Recovery Of Kidney Function Research Articles

Effect on Kidney Function Recovery Guiding Decongestion with VExUS in Patients with Cardiorenal Syndrome 1: A Randomized Control Trial

Plain Language SummaryDuring cardiorenal syndrome type 1 (CRS1), congestion is a major contributor to worsening renal function, but promoting decongestion with routine clinical evaluation is ineffective in some patients. The venous evaluation by ultrasound (VExUS) may optimize its management when evaluating for improvement in kidney function and other metrics related to decongestion. In this randomized clinical trial conducted in patients with CRS1, guiding decongestion with VExUS compared to the usual evaluation did not improve kidney function recovery, but decongestion was achieved more effectively.

Clinical approval of intra-peritoneal instilation of recombinant human granulocyte colony-stimulating factor for the treatment of acute peritonitis

To conduct a preliminary evaluation of the clinical use of recombinant human granulocyte colony-stimulating factor (G-CSF) for the treatment of acute peritonitis (AP).Material and methods. 20 patients. The causes of AP were perforated gastroduodenal ulcers – 7, colon perforation – 7, acute appendicitis – 3, small bowel perforation – 2, one case each of mesenteric thrombosis and uterine perforation. Diffuse AP was detected in 4 (20%) patients, generalized – in 16 (80%). The 1st, control, group and the 2nd, experimental groupб included 10 patients each. Similar basic treatment was used in both groups. Patients of the 2nd group at the end of the operation were injected intraperitoneally with a solution of G-CSF with 0.9% NaCl (5 μg/1 ml) at a dose of 10 μg per 1 kg of body weight. After the operation, the amount of glucose (AG), creatinine (AC) in blood plasma, prothrombin index (PI), nuclear index (NI), stress index (SI), leukocyte intoxication index (LII), neutrophil-lymphocyte index (NLI), neutrophil-mononuclear index (NMI), lymphocyte-monocyte index (LMI), immunological reactivity index (IRI).The results. NI in the 2nd group increased after a day (p<0.01), then prevailed almost all the time. SI after a day in both groups was almost not different. On the 3rd day, the SI in the 1st group significantly increased, and in the 2nd group, it decreased. Later there were opposite changes. After a day, LII decreased in both groups. After 3 days, LII decreased in the 1st group (p<0.05). In the 2nd group, after 3 days, LII increased significantly (p<0.01) and decreased after 7 days. NLI indicators changed similarly. In the 1st group, NMI significantly (p<0.05) decreased after 3 days and remained low. NMI significantly prevailed in the 2nd group, increased (p<0.01) after 5 days. In the 1st group, LMI decreased all the time. In the 2nd group, LMI increased (p<0.01) after 2 days, decreased after 3 days, and increased (p<0.05) after 5 days. IRI in the 1st group, after it increased for 3-5 days, then decreased. In the 2nd group, IRI changed like LMI. AG in the 1st group prevailed all the time. In the 1st group, AC increased for 5 days, in the 2nd group - it constantly decreased. PI in the 1st group decreased for 5 days, in the 2nd group it normalized after 3 days, then increased.Conclusions. 1. According to the complex of integral evaluation criteria, in patients with AP who underwent intraperitoneal instillation of G-CSF solution, signs of adequate functioning of cellular components of immune protection were found after the operation. 2. According to the complex of biochemical criteria, signs of an early reduction in the manifestations of intoxication and recovery of kidney and liver function were found in such patients. 3. The results of clinical approbation indicate the possibility and perspective of using this method of treatment for patients with AP.

Renal safety and survival among acutely ill hospitalized patients treated by blockers of the Renin-Angiotensin axis or loop diuretics: a single-center retrospective analysis

Background Concern exists regarding the renal safety of blocking the renin-angiotensin system (RAS) during acute illness, especially in the presence of volume depletion and hemodynamic instability. Methods We explored the impact of loop diuretics and RAS blockers on the likelihood of developing acute kidney injury (AKI) or acute kidney functional recovery (AKR) among inpatients. Adjusted odds ratio for AKI, AKR and mortality was calculated, using logistic regression models, with subgroup analysis for patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, corrected for blood pressure measurements. Results 53,289 patients were included. RAS blockade was associated with reduced adjusted odds ratio for both AKI (0.76, CI 0.70–0.83) AKR (0.55, 0.52–0.58), and mortality within 30 days (0.44, 0.41–0.48), whereas loop diuretics were associated with increased risk of AKI (3.75, 3.42–4.12) and mortality (1.71, 1.58–1.85) and reduced AKR (0.71, 0.66–0.75). Comparable impact of RAS blockers and loop diuretics on renal outcomes and death was found among 6,069 patients with eGFR < 30 ml/min/1.73m2. RAS inhibition and diuretics tended to increase the adjusted odds ratios for AKI and to reduce the likelihood of AKR in hypotensive patients. Conclusions Reduced blood pressure, RAS blockers and diuretics affect the odds of developing AKI or AKR among inpatients, suggesting possible disruption in renal functional reserve (RFR). As long as blood pressure is maintained, RAS inhibition seems to be safe and renoprotective in this population, irrespective of kidney function upon admission, and is associated with reduced mortality.

Successful Liberation from Acute Kidney Replacement Therapy in Critically Ill Patients: A Prospective Cohort Study

Introduction: Recovery of kidney function to liberate patients from acute kidney replacement therapy (AKRT) is recognized as a vital patient-centered outcome. The lack of specific guidelines providing specific recommendations on therapy interruption is an important obstacle. We aimed to determine the prevalence of successful discontinuation of AKRT and its predictive factors after the elaboration of clinical protocol with these recommendations. Methodology: A prospective cohort study was performed with 156 patients at a public Brazilian university hospital between July 2020 and July 2021. Results: Success and hospital discharge were achieved for most patients (84.6% and 89%, respectively). Multivariable logistic regression analysis showed that C-reactive protein (CRP), urine output, and creatinine clearance at the time of interruption were variables associated with discontinuation success (OR: 0.943, CI: 0.905–0.983, p = 0.006; OR: 1.078, CI: 1.008–1.173, p = 0.009 and OR: 1.091, CI: 1.012–1.213, p = 0.004; respectively). The areas under the curve for CRP, urine output, and creatinine clearance at the time of interruption were 0.78, 0.62, and 0.82, respectively. Both CRP and creatinine clearance were good predictors of successful liberation of AKRT. The optimal cutoff value of them had sensitivity and specificity of 0.88 and 0.87, 0.91 and 0.90, respectively. The use of noradrenalin at the time of interruption (OR: 0.143, CI: 0.047–0.441, p = 0.001) and successful discontinuation (OR: 3.745, CI: 1.047–13.393, p = 0.042) were identified as variables associated with hospital discharge. Conclusion: Our results show the factors related to success in discontinuing AKRT are the CRP, creatinine clearances, and urinary output at the time of AKRT interruption and it was associated with lower mortality.

Axillary mechanical circulatory support improves renal function prior to heart transplantation in patients with chronic kidney disease

Impaired kidney function is often associated with acute decompensation of chronic heart failure and portends a poor prognosis. Unfortunately, current data have demonstrated worse survival in patients with acute kidney injury than in patients with chronic kidney disease during durable LVAD placement as bridge therapy. Furthermore, end-stage heart failure patients undergoing combined heart-kidney transplantation have poorer short- and long-term survival than heart transplants alone. We evaluated the kidney function recovery in our heart failure population awaiting heart transplantation at our institution, supported by temporary Mechanical Circulatory Support (tMCS) with Impella 5.5. The protocol (#22004000) was approved by the Mayo Clinic institutional review board, after which we performed a retrospective review of all patients with acute on chronic heart failure and kidney disease in patients considered for only heart and kidney combined organ transplant and supported by tMCS between January 2020 and February 2021. Hemodynamic and kidney function trends were recorded and analyzed before and after tMCS placement and transplantation. After placement of tMCS, we observed a trend towards improvement in creatinine, Fick cardiac index, mixed venous saturation, and glomerular filtration rate (GFR), which persisted through transplantation and discharge. The average duration of support with tMCS was 16.5 days before organ transplantation. The median pre-tMCS creatinine was 2.1 mg/dL (IQR 1.75–2.3). Median hematocrit at the time of tMCS placement was 32% (IQR 32–34), and the median estimated glomerular filtration rate was 34 mL/min/BSA (34–40). The median GFR improved to 44 mL/min/BSA (IQR 45–51), and serum creatinine improved to 1.5 mg/dL (1.5–1.8) after tMCS. Median discharge creatinine was 1.1 mg/dL (1.19–1.25) with a GFR of 72 (65–74). None of these six patients supported with tMCS required renal replacement therapy after heart transplantation. Early adoption of Impella 5.5 in this patient population resulted in renal recovery without needing renal replacement therapies or dual organ transplantation and should be further evaluated.

The Use of Anti-Adrenergic Agents as a Predictor of AKI and Delayed Recovery of Kidney Function: The NARA-AKI Cohort Study

The Use of Anti-Adrenergic Agents as a Predictor of AKI and Delayed Recovery of Kidney Function: The NARA-AKI Cohort Study

The Effect of Fingolimod on Renal Ischemia/Reperfusion Injury in a Rat Model.

Ischemia/reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) that induces inflammation and oxidative stress. The main goal of the current study was to assess the impact of fingolimod on kidney IRI in rats. For this purpose, 18 male Wistar rats (220-250g) were divided into three groups including (i) Sham, (ii) I/R, and (iii) fingolimod+I/R. The last group was pretreated with a single dose of fingolimod (1mg/kg) (intraperitoneal injection) before induction of the I/R injury. Kidney function, oxidative stress marker (malondialdehyde), and antioxidant markers (catalase, superoxide dismutase, glutathione, glutathione peroxidase, and total antioxidant capacity) were determined in the kidney tissue of the rats. Moreover, kidney samples were taken for histological analysis. Fingolimod pre-treatment could significantly improve the glutathione peroxidase (p<0.01) and glutathione (p<0.001) activities along with the total antioxidant capacity levels (p<0.001) when compared to the I/R group. Moreover, significant recovery of kidney function and histology was seen in the fingolimod+ I/R group compared to the I/R group (p<0.01). Fingolimod pretreatment could improve renal function, antioxidant capacity, and histological alterations after I/R injury. Hence, it might protect the kidney against IRI-related kidney damage including AKI and transplantation.

Plasma Cystatin C Predicts Kidney Function Recovery in Patients Requiring Continuous Kidney Replacement Therapy (CKRT) for AKI

Plasma Cystatin C Predicts Kidney Function Recovery in Patients Requiring Continuous Kidney Replacement Therapy (CKRT) for AKI

Quercetin-targeted AKT1 regulates the Raf/MEK/ERK signaling pathway to protect against doxorubicin-induced nephropathy in mice

BackgroundDoxorubicin is an anthracycline antitumor agent commonly used in clinical practice, which has some nephrotoxicity and is often used to establish mouse models of kidney injury for basic medical research. This study will investigate the protective effect of quercetin on renal function in doxorubicin-induced nephropathy mice. MethodsC57BL/6 mice were divided into control, model, and quercetin low-, and high-dose groups. Serum and urine were collected to analyze markers of kidney function. H&E staining was used to detect pathological changes in renal tissues. Transmission electron microscopy was performed to observe the ultrastructural changes in renal tissues. Immunohistochemistry was performed to detect the changes of Ang II. RT-qPCR was performed to detect the changes of cytokines. ELISA was used to detect changes in serum inflammatory factors. Molecular docking was performed to verify the targeting relationship between quercetin and AKT1. Western blot was performed to detect Bax, Bcl-2, Cyt-c, AKT1, Raf, MEK, and ERK proteins. ResultsQuercetin could induce the recovery of kidney function in kidney-injured mice; H&E results showed that kidney tissue damage and tissue fibrosis were reduced in kidney-injured mice under quercetin. The mitochondrial swollen structure was destroyed by doxorubicin, while the mitochondrial structure was restored under quercetin. The levels of abnormal apoptotic proteins Bax and Bcl-2 were regulated to normal by quercetin. The high expression of Ang II caused by doxorubicin was down-regulated by quercetin. Abnormal inflammatory factors caused by doxorubicin were reversed by quercetin. Western blot experiments showed that quercetin regulated the protein levels of AKT1 and Raf/MEK/ERK and inhibited the detrimental effects of doxorubicin. ConclusionQuercetin may mitigate doxorubicin-induced kidney injury in mice by regulating renal cell inflammatory factors and Raf/MEK/ERK signaling pathway through AKT1 to promote recovery of renal function.

Pickering Syndrome: An Overlooked Renovascular Cause of Recurrent Heart Failure.

ABSTRACTRecurring and rapidly developing (flash) pulmonary edema is the hallmark of Pickering syndrome, affecting patients with hypertension and atherosclerotic renal artery stenosis (either bilateral or unilateral) in a solitary functioning kidney, and impaired renal function. We herein report on a series of consecutive patients with recurrent hospital admissions for pulmonary edema, impaired renal function (chronic kidney disease class 4-5), and atherosclerotic bilateral renal artery stenosis, in whom Pickering syndrome had been long neglected. We also describe a streamlined diagnostic strategy entailing little or no need for contrast medium, thus carrying no risks of further worsening of renal function. This allowed us to make the correct diagnosis and opened the way to revascularization by percutaneous transluminal renal angioplasty with stent, which provided swift recovery of kidney function with resolution of pulmonary congestion and long-term pulmonary edema- and dialysis-free survival in all cases. In summary, these findings support the following key messages: (1) considering the diagnosis of Pickering syndrome, followed by searching atherosclerotic renal artery stenosis, is an essential step toward a life-saving revascularization that avoids dialysis and an otherwise poor outcome; and (2) a simplified strategy entailing little or no need for contrast medium, carrying no associated risks of deteriorating renal function, permits the diagnosis of Pickering syndrome.

Probiotics in septic acute kidney injury, a double blind, randomized control trial

Introduction During acute kidney injury (AKI) due to sepsis, the intestinal microbiota changes to dysbiosis, which affects the kidney function recovery (KFR) and amplifies the injury. Therefore, the administration of probiotics could improve dysbiosis and thereby increase the probability of KFR. Methods In this double-blind clinical trial, patients with AKI associated with sepsis were randomized (1:1) to receive probiotics or placebo for 7 consecutive days, with the objectives of evaluate the effect on KFR, mortality, kidney replacement therapy (KRT), urea, urine volume, serum electrolytes and adverse events at day 7. Results From February 2019 to March 2022, a total of 92 patients were randomized, 48 to the Probiotic and 44 to Placebo group. When comparing with placebo, those in the Probiotics did not observe a higher KFR (HR 0.93, 0.52–1.68, p = 0.81), nor was there a benefit in mortality at 6 months (95% CI 0.32–1.04, p = 0.06). With probiotics, urea values decreased significantly, an event not observed with placebo (from 154 to 80 mg/dl, p = 0.04 and from 130 to 109 mg/dl, p = 0.09, respectively). Urinary volume, need for KRT, electrolyte abnormalities, and adverse events were similar between groups. (ClinicalTrial.gov NCT03877081) (registered 03/15/2019). Conclusion In AKI related to sepsis, probiotics for 7 consecutive days did not increase the probability of KFR, nor did other variables related to clinical improvement, although they were safe.

Extracorporeal light-chain elimination in myeloma with simple medium cutoff membrane hemodialysis: a retrospective cohort study.

We determined the efficacy of free light chain (FLC) removal by regular dialysis equipment (high-flux filtration) with medium cutoff (MCO) membrane hemodialysis (HD) as an adjuvant treatment to standard chemotherapy for patients with acute kidney injury complicating multiple myeloma (MM) and its impact on further dialysis dependency. Sixty patients with acute dialysis-dependent renal failure secondary to MM were treated with MCO-HD (55 patients) or HCO (high cutoff)-HD (5 patients) as a control. FLC serum concentration, total protein, immunoglobulins, and LDH were measured throughout the dialysis therapy. The kidney function of the patients was followed up for 1 year. The median age was 69 years; 25 female and 35 male patients were enrolled. HD significantly reduced FLC kappa levels in the MCO/HCO group by 58%/84% (MCO/HCO group; p < 0.05) and FLC lambda by 39%/33% (MCO/HCO group; p < 0.05). Single HD data (MCO) showed a relative reduction of 70% in kappa and 37% in lambda FLC concentration, as expected by the different sizes of the light chains. Renal function improved significantly and continuously from starting creatinine 5.7/3.8 mg/dl (MCO/HCO group) before HD to 1.4/2.0 mg/dl (MCO/HCO group; p < 0.001) after 1 year. No significant alteration of total protein, immunoglobulins, and LDH concentrations by HD (HCO and MCO group) was observed. After 1 year, 37 of 60 patients were alive and 34 of them were off dialysis. FLC elimination with MCO-HD is effective, technically easy, and less cost-intensive as compared with HCO-HD. Kidney function recovery in MM patients is achievable.

Outcomes Associated with Sodium-Glucose Cotransporter-2 Inhibitor Use in Acute Heart Failure Hospitalizations Complicated by AKI.

While sodium-glucose cotransporter-2 inhibitor (SGLT2i) use during acute heart failure (AHF) hospitalizations is associated with symptomatic improvement, reduction in re-hospitalizations, and mortality, these medications are often withheld during acute kidney injury (AKI) due to concerns about worsening glomerular filtration rate.We aimed to investigate the safety of SGLT2i exposure during AKI among patients hospitalized with AHF. We hypothesized that SGLT2i exposure would not worsen mortality but may prolong return of creatinine to baseline. This is a retrospective study of adults hospitalized across 5 Yale New Haven Health System hospitals between January 2020 and May 2022 with AHF complicated by KDIGO-defined AKI. Patients with stage 5 chronic kidney disease and those with potential contraindications to SGLT2i were excluded. We tested the association of SGLT2i use with kidney function recovery at 14 days and death at 30 days using time-varying, multivariable Cox-regression analyses. Of 3305 individuals hospitalized with AHF and AKI, 356 received SGLT2i following AKI diagnosis either as initiation or continuation. The rate of renal recovery was not significantly different among those exposed and unexposed to SGLT2i following AKI (adjusted HR 0.94, 95% CI 0.79-1.11, p=0.46). SGLT2i exposure was associated with lower risk of 30-day mortality (adjusted HR 0.45, 95% CI 0.23-0.87, p=0.02). Sensitivity analyses using an inverse probability weighted time-varying Cox regression analysis and using alternate definitions of AHF with different NT-proBNP cutoffs yielded similar results. Rates of renal recovery were similar between the exposed and unexposed cohorts regardless of the proximity of SGLT2i exposure to AKI diagnosis. In adults experiencing AHF-associated AKI, exposure to SGLT2i was associated with decreased mortality and no delay in renal recovery. Prospective studies are needed to elucidate the impact of SGLT2i exposure during AKI, particularly during heart failure hospitalizations.

A comprehensive description of kidney disease progression after acute kidney injury from a prospective, parallel-group cohort study

Acute kidney injury (AKI) is associated with adverse long-term outcomes, but many studies are retrospective, focused on specific patient groups or lack adequate comparators. The ARID (AKI Risk in Derby) Study was a five-year prospective parallel-group cohort study to examine this. Hospitalized cohorts with and without exposure to AKI were matched 1:1 for age, baseline kidney function, and diabetes. Estimated glomerular filtration rate (eGFR) and the urinary albumin:creatinine ratio (uACR) were measured at three-months, one-, three- and five-years. Outcomes included kidney disease progression, heart failure episodes and mortality. In 866 matched individuals, kidney disease progression at five years was found to be significantly increased in 30% of the exposed group versus 7% of those non-exposed (adjusted odds ratio 2.49 [95% confidence interval 1.43 to 4.36]). In the AKI group, this was largely characterized by incomplete recovery of kidney function by three months. Further episodes of AKI during follow-up were significantly more common in the exposed group (odds ratio 2.71 [1.94 to 3.77]) and had an additive effect on risk of kidney disease progression. Mortality and heart failure episodes were more frequent in the exposed group, but the association with AKI was no longer significant when models were adjusted for three-month eGFR and uACR. In a general hospitalized population, kidney disease progression after five years was common and strongly associated with AKI. Thus, the time course of changes and the attenuation of associations with adverse outcomes after adjustment for three-month eGFR and uACR suggest non-recovery of kidney function is an important assessment in post-AKI care and a potential future target for intervention. STUDY REGISTRATION: ISRCTN25405995.

Recovery of kidney function after acute kidney disease-a multi-cohort analysis.

There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. We identified incident AKD defined by serum creatinine changes within 48h, 7days and 90days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. There were 464868 incident cases, median age 67-75years. At 1year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48h, 7days, 90days and 365days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90days was frequently not sustained at 1year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90days) is at least prognostically similar to KDIGO AKI (7days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.

A 71-year-old male with a life-threatening recurrence of hemolytic anemia, thrombocytopenia, and acute kidney injury after pembrolizumab therapy: a case report

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, their use has been restricted in patients with preexisting autoimmune diseases due to concerns about increased risk of immune-related adverse events (irAEs).Case presentationWe present a case of a patient with stage IV lung adenocarcinoma and a history of complement-mediated autoimmune hemolytic anemia in remission. After receiving a single dose of pembrolizumab, the patient experienced life-threatening recurrent hemolytic anemia, de novo thrombocytopenia, diarrhea, myocarditis, and acute kidney injury. Laboratory tests confirmed the diagnosis of Evan's syndrome, with positive PAIgG and direct antiglobulin test. Treatment with intravenous methylprednisolone at a dose of 2 mg/kg resulted in a favorable response, with resolution of symptoms and rapid recovery of kidney function. The probable cause of pre-renal hypoperfusion (evidenced by a BUN-to-creatinine ratio of 48.1) leading to acute tubular injury was attributed to pembrolizumab-induced diarrhea.ConclusionsThis case illustrates a life-threatening recurrence of complement-mediated autoimmune hemolytic anemia induced by ICIs. Clinicians should carefully consider the expected efficacy and potential toxicity before initiating ICIs therapy in patients with preexisting autoimmune diseases. Additionally, the occurrence of acute kidney injury during ICIs therapy adds complexity and requires careful differential diagnosis.

Renin-Angiotensin-Aldosterone System Blockade after AKI with or without Recovery among US Veterans with Diabetic Kidney Disease.

Among patients with CKD, optimal use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers after AKI is uncertain. Despite these medications' ability to reduce risk of mortality and other adverse outcomes, there is concern that ACEi/ARB use may delay recovery of kidney function or precipitate recurrent AKI. Prior studies have provided conflicting data regarding the optimal timing of these medications after AKI and have not addressed the role of kidney recovery in determining appropriate timing. This study in US Veterans with diabetes mellitus and proteinuria demonstrated an association between ACEi/ARB use and lower mortality. This association was more pronounced with earlier post-AKI ACEi/ARB use and was not meaningfully affected by initiating ACEis/ARBs before versus after recovery from AKI. Optimal use of angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) after AKI is uncertain. Using data derived from electronic medical records, we sought to estimate the association between ACEi/ARB use after AKI and mortality in US military Veterans with indications for such treatment (diabetes and proteinuria) while accounting for AKI recovery. We used ACEi/ARB treatment after hospitalization with AKI (defined as serum creatinine ≥50% above baseline concentration) as a time-varying exposure in Cox models. The outcome was all-cause mortality. Recovery was defined as return to ≤110% of baseline creatinine. A secondary analysis focused on ACEi/ARB use relative to AKI recovery (before versus after). Among 54,735 Veterans with AKI, 31,146 deaths occurred over a median follow-up period of 2.3 years. Approximately 57% received an ACEi/ARB <3 months after hospitalization. In multivariate analysis with time-varying recovery, post-AKI ACEi/ARB use was associated with lower risk of mortality (adjusted hazard ratio [aHR], 0.74; 95% confidence interval [CI], 0.72 to 0.77). The association between ACEi/ARB use and mortality varied over time, with lower mortality risk associated with earlier initiation ( P for interaction with time <0.001). In secondary analysis, compared with those with neither recovery nor ACEi/ARB use, risk of mortality was lower in those with recovery without ACEi/ARB use (aHR, 0.90; 95% CI, 0.87 to 0.94), those without recovery with ACEi/ARB use (aHR, 0.69; 95% CI, 0.66 to 0.72), and those with ACEi/ARB use after recovery (aHR, 0.70; 95% CI, 0.67 to 0.73). This study demonstrated lower mortality associated with ACEi/ARB use in Veterans with diabetes, proteinuria, and AKI, regardless of recovery. Results favored earlier ACEi/ARB initiation.

Evaluation of Proenkephalin A 119–159 for liberation from renal replacement therapy: an external, multicenter pilot study in critically ill patients with acute kidney injury

IntroductionRecent evidence suggests an association of plasma Proenkephalin A 119–159 (penKid) with early and successful liberation from continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury. However, these exploratory results are derived from a monocentric trial and therefore require external validation in a multicenter cohort.MethodsData and plasma samples from the “Effect of Regional Citrate Anticoagulation versus Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury—A Randomized Clinical Trial” (RICH Trial) were used for this validation study. PenKid was measured in all plasma samples available at CRRT initiation and at day 3 of CRRT. Patients were categorized into low and high penKid groups with a cutoff at 100 pmol/l. Competing-risk time-to-event analyses were performed. Competing risk endpoints were successful and unsuccessful liberation from CRRT, the latter meaning death or initiation of a new RRT within one week of discontinuation of primary CRRT. Then penKid was compared to urinary output.ResultsLow pre-CRRT penKid levels at CRRT initiation were not associated with early and successful liberation from CRRT compared to patients with high pre-CRRT penKid levels [subdistribution hazard ratio (sHR) 1.01, 95% CI 0.73–1.40, p = 0.945]. However, the landmark analysis on day 3 of ongoing CRRT demonstrated an association between low penKid levels and successful liberation from CRRT (sHR 2.35, 95% CI 1.45–3.81, p < 0.001) and an association between high penKid levels and unsuccessful liberation (sHR 0.46, 95% CI 0.26–0.80, p = 0.007). High daily urinary output (> 436 ml/d) was even stronger associated with successful liberation (sHR 2.91, 95% CI 1.80–4.73, p < 0.001) compared to penKid.DiscussionThis study suggests that penKid may be a competent biomarker to monitor the recovery of kidney function during CRRT. This is in line with previous findings and investigated this concept in a multicenter cohort. Again, low penKid was associated with early and successful CRRT liberation, but was outperformed by high daily urinary output. The findings of this study now warrant further evaluation in prospective studies or a randomized controlled trial.Trial registration The RICH Trial was registered at clinicaltrials.gov: NCT02669589. Registered 01 February 2016.

Kidney Injury in Critically Ill Patients with COVID-19 - From Pathophysiological Mechanisms to a Personalized Therapeutic Model.

Acute kidney injury is a common complication of COVID-19, frequently fuelled by a complex interplay of factors. These include tubular injury and three primary drivers of cardiocirculatory instability: heart-lung interaction abnormalities, myocardial damage, and disturbances in fluid balance. Further complicating this dynamic, renal vulnerability to a "second-hit" injury, like a SARS-CoV-2 infection, is heightened by advanced age, chronic kidney disease, cardiovascular diseases, and diabetes mellitus. Moreover, the influence of chronic treatment protocols, which may constrain the compensatory intrarenal hemodynamic mechanisms, warrants equal consideration. COVID-19-associated acute kidney injury not only escalates mortality rates but also significantly affects long-term kidney function recovery, particularly in severe instances. Thus, the imperative lies in developing and applying therapeutic strategies capable of warding off acute kidney injury and decelerating the transition into chronic kidney disease after an acute event. This narrative review aims to proffer a flexible diagnostic and therapeutic strategy that recognizes the multi-faceted nature of COVID-19-associated acute kidney injury in critically ill patients and underlines the crucial role of a tailored, overarching hemodynamic and respiratory framework in managing this complex clinical condition.

The use of anti-adrenergic agents as a predictor of acute kidney injury and delayed recovery of kidney function: the NARA-AKI cohort study.

Association of preoperative regular use of anti-adrenergic agents with postoperative acute kidney injury (AKI) and with trajectory of kidney function after AKI is still unknown. In a retrospective cohort study, adults undergoing non-cardiac surgery under general anesthesia were included. Obstetric or urological surgery, missing data, or preoperative dialysis was excluded. The exposure of interest was preoperative regular use of anti-adrenergic agents. The outcomes were AKI within 1 week postoperatively and trajectories of kidney function within 2 weeks postoperatively among patients with AKI. Multivariable logistic regression models were used to examine the association of anti-adrenergic agents with AKI. Linear mixed-effects models were used to compare the trajectories of postoperative kidney function after AKI between patients with and without anti-adrenergic agents. Among 5168 patients, 245 had used anti-adrenergic agents. A total of 309 (6.0%) developed AKI, and the use of anti-adrenergic agents was independently associated with postoperative AKI even after adjustment for preoperative and intraoperative potential confounders [odds ratio (95% confidence interval): 1.76 (1.14-2.71)]. The association was similar across preexisting hypertension or cardiovascular disease. Analyses restricted to patients with AKI suggested that the timing and stage of AKI were similar among those with and without anti-adrenergic agents; however, the recovery of kidney function was delayed among those with anti-adrenergic agents (P for interaction = 0.004). The use of anti-adrenergic agents was associated with postoperative AKI and delayed recovery of kidney function after AKI. Temporary withdrawal of anti-adrenergic agents during perioperative periods may contribute to prevent AKI and shorten the duration of AKI.