as KDIGO 3 and their mortality is notable. Nevertheless, the mortality and the need for dialysis depends on the pathophysiological mechanism their AKI, as CS, MOF, and Mixed Etiologies are the pathophysiological mechanisms associated with poorest prognosis; and Viral Renal Tropism, Sepsis, and Ischemic Injury are related to the best outcomes.

#3235 ELECTROLYTE DISORDERS IN COMMUNITY-ACQUIRED ACUTE KIDNEY INJURY

Abstract Background and Aims The kidney plays a decisive role in regulating the homeostasis of the internal environment. Acute kidney injury (AKI) compromises the kidney's ability to maintain this regulation intact, and the appearance of various electrolyte disorders is to be expected in this situation. There are few data in the literature that describe these alterations in patients with community-acquired AKI (CA-AKI). The purpose of this study is to analyze the incidence of electrolyte disorders in a cohort of patients with CA-AKI admitted to the nephrology service of a tertiary level hospital. Method This is a single-center, observational, longitudinal, and retrospective study based on a cohort of patients with CA-AKI admitted to the Nephology Service of a third level hospital from January 2010 to December 2018. We analyzed the incidence of changes in sodium, potassium, chloride, bicarbonate, calcium, and phosphorus in these patients and their clinical consequences during admission and follow-up after hospital discharge. Results A total of 639 patients were included in the final analyses. The mean age was 72,93±13,38 years. 61,7% were men. Charlson comorbidity index was 5,87 ±2,4 points. The length of stay was 11,63±10,14 days. In view of the Etiology of AKI, 72,1% had prerenal AKI and 27,9% non-prerenal. 436 patients had a history of previous chronic kidney disease (CKD) (68.23%). AKI KDIGO stages were: stage I, 105 cases (16.4%); stage II, 67 cases (10.5%); stage III 467 cases (63.1%). Hemodialysis (HD) was required in 114 patients (17.8 %). 62 patients (9.7 %) died during hospital stay. The percentage of patients with alterations in the different ions was: chlorine 54%, potassium 60.1%, sodium 45.23%, bicarbonate 85.67%, calcium 52.68%, phosphorus 54.49%. The most frequent ionic alterations at a global level were low bicarbonate (78.3%), hyperkalemia (53.05%), hypocalcemia (49.6%) and hyponatremia (41.5%). No significant differences were observed in these percentages when comparing patients with previous CKD with respect to carriers of normal baseline renal function (glomerular filtration rate &amp;gt; 60 ml/min). When analyzing whether electrolyte alterations occurred simultaneously: 2.2% of cases did not present any, 6.3% only one, 18.2% two, 26.4% three, 26.1% four, 14.9% five and 5.9% six simultaneous alterations. In the univariate analysis, patients with hypernatremia (Chi square 22.7; p &amp;lt; 0.001), hyperkalemia (Chi square 9.7; p = 0.008) and hyperphosphatemia (Chi square 18.5; p &amp;lt; 0.001) had higher mortality during admission. In the multivariate analysis using logistic regression, the variables that were independently associated with mortality during hospitalization were phosphorus (OR 1.425; 95% CI 1.212 - 1.676) and chlorine (OR 1.045; 95% CI 1.002 - 1.089). In the follow-up after hospital discharge, the Kaplan-Meier curves in the univariate analysis showed higher mortality in patients who presented hyperkalemia (log rank test: Chi square 15.5; p &amp;lt; 0.0001), hypernatremia (log rank test: Chi square 47.7; p &amp;lt; 0.0001), hypocalcemia (log rank test: Chi square 6.73; p &amp;lt; 0.034) and hyperphosphatemia (log rank test: Chi square 10.24; p &amp;lt; 0.006). In the multivariate analysis using Cox regression, the variables that were independently associated with mortality after hospital discharge were sodium (Exp(B) 1.001; 95% CI 1.002 - 1.048; p = 0.048), potassium (Exp(B) 1.140; 95% CI 1.055 - 1.233; p = 0.001) and phosphorus (Exp(B) 1.087; 95% CI 1.023 - 1.048; p = 0.154). Conclusion In our series of patients with CA-AKI, we detected a high prevalence of electrolyte disorders, without a history of previous CKD having any influence on it. The most frequent was the finding of three or four simultaneous alterations. Phosphorus and chlorine independently influenced mortality during admission. In the follow-up after hospital discharge, sodium, potassium, and phosphorus were independent predictors of mortality. The clinician who treats cases of CA-AKI must expect the appearance of frequent electrolyte disorders and must be prepared for their correct management.

CARC4: Incidence, Outcomes, and Risk Factors of Acute Kidney Injury in Patients on Percutaneous Mechanical Circulatory Support with Impella 5.0 and 5.5 for Cardiogenic Shock

Purpose: Use of temporary mechanical circulatory devices (tMCS) such as the transaxial flow pump (ImpellaTM. Abiomed, Danvers, MA) for CS-HF is growing. Despite advances in tMCS investigations have found AKI is highly prevalent and strongly associated with mortality in CS patients supported with MCS. We identified pre and post implant risk factors of AKI in CS-HF patients supported with Impella 5.0 and 5.5. Methods: Single center retrospective analysis of 144 Impella 5.0/5.5 devices from 01/2012 to 07/2022 for CS-HF. Patients with non heart failure etiology (n=5) and pre-implant renal replacement therapy (RRT. n=44) were excluded. Demographics and pre-implant chacteristics of patients) as well as post-implant outcomes including mortality, heart replacement therapy (HRT) with ventricular assist device (VAD) or heart transplant (HTX), and native heart survival at discharge were compared between patients with and without acute kidney injury (AKI). AKI was defined as rise in Creatinine 1.5 x baseline or new need for RRT. Logistic regression was used to find independent predictors of post-implant AKI and spearmann correlation was used to find associations with 90-day kidney function defined as fold change in creatine from baseline to peak 90 day values). Results: The final cohort consisted of 96 patients with mean duration of Impella support of 10±12 days.. Of the remaining 96 devices 57 (59.4%) developed AKI with 9 requiring RRT (9.4%). Patients with AKI had higher mortality (42.1% vs 17.9%, p=0.04), lower HRT (43.9% vs 56.4%, p=0.04) and less native heart survival (discharged without HRT) (14.0% vs 25.6%, p=0.04) than those without AKI. Demographics and pre-implant characteristics are shown in in Table 1. Pre-implant creatinine, lactate dehydrogenase (LDH), total bilirubin, Model for End Stage Liver Disease (MELD), and mean right atrial pressure to pulmonary capillary wedge pressure (mRAP/PCWP) as well as post-implant hemolysis (rise in plasma free hemoglobin > 20 or LDH 2.5 x upper limit of normal) were higher in patients with AKI. On logistic regression with backwards selection independent predictors of AKI included pre-implant mRAP/PCWP (OR 33.5 95%CI 1.6-708.8, p=0.02) and post-implant hemolysis (OR 5.6 95%CI 2.1-31.5, p=0.045) (Table 2). On spearman correlation (Table 3) only pre-implant mRAP/PCWP and post-implant LDH:Upper limit of normal LDH were associated with worse long term kidney function defined as fold change of 90-day peak creatinine from baseline. Conclusions: AKI is associated with higher mortality after Impella 5.0 and 5.5 insertion. The etiology of AKI in patients with cardiogenic shock supported by Impella 5.0 and 5.5 is multifactorial but clearly related to venous congestion and hemolysis. Optimization of patient’s fluid status when the device is inserted and avoidance of hemolysis during device support play key roles in reducing AKI in this group of high risk patients.

Single-cell sequencing reveals homogeneity and heterogeneity of the cytopathological mechanisms in different etiology-induced AKI

Homogeneity and heterogeneity of the cytopathological mechanisms in different etiology-induced acute kidney injury (AKI) are poorly understood. Here, we performed single-cell sequencing (scRNA) on mouse kidneys with five common AKI etiologies (CP-Cisplatin, IRI-Ischemia-reperfusion injury, UUO-Unilateral ureteral obstruction, FA-Folic acid, and SO-Sodium oxalate). We constructed a potent multi-model AKI scRNA atlas containing 20 celltypes with 80,689 high-quality cells. The data suggest that compared to IRI and CP-AKI, FA- and SO-AKI exhibit injury characteristics more similar to UUO-AKI, which may due to tiny crystal-induced intrarenal obstruction. Through scRNA atlas, 7 different functional proximal tubular cell (PTC) subtypes were identified, we found that Maladaptive PTCs and classical Havcr1 PTCs but not novel Krt20 PTCs affect the pro-inflammatory and pro-fibrotic levels in different AKI models. And cell death and cytoskeletal remodeling events are widespread patterns of injury in PTCs. Moreover, we found that programmed cell death predominated in PTCs, whereas apoptosis and autophagy prevailed in the remaining renal tubules. We also identified S100a6 as a novel AKI-endothelial injury biomarker. Furthermore, we revealed that the dynamic and active immune (especially Arg1 Macro_2 cells) -parenchymal cell interactions are important features of AKI. Taken together, our study provides a potent resource for understanding the pathogenesis of AKI and early intervention in AKI progression at single-cell resolution.

Comparison of profile and short-term outcome of acute kidney injury between steroid sensitive and steroid resistant nephrotic syndrome

Background: Acute kidney injury (AKI), a severe complication of nephrotic syndrome (NS) is being more prevalent in recent times. Objectives were: 1) Determine incidence, etiology, short term outcome of AKI in children hospitalised with NS. 2) Compare above variables in steroid sensitive nephrotic syndrome (SSNS) versus steroid resistant nephrotic syndrome (SRNS). Methods: Prospective observational study over 18 months including all consecutive nephrotics hospitalized with AKI. AKI defined according to KDIGO criteria with baseline creatinine taken as lowest value in last 6 months/ nadir during stay. Secondary NS were excluded. Demographics, clinical features, labs, hospital course, treatment and follow up at 3 months were recorded. SSNS and SRNS were compared. Results: The incidence of AKI in hospitalised nephrotics (30/304) was 9.8%, 30 patients (16 boys) with mean age 4.08 years (± 4.04 SD). Common etiologies of AKI were infection (60%), nephrotoxic drugs, hypovolemia, and thrombosis in decreasing order. Nephrotics developing AKI had a longer hospital stay versus those without AKI (p&lt;0.001). The 2/30 patients died (6%), 10/30 (33.3%) required PICU, 7/30 (26%) needed RRT. Among discharged patients 4/28(14.28%) had persistent deranged renal functions at 3 months follow up, all of whom belonged to SRNS category. Comparison of 14 patients in SSNS with 16 in SRNS showed UTI (31.3%), drugs (25%), systemic infection (31.3%), thrombosis (12.5%) as etiologies in SRNS. Systemic infection (42.9%), drugs (21.4%), UTI (14.3%) and hypovolemia (21.4%) were causes in SSNS. Mortality rate, need for PICU (p=1.0), RRT (p=1.0) was similar (6%,37.5%, 25%) Vs (7%,28.5%, 21.4%). Conclusions: AKI is seen in up to a tenth of children with NS equally in SSNS and SRNS. While etiology and severity of AKI in the 2 groups is similar, short-term outcome in SRNS is more ominous.

Acute kidney injury post-abdominal surgery in infants: implications for prevention and management.

Acute kidney injury (AKI) is common in critically ill infants and is associated with long-term sequelae including hypertension and chronic kidney disease. The etiology of AKI in infants is multifactorial. There is robust literature highlighting the risk of AKI after cardiothoracic surgery in infants. However, risk factors and outcomes for AKI in infants after abdominal surgery remains limited. This article reviews the epidemiology and association of abdominal surgery with postoperative AKI and suggests methods for AKI management and prevention. Postoperative AKI may result from hemodynamic shifts, hypoxia, exposure to nephrotoxic medications, and inflammation. Infants in the intensive care unit after intraabdominal surgeries have a unique set of risk factors that predispose them to AKI development. Prematurity, sepsis, prolonged operation time, emergent nature of the procedure, and diagnosis of necrotizing enterocolitis increase risk of AKI after intrabdominal surgeries. Prevention, early diagnosis, and management of AKI post-abdominal surgery is imperative to clinical practice. Close monitoring of urine output, serum creatinine, and fluid status is necessary in infants after abdominal surgery. A recent study suggests elevated levels of a urinary biomarker, neutrophil gelatinase-associated lipocalin (NGAL), 24 h after an abdominal procedure may improve early prediction of AKI. Identification of risk factors, avoidance of nephrotoxic medications, careful fluid balance, early detection of AKI, and maintenance of hemodynamic stability is imperative to potentially prevent and/or mitigate AKI.

White paper on mitigating risk factors for acute kidney injury in TAVR: A protocol to decrease TAVR-associated AKI

Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) portends a poor prognosis. In the TVT registry, AKI after TAVR occurred in 10% of the patients. The etiology of AKI after TAVR is multifactorial but contrast volume remains one of the few modifiable risk factors. As patients referred for TAVR have multiple touch points within a siloed healthcare system, there remains an unmet clinical need of a well-defined clinical pathway to minimize the risk of AKI from the time of referral for TAVR to the completion of the procedure. This white paper aims to provide such a clinical pathway.

Clinico-Etiological Spectrum and Outcome in Patients With Septic Acute Kidney Injury and Its Comparison With Non-septic Acute Kidney Injury: A Hospital-Based Prospective Study Conducted in a Tertiary Care Hospital in North India.

Background Acute kidney injury (AKI) is a heterogenous syndrome defined by the impairment of kidney filtration and excretory function over days to weeks, resulting in the retention of nitrogenous and other waste products normally cleared by the kidneys. In addition, AKI is frequently recognized to be associated with sepsis and contributes to an unfavorable outcome in sepsis. This study was undertaken to study and compare the etiology and clinical profile of patients with septic and non-septicAKI and to study and compare the outcome in both groups. Materials and methods This is a prospective, observational, and comparative study with a total sample size of 200 patients selected randomly having sustained an acute kidney injury. Data was collected, recorded, analyzed, and compared for two groups of patients with septic and non-septic AKI. Results A total of 200 cases of AKIwere enrolled, out of which 120 (60%) were due to non-septic etiology and 80 (40%) were of septic etiology. Urosepsis (37.5%) due to various urinary tract infections including pyelonephritis and chest sepsis (18.75%) including community-acquired pneumonia (CAP) and aspiration pneumoniawere the predominant causes of sepsis. AKI secondary to nephrotoxic agents (27.5%) was the commonest cause in the non-septic group, followed by glomerulonephritis (13.3%), vitamin D intoxication-related hypercalcemia (12.5%), acute gastroenteritis (10.8%), etc. Patients of septic AKI had a significantly higher mean of maximum urea and creatinine than their non-septic AKI counterparts. In addition to having an increased duration of hospital stay, mortality was significantly higher in patients with septic AKI (27.5%) than in patients with non-septic AKI (4.1%). However, sepsis had no effect on renal functions, measured by urea and creatinine, at discharge. In patients with AKI, certain factors were found to increase the risk of mortality. These factors include being over 65 years old, needing mechanical ventilation or vasopressors, requiring renal replacement therapy (RRT), and having multiorgan dysfunction syndrome (MODS), septic shock, or acute coronary syndrome (ACS). However, pre-existing conditions such as diabetes, hypertension, malignancy, previous stroke, chronic kidney disease (CKD), and chronic liver disease (CLD) did not affect the overall mortality risk. Conclusion In the septic AKI group, urosepsis was the most frequent etiology of AKI, whilethe most frequent etiology of AKIin the non-septic group was nephrotoxin exposure. Patients with septic AKI had considerably longer hospital stays and greater in-hospital mortality rates than patients with non-septic AKI. The renal functions as determined by urea and creatinine at discharge were unaffected by sepsis. Finally, death was significantly impacted by age of >65 years, the necessity for mechanical ventilation, the use of vasopressors and RRT, and the presence of MODS, septic shock, and ACS.

Diagnostic and prognostic performance of urinary neutrophil gelatinase-associated lipocalin in patients with cirrhosis and acute kidney injury.

Acute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) could help discriminate between different etiologies of AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI. One hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml [95% CI 423-2105 ng/ml] vs. 109 ng/ml [95% CI 52-192 ng/ml]; p < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR [aOR], 6.17; 95% CI 1.41-27.03; p = 0.016). In multivariable analysis (adjusted for age, Model for End-Stage Liver Disease, acute-on-chronic liver failure, leukocytes, and type of AKI), uNGAL was an independent predictor of in-hospital mortality (aOR, 1.74; 95% CI 1.26-2.38; p = 0.001). uNGAL is an adequate biomarker for making a differential diagnosis of AKI in cirrhosis and predicting the response to terlipressin and albumin in patients with HRS-AKI. In addition, it is an independent predictor of in-hospital mortality.

Factors Associated with Mortality and Long-Term Outcomes of Pediatric Acute Kidney Injury in a Resource Limited Setting

Introduction: Despite being a leading cause of morbidity and mortality globally, acute kidney injury (AKI) is worse in resource-limited areas. This study explores AKI incidence, inhospital mortality, and long-term outcomes in resource-limited settings. Methods: This was a prospective study of children with AKI from 2014 to 2019. KDIGO 2012 defined AKI. We assessed the etiology, inhospital mortality, and long-term outcome of AKI in a mission hospital. Results: Only 169 of 201 AKI patients had complete data. The ages ranged from 1.08 months to 17.5 years; 65.7% were male and 65.1% were from lower socioeconomic class. The incidence of AKI was 59.6 cases per 1,000 persons (95% CI: 5.42, 47.1). Most patients had stage 1 KDIGO AKI (91; 53.8%). 1–5 years old had the highest incidence of AKI (65; 38.5%); sepsis (26.6%), severe malaria (15.4%), and nephrotic syndrome (14.8%) were common AKI causes. Fever (72.8%), pallor (52.1%), and vomiting (45.6%) were the most common symptoms. Thirty-two (27.8%) patients had high blood pressure. Inhospital mortality was 14.8% (95% CI: 9.8, 21.1). The cumulative incidence of AKI-related mortality was 93.2 per 1,000 person-years. Poor outcome was associated with breathlessness, hyponatremia, and leukocytosis. Kaplan-Meier survival curve showed 81% (CI: 74–87%) survival after 5 years of AKI. On Cox proportional-hazards analysis, the absence of breathlessness (HR: 2.537, 95%: CI 1.210–5.317) and hyponatremia (HR: 2.914, 95% CI: 1.343–6.324) were associated with increased survival. Conclusion: In resource-limited settings, infectious diseases and nephrotic syndrome are common causes of AKI. Factors associated with mortality include breathlessness and hyponatremia.

Acute kidney injury in diabetes mellitus: Epidemiology, diagnostic, and therapeutic concepts.

Acute kidney injury (AKI) and diabetes mellitus (DM) are public health problems that cause a high socioeconomic burden worldwide. In recent years, the landscape of AKI etiology has shifted: Emerging evidence has demonstrated that DM is an independent risk factor for the onset of AKI, while an alternative perspective considers AKI as a bona fide complication of DM. Therefore, it is necessary to systematically characterize the features of AKI in DM. In this review, we summarized the epidemiology of AKI in DM. While focusing on circulation- and tissue-specific microenvironment changes after DM, we described the active cellular and molecular mechanisms of increased kidney susceptibility to AKI under DM stress. We also reviewed the current diagnostic and therapeutic strategies for AKI in DM recommended in the clinic. Updated recognition of the epidemiology, pathophysiology, diagnosis, and medications of AKI in DM is believed to reveal a path to mitigate the frequency of AKI and DM comorbidity that will ultimately improve the quality of life in DM patients.

Kidney Injury in Children after Hematopoietic Stem Cell Transplant

Hematopoietic cell transplant (HCT), used for treatment of many malignant and non-malignant pediatric diseases, is associated with serious complications, limiting this therapy's benefit. Acute kidney injury (AKI), seen often after HCT, can occur at different stages of the transplant process and contributes to morbidity and mortality after HCT. The etiology of AKI is often multifactorial, including kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and other transplant-related complications such as transplant-associated thrombotic microangiopathy and sinusoidal obstructive syndrome. Early recognition of AKI is crucial to prevent further AKI and associated complications. Initial management includes identifying the etiology of AKI, preventing further kidney hypoperfusion, adjusting nephrotoxic medications, and preventing fluid overload. Some patients will require further support with kidney replacement therapy to manage fluid overload and AKI. Biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin can aid in detecting AKI before a rise in serum creatinine, allowing earlier intervention. Long-term kidney dysfunction is also prominent in this population. Therefore, long-term follow-up and monitoring of renal function (glomerular filtration rate, microalbuminuria) is required along with management of hypertension, which can contribute to chronic kidney disease.