Acute Respiratory Distress Syndrome and Risk of AKI among Critically Ill Patients

Background and objectives

Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients.

Design, setting, participants, & measurements

This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded.

Results

This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001).

Conclusions

ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.     

Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary bypass

Summary

Background and objectives

Acute kidney injury (AKI) complicating cardiopulmonary bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop AKI after CPB using semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were to quantitatively validate these findings with ELISA and evaluate the diagnostic performance of hepcidin-25 for AKI.

Design, setting, participants, & measurements

A nested, case-control analysis of urinary hepcidin-25 in AKI (n = 22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data at the following times: preoperatively; the start of CPB; 1 hour on CPB; on arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5. The diagnostic performance of hepcidin-25 was then evaluated in the entire prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50% from baseline, within 72 hours postoperatively.

Results

Urinary hepcidin-25/Cr ratio was significantly elevated in all patients at POD 1 compared with baseline (P < 0.0005) and was also significantly elevated in non-AKI versus AKI patients at POD 1 (P < 0.0005). Increased log₁₀ hepcidin-25/Cr ratio was strongly associated with avoidance of AKI on univariate analysis. On multivariate analysis, the log₁₀ hepcidin-25/Cr ratio (P < 0.0001) was associated with avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68, specificity 0.68, and negative predictive value 0.96.

Conclusions

Elevated urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond postoperative day 1.     

A Prospective International Multicenter Study of AKI in the Intensive Care Unit

Background and objectives

AKI is frequent and is associated with poor outcomes. There is limited information on the epidemiology of AKI worldwide. This study compared patients with AKI in emerging and developed countries to determine the association of clinical factors and processes of care with outcomes.

Design, setting, participants, & measurements

This prospective observational study was conducted among intensive care unit patients from nine centers in developed countries and five centers in emerging countries. AKI was defined as an increase in creatinine of ≥0.3 mg/dl within 48 hours.

Results

Between 2008 and 2012, 6647 patients were screened, of whom 1275 (19.2%) developed AKI. A total of 745 (58% of those with AKI) agreed to participate and had complete data. Patients in developed countries had more sepsis (52.1% versus 38.0%) and higher Acute Physiology and Chronic Health Evaluation (APACHE) scores (mean±SD, 61.1±27.5 versus 51.1±25.2); those from emerging countries had more CKD (54.3% versus 38.3%), GN (6.3% versus 0.9%), and interstitial nephritis (7.0% versus 0.6%) (all P<0.05). Patients from developed countries were less often treated with dialysis (15.5% versus 30.2%; P<0.001) and started dialysis later after AKI diagnosis (2.0 [interquartile range, 0.75–5.0] days versus 0 [interquartile range, 0–5.0] days; P=0.02). Hospital mortality was 22.0%, and 13.3% of survivors were dialysis dependent at discharge. Independent risk factors associated with hospital mortality included older age, residence in an emerging country, use of vasopressors (emerging countries only), dialysis and mechanical ventilation, and higher APACHE score and cumulative fluid balance (developed countries only). A lower probability of renal recovery was associated with residence in an emerging country, higher APACHE score (emerging countries only) and dialysis, while mechanical ventilation was associated with renal recovery (developed countries only).

Conclusions

This study contrasts the clinical features and management of AKI and demonstrates worse outcomes in emerging than in developed countries. Differences in variations in care may explain these findings and should be considered in future trials.     

AKI in Low-Risk versus High-Risk Patients in Intensive Care

Background and objectives

AKI in critically ill patients is usually part of multiorgan failure. However, nonrenal organ failure may not always precede AKI and patients without evidence of these organ failures may not be at low risk for AKI. This study examined the risk and outcomes associated with AKI in critically ill patients with and without cardiovascular or respiratory organ failures at presentation to the intensive care unit (ICU).

Design, setting, participants, & measurements

A large, academic medical center database, with records from July 2000 through October 2008, was used and the authors identified a low-risk cohort as patients without cardiovascular and respiratory organ failures defined as not receiving vasopressor support or mechanical ventilation within the first 24 hours of ICU admission. AKI was defined using Kidney Disease Improving Global Outcomes criteria. The primary end points were moderate to severe AKI (stages 2–3) and risk-adjusted hospital mortality.

Results

Of 40,152 critically ill patients, 44.9% received neither vasopressors nor mechanical ventilation on ICU day 1. Stages 2–3 AKI occurred less frequently in the low-risk patients versus high-risk patients within 24 hours (14.3% versus 29.1%) and within 1 week (25.7% versus 51.7%) of ICU admission. Patients developing AKI in both risk groups had higher risk of death before hospital discharge. However, the adjusted odds of hospital mortality were greater (odds ratio, 2.99; 95% confidence interval, 2.62 to 3.41) when AKI occurred in low-risk patients compared with those with respiratory or cardiovascular failures (odds ratio, 1.19; 95% confidence interval, 1.09 to 1.3); interaction P<0.001.

Conclusions

Patients admitted to ICU without respiratory or cardiovascular failure have a substantial likelihood of developing AKI. Although survival for low-risk patients is better than for high-risk patients, the relative increase in mortality associated with AKI is actually greater for low-risk patients. Strategies aimed at preventing AKI should not exclude ICU patients without cardiovascular or respiratory organ failures.     

The ABO Histo-Blood Group and AKI in Critically Ill Patients with Trauma or Sepsis

Background and objective

ABO blood types are determined by antigen modifications on glycoproteins and glycolipids and associated with altered plasma levels of inflammatory and endothelial injury markers implicated in AKI pathogenesis. We sought to determine the association of ABO blood types with AKI risk in critically ill patients with trauma or sepsis.

Design, setting, participants, & measurements

We conducted two prospective cohort studies at an urban, academic, level I trauma center and tertiary referral center; 497 patients with trauma admitted to the surgical intensive care unit between 2005 and 2010 with an injury severity score >15 and 759 patients with severe sepsis admitted to the medical intensive care unit between 2008 and 2013 were followed for 6 days for the development of incident AKI. AKI was defined by Acute Kidney Injury Network creatinine and dialysis criteria.

Results

Of 497 patients with trauma, 134 developed AKI (27%). In multivariable analysis, blood type A was associated with higher AKI risk relative to type O among patients of European descent (n=229; adjusted risk, 0.28 versus 0.14; risk difference, 0.14; 95% confidence interval, 0.03 to 0.24; P=0.02). Of 759 patients with sepsis, AKI developed in 326 (43%). Blood type A again conferred higher AKI risk relative to type O among patients of European descent (n=437; adjusted risk, 0.53 versus 0.40; risk difference, 0.14; 95% confidence interval, 0.04 to 0.23; P=0.01). Findings were similar when analysis was restricted to those patients who did not develop acute respiratory distress syndrome or were not transfused. We did not detect a significant association between blood type and AKI risk among individuals of African descent in either cohort.

Conclusions

Blood type A is independently associated with AKI risk in critically ill patients with trauma or severe sepsis of European descent, suggesting a role for ABO glycans in AKI susceptibility.     

Validation of the Kidney Disease Improving Global Outcomes Criteria for AKI and Comparison of Three Criteria in Hospitalized Patients

Background and objectives

AKI is a major clinical problem and predictor of outcome in hospitalized patients. In 2013, the Kidney Disease: Improving Global Outcomes (KDIGO) group published the third consensus AKI definition and classification system after the Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Kidney Disease (RIFLE) and the Acute Kidney Injury Network (AKIN) working group systems. It is unclear which system achieves optimal prognostication in hospital patients.

Design, setting, participants, & measurements

A retrospective observational study using hospital laboratory, admission, and discharge databases was performed that included adult patients admitted to a teaching hospital in Tokyo, Japan between April 1, 2008, and October 31, 2011. AKI occurring during each hospital stay was identified, and discriminative ability of each AKI classification system based on serum creatinine for the prediction of hospital mortality was assessed. The receiver operating characteristic curve, a graphical measure of test performance, and the area under the curve were used to evaluate how classifications preformed on the study population.

Results

In total, 49,518 admissions were studied, of which 11.0% were diagnosed with RIFLE criteria and 11.6% were diagnosed with KDIGO criteria, but only 4.8% were diagnosed with AKIN criteria. Overall hospital mortality was 3.0%. AKI staging and hospital mortality were closely correlated in all systems. Discrimination for hospital mortality was similar for RIFLE and KDIGO criteria (area under the curve=0.77 versus 0.78; P=0.02), whereas AKIN discrimination was inferior (area under the curve=0.69 versus RIFLE [P<0.001] versus KDIGO [P<0.001]).

Conclusion

Among hospital patients, KDIGO and RIFLE criteria achieved similar discrimination, but the discrimination of AKIN was inferior.     

Plasma Catalytic Iron,AKI, and Death among Critically Ill Patients

Background and objectives

Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.

Design, settings, participants, & measurements

A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.

Results

ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31–3.65] versus 0.29 µmol/l [0.22–0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r_s=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (r_s=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.

Conclusions

Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.     

Modality of RRT and Recovery of Kidney Function after AKI in Patients Surviving to Hospital Discharge

Background and objectives

Observational evidence has suggested that RRT modality may affect recovery after AKI. It is unclear whether initial choice of intermittent hemodialysis or continuous RRT affects renal recovery, survival, or development of ESRD in critically ill patients when modality choice is made primarily on hemodynamics.

Design, setting, participants, & measurements

We performed a retrospective cohort study examining adults (≥18 years old) admitted to intensive care units from 2000 to 2008 who received RRT for AKI and survived to hospital discharge or 90 days. We analyzed renal recovery (alive and not requiring RRT) and reasons for nonrecovery (death or ESRD) at 90 and 365 days. Conditional multivariable logistic regression was used to assess differences in renal recovery at 90 and 365 days between continuous RRT and intermittent hemodialysis. Models were stratified by propensity for continuous RRT and adjusted for age and reference creatinine.

Results

Of 4738 patients with Kidney Disease Improving Global Outcomes stage 3 AKI, 1338 (28.2%) received RRT, and 638 (47.7%) survived to hospital discharge (353 intermittent hemodialysis and 285 continuous RRT). Recovery from AKI was lower for intermittent hemodialysis versus continuous RRT at 90 days (66.6% intermittent hemodialysis versus 75.4% continuous RRT; P=0.02) but similar at 365 days (54.1% intermittent hemodialysis versus 59.6% continuous RRT; P=0.17). In multivariable analysis, there was no difference in odds of recovery at 90 or 365 days for patients initially treated with continuous RRT versus intermittent hemodialysis (90 days: odds ratio, 1.19; 95% confidence interval, 0.91 to 1.55; P=0.20; 365 days: odds ratio, 0.93; 95% confidence interval, 0.72 to 1.2; P=0.55).

Conclusions

We found no significant difference in hazards for nonrecovery or reasons for nonrecovery (mortality or ESRD) with intermittent hemodialysis versus continuous RRT. These results suggest that, when initial RRT modality is chosen primarily on hemodynamics, renal recovery and clinical outcomes in survivors are similar between intermittent hemodialysis and continuous RRT.     

Relationship between acute kidney injury before thoracic endovascular aneurysm repair and in-hospital outcomes in patients with type B acute aortic dissection

Objective Acute kidney injury (AKI) frequently occurs after catheter-based interventional procedures and increases mortality. However, the implications of AKI before thoracic endovascular aneurysm repair (TEVAR) of type B acute aortic dissection (AAD) remain unclear. This study evaluated the incidence, predictors, and in-hospital outcomes of AKI before TEVAR in patients with type B AAD. Methods Between 2009 and 2013, 76 patients were retrospectively evaluated who received TEVAR for type B AAD within 36 h from symptom onset. The patients were classified into no-AKI vs. AKI groups, and the severity of AKI was further staged according to kidney disease: improving global outcomes criteria before TEVAR. Results The incidence of preoperative AKI was 36.8%. In-hospital complications was significantly higher in patients with preoperative AKI compared with no-AKI (50.0% vs. 4.2%, respectively; P < 0.001), including acute renal failure (21.4% vs. 0, respectively; P < 0.001), and they increased with severity of AKI (P < 0.001). The maximum levels of body temperature and white blood cell count were significantly related to maximum serum creatinine level before TEVAR. Multivariate analysis showed that systolic blood pressure on admission (OR: 1.023; 95% CI: 1.003–1.044; P = 0.0238) and bilateral renal artery involvement (OR: 19.076; 95% CI: 1.914–190.164; P = 0.0120) were strong predictors of preoperative AKI. Conclusions Preoperative AKI frequently occurred in patients with type B AAD, and correlated with higher in-hospital complications and enhanced inflammatory reaction. Systolic blood pressure on admission and bilateral renal artery involvement were major risk factors for AKI before TEVAR.     

Follow-Up Renal Assessment of Injury Long-Term After Acute Kidney Injury (FRAIL-AKI)

Background and objectives

Novel urinary kidney damage biomarkers detect AKI after cardiac surgery using cardiopulmonary bypass (CPB-AKI). Although there is growing focus on whether AKI leads to CKD, no studies have assessed whether novel urinary biomarkers remain elevated long term after CPB-AKI. We assessed whether there was clinical or biomarker evidence of long-term kidney injury in patients with CPB-AKI.

Design, setting, participants, & measurements

We performed a cross-sectional evaluation for signs of chronic kidney injury using both traditional measures and novel urinary biomarkers in a population of 372 potentially eligible children (119 AKI positive and 253 AKI negative) who underwent surgery using cardiopulmonary bypass for congenital heart disease at Cincinnati Children’s Hospital Medical Center between 2004 and 2007. A total of 51 patients (33 AKI positive and 18 AKI negative) agreed to long-term assessment. We also compared the urinary biomarker levels in these 51 patients with those in healthy controls of similar age.

Results

At long-term follow-up (mean duration±SD, 7±0.98 years), AKI-positive and AKI-negative patients had similarly normal assessments of kidney function by eGFR, proteinuria, and BP measurement. However, AKI-positive patients had higher urine concentrations of IL-18 (48.5 pg/ml versus 20.3 pg/ml [P=0.01] and 20.5 pg/ml [P<0.001]) and liver-type fatty acid–binding protein (L-FABP) (5.9 ng/ml versus 3.9 ng/ml [P=0.001] and 3.2 ng/ml [P<0.001]) than did AKI-negative patients and healthy controls.

Conclusions

Novel urinary biomarkers remain elevated 7 years after an episode of CPB-AKI in children. However, there is no conventional evidence of CKD in these children. These biomarkers may be a more sensitive marker of chronic kidney injury after CPB-AKI. Future studies are needed to understand the clinical relevance of persistent elevations in IL-18, kidney injury molecule-1, and L-FABP in assessments for potential long-term kidney consequences of CPB-AKI.     

Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

Background

Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity.

Objective

Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III.

Methods

Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C₁₅ and Ob₁₅) and 30 (C₃₀ and Ob₃₀) consecutive weeks. Obesity was determined by adiposity index.

Results

The Ob₁₅ group was similar to the C₁₅ group regarding the expression of myocardial collagen type I; however, expression in the Ob₃₀ group was less than C₃₀ group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob₃₀ when compared with Ob₁₅. Obesity did not affect collagen type III expression.

Conclusion

This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression.     

Fluid Balance,Diuretic Use,and Mortality in Acute Kidney Injury

Summary

Background and objectives

Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients.

Design, setting, participants, & measurements

Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria.

Results

306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P = 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased.

Conclusions

A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance.     

AKI in Hospitalized Children: Comparing the pRIFLE,AKIN, and KDIGO Definitions

Background and objectives

Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.

Design, setting, participants, & measurements

Observational, electronic medical record–enabled study of 14,795 hospitalizations at the Lucile Packard Children’s Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov–Smirnov tests, respectively.

Results

AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%–1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.

Conclusions

Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.     

Renal Outcomes in Critically Ill Patients Receiving Propofol or Midazolam

Background and objectives

Propofol has been shown to provide protection against renal ischemia/reperfusion injury experimentally, but clinical evidence is limited to patients undergoing cardiac surgery. There are no data about its association with oliguria and AKI in critically ill patients.

Design, setting, participants, & measurements

We obtained data from the Multiparameter Intelligent Monitoring in Intensive Care II database (2001–2008). Patient selection criteria included adult patients in their first intensive care unit (ICU) admission, need for mechanical ventilation, and treatment with propofol or midazolam. Propensity score analysis (1:1) was used and renal-related outcomes (AKI, oliguria, cumulative fluid balance, and need for RRT) were evaluated during the first 7 days of ICU stay.

Results

There were 1396 propofol/midazolam-matched patients. AKI in the first 7-day ICU time period was statistically lower in propofol-treated patients compared with midazolam-treated patients (55.0% versus 67.3%, P<0.001). Propofol was associated with lower AKI incidence using both urine output (45.0% versus 55.7%, P<0.001) and serum creatinine criteria (28.8% versus 37.2%, P=0.001). Patients receiving propofol had oliguria (<400 ml/d) less frequently (12.4% versus 19.6%, P=0.001) and had diuretics prescribed less often (8.5% versus 14.3%, P=0.001). In addition, during the first 7 days of ICU stay, patients receiving propofol less frequently achieved cumulative fluid balance >5% of body weight (50.1% versus 58.3%, P=0.01). The need for RRT in the first 7 days of ICU stay was also less frequent in propofol-treated patients (3.4% versus 5.9%, P=0.03). ICU mortality was lower in propofol-treated patients (14.6% versus 29.7%, P<0.001).

Conclusions

In this large, propensity-matched ICU population, patients treated with propofol had a lower risk of AKI, fluid-related complications, and need for RRT.     

HMG–CoA Reductase Activation and Urinary Pellet Cholesterol Elevations in Acute Kidney Injury

Summary

Background and objectives

Experimental acute kidney injury (AKI) activates the HMG–CoA reductase (HMGCR) gene, producing proximal tubule cholesterol loading. AKI also causes sloughing of proximal tubular cell debris into tubular lumina. This study tested whether these two processes culminate in increased urinary pellet cholesterol content, and whether the latter has potential AKI biomarker utility.

Design, setting, participants, & measurements

Urine samples were collected from 29 critically ill patients with (n = 14) or without (n= 15) AKI, 15 patients with chronic kidney disease, and 15 healthy volunteers. Centrifuged urinary pellets underwent lipid extraction, and the extracts were assayed for cholesterol content (factored by membrane phospholipid phosphate content). In vivo HMGCR activation was sought by measuring levels of RNA polymerase II (Pol II), and of a gene activating histone mark (H3K4m3) at exon 1 of the HMGCR gene (chromatin immunoprecipitation assay of urine chromatin samples).

Results

AKI+ patients had an approximate doubling of urinary pellet cholesterol content compared with control urine samples (versus normal; P < 0.001). The values significantly correlated (r, 0.5; P < 0.01) with serum, but not urine, creatinine concentrations. Conversely, neither critical illness without AKI nor chronic kidney disease raised pellet cholesterol levels. Increased HMGCR activity in the AKI+ patients was supported by three- to fourfold increased levels of Pol II, and of H3K4m3, at the HMGCR gene (versus controls or AKI− patients).

Conclusions

(1) Clinical AKI, like experimental AKI, induces HMGCR gene activation; (2) increased urinary pellet cholesterol levels result; and (3) urine pellet cholesterol levels may have potential AKI biomarker utility. The latter will require future testing in a large prospective trial.     

Peripheral Edema,Central Venous Pressure,and Risk of AKI in Critical Illness

Background and objectives

Although venous congestion has been linked to renal dysfunction in heart failure, its significance in a broader context has not been investigated.

Design, setting, participants, & measurements

Using an inception cohort of 12,778 critically ill adult patients admitted to an urban tertiary medical center between 2001 and 2008, we examined whether the presence of peripheral edema on admission physical examination was associated with an increased risk of AKI within the first 7 days of critical illness. In addition, in those with admission central venous pressure (CVP) measurements, we examined the association of CVPs with subsequent AKI. AKI was defined using the Kidney Disease Improving Global Outcomes criteria.

Results

Of the 18% (n=2338) of patients with peripheral edema on admission, 27% (n=631) developed AKI, compared with 16% (n=1713) of those without peripheral edema. In a model that included adjustment for comorbidities, severity of illness, and the presence of pulmonary edema, peripheral edema was associated with a 30% higher risk of AKI (95% confidence interval [95% CI], 1.15 to 1.46; P<0.001), whereas pulmonary edema was not significantly related to risk. Peripheral edema was also associated with a 13% higher adjusted risk of a higher AKI stage (95% CI, 1.07 to 1.20; P<0.001). Furthermore, levels of trace, 1+, 2+, and 3+ edema were associated with 34% (95% CI, 1.10 to 1.65), 17% (95% CI, 0.96 to 1.14), 47% (95% CI, 1.18 to 1.83), and 57% (95% CI, 1.07 to 2.31) higher adjusted risk of AKI, respectively, compared with edema-free patients. In the 4761 patients with admission CVP measurements, each 1 cm H₂O higher CVP was associated with a 2% higher adjusted risk of AKI (95% CI, 1.00 to 1.03; P=0.02).

Conclusions

Venous congestion, as manifested as either peripheral edema or increased CVP, is directly associated with AKI in critically ill patients. Whether treatment of venous congestion with diuretics can modify this risk will require further study.     

Factors associated with delayed gastric emptying after pancreaticoduodenectomy

Background

The factors associated with delayed gastric emptying (DGE) after a pancreaticoduodenectomy (PD) are not definitively known.

Methods

From November 2011 through to May 2012, data were prospectively collected on 711 patients undergoing a pancreaticoduodenectomy or total pancreatectomy as part of the American College of Surgeons-National Surgical Quality Improvement Program Pancreatectomy Demonstration Project. Bivariate and multivariate models were employed to determine the factors that predicted DGE.

Results

In the 711 patients, the overall rate of DGE was 20.1%. In a bivariate analysis, intra-operative factors such as pylorus-preservation (47.1% versus 43.7%, P = 0.40), intra-operative drain placement (85.5%, versus 85.1%, P = 0.91) and an antecolic compared with a retrocolic gastrojejunostomy (60.1% versus 65.1%, P = 0.26) were not different between the DGE and no DGE groups. Pancreatic fistula formation (31.2% versus 10.1%), post-operative sepsis (21.7% versus 7.0%), organ space surgical site infection (SSI) (23.9% versus 7.9%), need for percutaneous drainage (23.0% versus 10.6%) and reoperation (10.6% versus 3.1%) were higher in patients with DGE (P < 0.0001). In a multivariable model, only pancreatic fistula, post-operative sepsis and reoperation were independently associated with DGE.

Discussion

In this multicentre study, only post-operative complications were associated with DGE. Neither pylorus preservation nor route of enteric reconstruction (antecolic versus retrocolic) was associated with delayed gastric emptying.     

Prophylactic positive end-expiratory pressure and postintubation hemodynamics: An interventional, randomized study

OBJECTIVE:

To investigate the hemodynamic and outcome effects of implementing prophylactic positive end-expiratory pressure (PEEP) versus zero end-expiratory pressure (ZEEP) in patients during the postintubation period in the emergency setting.

METHODS:

The present study was a prospective, single-centre, interventional, single-blinded randomized trial performed in a 16-bed medical intensive care unit. The study cohort consisted of consecutive patients who urgently required intubation. During the postintubation period, patients received either 5 cmH₂O PEEP or ZEEP. The primary aim was to assess the variation in mean arterial pressure (MAP) from baseline up to 90 min postintubation. The secondary aim was to determine the mean duration of intubation, level of MAP support after intubation and 28-day mortality.

RESULTS:

Seventy-five consecutive patients with similar mean (± SD) baseline characteristics and preintubation MAP (76±18 mmHg in the ZEEP group and 78.5±23 mmHg in the PEEP group, P=Not significant [NS]) were studied. The final analysis was performed in 33 patients in the ZEEP group and 30 patients in the PEEP group. Regarding outcome measures following intubation, delta MAP (ie, the difference between the lowest MAP values from baseline) was not differentially affected in either group (P=NS); the mean durations of intubation were similar (ZEEP 9.2±8.5 days versus PEEP 9.2±8.8 days, P=NS); 28-day mortality was not discriminative (ZEEP 14 of 33, PEEP nine of 30; P=NS); and levels of MAP support after intubation were comparable between the two groups. .

CONCLUSION:

In the present trial, there was no evidence that implementing a prophylactic PEEP of 5 cmH₂O adversely affects short-term hemodynamics or outcome in medical intensive care patients during the postintubation period.     

AKI in Children Hospitalized with Nephrotic Syndrome

Background and objectives

Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome.

Design, setting, participants, & measurements

Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition.

Results

AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001).

Conclusions

AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.     

Incorporation of Biomarkers with the Renal Angina Index for Prediction of Severe AKI in Critically Ill Children

Background and objectives

Novel AKI biomarkers carry variable performance for prediction of AKI in patients with heterogeneous illness. Until utility is demonstrated in critically ill patients outside of the cardiopulmonary bypass population, AKI biomarkers are unlikely to gain widespread implementation. Operationalization of an AKI risk stratification methodology, termed renal angina, was recently reported to enhance prediction at the time of intensive care unit admission for persistent severe AKI. The renal angina index (RAI) was developed to provide the clinical context to direct AKI biomarker testing. This study tested the hypothesis that incorporation of AKI biomarkers in patients fulfilling renal angina improves the prediction of persistent severe AKI.

Design, setting, participants, & measurements

In a multicenter study of 214 patients admitted to the pediatric intensive care unit with sepsis, the discrimination of plasma neutrophil gelatinase–associated lipocalin (NGAL), matrix metalloproteinase-8 (MMP-8), and neutrophil elastase-2 (Ela-2) were determined individually and in combination with the RAI for severe AKI. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated.

Results

Individual biomarkers demonstrated marginal discrimination for severe AKI (area under curve [AUC]: NGAL, 0.72; MMP-8, 0.68; Ela-2, 0.72), inferior to prediction by the clinical model of the RAI (AUC=0.80). Incorporation of each biomarker significantly added to the renal angina model AKI prediction (AUC=0.80, increased to 0.84–0.88; P<0.05 for each). The inclusion of each biomarker with the RAI demonstrated NRI (0.512, 0.428, and 0.545 for NGAL, MMP-8, and Ela-2, respectively; all P<0.03) and IDI (0.075 for Ela-2). The inclusion of both Ela-2 and NGAL with RAI demonstrated an NRI of 0.871 (P<0.001) and an IDI of 0.1 (P=0.01).

Conclusions

This study shows that incorporation of AKI biomarkers into the RAI improves discrimination for severe AKI. The RAI optimizes the utility of AKI biomarkers in a heterogeneous, critically ill patient population.