Small Increases In Serum Creatinine Research Articles

Early Creatinine Changes After Aortic Valve Replacement and Late Survival, Heart Failure, and Chronic Kidney Disease in a National Registry

BackgroundThe impact of small increases in serum creatinine after surgical aortic valve replacement (SAVR) that fail to meet the acute kidney injury stage 1 criteria is unknown. The aim of this study was to investigate prognosis after primary SAVR in patients with small increases in postoperative serum creatinine. MethodsThis observational cohort study included all adult patients who underwent primary SAVR in Sweden from 2009 to 2022. The primary outcome was all-cause mortality. Secondary outcomes were chronic kidney disease and heart failure. Regression standardization addressed confounding. ResultsIn 16,766 patients, 4074 (24.2%) had no change in postoperative serum creatinine, 5764 (34.3%) had a small increase in postoperative serum creatinine (0.06 mg/dL ≤ Δserum creatinine <0.3 mg/dL), and 2753 (16.4%) fulfilled the Kidney Disease Improving Global Outcomes acute kidney injury stage 1 criteria. The mean age was 67 years, and 31% of patients were female. No significant difference in long-term all-cause mortality was observed in the no change group at 13 years compared with the small increase group (absolute survival difference, 2.3% [95% CI, 0%-4.6%]). A stepwise increase in the risk of 30-day mortality was observed with increasing changes in serum creatinine. At 13 years of follow-up, there was a significant difference in the risk of chronic kidney disease (absolute difference, 2.8% [95% CI, 1.0%-4.5%]) and heart failure (absolute difference, 3.5% [95% CI, 1.3%-5.7%]) between the no change and small increase groups. ConclusionsA small increase in postoperative serum creatinine after SAVR was associated with an increased risk of adverse outcomes. The acute kidney injury definition may benefit from including more reliable and specific biomarkers together with small creatinine increases to detect kidney injury.

Early and minimal changes in serum creatinine can predict prognosis in elderly patients receiving invasive mechanical ventilation: A retrospective observational study

BackgroundEmerging evidence suggests that minimal acute kidney injury (stage 1 AKI) is associated with increased hospital mortality rates. However, for those who do not meet the AKI diagnostic criteria, whether a small increase in serum creatinine (SCr) levels is associated with an increased mortality rate in elderly patients is not known. Therefore, we aimed to investigate small elevations in SCr of <26.5 µmol/L within 48 h after invasive mechanical ventilation (MV) on the short-term mortality of critically ill patients in the geriatric population. MethodsWe conducted a retrospective, observational, multicenter cohort study enrolling consecutive elderly patients (≥75 years) who received invasive MV from January 2008 to December 2020. Recursive partitioning was used to calculate the ratio of SCr rise from baseline within 48 h after MV and divided into six groups, (1) <10%, (2) 10%–<20%, (3) 20%–<30%, (4) 30%–<40%, (5) 40%–<50%, and (6) ≥50%, where the reference interval was defined as the ratio <10% based on an analysis, which confirmed that the lowest mortality risk was found in this range. Clinical data and laboratory data were noted. Their general conditions and clinical characteristics were compared between the six groups. Prognostic survival factors were identified using Cox regression analysis. Kaplan–Meier survival analysis was employed for the accumulative survival rate. ResultsA total of 1292 patients (1171 men) with a median age of 89 (interquartile range: 85–92) with MV were suitable for further analysis. In all, 376 patients had any stage of early AKI, and 916 patients had no AKI. Among 916 non-AKI patients, 349 patients were in the ratio <10%, 291 in the 10%–<20% group, 169 in the 20%–<30% group, 68 in the 30%–<40% group, 25 in the 40%–<50% group, and 14 in the ≥50% group. The 28-day mortality rates in the six groups from the lowest (<10%) to the highest (≥50%) were 8.0%, 16.8%, 28.4%, 54.4%, 80.0%, and 85.7%, respectively. In the multivariable-adjusted analysis, patients with a ratio of 10%–<20% (hazard ratio [HR]=2.244; 95% confidence interval [CI]: 1.410 to 3.572; P=0.001), 20%–<30% (HR=3.822; 95% CI: 2.433 to 6.194; P <0.001), 30%–<40% (HR=10.472; 95% CI: 6.379 to 17.190; P <0.001), 40%–<50% (HR=13.887; 95% CI: 7.624 to 25.292; P <0.001), and ≥50% (HR=13.618; 95% CI: 6.832 to 27.144; P <0.001) had relatively higher 28-day mortality rates. The 90-day mortality rates in the six strata were 30.1%, 35.1%, 45.0%, 60.3%, 80.0%, and 85.7%, respectively. Significant interactions were also observed between the ratio and 90-day mortality: patients with a ratio of 10%–<20% (HR=1.322; 95% CI: 1.006 to 1.738; P=0.045), 20%–<30% (HR=1.823; 95% CI: 1.356 to 2.452; P <0.001), 30%–<40% (HR=3.751; 95% CI: 2.601 to 5.410; P <0.001), 40%–<50% (HR=5.735; 95% CI: 3.447 to 9.541; P <0.001), and ≥50% (HR=6.305; 95% CI: 3.430 to 11.588; P <0.001) had relatively higher 90-day mortality rates. ConclusionsOur study suggests that a ≥ 10% SCr rise from baseline within 48 h after MV was independently associated with short-term all-cause mortality in mechanically ventilated elderly patients.

Adenosine Triphosphate Citrate Lyase and Fatty Acid Synthesis Inhibition

Adenosine triphosphate citrate lyase (ACLY) is a key regulatory enzyme of glucose metabolism, cholesterol and fatty acid synthesis, and the inflammatory cascade. Bempedoic acid, an ACLY inhibitor, significantly reduces atherogenic lipid markers, including low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and apolipoprotein B. Additional effects of ACLY inhibition include antitumor growth; reduction of triglycerides and proinflammatory molecules such as high-sensitivity C-reactive protein; less insulin resistance; reduction of hepatic lipogenesis; and weight loss. While numerous ACLY inhibitors have been identified, most of the clinical data have focused on bempedoic acid. The Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) program was a series of phase 3 clinical trials that evaluated its effects on lipid parameters and safety, leading to US Food and Drug Administration approval in 2020. CLEAR Outcomes was a phase 3, double-blind, randomized, placebo-controlled trial in individuals with a history of statin intolerance, serum LDL-C level of 100 mg/dL or higher, and a history of, or at high risk for, cardiovascular disease. Bempedoic acid modestly reduced the primary 4-way cardiovascular composite end point as well as the individual components of myocardial infarction and coronary revascularization but did not reduce stroke, cardiovascular death, or all-cause mortality. Rates of gout and cholelithiasis were higher with bempedoic acid, and small increases in serum creatinine, uric acid, and hepatic-enzyme levels were also observed. ACLY inhibition with bempedoic acid has been established as a safe and effective therapy in high-risk patients who require further LDL-C lowering, particularly for those with a history of statin intolerance. The recently published CLEAR Outcomes trial revealed modest reductions in cardiovascular events with bempedoic acid, proportional to its LDL-C lowering, in high-risk individuals with statin intolerance and LDL-C levels of 100 mg/dL or higher. The additional effects of ACLY inhibition have prompted a more thorough search for novel ACLY inhibitors for conditions such as cancer, hypertriglyceridemia, chronic inflammation, type 2 diabetes, fatty liver disease, obesity, and metabolic syndrome. Similarly, therapies that reduce fatty acid synthesis are being explored for their use in cardiometabolic conditions.

A Small Increase in Serum Creatinine within 48 h of Hospital Admission Is an Independent Predictor of In-Hospital Adverse Outcomes in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: Findings from the Improving Care for Cardiovascular Disease in the China Project.

Acute kidney injury (AKI) is a common complication of percutaneous coronary intervention (PCI) that has been associated with high morbidity and mortality in patients with STEMI. Acute tubular damage may be reflected by serum creatinine (Scr) values that do not meet the criteria for AKI. This analysis included 19,424 patients from the Improving Care for Cardiovascular Disease in China, Acute Coronary Syndrome Project (n = 5,221 (36.8%), patients with a small increase in Scr within 48 h of hospitalization; n = 14,203 patients with no increase in Scr). The primary outcome was the incidence of major adverse cardiovascular events (MACE). Secondary outcomes included the incidence of massive hemorrhage, in-hospital death, atrial fibrillation, heart failure, cardiogenic shock, cardiac arrest, and stroke. Logistic regression analysis was used to evaluate associations between a small increase in Scr within 48 h of hospitalization (>0.1 to <0.3 mg/dl) and MACE or massive hemorrhage during hospitalization. Patients with a small increase in Scr within 48 h of hospitalization were significantly more likely to experience MACE (11.2% vs. 9.1%; P < 0.001) or massive hemorrhage (3.2% vs. 2.2%; P < 0.001) compared to patients with no increase in Scr, but there was no significant difference in in-hospital mortality (0.8% vs. 0.9%; P=0.301). Logistic regression analysis showed that a small increase in Scr within 48 h of hospital admission was a risk factor for MACE (OR, 1.168; 95% CI, 1.044-1.306; P=0.006) or massive hemorrhage (OR, 1.413; 95% CI, 1.164-1.715; P < 0.001). Other risk factors included age ˃65 years, history of heart failure, use of glycoprotein IIb/IIIa inhibitors, aspirin or ACEI/ARB, LVEF <40%, Killip class III-IV, and increased SBP and heart rate. A small increase in Scr during hospitalization in patients with STEMI undergoing primary PCI that does not meet the criteria for AKI is a risk factor for in-hospital adverse outcomes. This effect is maintained in patients with normal Scr at hospitalization. Trial Registration. Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02306616.

Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients

BackgroundBempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain.MethodsWe conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (“statin-intolerant” patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization.ResultsA total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P=0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P=0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P=0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels.ConclusionsAmong statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.)

The Rheumatoid Arthritis and MUScle (RAMUS) Study: Protocol for an observational single-arm study of skeletal muscle in patients with rheumatoid arthritis receiving tofacitinib.

People with rheumatoid arthritis (RA) are disproportionately affected by sarcopenia, the generalised loss of muscle strength and mass, consequently facing an increased risk of falls, functional decline and death. Currently, there are no approved pharmacological treatments for sarcopenia. RA patients who start tofacitinib (a Janus kinase inhibitor) develop small increases in serum creatinine that are not explained by renal function changes and could reflect sarcopenia improvement. The RAMUS Study is a proof of concept, single-arm observational study in which patients with RA who commence tofacitinib according to routine care will be offered participation according to eligibility criteria. Participants will undergo lower limb quantitative magnetic resonance imaging, whole-body dual energy x-ray absorptiometry, joint examination, muscle function testing and blood tests at three time points: prior to starting tofacitinib and 1 and 6 months afterwards. Muscle biopsy will be performed before and 6 months after starting tofacitinib. The primary outcome will be lower limb muscle volume changes following treatment initiation. The RAMUS Study will investigate whether muscle health improves following tofacitinib treatment for RA. Identifying a potential pharmacological treatment for sarcopenia could have important implications for individuals with RA and for older people in general. ISRCTN registry ID: 13364395.

Radiographic Contrast Media and the Kidney.

AKI is a potential complication of intravascular iodinated contrast exposure. Contrast-associated AKI, which typically manifests as small and transient decrements in kidney function that develop within several days of contrast administration, is associated with serious adverse outcomes, including progressive kidney dysfunction and death. However, a causal link between the small increases in serum creatinine that characteristically occur with contrast-associated AKI and serious adverse outcomes remains unproven. This is important given mounting evidence that clinically indicated, potentially lifesaving radiographic procedures are underutilized in patients with CKD. This has been hypothesized to be related to provider concern about precipitating contrast-associated AKI. Intravascular gadolinium-based contrast, an alternative to iodinated contrast that is administered with magnetic resonance imaging, has also been linked with potential serious adverse events, notably the development of nephrogenic systemic fibrosis in patients with severe impairment in kidney function. Patients hospitalized in the intensive care unit frequently have clinical indications for diagnostic and therapeutic procedures that involve the intravascular administration of contrast media. Accordingly, critical care providers and others treating critically ill patients should possess a sound understanding of the risk factors for and incidence of such outcomes, the ability to perform evidence-based risk-benefit assessments regarding intravascular contrast administration, and knowledge of empirical data on the prevention of these iatrogenic complications.

Goal Directed Perfusion Is Not Associated with a Decrease in Acute Kidney Injury in Patients Predicted to Be at High Risk for Acute Renal Failure after Cardiac Surgery

Small increases in serum creatinine postoperatively reflect an acute kidney injury (AKI) that likely occurred during cardiopulmonary bypass (CPB). Maintaining adequate oxygen delivery (DO2) during CPB, known as GDP (goal-directed perfusion), improves outcomes. Whether GDP improves outcomes of patients at high risk for acute renal failure (ARF) is unknown. Forty-seven adult patients undergoing cardiac surgery with CPB utilizing GDP with Cleveland Clinic Acute Renal Failure Score of 3 or greater were compared with a matched cohort of patients operated upon using a flow-directed strategy. CPB flow in the GDP cohort was based on a DO2 goal of 260 mL/min/m2. Serum creatinine values were used to determine whether postoperative AKI occurred according to AKIN (Acute Kidney Injury Network) guidelines. We examined the distribution of all variables using proportions for categorical variables and means (standard deviations) for continuous variables and compared treatment groups using t tests for categorical variables and tests for differences in distributions for continuous and count variables. We used inverse probability of treatment weighting to adjust for treatment selection bias. In adjusted models, GDP was not associated with a decrease in AKI (odds ratio [OR]: .97; confidence interval [CI]: .62, 1.52), but was associated with higher odds of ARF (OR: 3.13; CI: 1.26, 7.79), mortality (OR: 3.35; CI: 1.14, 9.89), intensive care unit readmission (OR: 2.59; CI: 1.31, 5.15), need for intraoperative red blood cell transfusion (OR: 2.02; CI: 1.26, 3.25), and postoperative platelet transfusion (OR: 1.78; CI: 1.05, 3.01) when compared with the historic cohort. In patients who are at high risk for postoperative renal failure, GDP was not associated with a decrease in AKI when compared to the historical cohort managed traditionally by determining CPB flows based on body surface area. Surprisingly, the GDP cohort performed significantly worse than the retrospective control group in terms of ARF, mortality, intensive care unit readmission, and RBC and platelet transfusions.

Goal Directed Perfusion Is Not Associated with a Decrease in Acute Kidney Injury in Patients Predicted to Be at High Risk for Acute Renal Failure after Cardiac Surgery.

Small increases in serum creatinine postoperatively reflect an acute kidney injury (AKI) that likely occurred during cardiopulmonary bypass (CPB). Maintaining adequate oxygen delivery (DO2) during CPB, known as GDP (goal-directed perfusion), improves outcomes. Whether GDP improves outcomes of patients at high risk for acute renal failure (ARF) is unknown. Forty-seven adult patients undergoing cardiac surgery with CPB utilizing GDP with Cleveland Clinic Acute Renal Failure Score of 3 or greater were compared with a matched cohort of patients operated upon using a flow-directed strategy. CPB flow in the GDP cohort was based on a DO2 goal of 260 mL/min/m2. Serum creatinine values were used to determine whether postoperative AKI occurred according to AKIN (Acute Kidney Injury Network) guidelines. We examined the distribution of all variables using proportions for categorical variables and means (standard deviations) for continuous variables and compared treatment groups using t tests for categorical variables and tests for differences in distributions for continuous and count variables. We used inverse probability of treatment weighting to adjust for treatment selection bias. In adjusted models, GDP was not associated with a decrease in AKI (odds ratio [OR]: .97; confidence interval [CI]: .62, 1.52), but was associated with higher odds of ARF (OR: 3.13; CI: 1.26, 7.79), mortality (OR: 3.35; CI: 1.14, 9.89), intensive care unit readmission (OR: 2.59; CI: 1.31, 5.15), need for intraoperative red blood cell transfusion (OR: 2.02; CI: 1.26, 3.25), and postoperative platelet transfusion (OR: 1.78; CI: 1.05, 3.01) when compared with the historic cohort. In patients who are at high risk for postoperative renal failure, GDP was not associated with a decrease in AKI when compared to the historical cohort managed traditionally by determining CPB flows based on body surface area. Surprisingly, the GDP cohort performed significantly worse than the retrospective control group in terms of ARF, mortality, intensive care unit readmission, and RBC and platelet transfusions.

The Clinical Utility of Kinetic Glomerular Filtration Rate in the Assessment of Renal Function and Prediction of Outcomes Among Critically Ill Patients With Acute Kidney Injury: A Single-Center Retrospective Cohort Study

Objective: To determine the discriminatory ability of kinetic glomerular filtration rate (kGFR) to detect acute kidney injury (AKI) when compared with established GFR equations and criteria and relating it to mortality, renal replacement therapy initiation and renal recovery. Methods: This was a retrospective analysis using data from chart review of 109 intensive care unit (ICU) patients at the University of Santo Tomas Hospital (USTH). The renal function estimates using Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi), modification of diet in renal disease (MDRD), Kidney Disease Improving Global Outcomes Acute Kidney Injury (KDIGO AKI), as well as kinetic GFR equations were compared and correlated with renal and cardiovascular outcomes. Results: The renal function assessed by kGFR, CKD-Epi, MDRD and KDIGO staging based on serum creatinine (SCr) showed no significant association with mortality outcomes. However, AKI diagnosed based on urine output (UO), and combined SCr and urine output (KDIGO) showed association with all-cause mortality. The UO detected severe stages of AKI while SCr (based on KDIGO) better identified the earlier stages of AKI. The criteria for KDIGO AKI when combined also shows mortality prediction since it joins together the effects of SCr and UO. There was a remarkable 3.5 times increase in hemodialysis initiation (p=0.0001) and 12.89 times increase in peritoneal dialysis initiation (p=0.01) for every stage increase in the KDIGO classification. kGFR, CKD-Epi and MDRD have 5%, 6%, and 6% decrease, respectively in the odds of initiating hemodialysis. There was however, no association for peritoneal dialysis. Conclusion: kGFR was the least able in detecting AKI and KDIGO AKI criteria remains to be the standard in identifying AKI in the critical care setting. Increase in SCr was a sensitive tool in diagnosing AKI due to its ability to detect AKI based on a small increase in SCr regardless of the baseline renal function. Decreasing UO, however, is the prognosticating variable in KDIGO AKI criteria, in that it portends higher probability of initiation of renal replacement therapy (RRT) and ultimately higher mortality when present.

BK Viremia Was Not Associated with Acute Kidney Injury in Hematopoietic Cell Transplant Recipients

Introduction Acute kidney injury (AKI) is common in hematopoietic cell transplant (HCT) recipients. Few studies have evaluated whether BK polyomavirus (BKV) infections are associated with kidney disease in the HCT population, and results have not been conclusive. Objectives Using retrospectively collected BK plasma viral loads from a large cohort of HCT recipients, we assessed the relationship between plasma BKV replication and AKI through an analysis of BK viral load kinetics, the occurrence of AKI, and change in serum creatinine. Methods Weekly BK viral loads were obtained during the first 100 days after HCT in 403 patients between 2007-2014 (Hill et al., Blood 2017). We defined AKI according to KDIGO (Kidney Disease Improving Global Outcomes) criteria and recovery from AKI as a reduction in serum creatinine to within ten percent of baseline, both sustained for 48 hours. Viral load kinetics of interest included peak viral load, area under the curve (AUC) and cross-sectional BK viral load (log10 BK viral load). Using these weekly longitudinal measures, we estimated the relationships between BKV kinetics and AKI using generalized linear models with robust variance estimates for the outcomes of 1) mean change in serum creatinine (from baseline) and 2) odds of AKI episodes, each adjusted for acute graft versus host disease, use of nephrotoxic medications (cidofovir, foscarnet), bilirubin, conditioning regimen, age, sex, and cell source. Results Fifty-four percent (218/402) of HCT recipients had detection of BKV in at least one sample, and twenty-eight percent (113/403) had at least one BK viral load ≥ 10,000 copies/mL in the first 100 days. Sixty-eight percent (275/403) had at least one AKI episode median onset by day 27 (range 1-98). Logistic regression models did not show significant associations for log10BK viral load, peak viral load and AUC with odds of subsequent AKI (Figure1). In the linear models, BK viral load kinetics were associated with small increases in mean serum creatinine (mg/dL) by 0.025 for each log10 increase (95% CI, 0.01-0.04; p Conclusion Increased plasma BK viral load was associated with small increases in serum creatinine after allogeneic HCT, but the clinical importance of these changes is low. We found no statistically significant association between plasma BKV detection and development of AKI.

Validation of International Club of Ascites subclassification of stage 1 acute kidney injury in chronic liver disease.

Background and AimAcute kidney injury (AKI) commonly occurs in patients with chronic liver disease (CLD). As per the International Club of Ascites, AKI is classified into three stages; stage 1 has recently been divided into subgroups 1A and 1B. We performed a prospective study to validate the association between subgrouping and outcome.MethodsThis study was conducted using decompensated cirrhosis (DC) patients hospitalized in the Gastroenterology ward between August 2016 and May 2018. Demographic, clinical, and laboratory parameters were compared between AKI 1A and AKI 1B patients. The duration of hospitalization and outcome were compared.ResultsA total of 528 subjects were enrolled; 296 (56.1%) had AKI, and of them, 61.48% (n = 182) had stage 1, 20.95% (n = 62) had stage 2, and 17.57% (n = 52) had stage 3 AKI. Of the enrolled patients, 100 (54.94%) had early (AKI 1A) and 82 (45.06%) had late stage 1 AKI (AKI 1B). Patients with AKI 1B had higher total leucocyte count, total bilirubin, serum urea, serum creatinine (SCr), model for end‐stage liver disease (MELD), MELD‐Na+, and child‐turcotte‐pugh (CTP) score and decreased serum albumin than AKI 1A. The prevalence of hepatorenal syndrome (HRS), acute on chronic liver failure (ACLF) were higher in AKI 1B patients, and they had a prolonged hospital stay compared to AKI 1A patients. Furthermore, AKI 1B patients had significantly lower survival both at 28 days and 90 days.ConclusionOur study validates the subclassification of stage 1 AKI. Patients with AKI 1B more often progress to higher AKI stages with significantly lower 28‐day and 90‐day survival rates. Results justify subclassification and suggest the need for early intervention. The small increase in SCr should be viewed with caution in AKI stage 1A.

Acute Kidney Injury at Admission Is a Better Predictor of Mortality than Its Persistence at 48 h in Patients with Acute-on-chronic Liver Failure.

Background and Aims: Acute kidney injury (AKI) occurs commonly in patients with acute-on-chronic liver failure (ACLF). However, there are scant data regarding the impact of AKI on survival in ACLF. We performed a prospective study to evaluate the impact of AKI on survival in ACLF.Methods: This study was conducted in ACLF patients hospitalized in the Gastroenterology Department of Sriram Chandra Bhanja Medical College (India) between October 2016 and February 2018. Demographic, clinical and laboratory parameters were recorded, and outcomes were compared between patients with and without AKI and between patients with persistent AKI and AKI reversal at 48 h.Results: We screened 439 chronic liver disease patients as per the Asian Pacific Association for the Study of the Liver criteria and found that 113 (25.7%) of them had ACLF and 78 (69%) of them had AKI as per the Acute Kidney Injury Network criteria. ACLF patients with AKI had reduced 28-day survival (44.9% vs. 74.3%; p = 0.004) and 90-day survival (25.6% vs. 51.4%; p = 0.007), in comparison to ACLF patients without AKI. However, when comparison was made between AKI reverters and AKI persisters at 48 h, survival was comparable for both at 28 days and 90 days. Further, about one-tenth of ACLF patients with AKI died within 48 h of hospitalization.Conclusions: Over two-thirds of ACLF patients had AKI. Although ACLF itself is a predictor of reduced survival, a very small increase in serum creatinine further worsens survival. Importantly, AKI at admission is a better predictor of early mortality in ACLF patients since recovery from AKI at 48 h does not improve survival.

Editor's Choice- What do small serum creatinine changes tell us about outcomes after acute myocardial infarction?

Acute kidney injury (AKI), mostly defined as a rise in serum creatinine concentration of more than 0.5 mg/dl, is a common, serious, and potentially preventable complication of percutaneous coronary intervention and is associated with adverse outcomes including an increased risk of inhospital mortality. Recent data from the National Cardiovascular Data Registry/Cath-PCI registry including 985,737 consecutive patients undergoing percutaneous coronary intervention suggest that approximately 7% experienced AKI with a reported incidence of 3-19%. In patients undergoing primary percutaneous coronary intervention for acute myocardial infarction (AMI), AKI occurs more frequently with rates up to 20% depending on patient and procedural characteristics. However, varying definitions of AKI limit comparisons of AKI rates across different studies. Recently, most studies have adopted the Acute Kidney Injury Network (AKIN) criteria for definition and classification of AKI. Beyond the AKIN criteria for AKI, other classifications such as the risk, injury, failure, loss and end-stage kidney disease (RIFLE) and kidney disease: improving global outcomes (KDIGO) criteria are used to define AKI. Notably, even small increases in serum creatinine beyond AKI may be associated with adverse outcomes including increased hospital length of stay and excess. Acute kidney injury (AKI) is a serious and potentially preventable complication of percutaneous coronary intervention (PCI). Worsening renal function is associated with adverse outcomes including a higher rate of in-hospital mortality. In patients undergoing primary PCI for acute myocardial infarction (AMI), AKI occurs up to 20% of such individuals. Varying definitions of AKI limit comparisons of AKI rates across different studies. Additionally, even small increases in serum creatinine beyond lavels meeting AKI definitions may be associated with adverse outcomes including increased hospital length of stay.

Traitement non dialytique de l’insuffisance rénale aiguë

Acute kidney injury is frequently encountered in patients in intensive care units and is associated with higher risk of mortality and chronic renal failure. Even small increases in serum creatinine are associated with adverse outcomes. Many interventions have been proposed to prevent or treat acute kidney injury in patients in intensive care units. However, no intervention has proved its efficacy in large randomized control trials. This review presents the various attempts aiming at acute kidney injury improvement in patients in intensive care units published over the recent years: hemodynamic interventions, “usual” drugs used in intensive care units, modulation of inflammation and hemostasis, remote ischemic conditioning, drugs specifically dedicated for acute kidney injury, and stimulation of renal recovery.

Evaluating the role of atazanavir/cobicistat and darunavir/cobicistat fixed-dose combinations for the treatment of HIV-1 infection.

Atazanavir/cobicistat (ATV/c) and darunavir/cobicistat (DRV/c) are newly approved once daily fixed-dose protease inhibitor combinations for the treatment of HIV-1 infection. Studies in healthy volunteers have established bioequivalence between cobicistat and ritonavir as pharmacoenhancers of both atazanavir (ATV) and darunavir (DRV). In addition, two randomized clinical trials (one Phase II and one Phase III noninferiority trial with a 144-week followup period) demonstrated that cobicistat had sustainable and comparable efficacy and safety to ritonavir as a pharmacoenhancer of ATV through 144 weeks of treatment in HIV-1-infected patients. Furthermore, one Phase III, open-label, single-arm, clinical trial reflected virologic and immunologic responses and safety outcomes consistent with prior published data for DRV/ritonavir 800/100 mg once daily, supporting the use of DRV/c 800/150 mg once daily for future treatment of treatment-naïve and -experienced HIV-1-infected patients with no DRV resistance-associated mutations. Low rates of virologic failure secondary to resistance to antiretroviral regimens were present in these clinical studies. Most notable adverse events in the ATV studies were hyperbilirubinemia and in the DRV study rash. Small increases in serum creatinine and minimally reduced estimated glomerular filtration rate Cockcroft–Gault calculation (eGFRCG) were observed in ATV/c and DRV/c clinical studies consistent with other studies evaluating elvitegravir/cobicistat/tenofovir/emtricitabine for the treatment of HIV-1 infection. These renal parameter changes occurred acutely in the first few weeks and plateaued off for the remaining study periods and are not necessarily clinically relevant. Cobicistat has numerous advantages compared to ritonavir such as fewer drug–drug interactions, being devoid of anti-HIV-1 activity, as well as it has better solubility affording coformulation with other antiretrovirals as simplified fixed-dose combinations. Overall, the recent approval of ATV/c and DRV/c offers HIV patients opportunities for improved adherence to lifelong treatment. Future studies are warranted to determine the efficacy and safety of ATV/c and DRV/c in treatment-experienced patients.

Impact of acute kidney injury on prognosis of patients with liver cirrhosis and ascites: A retrospective cohort study.

Acute kidney injury (AKI) is a common complication in patients with liver cirrhosis, and its impact on the clinical course is increasingly recognized. Diagnostic classification systems for AKI in cirrhosis have been suggested. The prognostic significance of the respective AKI stages remains to be evaluated in decompensated cirrhosis with ascites. Data of consecutive patients with cirrhosis and ascites undergoing paracentesis at a tertiary care center were analyzed. AKI was defined as an increase in serum creatinine of ≥ 0.3 mg/dL or by ≥ 50% within 7 days after paracentesis, and classified according to (i) revised Acute Kidney Injury Network (AKIN) criteria and (ii) modified AKI criteria for cirrhosis (C-AKI). In contrast to AKIN, C-AKI stage A discriminates prognosis based on an absolute creatinine cut-off at < 1.5 mg/dL versus C-AKI stage B at ≥ 1.5 mg/dL. The final study cohort included 239 patients. Median transplant-free survival was 768 days (95% confidence interval [CI]: 331-1205 days) without AKI, 198 (0-446) in AKI-1, 91 (0-225) in AKI-2, 19 (0-40) and in AKI-3, whereas it was 89 (20-158) days in C-AKI-A, 384 (0-1063) in C-AKI-B, and 22 (7-776) in C-AKI-C. Mild AKI was already associated with significantly increased 30-day mortality (AKI-1:26.4%, C-AKI-A:33.3%) as compared with patients without AKI (14.3%), even when serum creatinine remained within normal range (< 1.2 mg/dL) we observed a significant 30-day mortality. AKIN criteria-considering small increases in serum creatinine rather than absolute thresholds-seem to be more accurate for estimating prognosis of AKI after paracentesis than C-AKI criteria. Even patients developing AKI-1 with "normal" serum creatinine are at increased risk for mortality.

Objectively measured sedentary time, physical activity and kidney function in people with recently diagnosed Type2 diabetes: a prospective cohort analysis.

AimTo assess the prospective association between objectively measured physical activity and kidney function over 4 years in people with Type 2 diabetes.MethodsIndividuals (120 women and 206 men) participating in the ADDITION‐Plus trial underwent assessment of sedentary time (SED‐time), time spent in moderate‐to‐vigorous‐intensity physical activity (MVPA) and total physical activity energy expenditure (PAEE) using a combined heart rate and movement sensor, and kidney function [estimated glomerular filtration rate (eGFR), serum creatinine and urine albumin‐to‐creatinine ratio (ACR)] at baseline and after 4 years of follow‐up. Multivariate regression was used to quantify the association between change in SED‐time, MVPA and PAEE and kidney measures at four‐year follow‐up, adjusting for change in current smoking status, waist circumference, HbA1c, systolic blood pressure, triglycerides and medication usage.ResultsOver 4 years, there was a decline in eGFR values from 87.3 to 81.7 ml/min/1.73m2 (P < 0.001); the prevalence of reduced eGFR (eGFR < 60 ml/min/1.73m2) increased from 6.1 to 13.2% (P < 0.001). There were small increases in serum creatinine (median: 81–84 μmol/l, P < 0.001) and urine ACR (median: 0.9–1.0 mg/mmol, P = 0.005). Increases in SED‐time were associated with increases in serum creatinine after adjustment for MVPA and cardiovascular risk factors (β = 0.013, 95% CI: 0.001, 0.03). Conversely, increases in PAEE were associated with reductions in serum creatinine (β = –0.001, 95% CI: –0.003, –0.0001).ConclusionReducing time spent sedentary and increasing overall physical activity may offer intervention opportunities to improve kidney function among individuals with diabetes. (Trial Registry no. ISRCTN 99175498)

Renal Failure and Heart Surgery

CSA-AKI is common after cardiac surgery, and even small increases in serum creatinine are associated with significant increases morbidity and mortality. A variety of risk factors have been identified for the development of CSA-AKI, but a precise precipitating event or events which lead to this complication have yet to be identified. Moreover, current diagnostic methods for detecting AKI lag behind the point of injury by 24-48 hours. Current technologies to close this gap include biomarkers and cerebral autoregulation monitoring data, but clear methodologies for their use have yet to be perfected. There have similarly been many failed interventions aimed at ameliorating AKI, though goal-directed perfusion strategies on CPB may hold promise.

The role of medications and their management in acute kidney injury.

Prior to 2002, the incidence of acute renal failure (ARF) varied as there was no standard definition. To better understand its incidence and etiology and to develop treatment and prevention strategies, while moving research forward, the Acute Dialysis Quality Initiative workgroup developed the RIFLE (risk, injury, failure, loss, end-stage kidney disease) classification. After continued data suggesting that even small increases in serum creatinine lead to worse outcomes, the Acute Kidney Injury Network (AKIN) modified the RIFLE criteria and used the term acute kidney injury (AKI) instead of ARF. These classification and staging systems provide the clinician and researcher a starting point for refining the understanding and treatment of AKI. An important initial step in evaluating AKI is determining the likely location of injury, generally classified as prerenal, renal, or postrenal. There is no single biomarker or test that definitively defines the mechanism of the injury. Identifying the insult(s) requires a thorough assessment of the patient and their medical and medication histories. Prerenal injuries arise primarily due to renal hypoperfusion. This may be the result of systemic or focal conditions or secondary to the effects of drugs such as nonsteroidal anti-inflammatory drugs, calcineurin inhibitors (CIs), and modulators of the renin–angiotensin–aldosterone system. Renal, or intrinsic, injury is an overarching term that represents complex conditions leading to considerable damage to a component of the intrinsic renal system (renal tubules, glomerulus, vascular structures, inter-stitium, or renal tubule obstruction). Acute tubular necrosis and acute interstitial nephritis are the more common types of intrinsic renal injury. Each type of injury has several drugs that are implicated as a possible cause, with antiinfectives being the most common. Postrenal injuries that result from obstruction block the flow of urine, leading to hydronephrosis and subsequent damage to the renal parenchyma. Drugs associated with tubular obstruction include acyclovir, methotrexate, and several antiretrovirals. Renal recovery from drug-induced AKI begins once the offending agent has been removed, if clinically possible, and is complete in most cases. It is uncommon that renal replacement therapy will be needed while recovery occurs. Pharmacists can play a pivotal role in identifying possible causes of drug-induced AKI and limit their toxic effect by identifying those most likely to cause or contribute to injury. Dose adjustment is critical during changes in renal function, and the pharmacist can ensure that optimal therapy is provided during this critical time.