Risk of poor outcomes with novel and traditional biomarkers at clinical AKI diagnosis

Summary

Background and objectives

Studies have evaluated acute kidney injury (AKI) using biomarkers in various settings, but their prognostic utility within current practice is unclear. Thus, we sought to determine the prognostic utility of newer biomarkers or traditional markers (fractional excretion of sodium [FeNa] and urea [FeUrea] and microscopy) over clinical assessment alone.

Design, setting, participants, & measurements

This is a prospective cohort study of adults on the first day of meeting AKI criteria. We measured urine concentrations of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and IL-18 and determined FeNa, FeUrea, and microscopy score for casts and tubular cells. Primary outcome was worsened AKI stage from enrollment to peak serum creatinine or in-hospital death.

Results

In 249 recipients, 57% were ≥65 years old, 48% were from intensive care, and mean baseline GFR was 69 ± 30 ml/min per 1.73 m². AKI was considered prerenal in 164 (66%), acute tubular necrosis (ATN) in 51 (20%), and “other” in 34 (14%). All mean protein biomarker concentrations, FeNa, FeUrea, and microscopy scores were statistically different between prerenal and ATN. Seventy-two patients (29%) developed the primary outcome. There was an approximate three-fold increase in adjusted risk for the outcome for upper versus lower values of NGAL, KIM-1, IL-18, and microscopy score (P values <0.05). Net reclassification improved after adding these to baseline clinical assessment. FeNa and FeUrea were not useful.

Conclusions

On the first day of AKI, urine protein biomarkers and microscopy significantly improve upon clinical determination of prognosis, indicating their potential utility in current practice.     

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.     

Association between AKI and Long-Term Renal and Cardiovascular Outcomes in United States Veterans

Background and objectives

AKI is associated with major adverse kidney events (MAKE): death, new dialysis, and worsened renal function. CKD (arising from worsened renal function) is associated with a higher risk of major adverse cardiac events (MACE): myocardial infarction (MI), stroke, and heart failure. Therefore, the study hypothesis was that veterans who develop AKI during hospitalization for an MI would be at higher risk of subsequent MACE and MAKE.

Design, setting, participants, & measurements

Patients in the Veterans Affairs (VA) database who had a discharge diagnosis with International Classification of Diseases, Ninth Revision, code of 584.xx (AKI) or 410.xx (MI) and were admitted to a VA facility from October 1999 through December 2005 were selected for analysis. Three groups of patients were created on the basis of the index admission diagnosis and serum creatinine values: AKI, MI, or MI with AKI. Patients with mean baseline estimated GFR<45 ml/min per 1.73 m² were excluded. The primary outcomes assessed were mortality, MAKE, and MACE during the study period (maximum of 6 years). The combination of MAKE and MACE—major adverse renocardiovascular events (MARCE)—was also assessed.

Results

A total of 36,980 patients were available for analysis. Mean age±SD was 66.8±11.4 years. The most deaths occurred in the MI+AKI group (57.5%), and the fewest (32.3%) occurred in patients with an uncomplicated MI admission. In both the unadjusted and adjusted time-to-event analyses, patients with AKI and AKI+MI had worse MARCE outcomes than those who had MI alone (adjusted hazard ratios, 1.37 [95% confidence interval, 1.32 to 1.42] and 1.92 [1.86 to 1.99], respectively).

Conclusions

Veterans who develop AKI in the setting of MI have worse long-term outcomes than those with AKI or MI alone. Veterans with AKI alone have worse outcomes than those diagnosed with an MI in the absence of AKI.     

Hospital-acquired Acute Kidney Injury: An Analysis of Nadir-to-Peak Serum Creatinine Increments Stratified by Baseline Estimated GFR

Summary

Background and objectives

Serum creatinine (sCr) increments currently used to define acute kidney injury (AKI) do not take into consideration the baseline level of kidney function. The objective of this study was to establish whether baseline estimated GFR (eGFR) provides additional risk stratification to sCr-based increments for defining AKI.

Design, setting, participants, & measurements

29,645 adults hospitalized at an acute care facility were analyzed. Hospital-acquired AKI was defined by calculating the difference between the nadir and subsequent peak sCr.

Results

Different thresholds of nadir-to-peak sCr were found to be independently associated with increased in-hospital mortality according to baseline eGFR strata. A nadir-to-peak sCr minimum threshold of ≥0.2, ≥0.3, and ≥0.5 mg/dl was required to be independently associated with increased in-hospital mortality among patients with baseline eGFR ≥60 ml/min per 1.73 m² (odds ratio [OR] 1.67; 95% confidence interval [CI] 1.13 to 2.47), 30 to 59 ml/min per 1.73 m² (OR 2.69; 95% CI, 1.82 to 3.97), and <30 ml/min per 1.73 m² (OR 2.15; 95% CI 1.02 to 4.51), respectively. There was a significant interaction between the nadir-to-peak sCr and baseline eGFR for in-hospital mortality (P < 0.001). Using these thresholds, survivors of AKI episodes had an increased hospital length of stay and were more likely to be discharged to a facility rather than home. Sensitivity analyses showed a significant interaction between baseline eGFR strata and relative increases in sCr, as well as absolute and relative decreases in eGFR for in-hospital mortality (P < 0.001).

Conclusions

This study suggests that future sCr-based definitions of AKI should take into consideration baseline eGFR.     

Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery: The Effect of Baseline Renal Function on Diagnostic Performance

Background and objectives: Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules after injury, potentially allowing early identification of acute kidney injury (AKI) after cardiac surgery. However, the diagnostic performance of NGAL has varied widely in clinical studies, and it remains unknown what factors modify the relationship between NGAL and AKI. We hypothesized the relationship between urinary NGAL and AKI would vary with baseline renal function, allowing a stratified analysis to improve diagnostic performance of this novel biomarker.Design, setting, participants, & measurements: We performed a prospective observational study in 426 adult cardiac surgical patients. Urinary NGAL was serially determined, commencing preoperatively and continuing 24 hours postoperatively. AKI was defined as increase in serum creatinine from baseline by either >50% or >0.3 mg/dl within 48 hours postoperatively. Patients were stratified by baseline estimated GFR (eGFR). NGAL levels were compared between patients with and without AKI and diagnostic characteristics determined according to baseline eGFR.Results: In patients with baseline eGFR ≥60 ml/min, urinary NGAL was higher at all postoperative time points in patients who developed AKI compared with those who did not. In patients with baseline eGFR <60 ml/min, urinary NGAL did not differ at any time between those who did and those who did not develop AKI. Postoperative NGAL best identified AKI in patients with baseline eGFR 90 to 120 ml/min.Conclusions: The relationship between urinary NGAL and AKI after cardiac surgery varies with baseline renal function, with optimal discriminatory performance in patients with normal preoperative function.Acute Kidney Injury (AKI) is a common complication after cardiac surgery, with reported incidence varying from 20% to 50% depending on the definition used (1–4). Early detection of injury is desirable to facilitate early intervention aimed at limiting associated morbidity and mortality. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules in response to injury, and an acute rise in urinary NGAL has been reported to accurately identify evolving AKI in both pediatric and adult populations within 2 to 8 hours of cardiac surgery (5–9). However, other studies have found urinary NGAL to have only modest discriminant ability for AKI after cardiac surgery (3,10). Studies reporting excellent discriminant ability have generally excluded patients with preoperative renal dysfunction, whereas those studies reporting a more modest performance have included patients with a heterogeneous mix of baseline renal function. Although it is unknown whether baseline renal function modifies the relationship between NGAL and AKI, the existence of such a relationship may contribute to the limited predictive ability in these studies. Although NGAL is proposed as a real-time marker of acute renal injury rather than renal function, the nonlinear relationship between GFR and serum creatinine may mean that a relatively larger injury, producing a larger reduction in GFR, is required to cause a rise in serum creatinine sufficient to meet diagnostic criteria for AKI in a patient with normal baseline GFR. Conversely, a much smaller injury (and smaller incremental reduction in GFR) may be sufficient to cause a rise in creatinine that would diagnose AKI in a patient with impaired GFR at baseline. If true, the diagnostic utility of urinary NGAL for a creatinine-based diagnosis of AKI may be enhanced using an approach stratified by baseline renal function. We have previously reported a modest performance of urinary NGAL for early identification of evolving AKI in a large, unselected adult population undergoing cardiac surgery, with a wide range of baseline renal function. In this posthoc analysis we sought to investigate this potential source of effect modification to the relationship between NGAL and postoperative AKI. We hypothesized that the relationship between postoperative urinary NGAL and AKI would vary with baseline renal function, measured by estimated GFR (eGFR). We further hypothesized that the diagnostic performance of NGAL for postoperative AKI would be improved using an analysis stratified by baseline function, allowing the use of different diagnostic thresholds.     

Factors Associated with Recovery of Renal Function following Radical Nephrectomy for Kidney Neoplasms

Background and objectives

Partial nephrectomy or radical nephrectomy is the standard of care for patients with kidney neoplasms, but surgery may result in loss of renal function. We sought to identify patient characteristics associated with renal functional recovery following radical nephrectomy.

Design, setting, participants, & measurements

We performed a retrospective study among 572 patients with kidney neoplasms who underwent RN between 2006 and 2013. The primary endpoint was recovery of postoperative eGFR to the preoperative level. We plotted the trajectory of each patient’s eGFR from their first postoperative visit up to 3 years after surgery. Cumulative incidence and competing risks regression estimated associations between patient and clinical characteristics and eGFR recovery, stratified by preoperative eGFR.

Results

Median age was 61.5 years; 68% of patients were male, and 89% were white. Overall, eGFR increased over time following an initial postoperative decrease. Median postoperative follow-up among survivors was 10.8 (minimum, 0.03; maximum, 36.0) months; during follow-up, 263 patients achieved eGFR recovery. Median time to eGFR recovery was 25.3 months. Two-year cumulative incidence of eGFR recovery was 49% overall and 44% and 58% among those with preoperative eGFR≥60 and <60 ml/min per 1.73 m², respectively (P<0.001). On multivariable analysis, younger age at surgery and female sex were significantly associated with a higher chance of eGFR recovery among patients with preoperative eGFR<60 ml/min per 1.73 m². Among patients with preoperative eGFR≥60 ml/min per 1.73 m², hypertension was significantly associated with a lower chance of eGFR recovery, whereas increased tumor size was significantly associated with a higher chance of eGFR recovery.

Conclusions

Overall, almost half of the patients in this study recovered to their preoperative eGFR by 2 years following surgery. Distributions of preoperative risk factors differed by preoperative eGFR, leading to distinct factors that were significantly associated with chance of eGFR recovery.     

Urinary Biomarkers and Renal Recovery in Critically Ill Patients with Renal Support

Summary

Background and objectives

Despite significant advances in the epidemiology of acute kidney injury (AKI), prognostication remains a major clinical challenge. Unfortunately, no reliable method to predict renal recovery exists. The discovery of biomarkers to aid in clinical risk prediction for recovery after AKI would represent a significant advance over current practice.

Design, setting, participants, & measurements

We conducted the Biological Markers of Recovery for the Kidney study as an ancillary to the Acute Renal Failure Trial Network study. Urine samples were collected on days 1, 7, and 14 from 76 patients who developed AKI and received renal replacement therapy (RRT) in the intensive care unit. We explored whether levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary hepatocyte growth factor (uHGF), urinary cystatin C (uCystatin C), IL-18, neutrophil gelatinase-associated lipocalin/matrix metalloproteinase-9, and urine creatinine could predict subsequent renal recovery.

Results

We defined renal recovery as alive and free of dialysis at 60 days from the start of RRT. Patients who recovered had higher uCystatin C on day 1 (7.27 versus 6.60 ng/mg·creatinine) and lower uHGF on days 7 and 14 (2.97 versus 3.48 ng/mg·creatinine; 2.24 versus 3.40 ng/mg·creatinine). For predicting recovery, decreasing uNGAL and uHGF in the first 14 days was associated with greater odds of renal recovery. The most predictive model combined relative changes in biomarkers with clinical variables and resulted in an area under the receiver-operator characteristic curve of 0.94.

Conclusions

We showed that a panel of urine biomarkers can augment clinical risk prediction for recovery after AKI.     

Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury

Summary

Background and objectives

To date there is no reliable marker for the differentiation of prerenal and intrinsic acute kidney injury (AKI). We investigated whether urinary calprotectin, a mediator protein of the innate immune system, may serve as a diagnostic marker in AKI.

Design, setting, participants, & measurements

This was a cross-sectional study with 101 subjects including 86 patients with AKI (34 prerenal, 52 intrinsic including 23 patients with urinary tract infection) and 15 healthy controls. Assessment of urinary calprotectin concentration was by ELISA and immunohistochemistry of kidney biopsy specimens using a calprotectin antibody. Inclusion criteria were: admission to hospital for AKI stage 1 to 3 (Acute Kidney Injury Network); exclusion criteria were: prior renal transplantation and obstructive uropathy.

Results

Median urinary calprotectin was 60.7 times higher in intrinsic AKI (1692 ng/ml) than in prerenal AKI (28 ng/ml, p <0.01). Urinary calprotectin in prerenal disease was not significantly different from healthy controls (45 ng/ml, p = 0.25). Receiver operating curve curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.97) in predicting intrinsic AKI. A cutoff level of 300 ng/ml provided a sensitivity of 92.3% and a specificity of 97.1%. Calculating urinary calprotectin/creatinine ratios did not lead to a further increase of accuracy. Immunostainings of kidney biopsies were positive for calprotectin in intrinsic AKI and negative in prerenal AKI.

Conclusions

Accuracy of urinary calprotectin in the differential diagnosis of AKI is high. Whereas calprotectin levels in prerenal disease are comparable with healthy controls, intrinsic AKI leads to highly increased calprotectin concentrations.     

Associations among Estimated Glomerular Filtration Rate,Proteinuria, and Adverse Cardiovascular Outcomes

Summary

Background and objectives

Most studies of chronic kidney disease (CKD) and outcomes focus on mortality and ESRD, with limited data on other adverse outcomes. This study examined the associations among proteinuria, eGFR, and adverse cardiovascular (CV) events.

Design, setting, participants, & measurements

This was a population-based longitudinal study with patients identified from province-wide laboratory data from Alberta, Canada, between 2002 and 2007. Selected for this study from a total of 1,526,437 patients were 920,985 (60.3%) patients with at least one urine dipstick measurement and 102,701 patients (6.7%) with at least one albumin-creatinine ratio (ACR) measurement. Time to hospitalization was considered for one of four indications: congestive heart failure (CHF), coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), peripheral vascular disease (PVD), and stroke/transient ischemic attacks [TIAs] (cerebrovascular accident [CVA]/TIA).

Results

After a median follow-up of 35 months, in fully adjusted models and compared with patients with estimated GFR (eGFR) of 45 to 59 ml/min per 1.73 m² and no proteinuria, patients with heavy proteinuria by dipstick and eGFR ≥ 60 ml/min per 1.73 m² had higher rates of CABG/PCI and CVA/TIA. Similar results were obtained in patients with proteinuria measured by ACR.

Conclusions

Risks of major CV events at a given level of eGFR increased with higher levels of proteinuria. The findings extend current data on risk of mortality and ESRD. Measurement of proteinuria is of incremental prognostic benefit at every level of eGFR. The data support use of proteinuria measurement with eGFR for definition and risk stratification in CKD.     

Assessment of KDIGO Definitions in Patients with Histopathologic Evidence of Acute Renal Disease

Background and objectives

AKI is a clinical syndrome with various causes involving glomerular, interstitial, tubular, and vascular compartments of the kidney. Acute kidney disease (AKD) is a new concept that includes both AKI and the conditions associated with subacute decreases in GFR (AKD/non-AKI). This study aimed to investigate the correlation between AKI/AKD defined by clinical presentation and diffuse histologic criteria for acute abnormalities based on renal biopsy.

Design, setting, participants, & measurements

All 303 patients who were histologically diagnosed as having acute tubular necrosis (ATN), acute tubulointerstitial nephritis, cellular crescentic GN, acute thrombotic microangiopathy, or complex lesions on renal biopsy from January 2009 to December 2011 were enrolled in the study. The 2012 Kidney Disease Improving Global Outcomes AKD/AKI definitions were applied to classify patients as follows: AKI, AKD/non-AKI, non-AKD, or unclassified.

Results

A total of 273 patients (90.1%) met the AKD criteria; 198 patients (65.3%) were classified as having AKI according to serum creatinine (SCr) and urine output criteria. The urine output criteria added 4.3% to the SCr criteria and reclassified 6.7% of the AKI cases into higher stages. Of patients with ATN on pathology, 79.2% met AKI criteria; this was a higher percentage than for those who had other individual pathologic lesions (50%–64%). The major cause of not being defined as having AKI was a slower SCr increase than that required by the definition of AKI (98, 93.3%). Patients with AKI had more severe clinical conditions and worse short-term renal outcome than those in the non-AKI group.

Conclusions

Diffuse, acute abnormality defined by renal biopsy and AKI defined by clinical presentation are two different entities. Most patients who have diffuse acute histologic findings met the criteria for AKD, whereas only two thirds met the definition of AKI.     

Neutrophil Gelatinase-Associated Lipocalin as an Early Sign of Diabetic Kidney Injury in Children

Objective:

There is some evidence indicating that histopathological changes in type 1 diabetes mellitus (T1DM) emerge before onset of microalbuminuria. The aim of our study was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) levels can be considered as an early sign of diabetic kidney injury.

Methods:

Urine NGAL (uNGAL) levels and urinary NGAL/creatinine ratio (uNGAL/Cr) were assessed in 76 patients with T1DM and compared with the findings of 35 healthy individuals. The relationship of uNGAL levels with diabetes duration, body mass index (BMI), serum lipids, HbA1c, and microalbuminuria was also evaluated.

Results:

Mean uNGAL (100.16±108.28 ng/mL) and uNGAL/Cr (118.93-117.97 ng/mg) levels in both microalbuminuric and non-microalbuminuric diabetic patients were found to be higher than those in the control group (uNGAL: 21.46±18.59 ng/mL and uNGAL/Cr: 32.1±51.48 ng/mg) (p=0.0001).

Conclusion:

Urine NGAL level increases in the very early phase of T1DM before microalbuminuria develops. The patients with T1DM should be considered to have diabetic kidney injury from the time of diagnosis on and preventive interventions need to be initiated at an early stage to preclude the progression to end-stage renal disease.     

Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience

Summary

Background and objectives

Autosomal dominant polycystic kidney disease (ADPKD), a frequent cause of end-stage renal disease, has no cure. V2-specific vasopressin receptor antagonists delay disease progression in animal models.

Design, setting, participants, and measurements

This is a prospectively designed analysis of annual total kidney volume (TKV) and thrice annual estimated GFR (eGFR) measurements, from two 3-year studies of tolvaptan in 63 ADPKD subjects randomly matched 1:2 to historical controls by gender, hypertension, age, and baseline TKV or eGFR. Prespecified end points were group differences in log-TKV (primary) and eGFR (secondary) slopes for month 36 completers, using linear mixed model (LMM) analysis. Sensitivity analyses of primary and secondary end points included LMM using all subject data and mixed model repeated measures (MMRM) of change from baseline at each year. Pearson correlation tested the association between log-TKV and eGFR changes.

Results

Fifty-one subjects (81%) completed 3 years of tolvaptan therapy; all experienced adverse events (AEs), with AEs accounting for six of 12 withdrawals. Baseline TKV (controls 1422, tolvaptan 1635 ml) and eGFR (both 62 ml/min per 1.73 m²) were similar. Control TKV increased 5.8% versus 1.7%/yr for tolvaptan (P < 0.001, estimated ratio of geometric mean 0.96 [95% confidence interval 0.95 to 0.97]). Corresponding annualized eGFR declined: −2.1 versus −0.71 ml/min per 1.73 m²/yr (P = 0.01, LMM group difference 1.1 ml/min per 1.73 m²/yr [95% confidence interval 0.24 to 1.9]). Sensitivity analyses including withdrawn subjects were similar, whereas MMRM analyses were significant at each year for TKV and nonsignificant for eGFR. Increasing TKV correlated with decreasing eGFR (r = −0.21, P < 0.01).

Conclusion

ADPKD cyst growth progresses more slowly with tolvaptan than in historical controls, but AEs are common.     

A Nurse-coordinated Model of Care versus Usual Care for Stage 3/4 Chronic Kidney Disease in the Community: A Randomized Controlled Trial

Summary

Background and objectives

It is unclear how to optimally care for chronic kidney disease (CKD). This study compares a new coordinated model to usual care for CKD.

Design, setting, participants, & measurements

A randomized trial in nephrology clinics and the community included 474 patients with median estimated GFR (eGFR) 42 ml/min per 1.73 m² identified by laboratory-based case finding compared care coordinated by a general practitioner (controls) with care by a nurse-coordinated team including a nephrologist (intervention) for a median (interquartile range [IQR]) of 742 days. 32% were diabetic, 60% had cardiovascular disease, and proteinuria was minimal. Guided by protocols, the intervention team targeted risk factors for adverse kidney and cardiovascular outcomes. Serial eGFR and clinical events were tracked.

Results

The average decline in eGFR over 20 months was −1.9 ml/min per 1.73 m². eGFR declined by ≥4 ml/min per 1.73 m² within 20 months in 28 (17%) intervention patients versus 23 (13.9%) control patients. Control of BP, LDL, and diabetes were comparable across groups. In the intervention group there was a trend to greater use of renin-angiotensin blockers and more use of statins in those with initial LDL >2.5 mmol/L. Treatment was rarely required for anemia, acidosis, or disordered mineral metabolism. Clinical events occurred in 5.2% per year.

Conclusions

Patients with stage 3/4 CKD identified through community laboratories largely had nonprogressive kidney disease but had cardiovascular risk. Over a median of 24 months, the nurse-coordinated team did not affect rate of GFR decline or control of most risk factors compared with usual care.     

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.     

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.     

Risk factors for acute kidney injury in overweight patients with acute type A aortic dissection: a retrospective study

Background

To identify risk factors for acute kidney injury (AKI) in overweight patients who underwent surgery for acute type A aortic dissection (TAAD).

Methods

A retrospective study including 108 consecutive overweight patients [body mass index (BMI) ≥24] between December 2009 and April 2013 in Beijing Anzhen Hospital has been performed. AKI was defined by Acute Kidney Injury Network (AKIN) criteria, which is based on serum creatinine (sCr) or urine output.

Results

The mean age of the patients was 43.69±9.66 years. Seventy-two patients (66.7%) developed AKI during the postoperative period. A logistic regression analysis was performed to identify two independent risk factors for AKI: elevated preoperative sCr level and 72-h drainage volume. Renal replacement therapy (RRT) was required in 15 patients (13.9%). The overall postoperative mortality rate was 7.4%, 8.3% in AKI group and 5.6% in non-AKI group. There is no statistically significant difference between the two groups (P=0.32).

Conclusions

A higher incidence of AKI (66.7%) in overweight patients with acute TAAD was confirmed. The logistic regression model identified elevated preoperative sCr level and 72-h drainage volume as independent risk factors for AKI in overweight patients. We should pay more attention to prevent AKI in overweight patients with TAAD.     

Subacute Kidney Injury in Hospitalized Patients

Background and objectives

The epidemiology of AKI and CKD has been described. However, the epidemiology of progressively worsening kidney function (subacute kidney injury [s-AKI]) developing over a longer time frame than defined for AKI (7 days), but shorter than defined for CKD (90 days), is completely unknown.

Design, setting, participants, & measurements

This retrospective study used a hospital laboratory and admission database. Adult patients admitted to a teaching hospital in Tokyo, Japan, between April 1, 2008, and October 31, 2011, were included. s-AKI was classified into three grades of severity (mild, moderate, severe) in accordance with the Risk, Injury, and Failure categories of the Risk, Injury, Failure, Risk, Loss, and ESRD classification, but did not use its time frame. Kidney injury (AKI and s-AKI) occurring during each hospital stay was identified, and logistic regression analysis was performed to assess their effect on hospital mortality.

Results

Of 56,567 patients admitted to the hospital during the study period, 49,518 were included. Of these, 87.8% had no evidence of kidney dysfunction, 11.0% had AKI, and 1.1% had s-AKI. Patients with s-AKI had mild renal dysfunction in 82.7% of cases, moderate in 12.1%, and severe in 5.0%. Worsening s-AKI category was linearly correlated with hospital mortality, as previously described for AKI (no injury: 1.2%, mild: 6.5%, moderate: 12.9%, severe: 20.7%). Although mortality (8.0% versus 17.5%) and need for renal replacement therapy (0.2% versus 2.2%) were lower in patients with s-AKI than in those with AKI, multivariable regression analysis confirmed that s-AKI was an independent risk factor for hospital mortality (odds ratio (OR), 5.44; 95% confidence interval [95% CI], 3.89 to 7.44); the OR with AKI was 14.8 (95% CI, 13.2 to 16.7).

Conclusions

Close to 1% of hospitalized patients develop s-AKI. This condition is independently associated with increased hospital mortality, and the risk for death increases with s-AKI severity. Patients with s-AKI had a better outcome and were less likely to require renal replacement therapy than patients with AKI.     

GFR Decline and Mortality Risk among Patients with Chronic Kidney Disease

Summary

Background and objectives

Estimates of the effect of estimated GFR (eGFR) decline on mortality have focused on populations with normal kidney function, or have included limited information on factors previously shown to influence the risk of death among patients with CKD.

Design, setting, participants, & measurements

We retrospectively assessed the effect of rate of eGFR decline on survival of patients with CKD receiving primary care through a large integrated health care system in central Pennsylvania between January 1, 2004, and December 31, 2009.

Results

A total of 15,465 patients were followed for a median of 3.4 years. Median rates of eGFR change by those in the lower, middle, and upper tertiles of eGFR slope were −4.8, −0.6, and 3.5 ml/min per 1.73 m²/yr, respectively. In Cox proportional hazard modeling for time to death, adjusted for baseline proteinuria, changes in nutritional parameters, and episodes of acute kidney injury during follow-up (among other covariates), the hazard ratio for those in the lower (declining) and upper (increasing) eGFR tertiles (relative to the middle, or stable, tertile) was 1.84 and 1.42, respectively. Longitudinal changes in nutritional status as well as episodes of acute kidney injury attenuated the risk only modestly. These findings were consistent across subgroups.

Conclusions

eGFR change over time adds prognostic information to traditional mortality risk predictors among patients with CKD. The utility of incorporating eGFR trends into patient-risk assessment should be further investigated.     

Is There any Difference Between the Glomerular Filtration Rate of Patients With Chronic Hepatitis B and C and Patients With Cirrhosis?

Background

Renal dysfunction is a major determinant of the Model of End-stage Liver Disease (MELD) score. The implementation of the MELD score has shifted allocation of livers to patients with renal dysfunction.

Objectives

The aim of our study was the assessment of estimated Glomerular Filtration Rate (eGFR) by the Modification of Diet in Renal Disease 4 (MDRD4) method in patients with HBV chronic hepatitis, HCV chronic hepatitis, and cirrhosis (CH) caused by these viruses to detect any differences in renal function among these diseases.

Patients and Methods

We performed a cross-sectional analysis of all consecutive patients with HBV chronic hepatitis, HCV chronic hepatitis, and cirrhosis caused by these viruses hospitalized during a 4 year period in the Gastroenterology and Hepatology department of the Emergency County Hospital Timisoara, Romania. The eGFR was assessed by the MDRD4 method. Statistical analysis (unpaired t-test, ANOVA, Chi Square test) was performed using OpenEpi 2.3.1.

Results

HBV chronic hepatitis, HCV chronic hepatitis, and cirrhosis secondary to these viruses were associated with a reduction of the GFR. The eGFR was higher in patients with HBV chronic hepatitis than in patients with HCV chronic hepatitis (P &lt; 0.001). Patients with cirrhosis secondary to HBV infection had a higher eGFR than patients with cirrhosis secondary to HCV (P = 0.01). The eGFR of patients with HCV chronic hepatitis was higher than the eGFR of patients with cirrhosis due to this virus (P &lt; 0.001).

Conclusions

Functional renal impairment in diseases caused by HCV was more important than in diseases caused by HBV. The eGFR was statistically lower in cirrhosis secondary to HCV than in HCV chronic hepatitis.