Need For Requiring Renal Replacement Therapy Research Articles

Decreased need for RRT in liver transplant recipients after pretransplant treatment of hepatorenal syndrome-type 1 with terlipressin.

Hepatorenal syndrome-acute kidney injury (HRS-AKI), a serious complication of decompensated cirrhosis, has limited therapeutic options and significant morbidity and mortality. Terlipressin improves renal function in some patients with HRS-1, while liver transplantation (LT) is a curative treatment for advanced chronic liver disease. Renal failure post-LT requiring renal replacement therapy (RRT) is a major risk factor for graft and patient survival. A post hoc analysis with a 12-month follow-up of LT recipients from a placebo-controlled trial of terlipressin (CONFIRM; NCT02770716) was conducted to evaluate the need for RRT and overall survival. Patients with HRS-1 were treated with terlipressin plus albumin or placebo plus albumin for up to 14 days. RRT was defined as any type of procedure that replaced kidney function. Outcomes compared between groups included the incidence of HRS-1 reversal, the need for RRT (pretransplant and posttransplant), and overall survival. Of the 300 patients in CONFIRM (terlipressin n = 199; placebo, n = 101), 70 (23%) underwent LT alone (terlipressin, n = 43; placebo, n = 27) and 5 had simultaneous liver-kidney transplant (terlipressin, n = 3, placebo, n = 2). The rate of HRS reversal was significantly higher in the terlipressin group compared with the placebo group (37%, n = 16 vs. 15%, n = 4; p = 0.033). The pretransplant need for RRT was significantly lower among those who received terlipressin ( p = 0.007). The posttransplant need for RRT, at 12 months, was significantly lower among those patients who received terlipressin and were alive at Day 365, compared to placebo ( p = 0.009). Pretransplant treatment with terlipressin plus albumin in patients with HRS-1 decreased the need for RRT pretransplant and posttransplant.

S1173 Terlipressin Treatment of Patients With Hepatorenal Syndrome Type 1 Decreased the Need for Renal Replacement Therapy in Transplant Recipients: A 12-Month Follow-Up of the CONFIRM Study

Introduction: Hepatorenal syndrome type 1 (HRS) is a rapid-onset renal failure in the setting of end-stage liver disease. While liver transplant (LT) is the definitive treatment, posttransplant renal failure requiring renal replacement therapy (RRT) is common and contributes to low patient survival rates. A randomized, placebo (PBO)-controlled study (CONFIRM; NCT02770716) demonstrated that terlipressin (TERLI) reversed HRS and reduced the need for RRT. This subgroup analysis of LT recipients from CONFIRM assessed whether TERLI treatment reduced the incidence of RRT and improved overall survival (OS) through 12-months posttransplant. Methods: Patients with HRS were treated with TERLI plus albumin (n=199) or PBO plus albumin (n=101) for up to 14 days. RRT was defined as any procedure that replaced nonendocrine kidney function including continuous hemofiltration and hemodialysis, intermittent hemodialysis, peritoneal dialysis, ultrafiltration, or other dialysis and filtration techniques. The incidence of verified HRS reversal (primary endpoint in CONFIRM), HRS reversal, the need for RRT (pretransplant; at Day 180 and Day 365 posttransplant), and OS at 12-months were compared between groups. Verified HRS reversal was defined as the percentage of patients with 2 consecutive qualified serum creatinine (SCr) values of ≤1.5 mg/dL at least 2 hours apart. HRS reversal was defined as the percentage of patients with a SCr value of ≤1.5 mg/dL while receiving treatment by Day 14 or day of discharge. Results: In total, 46 (23%) patients in the TERLI group and 29 (28%) patients in the PBO group received an LT (P=.290). Five of these patients (TERLI n=3; PBO n=2) received a simultaneous liver–kidney transplant. Verified HRS reversal was comparable between the TERLI group (30%, n=14) and the PBO group (17%, n=5; P=.168). HRS reversal was significantly higher in the TERLI group (37%, n=17) vs the PBO group (14%, n=4; P=.021). The pretransplant need for RRT was significantly lower in the TERLI group compared with PBO (P=.007; Figure). The posttransplant need for RRT was significantly lower in the TERLI vs PBO group at Day 180 (P=.017; Figure) and Day 365 (P=.009; Figure). Posttransplant 12-month OS in the TERLI group was 94% (n=43) compared with 83% (n=24) in the PBO group (P=.093). Conclusion: Patients with HRS who received TERLI treatment and an LT had a decreased need for RRT for up to 12-months posttransplant. These findings have implications for morbidity and mortality in patients with advanced cirrhosis.Figure 1.: Incidence of RRT by Treatment Group in Transplant Recipients in the CONFIRM Study, ITT population. Values at the bottom of each bar represent n/N. ITT, intent-to-treat; n, number of patients requiring RRT; N, number of patients who were alive at each timepoint; RRT, renal replacement therapy.

513 Fluid Over-Resuscitation in Burn Patients After Initial 24-Hours of Care is Associated with Increased Mortality

IntroductionFluid resuscitation is a cornerstone of modern burn care. Despite the use of well-established formulae to determine the appropriate amount of fluid resuscitation for the first 24 hours of care, there is increasing recognition that patients receive fluids in excess of predicted volumes, a phenomenon termed fluid creep. Underscoring the significance of this phenomenon is the association between large volumes of fluid resuscitation and adverse outcomes. Although research in non-burn ICU patients reveals a clear association between overall fluid intake and increased morbidity, minimal burn-related literature exists regarding fluid patterns after the initial 24-hour period and their impact on outcomes. We hypothesized that increased fluid administration after the standard initial resuscitation period is associated with increased morbidity and mortality.MethodsA retrospective chart review was performed for 113 patients with ≥20% TBSA burns admitted to an American Burn Association-verified burn center between 2010 and 2020. Patients admitted with Stevens-Johnson Syndrome and/or Toxic Epidermal Necrolysis, with length of stay ≤ 72 hours, who required renal replacement therapy (RRT) within 72 hours of admission, and those with withdrawal of care ≤ 7 days of admission were excluded. Univariate and multivariate logistic regression was used to determine the association between the primary outcome of in-hospital mortality and secondary outcomes of increased ventilator days, acute kidney injury, need for RRT, and hospital length of stay, with increasing total and net fluid volumes from days 2 through 7 of treatment. Additionally, the association between first OR day and total fluid volumes in the first week were assessed.ResultsMedian age was 41 years (IQR 23-55) and TBSA was 31% (IQR 24-43). 21 patients (18.6%) died during hospitalization. Increase in net fluid balance from days 2-7 were associated with increased mortality (OR 1.016, 95% CI 1.00 – 1.03, p = 0.013). Increasing total fluid volumes were significantly associated with increased ventilator days (OR 1.027, 95% CI 1.008-1.047, p = 0.006) and acute kidney injury (OR 1.003, 95% CI 1.000-1.006, p = 0.017). Early first OR day was associated with decreased net fluid balance between hospital days 2-7 (OR 0.993, 95% CI 0.989-0.997, p = 0.001).ConclusionsSimilar to studies on other ICU populations, increasing total fluid volumes and net fluid balance is associated with adverse outcomes in critically ill burn patients. Additionally, earlier initial OR is associated with less total fluid volumes and lower net fluid balance in the first week of hospitalization. Further investigation is needed to elucidate optimal markers of resuscitation in burn patients in an effort to decrease adverse fluid administration.

CALL-K score: predicting the need for renal replacement therapy in cardiogenic shock.

The clinical predictors and outcomes of patients with cardiogenic shock (CS) requiring renal replacement therapy (RRT) have not been studied previously. This study assesses the impact of RRT on mortality in patients with CS and aims to identify clinical factors that contribute to the need of RRT. Consecutive patients presenting with CS were included from a prospective registry of cardiac intensive care unit admissions at a single institution between 2014 and 2020. Of the 1030 patients admitted with CS, 123 (11.9%) received RRT. RRT was associated with higher 1-year mortality [adjusted hazard ratio = 1.62, 95% confidence interval (CI) 1.02-2.14], and a higher in-hospital incidence of sepsis [risk ratio = 2.76, P < 0.001], and pneumonia (risk ratio = 2.9, P = 0.001). Those who received RRT were less likely to receive guideline-directed medical treatment at time of discharge, undergo heart transplantation (2.4% vs. 11.5%, P = 0.002) or receive a durable left ventricular assist device (0.0% vs. 11.6%, P < 0.001). Five variables at admission best predicted the need for RRT (age, lactate, haemoglobin, use of pre-admission loop diuretics, and admission estimated glomerular filtration rate) and were used to generate the CALL-K 9-point risk score, with better discrimination than creatinine alone (P = 0.008). The score was internally validated (area under the curve = 0.815, 95% CI 0.739-0.835) with good calibration (Hosmer-Lemeshow P = 0.827). RRT is associated with worse outcomes, including a lower likelihood to receive advanced heart failure therapies in patients with CS. A risk score comprising five variables routinely collected at admission can accurately estimate the risk of needing RRT.

Early prediction of COVID-19-associated acute kidney injury: Are serum NGAL and serum Cystatin C levels better than serum creatinine?

BackgroundCoronavirus disease-2019 (COVID-19) is associated with a high risk of acute kidney injury (AKI), often requiring renal replacement therapy (RRT). Serum Cystatin C (sCysC) and serum Neutrophil Gelatinase-Associated Lipocalin (sNGAL) are emerging biomarkers for kidney injury, and were suggested to be superior to serum creatinine (sCr) in several clinical settings. Moreover, elevated sCysC is associated with disease severity and mortality in COVID-19. We aimed to assess the utility of sCysC and sNGAL for predicting COVID-19-associated AKI, need for RRT, and need for intensive care unit (ICU) admission, when measured at presentation to the emergency department (ED). MethodsPatients presenting to the ED with laboratory-confirmed COVID-19 were included. The primary outcome was development of COVID-19-associated AKI, while the secondary outcomes were need for RRT and ICU admission. ResultsAmong 52 COVID-19 patients, 22 (42.3%) developed AKI with 8/22 (36.4%) requiring RRT. Both sCr and sCysC demonstrated excellent performance for predicting AKI (AUC, 0.86 and 0.87, respectively) and need for RRT (AUC, 0.94 and 0.95, respectively). sNGAL displayed acceptable performance for predicting AKI (AUC, 0.81) and need for RRT (AUC, 0.87). ConclusionsSCr and sCysC measured at ED presentation are both highly accurate predictors of AKI and need for RRT, whereas sNGAL demonstrated adequate diagnostic performance. While sCyC was previously shown to be superior to sCr as a diagnostic biomarker of kidney injury in certain etiologies, our findings demonstrate that sCr is comparable to sCyC in the context of predicting COVID-19-associated AKI. Given the high sensitivity of these biomarkers for predicting the need for RRT, and as sCysC is associated with mortality in COVID-19 patients, we recommend their measurement for enabling risk stratification and early intervention.

One-Year Survival for Adult Venoarterial Extracorporeal Membrane Oxygenation Patients Requiring Renal-Replacement Therapy

Acute kidney injury (AKI) and chronic kidney disease (CKD) previously have been associated with in-hospital and long-term mortality of patients undergoing support with venoarterial extracorporeal membrane oxygenation (VA-ECMO). Patient selection criteria and survival prediction scores for VA-ECMO often include AKI or CKD, but exclude patients requiring renal replacement therapy (RRT). The need for RRT in ECMO patients is associated with increased intensive unit care and in-hospital mortality. The effect RRT has on mortality beyond hospital survival is not well-reported. The authors hypothesized that the timing of initiation (pre-ECMO v during ECMO) of RRT can have a significant impact on short- and long-term mortality. The authors categorized patients into 3 groups: those receiving RRT before initiation of ECMO, those initiated on RRT while on ECMO, and those who did not need RRT while on ECMO. The authors compared survival to decannulation, 30 days and 1 year between the 3 groups. A multivariate survival analysis also was conducted. This was a single center retrospective review of all patients receiving VA-ECMO. A total of 347 adult VA-ECMO extracorporeal membrane oxygenation patients. None, retrospective. The authors' cohort included 347 total patients, 39 required RRT before ECMO, 139 while on ECMO, and 169 did not require RRT while on ECMO. If RRT was initiated before ECMO, survival to decannulation was 48.72%, 46.6% if RRT was initiated on ECMO, and 73.96% for patients who did not need RRT while on ECMO. One-year survival was 25.64%, 23.74%, and 46.75%, respectively. There was no significant difference in survival between patients initiated on RRT before ECMO and those who required RRT while on ECMO. The authors demonstrated that the need for RRT before or while on ECMO has reduced short- and long-term survival when compared with those who did not need RRT while on ECMO. The authors believe that RRT is a marker for severe multiorgan failure and that, despite the benefits of RRT, high mortality will occur. This lack of mortality difference between patients previously on RRT and those newly requiring RRT may help clinicians in deciding to initiate ECMO for patients previously on RRT. Further investigation into complication rates between the groups is required.

MO646PATHOLOGICAL PROGNOSTIC FACTORS IN DIABETIC NEPHROPATHY: A RETROSPECTIVE STUDY

Abstract Background and Aims Kidney Biopsies (KB) performed in patients with Type-2 diabetes (T2D) usually aim at differentiating diabetic nephropathy (DN) from other kidney diseases. However, KB could also help refining patients’ prognosis, both in terms of renal survival, and in terms of patient survival. In 2010, the Renal Pathology Society developed a pathological classification of DN, but the prognostic value of the described items , is still imperfectly documented. We aimed to assess the prognostic performances of these items to predict renal and patient survival. Method Native KBs with diabetic and/or hypertensive nephropathy (DN/HN) performed in patients with T2D in four French centers were analyzed and scored according to the classification developed by the Renal Pathology Society. Clinical and biological data was collected from the patients’ records. Survival analyses were performed for renal survival (time to first dialysis or preemptive transplantation) and death after dichotomization of continuous data). For each of the analyses, we first established a model comprising clinical data only. We then assessed the benefit of adding each of the pathological item to the clinical model. Finally, we performed a backward stepwise analysis to identify items predictive of renal and/or patient survival. Results We analyzed 165 biopsies with DN/HN from patients with T2D and with at least 12 months of follow-up (unless they reached an endpoint during the first year). Among them, 73 (44%) were male, 155 (94%) had hypertension, 53 (34%) hematuria, 22 (15%) had proliferative diabetic retinopathy (DR), 33 (23%) had non-proliferative DR, 90 (62%) had no DR (20 had missing data). Mean (SD) age was 63 (11), median [IQR] eGFRCKD-EPI was 29 [18;45] ml/min/1.73m², urinary protein-to-creatinine ratio was 0.38 [0.14;0.83] g/mmol, HbA1c was 7 [6.2;8.2] % and diabetes duration before KB was 10 [5;19] years. The median [IQR] follow-up was 33 months[18;57]. During the follow-up, 43 (26%) patients died and 69 (42%) required renal replacement therapy (RRT). The percentage of ischemic glomeruli, and presence of more than one area of arteriolar hyalinosis (ah=2), were predictive of renal survival and improved the predictive value of the model when added to clinical parameters. Presence of at least one convincing Kimmelstiel–Wilson lesion (nodular glomerulosclerosis or Class III DN) was predictive of death and similarly improved the predictive model (See figure). Conclusion Pathological findings on KB, as classified by the Renal Pathology Society, carry significant prognostic value in patients with T2D and DN/HN. Vascular lesions (presence of arteriolar hyalinosis and less than 7% of ischemic glomeruli) predicted the need for RRT, while nodular glomerulosclerosis was predictive of death.

Response to Terlipressin and Albumin Is Associated With Improved Liver Transplant Outcomes in Patients With Hepatorenal Syndrome

Although terlipressin and albumin are effective at treating acute kidney injury-hepatorenal syndrome (AKI-HRS), liver transplantation (LT) is the best treatment. However, it is unclear if an effective treatment with terlipressin and albumin improves post-LT outcomes in these patients. The aim of this study was to evaluate the impact of response to treatment with terlipressin and albumin on posttransplant outcomes in patients with AKI-HRS. We analyzed two cohorts of patients with cirrhosis listed for LT between 2012 and 2016: 82 patients who developed AKI-HRS before LT and were treated with terlipressin and albumin and 259 patients without AKI-HRS who received transplants during the study period (control group). After LT, patients were followed up until discharge, every month for the first 3 months, and every 3months thereafter. Of the patients, 43 (52%) responded to terlipressin and albumin. Responders had a better 30-day transplant-free survival (60% vs. 33%, P=0.006), longer LT waiting list time (37 vs. 17days, P=0.041), and lower Model for End-Stage Liver Disease score at the time of LT (23 vs. 29, P=0.007). Among patients with AKI-HRS receiving transplant, nonresponders required renal replacement therapy (RRT) more frequently than responders (20% vs. 0%, P=0.024). Nonresponders had a significantly higher incidence of chronic kidney disease (CKD) at 1 year after LT than responders (65% vs. 31%, P=0.019). In multivariate analysis, nonresponse to terlipressin and albumin was found to be an independent predictor for CKD at 1 year after LT (subdistribution hazard ratio [SHR]=2.76, P=0.001), whereas responders did not have an increased risk (SHR=1.53, P=0.210). In patients with AKI-HRS, response to terlipressin and albumin reduces the need for RRT after LT and reduces the risk of CKD at 1 year after LT.

SGLT2 Inhibitors: Slowing of Chronic Kidney Disease Progression in Type 2 Diabetes.

Diabetic kidney disease (DKD) is a topic of increasing concern among clinicians involved in the management of type 2 diabetes mellitus (T2DM). It is a progressive and costly complication associated with increased risk of adverse cardiovascular (CV) and renal outcomes and mortality. Ongoing monitoring of the estimated glomerular filtration (eGFR) rate alongside the urine albumin:creatinine ratio (ACR) is recommended during regular T2DM reviews to enable a prompt DKD diagnosis or to assess disease progression, providing an understanding of adverse risk for each individual. Many people with DKD will progress to end-stage kidney disease (ESKD), requiring renal replacement therapy (RRT), typically haemodialysis or kidney transplantation. A range of lifestyle and pharmacological interventions is recommended to help lower CV risk, slow the advancement of DKD and prevent or delay the need for RRT. Emerging evidence concerning sodium-glucose co-transporter-2 inhibitor (SGLT2i) agents suggests a role for these medicines in slowing eGFR decline, enabling regression of albuminuria and reducing progression to ESKD. Improvements in renal end points observed in SGLT2i CV outcome trials (CVOTs) highlighted the possible impact of these agents in the management of DKD. Data from the canagliflozin CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) have since demonstrated the effectiveness of this medicine in reducing the risk of kidney failure and CV events in a population comprising individuals with T2DM and renal disease. CREDENCE was the first SGLT2i study to examine renal outcomes as the primary end point. Real-world studies have reaffirmed these outcomes in routine clinical practice. This article summarises the evidence regarding the use of SGLT2i medicines in slowing the progression of DKD and examines the possible mechanisms underpinning the renoprotective effects of these agents. The relevant national and international guidance for monitoring and treatment of DKD is also highlighted to help clinicians working to support this vulnerable group.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00930-x) contains supplementary material, which is available to authorized users.

Survival and renal recovery after acute kidney injury requiring dialysis outside of intensive care units

The incidence of acute kidney injury requiring dialysis (AKI-D) is increasing globally and it is usually associated to chronic kidney disease (CKD) and high mortality. Literature is lacking in short- and intermediate-term data on recovery of renal function after acute kidney injury (AKI). The objective was to evaluate the overall survival and renal recovery after an episode of AKI requiring dialysis out of intensive care units (ICUs). Retrospective study including patients admitted in two nephrology units along a period of 2years. Patients admitted to ICUs and renal transplant patients were excluded. Baseline renal function, mortality and glomerular filtration rate (GFR) improvement were evaluated. 151 consecutive adult patients with AKI requiring renal replacement therapy (RRT) were included. Mean age was 70.5 ± 15.2years, 60.3% were males. Median baseline creatinine (bCr) and baseline GFR (bGFR) were 1.4mg/dL and 46mL/min/1.73m2, respectively. After 1year of follow-up, we completed the monitoring of 94 patients: 64.9% had died, 10.6% were alive on dialysis and 24.5% were alive without need for RRT. Patients with bGFR > 60mL/min/1.73m2 prior to AKI episode had a slower but sustained GFR improvement through the follow-up in comparison with patients with bGFR < 60mL/min/1.73m2 whose recovery was incomplete. Patients with AKI requiring RRT have high short- and intermediate-term mortality and some require maintenance dialysis. Patients with GFR > 60mL/min/1.73m2 prior to AKI had a renal recovery closer to the basal renal function than in patients with a previously diminished GFR.

Safety and Efficacy of Bedside Peritoneal Dialysis Catheter Placement in the COVID-19 Era: Initial Experience at a New York City Hospital.

IntroductionAcute kidney injury (AKI) requiring renal replacement therapy (RRT) is common in critically ill patients with COVID-19. Unparalleled numbers of patients with AKI and shortage of dialysis machines and operative resources prompted consideration of expanded use of urgent-start peritoneal dialysis (PD) and evaluation of the safety and efficacy of bedside surgical placement of PD catheters.Study designBedside, open PD catheter insertions were performed in early April 2020, at a large academic center in New York City. Patients with SARS-CoV-2 infection and AKI and ambulatory patients with chronic kidney disease and impending need for RRT were included. Detailed surgical technique is described.ResultsFourteen catheters were placed at the bedside over 2 weeks, 11 in critically ill COVID-19 patients and three in ambulatory patients. Mean patient age was 61.9 years (43–83), and mean body mass index was 27.1 (20–37.6); four patients had prior abdominal surgery. All catheters were placed successfully without routine radiographic studies or intraoperative complications. One patient (7%) experienced primary nonfunction of the catheter requiring HD. One patient had limited intraperitoneal bleeding while anticoagulated, which was managed by mechanical compression of the abdominal wall and temporarily holding anticoagulation. All other catheters had an adequate function at 3–18 days of follow-up.ConclusionsBedside placement of PD catheters is safe and effective in ICU and outpatient clinic settings. Our surgical protocols allowed for optimization of critical hospital resources, minimization of hazardous exposure to healthcare providers and a broader application of urgent-start PD in selected patients. Long-term follow-up is warranted.

Basics of continuous renal replacement therapy in pediatrics.

In the last three decades, significant advances have been made in the care of children requiring renal replacement therapy (RRT). The move from the use of only hemodialysis and peritoneal dialysis to continuous venovenous hemofiltration with or without dialysis (continuous renal replacement therapy, CRRT) has become a mainstay in many intensive care units. The move to CRRT is the result of greater clinical experience as well as advances in equipment, solutions, vascular access, and anticoagulation. CRRT is the mainstay of dialysis in pediatric intensive care unit (PICU) for critically ill children who often have hemodynamic compromise. The advantages of this modality include the ability to promote both solute and fluid clearance in a slow continuous manner. Though data exist suggesting that approximately 25% of children in any PICU may have some degree of renal insufficiency, the true need for RRT is approximately 4% of PICU admissions. This article will review the history as well as the progress being made in the provision of this care in children.

Thrombotic Microangiopathy: An Under-Recognised Cause of Snake-bite-related Acute Kidney Injury.

Introduction:Thrombotic microangiopathy (TMA) as a cause of snake-bite-induced acute kidney injury (AKI) is rarely reported. Very little is known about the clinical course, optimal management, and prognosis of this entity. We describe a series of snake-bite-induced TMA and compare their outcomes with those without TMA.Methods:This was a single-center retrospective study of patients with AKI following snake envenomation admitted between January 2012 and December 2017. Demographic profile, clinical parameters, and outcomes were studied. TMA was diagnosed based on presence of triad of microangiopathic hemolytic anemia, thrombocytopenia, and AKI, and groups with and without TMA were compared.Results:Of 103 patients with AKI following snake bite, 19 (18.5%) had clinical evidence of TMA. All patients with TMA had advanced azotemia (mean peak serum creatinine 9.5 ± 3.0 mg/dL), with 18 (95%) requiring renal replacement therapy (RRT). Thirteen (68%) had either complete or partial recovery of renal functions, two (10%) progressed to end-stage renal disease, and one died (three patients were lost to follow-up). Age ≥50 years, presence of oliguria/anuria, anti-snake venom dose ≥10 vials, and urea ≥80 mg/dL at presentation were independently associated with TMA (P < 0.05). RRT requirement (95% vs. 57%), mean number of RRT sessions (18 vs. 4.5 sessions), and hospital stay ≥7 days (84% vs. 58%) were higher in patients with TMA (P < 0.05), but patient outcomes did not differ.Conclusions:In conclusion, TMA was seen in 18.5% of patients with snake-bite-related AKI in our study and was associated with almost universal need for RRT, longer duration on RRT, and hospital stay compared with patients without TMA.

Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial

Acute kidney injury (AKI) is common in patients with sepsis and has been associated with high mortality rates. The provision of thiamine to patients with sepsis may reduce the incidence and severity of sepsis-related AKI and thereby prevent renal failure requiring renal replacement therapy (RRT). To test the hypothesis that thiamine supplementation mitigates kidney injury in septic shock. This was a secondary analysis of a single-center, randomized, double-blind trial comparing thiamine to placebo in patients with septic shock. Renal function, need for RRT, timing of hemodialysis catheter placement, and timing of RRT initiation were abstracted. The baseline creatinine and worst creatinine values between 3 and 24 hours, 24 and 48 hours, and 48 and 72 hours were likewise abstracted. There were 70 patients eligible for analysis after excluding 10 patients in whom hemodialysis was initiated before study drug administration. Baseline serum creatinine in the thiamine group was 1.2 mg/dl (interquartile range, 0.8-2.5) as compared with 1.8 mg/dl (interquartile range, 1.3-2.7) in the placebo group (P = 0.3). After initiation of the study drug, more patients in the placebo group than in the thiamine group were started on RRT (eight [21%] vs. one [3%]; P = 0.04). In the repeated measures analysis adjusting for the baseline creatinine level, the worst creatinine levels were higher in the placebo group than in the thiamine group (P = 0.05). In this post hoc analysis of a randomized controlled trial, patients with septic shock randomized to receive thiamine had lower serum creatinine levels and a lower rate of progression to RRT than patients randomized to placebo. These findings should be considered hypothesis generating and can be used as a foundation for further, prospective investigation in this area.

Mortality prediction in patients with acute kidney injury requiring renal replacement therapy after cardiac surgery

Background and objectiveAcute kidney injury (AKI) is a common and potentially serious postoperative complication after cardiac surgery, and it remains a cause of major morbidity and mortality. The aim of our study was to assess the prognostic illness severity score and to estimate the significant risk factors for poor outcome of patients with AKI requiring renal replacement therapy (RRT) after cardiac surgery. Materials and methodsWe retrospectively analyzed data of adult (>18 years) patients (n=111) who underwent open heart surgery and had developed AKI with need for RRT. Prognostic illness severity scores were calculated and perioperative risk factors of lethal outcome were assessed at the RRT initiation time. We defined three illness severity scores: Acute Physiology and Chronic Health Evaluation (APACHE II) as a general score, Sequential Organ Failure Assessment (SOFA) as an organ failure score, and Liano score as a kidney-specific disease severity score. Logistic regression was also used for the multivariate analysis of mortality risk factors. ResultsHospital mortality was 76.5%. More than 7% of patients remained dialysis-dependent after their discharge from the hospital. The prognostic abilities of the scores were assessed for their discriminatory power. The area under the receiver-operating characteristic (ROC) curve of SOFA score was 0.719 (95% CI, 0.598–0.841), of Liano was 0.661 (95% CI, 0.535–0.787) and 0.668 (95% CI, 0.550–0.785) of APACHE II scores. From 16 variables analyzed for model selection, we reached a final logistic regression model, which demonstrated four variables significantly associated with patients’ mortality. Glasgow coma score<14 points (OR=3.304; 95% CI, 1.130–9.662; P=0.003), mean arterial blood pressure (MAP)<63.5mmHg (OR=3.872; 95% CI, 1.011–13.616; P=0.035), serum creatinine>108.5μmol/L (OR=0.347; 95% CI, 0.123–0.998; P=0.046) and platelet count<115×109/L (OR=3.731; 95% CI, 1.259–11.054; P=0.018) were independent risk factors for poor patient outcome. ConclusionsOur study demonstrated that SOFA score estimation is the most accurate to predict the fatal outcome in patients with AKI requiring RRT after cardiac surgery. Lethal patient outcome is related to Glasgow coma score, mean arterial blood pressure, preoperative serum creatinine and postoperative platelet count.

(1052) - Combined Renal Risk Score Predicts Post-Implant Renal Failure in Continuous-Flow Left Ventricular Assist Device (CF-LVAD) Patients

Acute kidney injury failure requiring renal replacement therapy (RRT) effects morbidity and mortality of patients on CF-LVAD support. Currently available MCS guidelines do not offer a decision-making algorithm for CF-LVAD candidates with poor baseline renal function. We reviewed records of 389 CF-LVAD patients implanted between January 2004 and August 2015 at a large academic institution. We compared preoperative renal function between those who did or did not require postoperative RRT, using serum creatinine (SCr), dipstick proteinuria, urine protein-creatinine ratio (UPCR) and estimated glomerular filtration rate (eGFR) by the MDRD equation. Patients were categorized based on requirement for RRT following CF-LVAD implantation. ROC curve analysis was performed to define appropriate cut-offs for significant risk factors. Overall, 44 CF-LVAD patients (11.6%) required post-implant RRT. Patients requiring RRT had significantly worse preoperative renal function than those who did not, as indicated by mean SCr (2.2 vs. 1.4 mg/dL, p<0.05) and mean UPCR (1.33 vs. 0.32, p<0.05). Low eGFR-MDRD (less than 40 mL/min/1.73 m2, OR 10.6, p<0.001) and elevated UPCR (greater than 0.55, OR 8.76, p<0.001) were independent predictors of RRT, as was dipstick proteinuria (greater than 2+ proteinuria, OR 8.09, p<0.001). We created a combined VAD renal risk score (CVRRS), where 2 = low eGFR + elevated UPCR; 1 = low eGFR or elevated UPCR; and 0 = normal eGFR and UPCR. The risk of postoperative RRT was significantly greater with a CVRRS of 2 (63.6%), compared with a CVRRS of 1 (19.6%) and CVRRS of 0 (2.2%), (p<0.001, Fig. 1A). CVRRS provided better discrimination for prediction of need for RRT than eGFR or UPCR alone (Fig. 1B). A CVRRS of 2 (low eGFR + elevated UPCR) is a significant predictor of RRT requirement after CF-LVAD implantation. We recommend its routine preoperative assessment in CF-LVAD candidates to guide expectations and decision-making.

Long-term Outcomes and Prognostic Factors for Patients Requiring Renal Replacement Therapy After Cardiac Surgery

ObjectiveTo examine long-term outcomes, including all-cause mortality, and the likelihood and timing of renal recovery among patients requiring renal replacement therapy (RRT) for acute kidney injury after cardiac surgery. Patients and MethodsThis is a single-center, historical, matched cohort study of post–cardiac surgery patients who required RRT from January 1, 2007, through December 31, 2012. We matched each case with 2 controls, each of whom did not require RRT after cardiac surgery, for age, sex, and type of surgery. The patients were followed up for 1 year after the start of RRT. The main outcomes were all-cause mortality in all patients and rate of renal function recovery in patients who required RRT. ResultsA total of 202 patients met the inclusion criteria. The unadjusted all-cause mortality among patients requiring RRT was 64% at 1 year vs 8% for matched controls. In multivariate analysis, the hazard ratio for all-cause mortality was 12.59 (95% CI, 8.24-19.68) for cases vs controls. Increased 1-year all-cause mortality was independently associated with increased age, a history of congestive heart failure, lower preoperative creatinine level, longer interval between surgery and starting RRT, and the need for mechanical ventilation or an intra-aortic balloon pump at the time of RRT. Renal recovery occurred in 34% of cases by 90 days and in 39% by 1 year. Of those who recovered renal function, 87% were within 90 days. Only 8 (4%) of the 186 patients were alive and continued to receive RRT at 1 year. ConclusionsThe need for RRT after cardiac surgery is an independent risk factor for mortality. In the case of survival, the chance of renal recovery is reasonable.

Acute kidney injury in survivors of surgery for severe traumatic brain injury: Incidence, risk factors, and outcome from a tertiary neuroscience center in India

Background. Non-neurological complications like acute kidney injury (AKI) can affect outcome of traumatic brain injury (TBI). This study aims to analyze the incidence, predictive factors, and impact of AKI in operated patients with severe TBI. Methods. We retrospectively reviewed the data of 395 patients who underwent surgery for severe TBI and survived to be discharged from the hospital over a 1-year period. Of these, 95 patients were finally included in the analysis. Their demographic data, laboratory parameters, and clinical courses were reviewed. Diagnosis and staging of AKI was made using Acute Kidney Injury Network (AKIN) criteria. Results. The incidence of AKI was 11.6% (11 patients). Out of the11 patients who had AKI, 7 were in stage I (63.6%), 3 were in stage II (27.3%), and 1 in stage III (9.1%). Nine Patients (81.8%) developed AKI within 5 days of admission. Aminoglycoside therapy had an association with occurrence of AKI. There was no mortality and none of the patients required renal replacement therapy (RRT). Renal function of all these patients returned to baseline before hospital discharge. Hospital stay and intensive care unit (ICU) stay were longer and Glasgow coma scale (GCS) was lower in patients with AKI when compared with patients without AKI group at discharge. Conclusion. Reversible AKI without need for RRT occurred in nearly12% of patients with severe TBI requiring surgical intervention. Aminoglycoside therapy was the only predictive factor for the occurrence of AKI. Patients with AKI have a longer period of mechanical ventilation, longer ICU and hospital stay, and poorer GCS at discharge.

A 13-Year Retrospective Analysis of Acute Kidney Injury Requiring Renal Replacement Therapy in Non Renal Solid Organ Transplantation.

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is associated with high mortality and progression toward chronic kidney disease (CKD). A few studies analyzed the impact of AKI in non renal solid organ transplant (NRSOT) recipients. The aim of this study was a 13-year retrospective analysis of AKI in NRSOT recipients identifying its clinical relevance on outcome and progression toward CKD. We analyzed (2001-2013) the percentage of NRSOT in the AKI population treated by RRT in our University Hospital. For each NRSOT recipient, we evaluated RIFLE, SOFA and the severity index ATN_ISS at RRT start. The percentage of AKI requiring RRT in the NRSOT population and for distinct transplanted organ (liver, heart or lung graft) was studied. Renal function (eGFR) was evaluated at the end of observation (30 days). We treated by RRT 2648 critically ill patients with AKI for a total of 20932 sessions performed: 291/2648 (10.99%) were NRSOT recipients. In the study period, 1673 liver, 317 heart and 34 lung transplantations were performed. We treated by RRT 174/1673 (10.4 %) liver, 83/317 (26.2 %) heart and 34/110 (30.9%) lung transplanted patients. NRSOT patients’ characteristics were: age 59.8±7.6 yrs, male 67.7%, serum creatinine 3.88±1.27 mg/dl, SOFA 12.8±3.1, RIFLE (Risk 12%, Injury 17.2%, Failure 70.8%) and ATN_ISS score 0.8±0.11. The prevalent cause of AKI was sepsis (44%). Mortality rate of NRSOT patients treated by RRT was 44.3% (129/291), 42.5% (74/174) for liver, 49.4% (41/83) for heart and 41.2% (14/34) for lung recipients, respectively. AKI was a complication of the early post-transplantation period since the need for RRT occurred in the first 30 days after surgery in 69.1% of NRSOT recipients (64.9% for liver, 60.2% for heart and 82.3% for lung, respectively). In survivors, mean serum creatinine at the end of the study period was 2.37±0.82 mg/dl (1.88±0.94 mg/dl in liver, 2.42±0.75 mg/dl in heart and 2.81±0.92 mg/dl in lung graft recipients, respectively). Our retrospective analysis revealed an increased incidence of AKI mainly due to sepsis in the NRSOT population. The occurrence of AKI requiring RRT in the first 30 days after transplantation was associated with a worse outcome and with progression toward CKD in survivors.

Chronic kidney disease rather than illness severity predicts medium- to long-term mortality and renal outcome after acute kidney injury.

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) continues to be associated with a hospital mortality of ∼50%. Longer-term outcomes have been less well studied. We sought to determine the influence of ventilation and of underlying chronic kidney disease (CKD) on medium and longterm mortality and renal outcomes. All patients requiring RRT for AKI in south west Scotland between 1 January 1994 and 31 December 2005 were followed prospectively. Survival of patients who were and were not ventilated and of those with and without underlying CKD was compared by odds ratio (OR), adjusting for age and sex. Renal outcomes were determined by interrogation of our biochemistry database. Three hundred and ninety-six patients with AKI received RRT. One hundred and seventy-six (44%) were ventilated and 98 (25%) had underlying CKD. Patients who required ventilation had a significantly worse 90-day survival than those who did not (OR 2.10 for death; 95% CI 1.34, 3.29) whereas underlying CKD did not predict such an early adverse outcome (OR 1.49; 95% CI 0.89, 2.50). By 5 years, patients who had been ventilated during the acute illness were no longer at increased risk (OR 0.79; 95% CI 0.38, 1.62) whereas the adverse effect of underlying CKD was statistically significant (OR 6.05; 95% CI 2.23, 16.5). Underlying CKD was also a strong predictor of the need for RRT during follow-up. In an unselected series of patients with AKI requiring RRT, underlying CKD rather than illness severity predicted medium- to long-term mortality.