Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults

Background and objectives

Comprehensive epidemiologic data on AKI are particularly lacking in Asian countries. This study sought to assess the epidemiology and clinical correlates of AKI among hospitalized adults in China.

Design, setting, participants, & measurements

This was a multicenter retrospective cohort study of 659,945 hospitalized adults from a wide range of clinical settings in nine regional central hospitals across China in 2013. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. The incidence of AKI in the cohort was estimated using a novel two-step approach with adjustment for the frequency of serum creatinine tests and other potential confounders. Risk factor profiles for hospital-acquired (HA) and community-acquired (CA) AKI were examined. The in-hospital outcomes of AKI, including mortality, renal recovery, length of stay, and daily cost, were assessed.

Results

The incidence of CA-AKI and HA-AKI was 2.5% and 9.1%, respectively, giving rise to an overall incidence of 11.6%. Although the risk profiles for CA-AKI and HA-AKI differed, preexisting CKD was a major risk factor for both, contributing to 20% of risk in CA-AKI and 12% of risk in HA-AKI. About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies. The in-hospital mortality of AKI was 8.8%. The risk of in-hospital death was higher among patients with more severe AKI. Preexisting CKD and need for intensive care unit admission were associated with higher death risk in patients at any stage of AKI. Transiency of AKI did not modify the risk of in-hospital death. AKI was associated with longer length of stay and higher daily costs, even after adjustment for confounders.

Conclusion

AKI is common in hospitalized adults in China and is associated with significantly higher in-hospital mortality and resource utilization.     

Cancer-Specific Mortality in Chronic Kidney Disease: Longitudinal Follow-Up of a Large Cohort

Summary

Background and objectives

Chronic kidney disease (CKD) is known to be associated with increased all-cause and cardiovascular mortality, but no large studies examined the cancer-specific mortality in non–dialysis-dependent CKD patients. Such outcome data are needed for proper allocation of resources and would help to develop better preventive services.

Design, setting, participants, & measurements

Between 1998 and 1999, 123,717 adults were recruited from four health screening centers in Taiwan. The estimated glomerular filtration rate was calculated using the four-variable Modification of Diet in Renal Disease Study equation for the Chinese. Mortality was ascertained by computer linkage to the national death registry after a median follow-up of 7.06 years. Cox proportional hazards regression models were used to estimate the impact of CKD on cancer-specific mortality.

Results

A higher risk for overall cancer mortality was found in CKD patients compared with non-CKD patients (adjusted hazard ratio, 1.2). CKD was associated with increased mortality from liver cancer, kidney cancer, and urinary tract cancer, with an adjusted hazard ratio of 1.74, 3.3, and 7.3, respectively. A graded relationship between the severity of renal impairment and cancer mortality was also found.

Conclusions

Patients with CKD had a higher mortality risk of liver cancer, kidney cancer, and urinary tract cancer. This is the first large study that showed an inverse association between renal function and liver cancer mortality. The increased mortality could be caused by higher cancer incidence or worse response to cancer treatment. Future research is warranted to clarify the mechanism.     

Vision-Threatening Retinal Abnormalities in Chronic Kidney Disease Stages 3 to 5

Summary

Background and objectives

Retinal abnormalities are common in inherited and acquired renal disease. This study determined the prevalence of retinal abnormalities in chronic kidney disease (CKD) stages 3 to 5.

Design, setting, participants, & measurements

One hundred fifty patients with CKD stages 3 to 5 and 150 age- and gender-matched hospital patients with CKD stages 1 to 2 underwent bilateral retinal photography. These images were reviewed for incidental abnormalities, microvascular (Wong and Mitchell classification) and diabetic retinopathy (Airlie House criteria), and macular degeneration (Seddon classification).

Results

Three (2%) patients with CKD stages 3 to 5 had retinal features characteristic of inherited renal disease (atrophy in Myopathy, Encephalopathy, Lactic Acidosis, Stroke-like episodes [MELAS] syndrome; and 2 with drusen in dense deposit disease). Fifty-nine (39%) patients had moderate-severe microvascular retinopathy (hemorrhages, exudates, etc.) compared with 19 (13%) with CKD stages 1 to 2. Forty-one (28%) had moderate-severe diabetic retinopathy (microaneurysms, exudates, etc.) compared with 16 (11%) with CKD stages 1 to 2. Ten (7%) had severe macular degeneration (geographic atrophy, hemorrhage, exudates, membranes) compared with one (1%) with CKD stages 1 to 2. Renal failure was an independent risk factor for microvascular retinopathy, diabetic retinopathy, and macular degeneration. Eleven (7.3%) patients with renal failure and one (0.7%) with CKD stages 1 to 2 had previously unrecognized vision-threatening retinal abnormalities that required immediate ophthalmologic attention.

Conclusions

Retinal abnormalities are common in CKD stages 3 to 5, and are more severe and more likely to threaten vision than in hospital patients with CKD stages 1 to 2.     

Epidemiology and Outcomes in Community-Acquired Versus Hospital-Acquired AKI

Background and objective

Compared with AKI in hospitalized patients, little is known about patients sustaining AKI in the community and how this differs from AKI in hospital. This study compared epidemiology, risk factors, and short- and long-term outcomes for patients with community-acquired (CA) and hospital-acquired (HA) AKI.

Design, setting, participants, & measurements

A total of 15,976 patients admitted to two district general hospitals between July 11, 2011, and January 15, 2012 were studied. Through use of an electronic database and the AKI Network classification, 686 patients with CA-AKI and 334 patients with HA-AKI were identified. Patients were followed up for 14 months, and data were collated on short-term and long-term renal and patient outcomes.

Results

The incidence of CA-AKI among all hospital admissions was 4.3% compared with an incidence of 2.1% of HA-AKI, giving an overall AKI incidence of 6.4%. Patients with CA-AKI were younger than patients with HA-AKI. Risks for developing HA and CA-AKI were similar and included preexisting CKD, cardiac failure, ischemic heart disease, hypertension, diabetes, dementia, and cancer. Patients with CA-AKI were more likely to have stage 3 AKI and had shorter lengths of hospital stay than patients with HA-AKI. Those with CA-AKI had better (multivariate-adjusted) survival than patients with HA-AKI (hazard ratio, 1.8 [95% CI, 1.44–2.13; P<0.001] for HA-AKI group). Mortality for the CA-AKI group was 45%; 43.7% of these deaths were acute in-hospital deaths. Mortality for the HA-AKI group was 62.9%, with 68.1% of these deaths being acute in-hospital deaths. Renal referral rates were low across the cohorts (8.3%). Renal outcomes were similar in both CA-AKI and HA-AKI groups, with 39.4% and 33.6% of patients in both groups developing de novo CKD or progression of preexisting CKD within 14 months, respectively.

Conclusion

Patients with CA-AKI sustain more severe AKI than patients with HA-AKI. Despite having risk factors similar to those of patients with HA-AKI, patients with CA AKI have better short- and long-term outcomes.     

Acute kidney injury episodes and chronic kidney disease risk in diabetes mellitus

Summary

Background and objectives

Prior studies have examined long-term outcomes of a single acute kidney injury (AKI) event in hospitalized patients. We examined the effects of AKI episodes during multiple hospitalizations on the risk of chronic kidney disease (CKD) in a cohort with diabetes mellitus (DM).

Design, setting, participants, & measurements

A total of 4082 diabetics were followed from January 1999 until December 2008. The primary outcome was reaching stage 4 CKD (GFR of <30 ml/min per 1.73 m²). AKI during hospitalization was defined as >0.3 mg/dl or a 1.5-fold increase in creatinine relative to admission. Cox survival models examined the effect of first AKI episode and up to three episodes as time-dependent covariates, on the risk of stage 4 CKD. Covariates included demographic variables, baseline creatinine, and diagnoses of comorbidities including proteinuria.

Results

Of the 3679 patients who met eligibility criteria (mean age = 61.7 years [SD, 11.2]; mean baseline creatinine = 1.10 mg/dl [SD, 0.3]), 1822 required at least one hospitalization during the time under observation (mean = 61.2 months [SD, 25]). Five hundred thirty of 1822 patients experienced one AKI episode; 157 of 530 experienced ≥2 AKI episodes. In multivariable Cox proportional hazards models, any AKI versus no AKI was a risk factor for stage 4 CKD (hazard ratio [HR], 3.56; 95% confidence interval [CI], 2.76, 4.61); each AKI episode doubled that risk (HR, 2.02; 95% CI, 1.78, 2.30).

Conclusions

AKI episodes are associated with a cumulative risk for developing advanced CKD in diabetes mellitus, independent of other major risk factors of progression.     

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Background and objectives

AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness.

Design, setting, participants, & measurements

A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed.

Results

In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (P<0.001) at hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median decrease, 33%). In 160 patients with known baseline, discharge creatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR<60 ml/min per 1.73 m² at hospital discharge compared with only 63 of 700 patients using eGFR based on unadjusted hospital creatinine (a 135% increase in potential CKD diagnoses; P<0.001).

Conclusion

Critical illness is associated with significant falls in serum creatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings.     

Sleep-Disordered Breathing and Excessive Daytime Sleepiness in Chronic Kidney Disease and Hemodialysis

Summary

Background and objectives

Sleep-disordered breathing (SDB) and excessive daytime sleepiness (EDS) are highly prevalent among hemodialysis (HD) patients. It is unclear to what extent SDB is associated with advanced chronic kidney disease (CKD; stages 4 to 5). This paper describes and compares the prevalence, severity, and patterns of SDB and EDS among patients with advanced CKD, HD-dependent patients, and community individuals without known renal disease.

Design, setting, participants, & measurements

Eighty-nine CKD and 75 HD patients were compared with 224 participants from the Sleep-Strategies Concentrating on Risk Evaluation Sleep-SCORE study of sleep and cardiovascular risk. Participants had in-home unattended polysomnography for quantifying SDB. EDS was defined by a score ≥10 on the Epworth Sleepiness Scale.

Results

The sample had a median age 58.1 years, was predominantly male (57.4%) and white (62.5%), and had a median body mass index of 28.1 kg/m². Controls and Sleep-SCORE Study CKD patients had significantly higher median total sleep time and sleep efficiency compared with HD patients. The adjusted odds of severe SDB were higher for CKD and HD groups compared with the controls. Nocturnal hypoxemia was significantly elevated in the HD group compared with the CKD group. There were similar proportions of participants with EDS between the controls (33%), the CKD patients (29.3%), and the HD patients (40.6%).

Conclusions

Severe SDB (predominantly obstructive) and EDS are common among advanced CKD and HD patients. EDS correlated modestly with severe SDB and its obstructive and mixed patterns in the HD group.     

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.     

Urinary Elafin and Kidney Injury in Hematopoietic Cell Transplant Recipients

Background and objectives

Graft-versus-host disease (GVHD) is associated with kidney injury after hematopoietic cell transplantation (HCT). Because plasma elafin levels correlate with skin GVHD, this study examined urinary elafin as a potential marker of renal inflammation and injury.

Design, setting, participants, & measurements

Urine was collected prospectively on 205 patients undergoing their first HCT from 2003 to 2010. Collections were done at baseline, weekly through day 100, and monthly through year 1 to measure elafin and urine albumin-to-creatinine ratio (ACR). Associations between urinary elafin levels and microalbuminuria, macroalbuminuria, AKI and CKD, and mortality were examined using Cox proportional hazards or linear regression models. Available kidney biopsy specimens were processed for immunohistochemistry.

Results

Mean urinary elafin levels to day 100 were higher in patients with micro- or macroalbuminuria (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in those with a normal ACR (adjusted mean difference, 1295 pg/ml; P<0.001). Mean urinary elafin levels were higher in patients with AKI compared with patients without AKI (adjusted mean difference, 558 pg/ml; P<0.01). The average urinary elafin levels within the first 100 days after HCT were higher in patients who developed CKD at 1 year than in patients without CKD (adjusted mean difference, 894 pg/ml; P=0.002). Among allogeneic recipients, a higher proportion of patients with micro- or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%, respectively) compared with patients with a normal ACR (58%; global P<0.01). Each increase in elafin of 500 pg/ml resulted in a 10% increase in risk of persistent macroalbuminuria (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.06 to 1.13; P<0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02 to 1.13, P<0.01). Renal biopsy specimens from a separate cohort of HCT survivors demonstrated elafin staining in distal and collecting duct tubules.

Conclusion

Higher urinary elafin levels are associated with an increased risk of micro- and macroalbuminuria, AKI and CKD, and death after HCT.     

Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease

Summary

Background and objectives

The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients.

Design, setting, participants, & measurements

We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan–Meier survival curves, and time-dependent analysis.

Results

Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality.

Conclusions

Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients.     

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.     

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.     

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.     

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.     

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.     

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.     

Rate of Kidney Function Decline and Risk of Hospitalizations in Stage 3A CKD

Background and objectives

Risk of hospitalizations is increased in patients with CKD. We sought to examine the association between rate of kidney function decline and risk of hospitalization in a cohort of patients with early CKD.

Design, settings, participants, & measurements

We built a cohort of 247,888 United States veterans who had at least one eGFR measurement between October 1999 and September 2003 and an additional eGFR between October 2003 and September 2004. We selected patients whose initial eGFR was between 45 and 59 ml/min per 1.73 m². Rate of eGFR change (in milliliters per minute per 1.73 m² per year) was categorized as no decline (>0), mild (0 to −1, and served as the referent group), moderate (−1 to −5), or severe (>−5) eGFR decline. We built survival models to examine the association between the rate of kidney function decline and the risk of hospitalization and readmission and linear regression to estimate length of hospital stay.

Results

Over a median observation of 9 years (interquartile range, 5.28–9.00), patients with moderate and severe eGFR decline exhibited a higher risk of hospitalizations (hazard ratio [HR], 1.22; 95% confidence interval [95% CI], 1.19 to 1.26; and HR, 1.33; 95% CI, 1.28 to 1.39, respectively). Among patients with moderate and severe eGFR decline, the association between the rate of decline and the risk of hospitalizations was more pronounced with an increased number of hospitalizations (P<0.01). Patients with moderate and severe eGFR decline had a higher risk of readmission (HR, 1.19; 95% CI, 1.13 to 1.26; and HR, 1.53; 95% CI, 1.43 to 1.63, respectively). Among patients with severe eGFR decline, the association between the rate of kidney function decline and the risk of readmission was stronger with an increased number of readmissions (P<0.01). Patients with moderate and severe eGFR decline experienced an additional length of stay of 1.40 (95% CI, 0.88 to 1.92) and 5.00 days per year (95% CI, 4.34 to 5.66), respectively.

Conclusions

The rate of kidney function decline is associated with a higher risk of hospitalizations, readmissions, and prolonged length of hospital stay.     

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.     

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.     

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.