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.     

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.     

Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven Model

Background and objectives

A knowledge of baseline serum creatinine (bSCr) is mandatory for diagnosing and staging AKI. With often missing values, bSCr is estimated by back-calculation using several equations designed for the estimation of GFR, assuming a “true” GFR of 75 ml/min per 1.73 m². Using a data set from a large cardiac surgery cohort, we tested the appropriateness of such an approach and compared estimated and measured bSCr. Moreover, we designed a novel data-driven model (estimated serum creatinine [eSCr]) for estimating bSCr. Finally, we analyzed the extent of AKI and mortality rate misclassifications.

Design, setting, participants, & measurements

Data for 8024 patients (2833 women) in our cardiac surgery center were included from 1997 to 2008. Measured and estimated bSCr were plotted against age for men and women. Patients were classified to AKI stages defined by the Kidney Disease Improving Global Outcomes (KDIGO) group. Results were compared with data from another cardiac surgery center in Zurich, Switzerland.

Results

The Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration formulae describe higher estimated bSCr values in younger patients, but lower values in older patients compared with the measured bSCr values in both centers. The Pittsburgh Linear Three Variables formula correctly describes the increasing bSCr with age, however, it underestimates the overall bSCr level, being in the range of the 25% quantile of the measured values. Our eSCr model estimated measured bSCr best. AKI stage 1 classification using all formulae, including our eSCr model, was incorrect in 53%–80% of patients in Vienna and in 74%–91% in Zurich; AKI severity (according to KDIGO stages) and also mortality were overestimated. Mortality rate was higher among patients falsely classified into higher KDIGO stages by estimated bSCr.

Conclusions

bSCr values back-estimated using currently available eGFR formulae are inaccurate and cannot correctly classify AKI stages. Our model eSCr improves the prediction of AKI but to a still inadequate extent.     

Derivation of Urine Output Thresholds That Identify a Very High Risk of AKI in Patients with Septic Shock

Background and objectives

To promote early detection of AKI, recently proposed pretest probability models combine sub–Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI.

Design, setting, participants, & measurements

This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality.

Results

Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval [95% CI], 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%).

Conclusions

Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed.     

Exploring Potential Reasons for the Temporal Trend in Dialysis-Requiring AKI in the United States

Background and objectives

The population incidence of dialysis-requiring AKI has risen substantially in the last decade in the United States, and factors associated with this temporal trend are not well known.

Design, setting, participants, & measurements

We conducted a retrospective cohort study using data from the Nationwide Inpatient Sample, a United States nationally representative database of hospitalizations from 2007 to 2009. We used validated International Classification of Diseases, Ninth Revision codes to identify hospitalizations with dialysis-requiring AKI and then, selected the diagnostic and procedure codes most highly associated with dialysis-requiring AKI in 2009. We applied multivariable logistic regression adjusting for demographics and used a backward selection technique to identify a set of diagnoses or a set of procedures that may be a driver for this changing risk in dialysis-requiring AKI.

Results

From 2007 to 2009, the population incidence of dialysis-requiring AKI increased by 11% per year (95% confidence interval, 1.07 to 1.16; P<0.001). Using backward selection, we found that the temporal trend in the six diagnoses, septicemia, hypertension, respiratory failure, coagulation/hemorrhagic disorders, shock, and liver disease, sufficiently and fully accounted for the temporal trend in dialysis-requiring AKI. In contrast, temporal trends in 15 procedures most commonly associated with dialysis-requiring AKI did not account for the increasing dialysis–requiring AKI trend.

Conclusions

The increasing risk of dialysis-requiring AKI among hospitalized patients in the United States was highly associated with the changing burden of six acute and chronic conditions but not with surgeries and procedures.     

Comparison of Diagnostic Criteria for Acute Kidney Injury in Cardiac Surgery

Background

There is considerable controversy regarding the diagnosis of Acute Kidney Injury (AKI), and there are over 30 different definitions.

Objective

To evaluate the incidence and risk factors for the development of AKI following cardiac surgery according to the RIFLE, AKIN and KDIGO criteria, and compare the prognostic power of these criteria.

Methods

Cross-sectional study that included 321 consecutive patients (median age 62 [53-71] years; 140 men) undergoing cardiac surgery between June 2011 and January 2012. The patients were followed for up to 30 days, for a composite outcome (mortality, need for dialysis and extended hospitalization).

Results

The incidence of AKI ranged from 15% - 51%, accordingly to the diagnostic criterion adopted. While age was associated with risk of AKI in the three criteria, there were variations in the remaining risk factors. During follow-up, 89 patients developed the outcome and all criteria were associated with increased risk in the univariate Cox analysis and after adjustment for age, gender, diabetes, and type of surgery. However, after further adjustment for extracorporeal circulation and the presence of low cardiac output, only AKI diagnosed by the KDIGO criterion maintained this significant association (HR= 1.89 [95% CI: 1.18 - 3.06]).

Conclusion

The incidence and risk factors for AKI after cardiac surgery vary significantly according to the diagnostic criteria used. In our analysis, the KDIGO criterion was superior to AKIN and RIFLE with regard its prognostic power.     

False-Positive Rate of AKI Using Consensus Creatinine–Based Criteria

Background and objectives

Use of small changes in serum creatinine to diagnose AKI allows for earlier detection but may increase diagnostic false–positive rates because of inherent laboratory and biologic variabilities of creatinine.

Design, setting, participants, & measurements

We examined serum creatinine measurement characteristics in a prospective observational clinical reference cohort of 2267 adult patients with AKI by Kidney Disease Improving Global Outcomes creatinine criteria and used these data to create a simulation cohort to model AKI false–positive rates. We simulated up to seven successive blood draws on an equal population of hypothetical patients with unchanging true serum creatinine values. Error terms generated from laboratory and biologic variabilities were added to each simulated patient’s true serum creatinine value to obtain the simulated measured serum creatinine for each blood draw. We determined the proportion of patients who would be erroneously diagnosed with AKI by Kidney Disease Improving Global Outcomes creatinine criteria.

Results

Within the clinical cohort, 75.0% of patients received four serum creatinine draws within at least one 48-hour period during hospitalization. After four simulated creatinine measurements that accounted for laboratory variability calculated from assay characteristics and 4.4% of biologic variability determined from the clinical cohort and publicly available data, the overall false–positive rate for AKI diagnosis was 8.0% (interquartile range =7.9%–8.1%), whereas patients with true serum creatinine ≥1.5 mg/dl (representing 21% of the clinical cohort) had a false–positive AKI diagnosis rate of 30.5% (interquartile range =30.1%–30.9%) versus 2.0% (interquartile range =1.9%–2.1%) in patients with true serum creatinine values <1.5 mg/dl (P<0.001).

Conclusions

Use of small serum creatinine changes to diagnose AKI is limited by high false–positive rates caused by inherent variability of serum creatinine at higher baseline values, potentially misclassifying patients with CKD in AKI studies.     

Contrast-Associated AKI and Use of Cardiovascular Medications after Acute Coronary Syndrome

Background and objectives

AKI after coronary angiography is associated with poor long-term outcomes. The relationship between contrast-associated AKI and subsequent use of prognosis-modifying cardiovascular medications is unknown.

Design, setting, participants, & measurements

A cohort study of 5911 participants 66 years of age or older with acute coronary syndrome who received a coronary angiogram in Alberta, Canada was performed between November 1, 2002, and November 30, 2008. AKI was identified according to Kidney Disease Improving Global Outcomes AKI criteria.

Results

In multivariable logistic regression models, compared with participants without AKI, those with stages 1 and 2–3 AKI had lower odds of subsequent use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker within 120 days of hospital discharge (adjusted odds ratio, 0.65; 95% confidence interval, 0.53 to 0.80 and odds ratio, 0.34; 95% confidence interval, 0.23 to 0.48, respectively). Subsequent statin and β-blockers use within 120 days of hospital discharge was significantly lower among those with stages 2–3 AKI (adjusted odds ratio, 0.44; 95% confidence interval, 0.31 to 0.64 and odds ratio, 0.46; 95% confidence interval, 0.31 to 0.66, respectively). These associations were consistently seen in patients with diabetes mellitus, heart failure, low baseline eGFR, and albuminuria; 952 participants died during subsequent follow-up after hospital discharge (mean=3.1 years). The use of each class of cardiovascular medication was associated with lower mortality, including among those who had experienced AKI.

Conclusions

Strategies to optimize the use of cardiac medications in people with AKI after coronary angiography might improve care.     

Urinary Biomarkers and Progression of AKI in Patients with Cirrhosis

Background and objectives

AKI is a common and severe complication in patients with cirrhosis. AKI progression was previously shown to correlate with in-hospital mortality. Therefore, accurately predicting which patients are at highest risk for AKI progression may allow more rapid and targeted treatment. Urinary biomarkers of structural kidney injury associate with AKI progression and mortality in multiple settings of AKI but their prognostic performance in patients with liver cirrhosis is not well known.

Design, setting, participants, & measurements

A multicenter, prospective cohort study was conducted at four tertiary care United States medical centers between 2009 and 2011. The study comprised patients with cirrhosis and AKI defined by the AKI Network criteria evaluating structural (neutrophil gelatinase–associated lipocalin, IL-18, kidney injury molecule-1 [KIM-1], liver-type fatty acid–binding protein [L-FABP], and albuminuria) and functional (fractional excretion of sodium [FENa]) urinary biomarkers as predictors of AKI progression and in-hospital mortality.

Results

Of 188 patients in the study, 44 (23%) experienced AKI progression alone and 39 (21%) suffered both progression and death during their hospitalization. Neutrophil gelatinase–associated lipocalin, IL-18, KIM-1, L-FABP, and albuminuria were significantly higher in patients with AKI progression and death. These biomarkers were independently associated with this outcome after adjusting for key clinical variables including model of end stage liver disease score, IL-18 (relative risk [RR], 4.09; 95% confidence interval [95% CI], 1.56 to 10.70), KIM-1 (RR, 3.13; 95% CI, 1.20 to 8.17), L-FABP (RR, 3.43; 95% CI, 1.54 to 7.64), and albuminuria (RR, 2.07; 95% CI, 1.05–4.10) per log change. No biomarkers were independently associated with progression without mortality. FENa demonstrated no association with worsening of AKI. When added to a robust clinical model, only IL-18 independently improved risk stratification on a net reclassification index.

Conclusions

Multiple structural biomarkers of kidney injury, but not FENa, are independently associated with progression of AKI and mortality in patients with cirrhosis. Injury marker levels were similar between those without progression and those with progression alone.     

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.     

Low Systemic Oxygen Delivery and BP and Risk of Progression of Early AKI

Background and objectives

The optimal hemodynamic management of patients with early AKI is unknown. This study aimed to investigate the association between hemodynamic parameters in early AKI and progression to severe AKI and hospital mortality.

Design, setting, participants, & measurements

This study retrospectively analyzed the data of all patients admitted to the adult intensive care unit in a tertiary care center between July 2007 and June 2009 and identified those with stage 1 AKI (AKI I) per the AKI Network classification. In patients in whom hemodynamic monitoring was performed within 12 hours of AKI I, hemodynamic parameters in the first 12 hours of AKI I and on the day of AKI III (if AKI III developed) or 72 hours after AKI I (if AKI III did not develop) were recorded. Risk factors for AKI III and mortality were identified using univariate and multivariate logistic regression analyses.

Results

Among 790 patients with AKI I, 210 (median age 70 years; 138 men) had hemodynamic monitoring within 12 hours of AKI I; 85 patients (41.5%) progressed to AKI III and 91 (43%) died in the hospital. AKI progressors had a significantly higher Sequential Organ Failure Assessment score (8.0 versus 9.6; P<0.001), lower indexed systemic oxygen delivery (DO₂I) (median 325 versus 405 ml/min per m²; P<0.001), higher central venous pressure (16 versus 13; P=0.02), and lower mean arterial blood pressure (MAP) (median 71 versus 74 mmHg; P=0.01) in the first 12 hours of AKI I compared with nonprogressors. Multivariate analysis confirmed that raised lactate, central venous pressure, and Sequential Organ Failure Assessment score as well as mechanical ventilation were independently associated with progression to AKI III; higher DO₂I and MAP were independently associated with a lower risk of AKI III but not survival. The associations were independent of sepsis, heart disease, recent cardiac surgery, or chronic hypertension.

Conclusions

Higher DO₂I and MAP in early AKI were independently associated with a lower risk of progression.     

Renal Arcuate Vein Microthrombi-Associated AKI

Backgrounds and objectives

This report describes six patients with AKI stages 2–3 (median admission creatinine level, 2.75 mg/dl [range, 1.58–5.44 mg/dl]), hematuria (five with hemoproteinuria), and unremarkable imaging with an unusual and unexplained histologic diagnosis on renal biopsy.

Design, setting, participants, & measurements

The patients were young adults who presented to two neighboring United Kingdom nephrology centers over a 40-month period (between July 2010 and November 2013). Four were male, and the median age was 22.5 years (range, 18–27 years). Their principal symptoms were flank pain or lower back pain. All had consumed alcohol in the days leading up to admission.

Results

Renal biopsy demonstrated microthrombi in the renal arcuate veins with a corresponding stereotypical, localized inflammatory infiltrate at the corticomedullary junction. All patients recovered to baseline renal function with supportive care (median, 17 days; range, 6–60 days), and none required RRT. To date, additional investigations have not revealed an underlying cause for these histopathologic changes. Investigations have included screening for thrombophilic tendencies, renal vein Doppler ultrasonographic studies, and testing for recreational drugs and alcohol (including liquid chromatography–mass spectrometry of urine) to look for so-called designer drugs. Inquiries to the United Kingdom National Poisons Information Centre have identified no other cases with similar presentation or histologic findings.

Conclusions

Increased awareness and additional study of future cases may lead to a greater understanding of the underlying pathophysiologic mechanisms that caused AKI in these patients.     

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.     

Nephrolithiasis as a Risk Factor for CKD: The Atherosclerosis Risk in Communities Study

Background and objectives

Previous studies demonstrated a higher risk of CKD in persons with a history of kidney stones, but these studies examined mostly white populations and did not evaluate important potential interactions such as race and plasma uric acid.

Design, setting, participants, & measurements

In 10,678 Atherosclerosis Risk in Communities (ARIC) study participants free of CKD at baseline (ARIC visit 4 in 1996–1998), we assessed the association between a history of nephrolithiasis (a time-varying variable, defined by a combination of self-report and diagnostic codes) and incident CKD (defined by diagnostic codes from linkage to hospitalizations and US Centers for Medicare and Medicaid Services’ records).

Results

At baseline, 856 participants had a history of nephrolithiasis; 322 developed nephrolithiasis during follow-up. Over a mean follow-up of 12 years, there were 1037 incident CKD events. Nephrolithiasis history was associated with a 29% (hazard ratio [HR], 1.29; 95% confidence interval [95% CI], 1.07 to 1.54) higher risk of CKD in demographic-adjusted analyses, but the association was no longer statistically significant after multivariable adjustment (HR, 1.09; 95% CI, 0.90 to 1.32). The multivariable-adjusted association was stronger among participants with plasma uric acid levels ≤6 mg/dl (HR, 1.34; 95% CI, 1.05 to 1.72) compared with those with levels >6 mg/dl (HR, 0.94; 95% CI, 0.70 to 1.28; P_interaction=0.05). There was no interaction of stone disease and race with incident CKD.

Conclusions

In this community-based cohort, nephrolithiasis was not an independent risk factor for incident CKD overall. However, risk of CKD was unexpectedly elevated in participants with stone disease and lower plasma uric acid levels.     

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.     

Outcomes After Post-Traumatic AKI Requiring RRT in United States Military Service Members

Background and objectives

Mortality and CKD risk have not been described in military casualties with post-traumatic AKI requiring RRT suffered in the Iraq and Afghanistan wars.

Design, setting, participants, & measurements

This is a retrospective case series of post-traumatic AKI requiring RRT in 51 military health care beneficiaries (October 7, 2001–December 1, 2013), evacuated to the National Capital Region, documenting in-hospital mortality and subsequent CKD. Participants were identified using electronic medical and procedure records.

Results

Age at injury was 26±6 years; of the participants, 50 were men, 16% were black, 67% were white, and 88% of injuries were caused by blast or projectiles. Presumed AKI cause was acute tubular necrosis in 98%, with rhabdomyolysis in 72%. Sixty-day all-cause mortality was 22% (95% confidence interval [95% CI], 12% to 35%), significantly less than the 50% predicted historical mortality (P<0.001). The VA/NIH Acute Renal Failure Trial Network AKI integer score predicted 60-day mortality risk was 33% (range, 6%–96%) (n=49). Of these, nine died (mortality, 18%; 95% CI, 10% to 32%), with predicted risks significantly miscalibrated (P<0.001). The area under the receiver operator characteristic curve for the AKI integer score was 0.72 (95% CI, 0.56 to 0.88), not significantly different than the AKI integer score model cohort (P=0.27). Of the 40 survivors, one had ESRD caused by cortical necrosis. Of the remaining 39, median time to last follow-up serum creatinine was 1158 days (range, 99–3316 days), serum creatinine was 0.85±0.24 mg/dl, and eGFR was 118±23 ml/min per 1.73 m². No eGFR was <60 ml/min per 1.73 m², but it may be overestimated because of large/medium amputations in 54%. Twenty-five percent (n=36) had proteinuria; one was diagnosed with CKD stage 2.

Conclusions

Despite severe injuries, participants had better in-hospital survival than predicted historically and by AKI integer score. No patient who recovered renal function had an eGFR<60 ml/min per 1.73 m² at last follow-up, but 23% had proteinuria, suggesting CKD burden.     

Clinical–Morphological Features and Outcomes of Lupus Podocytopathy

Background and objectives

Lupus podocytopathy, which is characterized by diffuse foot process effacement without peripheral capillary wall immune deposits and glomerular proliferation, has been described in SLE patients with nephrotic syndrome in case reports and small series. This study aimed to better characterize the incidence, clinical–morphologic features, and outcomes of such patients from a large Chinese cohort.

Design, setting, participants, & measurements

Lupus podocytopathy was identified from 3750 biopsies of SLE patients obtained from 2000 to 2013 that showed mild glomerular histology in patients with a clinical sign of nephrotic syndrome. The biopsy results were divided into three groups: glomerular minimal change, mesangial proliferation, and FSGS.

Results

Fifty (1.33%) cases were identified as lupus podocytopathy and included minimal change in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases. Extensive foot process effacement appeared in all the biopsies and mesangial electron-dense deposits were present in 47 biopsies. All patients demonstrated nephrotic syndrome, and the median proteinuria was 5.72 g/24 h (interquartile range [IQR], 3.82, 6.92). Seventeen (34%) cases presented with AKI. Forty-seven (94%) patients achieved remission after immunosuppressive therapy for a median time of 4 weeks (IQR, 2, 8). Compared with the patients with minimal change and mesangial proliferation, patients with FSGS showed significantly higher incidence of AKI and severe tubule–interstitial injury and a much lower complete remission rate. During follow-up of a median of 62 (IQR, 36, 84) months, renal relapses occurred in 28 (59.6%) patients. No patient died or developed ESRD.

Conclusions

The findings from this cohort study suggest that lupus podocytopathy may represent a special entity of lupus nephritis with distinct clinical–morphologic features. The differences in AKI incidence, tubular injury severity, and response to treatment between the patients with minimal change/mesangial proliferation and those with FSGS patterns indicate two different subtypes of lupus podocytopathy.     

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.     

Plasma Urate and Risk of a Hospital Stay with AKI: The Atherosclerosis Risk in Communities Study

Background and objectives

Higher urate levels are associated with higher risk of CKD, but the association between urate and AKI is less established. This study evaluated the risk of hospitalized AKI associated with urate concentrations in a large population-based cohort. To explore whether urate itself causes kidney injury, the study also evaluated the relationship between a genetic urate score and AKI.

Design, setting, participants, & measurements

A total of 11,011 participants from the Atherosclerosis Risk in Communities study were followed from 1996–1998 (baseline) to 2010. The association between baseline plasma urate and risk of hospitalized AKI, adjusted for known AKI risk factors, was determined using Cox regression. Interactions of urate with gout and CKD were tested. Mendelian randomization was performed using a published genetic urate score among the participants with genetic data (n=7553).

Results

During 12 years of follow-up, 823 participants were hospitalized with AKI. Overall, mean participant age was 63.3 years, mean eGFR was 86.3 ml/min per 1.73 m², and mean plasma urate was 5.6 mg/dl. In patients with plasma urate >5.0 mg/dl, there was a 16% higher risk of hospitalized AKI for each 1-mg/dl higher urate (adjusted hazard ratio, 1.16; 95% confidence interval, 1.10 to 1.23; P<0.001). When stratified by history of gout, the association between higher urate and AKI was significant only in participants without a history of gout (P for interaction=0.02). There was no interaction of CKD and urate with AKI, nor was there an association between genetic urate score and AKI.

Conclusions

Plasma urate >5.0 mg/dl was independently associated with risk of hospitalized AKI; however, Mendelian randomization did not provide evidence for a causal role of urate in AKI. Further research is needed to determine whether lowering plasma urate might reduce AKI risk.