Diagnosis Of Acute Kidney Injury Research Articles

#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<0.001). CaEF presented a positive and significant correlation to NaEF (ρ 0.574, p<0.001) and UreaEF (ρ 0.409, p<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<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 >1.6% for ATN, that was the best value for diagnosis in terms of sensitivity and specificity. CaEF>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. >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<0.001) made the least use of corticosteroids (51.6%; p>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<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<0.001). Preliminary tests show an impressive mortality of 69.61%, which is associated with the AKI pathophysiological mechanisms (p<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.

#5282 ACUTE KIDNEY INJURY IN INFECTIOUS DISEASE BY CORONAVIRUS IN BRAZIL: A STUDY ON INCIDENCE, RISK FACTORS, AND PROGNOSIS

Abstract Background and Aims Although diffuse alveolar damage and acute respiratory failure are the main features of COVID-19 disease in its severe form, renal involvement is frequent (4-37%). To assess the incidence of acute kidney injury (AKI) in Brazilian patients hospitalized with COVID-19 and to identify both the risk factors associated with its onset and those associated with its prognosis. Method This is a prospective cohort study of patients hospitalized with COVID-19 at a public and tertiary university hospital in São Paulo from March 2020 to May 2021, encompassing the first and second waves of the pandemic. Patients were followed up until the clinical outcome (discharge or death). The evaluation of renal function was performed by measuring serum creatinine and urinary output and the diagnosis of AKI was performed according to the KDIGO 2012 criteria. The occurrence of AKI was established as the dependent variable, using the Chi-Square Test for the comparison of categorical variables and the t Test for continuous variables. Afterwards, a multivariate analysis was performed using the logistic regression model, with calculations of the Odds Ratio (OR), including in the model all the variables that showed association with the outcome (p≤0.20). A similar procedure was performed after establishing death as the dependent variable. Results 887 patients with COVID-19 were analyzed, 54.6% were admitted to the intensive care unit (ICU) and 45.4% were admitted to the ward. The overall incidence of AKI was 48.1%, more frequent in the ICU (83.8 vs 17.1%, p<0.0001). Upon hospital admission, 487 patients were submitted to urine test I, of which 58.5% had hematuria and 51.5% had proteinuria. The overall mortality was 38.9%. The average time for the diagnosis of AKI was 6 days and AKI KDIGO 3 was the most frequent (60.2%). Acute renal support was indicated in 58.8% of patients. According to logistic regression, the risk factors for AKI were the use of diuretics (OR 2.2, CI 1.2-4.1, p<0.05), mechanical ventilation (OR 12.9, CI 4.3-38.2, p<0.05), VAD (OR 2.7, CI 0.9-7.7, p = 0.06), dyslipidemia (OR 0.54, CI 0.3-1.05, p = 0.07), proteinuria (OR 2, CI 1.1-3.4, p<0.05), hematuria (OR 2, CI 1.1-3.5, p<0.05), CKD (OR 2.6, CI 1.2-5.5, p<0.05), older age (OR 1.03, CI 1-1.07, p<0.05), CPK (OR 1.02, CI 1-1.07, p<0.05) and D-dimer (OR 1.02, CI 1.01-1.09, p<0.05). The risk factors for death were arterial hypertension (OR 1.7, CI 1-3, p = 0.05), use of mechanical ventilation (OR 12.9, CI 4.3-38.2, p<0.05), presence of proteinuria (OR 1.6, CI 0.9-2.7, p = 0.07), presence of AKI (OR 6, CI 2.9-12.2, p<0.05), mainly KDIGO 3 (OR 0.6, CI 0.2-1.3, p = 0.2), high D-dimer (OR 1, CI 1, p = 0.05), SOFA score (1.35, CI 1.1-1.6, p<0.05) and ATN-ISS score (OR 996.4, CI 4.8-203271, p<0.05). Finally, the variables that showed the difference in the profile of patients between the two waves of the pandemic were identified, being less frequent in the second wave male gender (OR 0.51, CI 0.35-0.74, p<0.05) and Caucasian ethnicity (OR 0.47, CI 0.2-0.8, p<0.05), and more frequent in the second wave the use of mechanical ventilation (OR 1.57, CI 1-2.3, p<0.05), proteinuria (OR 1.44, CI 1-2.1, p<0.05), higher D-dimer values (OR 1.09, CI 1-1.1, p<0.05) and ATN-ISS score (OR 40.9, CI 1.7-948.1, p<0.05). Conclusion AKI associated with severe COVID-19 in Brazil was more frequent than in the Chinese, European, and North American cohorts, and the risk factors associated with its development are the use of diuretics, mechanical ventilation, VAD, dyslipidemia, proteinuria, hematuria, CKD, older age, elevated CPK and D-dimer. Mortality was high and higher in patients with arterial hypertension, on mechanical ventilation, with proteinuria, with AKI, mainly KDIGO 3, high D-dimer, and higher SOFA and ATN-ISS. In the second wave, AKI severity was greater, but mortality was similar to that of the first wave, which may reflect both the effectiveness of vaccines against SARS-CoV-2, as well as the constant learning that frontline professionals have built throughout the pandemic, to provide greater support to its patients.

#6584 WEEKEND EFFECT IN ACUTE KIDNEY INJURY ADMISSIONS AND 1-YEAR RENAL OUTCOME

Abstract Background and Aims The “weekend effect” is the finding of worse outcomes in hospital admissions occurring over weekends. The reasons for this are still unclear but shorter staffing has been suggested to contribute. Little is known about the impact of the “weekend effect” on renal outcomes. We aim to analyze the impact of the weekend effect on patients admitted with acute kidney injury (AKI). We evaluated one-year renal outcome and mortality in patients admitted for AKI over weekends and weekdays. Method We conducted a retrospective analysis of all adult patients admitted in a tertiary medical center in Portugal over a period of 6 months with a diagnosis of AKI. Variables were retrieved using clinical and laboratory data. AKI was defined and severity was accessed according to Kidney Disease Improving Global Outcomes classification. Patients were categorized according to weekdays or weekend admission. Outcomes were in-hospital mortality, hemodialysis (HD) requirement and one-year mortality. Statistical significance was defined as a P-value <0.05 Results We included 163 patients with mean age of 69.8±16.2 years and 52.7% were male. The majority of patients were admitted on weekdays (74.2%, n = 121). Also, the majority had AKI stage 3 (65.6%, n = 107). Forty eight patients (29.4%) required HD during hospitalization and in-hospital mortality was 24.5%. There were no significant differences in HD requirement (31.4% vs 23.8%, p = 0.434), mortality (25.6% vs 21.4%, p = 0.680) nor HD requirement at discharge (25.6% vs 26.2%, p = 0.681) between weekday or weekend admissions. Of the 123 patients discharged, during the one-year follow-up 30.1% (n = 37) died and 7.3% (n = 9) required HD. There were no differences between weekdays or weekend admissions concerning mortality (32.2% vs 24.2%, p = 0,507) and HD requirement (7.8% vs 6.1%, p = 0,746) Conclusion In this cohort of patients with AKI there was no “weekend effect”, which reflects the adequacy of care independently of the day of admission. The retrospective design with a limited number of patients may have influenced the results. Further studies focusing on renal outcomes are required to better understand the occurence of the weekend effect and its long-term impact.

#3740 AFTER ALL A TYPICAL HUS

Abstract Background and Aims Typical Hemolytic Uremic Syndrome (HUS) is a thrombotic microangiopathy (TMA) characterized by the triad of acute renal failure, hemolytic anemia and thrombocytopenia. TMAs are classified into: Inherited or primary acquired (atypical HUS), secondary or infection associated. Infection with Shiga-toxin–producing Escherichia coli (E. coli), mainly of serotype O157:H7, is the most common cause of typical HUS, but other serotypes have been rarely associated such as Enteroagregative Escherichia coli (EAEC) serotype O104:H4. Method Case Report Results We report a case of a 51-years-old male with past medical history of arterial hypertension (treated with Perindopril) and IgGk Multiple Myeloma (MM) diagnosed 10 years prior submitted to two bone marrow autotransplants (9 and 4 years prior) and multiple chemotherapy agents including Carfilzomib-Pomalidomide-Dexamethasone (last cycle 4 days before the onset of symptoms). One week after returning from a trip to Brazil, he was admitted to the emergency department with a two-day history of non-bloody diarrhea (4-5 liquid stools per day) and asthenia, with similar positive familiar epidemiology. He denied abdominal pain, fever, nausea or vomiting. At physical examination, he was hypertensive (177/90 mmHg), anuric (12,5 ml/h), dehydrated and apyretic. Abdominal palpation was painless and there were no signs of peritoneal irritation. Laboratory tests showed hemoglobin 10.5 g/dl, new onset thrombocytopenia (261 000/uL » 21 000/uL), kidney disfunction (serum creatinine (sCr) 0.74 mg/dL to 9 mg/dL and serum urea (sU) 41 mg/dL to 260 mg/dL), hyperkaliemia (6 mEq/L) and metabolic acidosis (pH 7,39 and bicarbonate 18.4 mEq/L). LDH was 1949 U/L, C-reactive protein 30.6 mg/L, procalcitonin 3.77 ng/mL, haptoglobin <0.07 g/L and with normal complement levels (C3 and C4). Schistocytes were present in peripheral blood smear. The diagnosis of Acute Kidney Injury related with TMA was established and the patient was transferred to the Nephrology ward and urgent hemodialysis was started. Exhaustive study was performed showing normal renal ultrasound, non-nephrotic proteinuria (1.6 g/g), urinalysis showed leukocyturia and erythrocyturia. Autoimmune study including PR3-ANCA, MPO-ANCA, anti-GBM antibody, Anti-dsDNA antibody, anti-beta 2-glycoprotein I antibodies, anticardiolipin antibodies, anti-ADAMTS13 antibodies and ADAMTS13 activity, as well as study of complement C5, C'3, C'4, factor B, H and I, anti-factor H ac, AH 50 and CH50b were unremarkable. Blood and urine culture and antistreptolysin O titers were negative. Specific stool cultures for E. coli O157, Shigella, Salmonella, Yersinia and Campylobacter were negative. Stool evaluation for parasites were also negative. Viral serology for HIV, HBV, HCV and Plasmodium tests were negative. PCR stool was required due to high suspicion of E.coli infection. The suspicion of a Carfilzomib induced TMA was also raised, while molecular techniques results were awaited. MM was stable and treatment was held until recovery of kidney function. During hospitalization the patient recovered diuresis and creatinine decreased. On the 11th day of hospitalization, he was discharged but still depended on hemodialysis. Finally, stool PCR techniques identified aatA and aggR genes associated with EAEC O104:H4 allowing the diagnosis of acquired infectious HUS rather than drug-related TMA. One week after discharge, the dialysis was stopped due to sCr 3 mg/dL. Four months later, he resumed Carfilzomib and kidney function remained stable with sCr 0.9 mg/dL, despite sustained proteinuria of 1.2 g. Conclusion The authors emphasize the importance of considering other causes of TMA when E.coli O157 infection is excluded, namely drug-related causes (as Carfilzomib) or less frequent infectious agents such as EAEC O104:H4. This case reveals the importance of requesting PCR in the stool even when the E.coli test is negative. This is of particular relevance in immunosuppressed patients. This diagnosis allowed continuing MM treatment.

#5831 LIGHT CHAIN REMOVAL IN MULTIPLE MYELOMA PATIENTS WITH HFR-SUPRA HEMODIALYSIS: OUR EXPERIENCE

Abstract Background and Aims Kidney injury is a common complication in multiple myeloma (MM) and it has a negative prognostic implication. Most common cause of Acute Kidney Injury (AKI) in these patients is Light chain Cast Nephropathy, where free light chains precipitate in the tubules and bind with uromodulin, turning into intratubular casts that obstruct the tubules and also promote local giant cell reaction and interstitial inflammation and fibrosis. Free light chains (FLCs) can also damage the kidneys due to direct tubular toxicity when excessive amounts are reabsorbed by the proximal tubules. Targeted therapy to reduce FLC load can help recover renal function. Both total reduction and reduction speed are relevant for prognosis. FLC removal through extracorporeal techniques can be used as an adjuvant therapy, having an important part on the evolution of the disease. We gathered data from our experience treating MM patients with AKI with HFR-supra hemodialysis (HD) and analized the evolution and possible influence of this technique on renal recovery. Method This is an observational retrospective study. We included all patients with a diagnosis of multiple myeloma and acute kidney injury who received HFR-Supra hemodialysis in between years 2016-2022 in Hospital Virgen Macarena (Seville). We initially performed 6-10 daily HFR-Supra HD sessions and then modulated the frequency based on renal response (if renal replacement therapy had to be continued they underwent a usual hemodialysis regime 3 days a week). We continued these sessions until renal recovery was achieved or free light chain levels were reduced in agreement with the Hematology team. Measurement of pre and post dialysis FLCs was made always at first and last session and at least once in between, depending on the total number of sessions. Results 12 patients, with mean age at diagnosis 63.6 (43-86) years, presented with AKI stage KDIGO 3. 1 of them was oliguric. Median serum creatinine at diagnosis was 4.4 mg/dL [2,2-17], mean proteinuria was 4,1g/24 h [0,7-8,7] and 66,7% had positive Bence Jones proteinuria (mean 2,3g/24 h). 2 of the patients had previous chronic kidney disease stage 3a. All of them were diagnosed with Light Chain Multiple Myeloma (75% kappa, mean 10346 mg/L; 25% lambda, mean 5990 mg/L). Mean clonal bone marrow plasma cell was 20,7% [2-55]. According to the Revised International Staging System (R-ISS), 25% were stage 2 and 75% were stage 3. Renal biopsy was performed in 4 patients, all showed evidence of Cast Nephropathy. The indication for starting HFR-Supra HD was FLC removal in 9 patients, need of renal replacement therapy in 1 and both in 2 patients. We have experience in our center with using this therapy as an adyuvant treatment and often we start the technique in patients who present with AKI but would not necessarily have immediate need for renal replacement therapy. The goal is to remove FLCs and avoid further damage to the kidney tissue. Out of the 12 patients, 9 were able so stop dialysis (75%). They received a mean number of 12,4 [3-41] sessions in 3,7 [0,2-25] months). Free light chain removal per session was 24% on average [5-43%]. All of them were started on bortezomib-dexamethasone regime as initial chemotherapy for MM. As per renal recovery, at 3 months 33,3% achieved complete response, 11,1% partial response and 55,6% minimal response. At 1 year, 42,9% achieved complete response, 14,3% partial response and 42,9% minimal response. One-year survival rate was 91,7% (1 patient died from respiratory sepsis less than 1 month after diagnosis). Conclusion HFR-Supra hemodialyisis achieved a 24% free light chain removal per session on average. After presenting severe AKI (KDIGO 3), almost 43% of patients who received this adyuvant therapy obtained full renal recovery at 1 year and in 75% of patients withdrawal from hemodialysis was possible. 1 year survival was 91,7%.

Supramolecularly Engineered Reporters with Superoxide Anion‐Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury

AbstractWe report the “water‐in‐oil‐in‐water” preparation of kidney injury molecule‐1‐targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L‐serine‐modified poly(lactic‐co‐glycolic) acid (PLGA)‐encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2⋅−, a biomarker of AKI, triggers the oxidation of CPPO to 1,2‐dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L‐serine‐modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long‐lived CL (half‐lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non‐invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.

Supramolecularly Engineered Reporters with Superoxide Anion-Triggered Chemiluminescence for Early Diagnosis and Efficient Amelioration of Acute Kidney Injury.

We report the "water-in-oil-in-water" preparation of kidney injury molecule-1-targeting supramolecular chemiluminescence (CL) reporters (PCCS), consisting of L-serine-modified poly(lactic-co-glycolic) acid (PLGA)-encapsulated peroxyoxalate (CPPO), chlorin e6 (Ce6) and superoxide dismutase (SOD), for early diagnosis and amelioration of acute kidney injury (AKI). In this system, O2 ⋅- , a biomarker of AKI, triggers the oxidation of CPPO to 1,2-dioxetanedione and subsequent CL emission via CL resonance energy transfer to Ce6. The L-serine-modified PLGA stabilizes CPPO and Ce6 via noncovalent interactions, promoting long-lived CL (half-lives: ≈1000 s). Transcriptomics analysis shows that PCCS reporters reduce the inflammatory response through glutathione metabolism and inhibition of the tumor necrosis factor signaling pathway. The reporters are able to non-invasively detect AKI at least 12 h earlier than current assays, and their antioxidant properties allow simultaneous treatment of AKI.

Lessons Learnt from the Management of Severe COVID-19 Disease in a 93-year-old with Chronic Co-Morbidities at a Resource-constrained Centre in Nigeria – A Retrospective Single Case Study

Introduction: Severe COVID-19 infection is associated with significant mortality in the elderly. This is even more so, when the elderly patient with the disease also has multiple chronic co-morbidities, and is resident in a resource-constrained area.
 Aims/ Objectives: To outline management strategies employed, and important lessons learnt from the successful management of a case of severe COVID-19 disease in a 93-year-old with chronic co-morbidities in a resource-limited setting.
 Methods: We utilized a simple COVID-19 severity categorization algorithm on presentation, to assign the index patient to the appropriate COVID-19 disease severity class and subsequently employed patient’s serial, weekly clinical and laboratory parameters to guide a multi-specialty management protocol.
 Results: A 93-year-old man was referred to a tertiary hospital in Enugu during the second wave of the COVID-19 pandemic, with a 5-day-history of high grade fever, severe fatigue, and altered sensorium. He had been living with diabetes for 48years; recently had worsening glycemic control, and was yet to pass urine in the previous 12hours. He was also being managed conservatively for prostate carcinoma. Examination revealed signs of severe pneumonia and he was drowsy, dehydrated, and had asterixis. A diagnosis of acute kidney injury from septicemia, following community acquired pneumonia and possibly urinary tract infection was made, with COVID-19 infection as a differential. Samples were collected for laboratory investigations while he was recommended for intensive care unit admission for further care. Para-enteral broad spectrum antibiotics, intravenous fluid therapy, intranasal oxygen therapy, basal-bolus-insulin-regimen, and anti-coagulation prophylaxis were instituted. Following laboratory investigation results which included a positive COVID-19 test (clinically categorized as severe disease), severe systemic inflammation, evidence of uro-tract infection, intravascular thrombosis and severe renal impairment, the Nephrology, Infectious disease, Urology teams were invited to co-manage the patient alongside the Endocrinologists. After 27days of collaborative care, patient was discharged with resolution of his symptoms and signs.
 Conclusion: Multi-specialty collaborative care improves patients’ outcome even in the face of severe COVID-19 with associated co-morbidities in elderly patients. Severity stratification ensures life-saving timely care for severe COVID-19 disease.

The Importance of Urine Sediment Analysis in the Diagnosis and Management of Acute Kidney Injury

The Urine sediment analysis is an extremely valuable yet underutilized test. Our case discussion aims to highlight its diagnostic value and emphasize the role of physicians in the performance of the test as diagnosis and management strategies may differ, leading to clinical improvement and more specific therapeutic interventions.

Study of plasma neutrophil gelatinase-associated lipocalin as an early marker of acute kidney injury following contrast agents

Introduction: Acute kidney injury (AKI) is a common illness among hospitalized patients, which increases mortality and morbidity rate. Creatinine and neutrophil gelatinase-associated lipocalin (NGAL) are the most commonly conducted biomarkers of AKI. Objectives: The aim of current study was to assess NGAL as an early biomarker for AKI diagnosis following contrast agents. Patients and Methods: To follow the aim of the present case-control research, 165 individuals were entered the study; 80 patients were selected from Valiasr hospital of Zanjan city, and 85 healthy individuals were enrolled voluntarily. There were not any significant differences in sex distribution among healthy subjects. Plasma NGAL and creatinine were measured immediately before and at 12 and 72 hours post-contrast agents’ exposure. Results: There were 89 males and 76 females in the study groups. The mean age was 61.3 ± 18.2 years and 62.1 ± 17.2 years in the intervention and healthy groups, respectively. The mean of serum creatinine and NGAL level were 1.0± 0.2 mg/dL and 63.6 ±23.6 ng/mL in the control and 0.92 ± 0.23 mg/dL and 110 ± 82.3 ng/mL in the case group, respectively. There were remarkable different between serum NGAL and creatinine in the both groups. The NGAL level in the healthy and the patient group were 63.6 ± 23.6 ng/mL and 100.1 ± 121.7 ng/mL, respectively, which was considerably different between the case and control groups (P=0.01). The highest level of specificity and sensitivity were 86 and 55.5; they could be the main appropriate options for defining cut off. Conclusion: The findings showed, that NGAL level is an extremely specific and sensitive indicator for AKI diagnosis after 72 hours. Hence, this approach can open a novel insight into the AKI therapies.

Evaluation of Contrast-Enhanced Ultrasound in Diagnosis of Acute Kidney Injury of Patients in Intensive Care Unit.

Ultrasound can assess renal perfusion, but its role in the evaluation of acute kidney injury (AKI) is still unclear. This prospective cohort study was to investigate the value of contrast-enhanced ultrasound (CEUS) in the evaluation of AKI in intensive care unit (ICU) patients. Fifty-eight patients were recruited from ICU between October 2019 and October 2020, and CEUS was used to monitor the renal microcirculation perfusion within 24h after admission. Parameters included rise time (RT), time to peak intensity (TTP), amplitude of peak intensity (PI), area under the curve (AUC), time from peak to one half (TP1/2) of renal cortex and medulla. Ultrasonographical findings, demographics, laboratory, etc were collected for further analysis. There were 30 patients in the AKI group and 28 patients in the non-AKI group. The TTP, PI, TP1/2 of the cortex and the RT, TTP, TP1/2 of the medulla in the AKI group were significantly longer than in the non-AKI group (P < 0.05);. The TTP (OR = 1.261, 95% CI: 1.083-1.468, P = 0.003) (AUCs 0.733, Sen% 83.3, Spe%57.1), TP1/2 (OR = 1.079, 95% CI: 1.009-1.155, P = 0.027) (AUCs 0.658, Sen% 76.7, Spe%50.0) of the cortex and RT (OR = 1.453, 95% CI: 1.051-2.011, P = 0.024) (AUCs 0.686, Sen% 43.3, Spe%92.9) of the medulla were related to the AKI. Eight new-onset AKI cases occurred in the non-AKI group within 7 days, the RT, TTP, TP1/2 of the cortex and medulla were significantly longer in the new-onset AKI group than in the non-AKI group (P < 0.05), but serum creatinine and blood urea nitrogen were no differences between groups (P > 0.05). This study indicates CEUS can assess the renal perfusion in AKI. TTP and TP1/2 of the cortex and RT of the medulla can aid the diagnosis of AKI in ICU patients.

Paper-based multiplex colorimetric vertical flow assay with smartphone readout for point-of-care detection of acute kidney injury biomarkers

Acute kidney injury (AKI) is a serious renal emergency that is often underdiagnosed and associated with high mortality rates. Early diagnosis of AKI is crucial to improve patient prognosis and reduce healthcare costs. In this study, a paper-based colloidal gold multiplex vertical flow assay was developed for rapid detection of three AKI biomarkers, namely, NGAL, CysC, and RBP4, in a single test kit. In this system, specific capture antibodies were pre-immobilized on the sensing membrane at four spatially isolated immunoreactive sites. Gold nanoparticles were conjugated with detection antibodies as the colorimetrical labels. The resultant images could be read out qualitatively by the naked eyes or quantitatively by a smartphone-based readout device. Three AKI biomarkers could be simultaneously detected in 10–15 min. The detection sensitivity and specificity for clinical serum samples collected from 25 patients with AKI and 25 healthy individuals were determined as 92% and 88%. This vertical flow assay platform is easy to use, rapid, and low cost. It is a promising diagnostic tool for multiplex detection of disease biomarkers at point of care.

Acute kidney injury in patients with acute-on-chronic liver failure: clinical significance and management.

Acute-on-chronic-liver failure (ACLF) refers to a phenomenon in which patients with chronic liver disease develop multiple organ failure due to acute exacerbation of underlying liver disease. More than 10 definitions of ACLF are extant around the world, and there is lack of consensus on whether extrahepatic organ failure is a main component or a consequence of ACLF. Asian and European consortiums have their own definitions of ACLF. The Asian Pacific Association for the Study of the Liver ACLF Research Consortium does not consider kidney failure as a diagnostic criterion for ACLF. Meanwhile, the European Association for the Study of the Liver Chronic Liver Failure and the North American Consortium for the Study of End-stage Liver Disease do consider kidney failure as an important factor in diagnosing and assessing the severity of ACLF. When kidney failure occurs in ACLF patients, treatment varies depending on the presence and stage of acute kidney injury (AKI). In general, the diagnosis of AKI in cirrhotic patients is based on the International Club of Ascites criteria: an increase of 0.3 mg/dL or more within 48 hours or a serum creatinine increase of 50% or more within one week. This study underscores the importance of kidney failure or AKI in patients with ACLF by reviewing its pathophysiology, prevention methods, and treatment approaches.

Early continuous renal replacement therapy for postoperative patient with acute kidney injury following total pancreato-splenectomy: a case report

BackgroundAcute kidney injury is a devastating postoperative complication. Renal replacement therapy is a treatment modality for acute kidney injury. Continuous renal replacement therapy is the treatment of choice for patients with hemodynamic instability. The main question in the management of acute kidney injury is when to initiate the renal replacement therapy. Several studies have demonstrated improvement in patients with septic acute kidney injury, following early continuous renal replacement therapy. To date, no guidelines have been established on the perfect timing to initiate continuous renal replacement therapy. In this case report, we did an early continuous renal replacement therapy as an extracorporeal therapy for blood purification and renal support.Case presentationOur patient was a 46-year-old male of Malay ethnicity, undergoing total pancreatectomy due to a duodenal tumor. The preoperative assessment showed that the patient was high risk. Intraoperatively, massive surgical bleeding was sustained due to extensive tumor resection; thus, massive blood product transfusion was necessary. After the surgery, the patient suffered from postoperative acute kidney injury. We performed early continuous renal replacement therapy, within 24 hours after the diagnosis of acute kidney injury. Upon completion of continuous renal replacement therapy, the patient’s condition improved, and he was discharged from the intensive care unit on the sixth postoperative day.ConclusionThe timing for the initiation of renal replacement therapy remains controversial. It is clear that the “conventional criteria” for initiating renal replacement therapy need correction. We found that early continuous renal replacement therapy initiated in less than 24 hour after the postoperative acute kidney injury diagnosis gave our patient survival benefit.

Community Response to Acute Kidney Injury Due to Children's Syrup Preparations

The mortality rate for children with a diagnosis of acute kidney injury after consuming syrup preparations in Indonesia is very high. The number of syrup preparations in Indonesia found to be contaminated with Ethylene glycol (EG) or Diethylene glycol (DEG) reached 116 syrup products. There are three issues that will be investigated as a result of the contaminated syrup: (1) the public response to the policies and responsibilities of regulators (the Indonesian Ministry of Health and the Food and Drug Monitoring Agency (BPOM), (2) the public response to pharmacies in delivering safe medicines to patients, and (3) the public response to pharmacists who are responsible for the practice of pharmaceutical services in pharmacies. This research method is a qualitative descriptive study using a Google form questionnaire which is analyzed using the Guttman scale. The questionnaire meets the qualifications in testing the validity, reliability and normality of research data. The results showed that the level of public trust in the government (Ministry of Health and BPOM) was low, while the level of trust in pharmaceutical facilities at pharmacies and pharmacists was still quite above average.

The clinical significance of renal resistance index (RRI) and renal oxygen saturation (RrSO2) in critically ill children with AKI: a prospective cohort study

ObjectiveThe purpose of this study was to look into the clinical significance of the renal resistance index (RRI) and renal oxygen saturation (RrSO2) in predicting the development of acute kidney injury (AKI) in critically ill children. A new non-invasive method for the early detection and prediction of AKI needs to develop.MethodsPatients admitted to the pediatric intensive care unit (PICU) affiliated with the capital institute of pediatrics from December 2020 to March 2021 were enrolled consecutively. Data of clinical information, renal Doppler ultrasound, RrSO2, and hemodynamic index within 24 h of admission were prospectively collected. Patients were divided into two groups: the study group was AKI occurred within 72 h, while the control group did not. SPSS (version 25.0) was used to analyze the data, and P < 0.05 was considered a statistical difference.Results1) A total of 66 patients were included in this study, and the incidence of AKI was 19.70% (13/66). The presence of risk factors (shock, tumor, severe infection) increased the incidence of AKI by three times. 2) Univariate analysis showed significant differences in length of hospitalization, white blood cells (WBC), C-reactive protein (CRP), renal resistance index (RRI), and ejection fraction (EF) between the study and control groups (P < 0.05). There were no significant differences in renal perfusion semi-quantitative score (P = 0.053), pulsatility index (P = 0.051), pediatric critical illness score (PCIS), and peripheral vascular resistance index (P > 0.05). 3) Receiver operating characteristic (ROC) curve showed that if RRI > 0.635, the sensitivity, specificity, and AUC for predicting AKI were 0.889, 0.552, and 0.751, respectively; if RrSO2 < 43.95%, the values were 0.615, 0.719 and 0.609, respectively; if RRI and RrSO2 were united, they were 0.889, 0.552, and 0.766, respectively.ConclusionsThe incidence of AKI is high in PICU patients. And infection, RRI, and EF are risk factors for AKI in PICU patients. RRI and RrSO2 have certain clinical significance in the early prediction of AKI and may provide a new non-invasive method for early diagnosis and prediction of AKI.

Clinical and Biochemical Profile Associated with Renal Recovery after Acute Kidney Injury in A Mexican Population: Retrospective Cohort Study.

Background and Objectives: Our primary objective was to study the clinical and biochemical characteristics associated with acute kidney injury (AKI) remission in a group of Mexican patients. Materials and methods: We retrospectively enrolled 75 patients who were diagnosed with AKI and separated the sample into two groups: nonremitting patients (n = 27, 36%) vs. remitting patients (n = 48, 64%). Results: We found significant relationships between nonremitting AKI and previous diagnosis of chronic kidney disease (p = 0.009), higher serum creatinine (Cr) at admission (p < 0.0001), lower estimated glomerular filtration rate (eGFR) (p < 0.0001), maximum serum creatinine during hospitalization (p < 0.0001), higher fractional excretion of sodium (FENa) (p < 0.0003) and 24-h urine protein (p = 0.005), higher serum potassium on admission (p = 0.025), abnormal levels of procalcitonin (p = 0.006), and increased risk of death (p = 0.015). Conclusion: Chronic kidney disease (CKD), lower eGFR, higher levels of serum creatinine during hospitalization, higher FENa and 24-h urine protein, abnormal levels of procalcitonin, and higher serum potassium on admission were associated with nonremitting AKI. These findings may facilitate the rapid identification of patients at risk for nonremitting AKI based on clinical and biochemical characteristics. Furthermore, these findings may inform the design of timely strategies for the vigilance, prevention, and treatment of AKI.

Patient level factors increase risk of acute kidney disease in hospitalized children with acute kidney injury.

Studies in adults have shown that persistent kidney dysfunction ≥7-90 days following acute kidney injury (AKI), termed acute kidney disease (AKD), increases chronic kidney disease (CKD) and mortality risk. Little is known about the factors associated with the transition of AKI to AKD and the impact of AKD on outcomes in children. The aim of this study is to evaluate risk factors for progression of AKI to AKD in hospitalized children and to determine if AKD is a risk factor for CKD. Retrospective cohort study of children age ≤18 years admitted with AKI to all pediatric units at a single tertiary-care children's hospital between 2015 and 2019. Exclusion criteria included insufficient serum creatinine values to evaluate for AKD, chronic dialysis, or previous kidney transplant. A total of 528 children with AKI were included in the study. There were 297 (56.3%) hospitalized AKI survivors who developed AKD. Among children with AKD, 45.5% developed CKD compared to 18.7% in the group without AKD (OR 4.0, 95% CI 2.1-7.4, p-value <0.001 using multivariable logistic regression analysis including other covariates). Multivariable logistic regression model identified age at AKI diagnosis, PCICU and NICU admission, prematurity, malignancy, bone marrow transplant, previous AKI, mechanical ventilation, AKI stage, duration of kidney injury, and need for kidney replacement therapy during day 1-7 as risk factors for AKD after AKI. AKD is common among hospitalized children with AKI and multiple risk factors are associated with AKD. Children that progress from AKI to AKD are at higher risk of developing CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Survival outcomes in older patients with different stages of acute kidney injury defined by the addition of urine output criteria.

To the Editor: Globally, acute kidney injury (AKI) is a common life-threatening condition. AKI is more prevalent in elderly patients, with increasing mortality rates. Compared with younger patients, older patients with AKI have a higher risk of persistent injury and poorer prognoses.[1] Older individuals often have comorbidities, increasing their susceptibility to AKI. Kidney Disease: Improving Global Outcomes (KDIGO) criteria define and stage AKI based on the higher stage of AKI defined by either serum creatinine (SCr) level or urine output (UO).[2] However, the record of UO is difficult to access in clinic, the data on the value of UO combined with SCr for AKI diagnosis or prognosis in elderly patients are lacking. Therefore, the objectives of this study were to investigate whether UO would influence the classification of AKI and improve the accuracy of prediction of the clinical prognosis in elderly patients. We performed a retrospective cohort study to assess the survival outcomes of AKI in older patients with different stages of AKI based on SCr alone or the combination criteria. The study included male patients aged >65 years who presented to the Second Medical Center (Geriatric Department) of the Chinese People's Liberation Army General Hospital with AKI between January 1, 2008, and December 31, 2018. Patients with either dialysis-dependent end-stage kidney failure or incomplete medical history were excluded from the study. Recruited patients were followed up for >90 days after the AKI occurence to determine the clinical outcome of mortality. This study was registered in ChiCTR (http://www.chictr.org.cn/, ChiCTR2200055518) and was approved by the Ethics Committee of Chinese People's Liberation Army General Hospital (No. S2022–342-01). The informed consent of the present study was waived owing to the retrospective nature. The SCr diagnostic criteria defined in the KDIGO AKI guidelines were adopted to recruit patients; the criteria were as follows: (1) increase in SCr >26.5 μmol/L within 48 h or (2) increase in SCr exceeding 1.5-fold above the baseline value within 7 days. The severity of AKI was classified by the KDIGO staging criteria using the SCr criteria alone or a combination of SCr or UO criteria. AKI was staged into three stages for severity. Categorical variables were presented as as a percentage (%) and were compared using the chi-squared test. The Kaplan-Meier method and log-rank test were used to compare the overall survival rates among patients with different stages of AKI based on different classification criteria. Data were obtained from hospital electronic health records. Age, comorbidities, and accompanying conditions (such as mechanical ventilation, proteinuria) at AKI onset were included in univariable logistic regression analysis. Variables with P < 0.05 in the univariable regression analysis were included in the multivariable binary logistic regression equation as covariates to estimate odds ratios (ORs) of AKI stages for mortality. Statistical analyses were performed using SPSS version 22.0, for Windows (SPSS Inc., Chicago, IL, USA). A total of 1509 eligible patients who experienced AKI were included in the final cohort. Based on SCr criteria alone, patients were categorized as follows: stage 1 AKI (n = 1314; 87.1%), stage 2 AKI (n = 151; 10.0%), and stage 3 AKI (n = 44; 2.9%). According to the KDIGO criteria, the distribution of AKI was as follows: stage 1, 1023 (67.8%); stage 2, 290 (19.2%); and stage 3, 196 (13.0%). Overall, 556 patients (36.8%) died within 90 days. Compared with survival group, non-survival group had higher proportion of severe AKI (stage 3), either defined by the SCr criteria alone or the KDIGO criteria (SCr criteria: 4.1% [23/556] vs. 2.2% [21/953], P < 0001; KDIGO criteria: 27.2% [151/556] vs. 4.7% [45/953], P < 0001). The 90-day survival rate decreased from 65.7% (863/1314) in those with stage 1 to 45.7% (69/151) and 47.7% (21/44) for those with stages 2 and 3 AKI, respectively, based on SCr criteria. Kaplan-Meier curves for 90-day cumulative survival showed a significantly lower survival rate in stage 2 or stage 3 compared to stage 1 when categorized by SCr criteria alone (stage 2 vs. stage 1, hazard ratio [HR] = 1.92, 95% CI [1.42–2.58], P < 0.001; stage 3 vs. stage 1, HR = 1.72, 95% CI [1.02–2.90], P = 0.009) [Figure 1A]. However, there was no significant difference between stage 2 and stage 3 (stage 2 vs. stage 3, HR = 0.90, 95% CI [0.50–1.62], P = 0.659). In comparison, 90-day cumulative survival rate decreased gradually with the severity of AKI based on the combination criteria (stage 2 vs. stage 1, HR=2.05, 95% CI [1.64–2.54], P < 0.001; stage 3 vs. stage 1, HR = 5.08, 95% CI [3.74–6.91], P < 0.001; stage 3 vs. stage 2, HR = 2.49, 95% CI [1.75–3.53], P < 0.001) [Figure 1B]. The 90-day cumulative survival rate decreased from 73.6% (753/1023) in those with stage 1 AKI to 53.64% (155/290) and 23.0% (45/196) in those with stages 2 and 3 AKI, respectively, based on the combination criteria.Figure 1: Associations between AKI stages and 90-day cumulative survival. (A) Kaplan-Meier survival curves for 90-day cumulative survival of older AKI patients based on SCr criteria only. (B) Kaplan-Meier survival curves for 90-day cumulative survival of older AKI patients based on the combination of SCr and UO. AKI: Acute kidney injury; CI: Confidence interval; KDIGO: Kidney Disease: Improving Global Outcomes; SCr: Serum creatinine; UO: Urine output.Logistic regression analysis was performed to further evaluate the ORs of AKI stages for mortality. Age, baseline estimated glomerular filtration rate, hypertension, hyperlipidemia, myocardial infarction, atrial fibrillation, chronic heart failure, chronic obstructive pulmonary disease, tumor, anemia, mechanical ventilation, and proteinuria were significant in the univariable logistic regression analysis and included in the multivariable binary logistic regression equation as covariates. According to the multivariable binary logistic regression, the mortality risk of patients with stage 3 AKI and stage 1 when defined by the SCr criteria alone was not statistically significant in the adjusted model (adjusted OR = 1.65, 95% CI [0.80–3.41], P = 0.179), while the adjusted mortality risk in patients with stage 3 AKI were significantky greater compared with those with stage 1 AKI when defined by the combination criteria (adjusted OR = 7.03, 95% CI [4.72–10.49], P < 0.001) [Supplementary Table 1, https://links.lww.com/CM9/B438]. Large studies have shown that even small increases in SCr levels are independently associated with increased mortality. Compared to patients without AKI, the odds of mortality were progressively higher for patients at higher AKI stages based on SCr alone.[3] However, in this study, older patients with stage 3 AKI defined by SCr alone did not exhibit worse survival than those with stage 2 AKI. In older individuals, SCr is not considered an ideal biomarker for AKI stage. Our findings support this claim and further indicate the limited usefulness of SCr for classification and prognosis prediction. The rise in SCr is often blunted in elder population due to reduced muscle mass.[4] Older patients with AKI may have a higher incidence of pre-renal, nephrotoxic, and obstructive issues.[5] Moreover, older patients are more prone to decreased renal perfusion due to heart failure, dehydration, or depletion of effective circulating volume. These risk factors can directly result in oliguria rather than increase SCr. The addition of UO criteria to SCr criteria leads to an earlier recognition of AKI in elderly patients. In this study, AKI stages based on the combination of UO and SCr criteria have a better discriminative ability of mortality than that based on SCr alone. These findings confirm the absolute necessity to diagnose and stage AKI using criteria combined with SCr and UO. This study has a few limitations. First, this was a single-center retrospective study, and so the results may not be generalizable to older patients with AKI in other locations. Second, our analysis is based on a male veteran cohort, which also limits the generalizability of our findings. Studies in older women with AKI may yield different results. Finally, the outcomes of AKI could be confounded by different causes, which were not individually discussed. In conclusion, survival outcomes did not significantly worsen with more advanced AKI stage when defined by SCr alone in older male patients. With the addition of UO to the SCr criteria, mortality increased gradually with severity of AKI across all stages. It is necessity to diagnose and stage AKI using criteria combined with SCr and UO in older male AKI patients. Funding This work was supported by a grant from the Special Scientific Research Project of Military Health Care (No. 21BJZ17) Conflicts of interest None.