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.     

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.     

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.     

Referral Patterns and Outcomes in Noncritically Ill Patients with Hospital-Acquired Acute Kidney Injury

Summary

Background and objectives

Despite modern treatment, the case fatality rate of hospital-acquired acute kidney injury (HA-AKI) is still high. We retrospectively described the prevalence and the outcome of HA-AKI without nephrology referral (nrHA-AKI) and late referred HA-AKI patients to nephrologists (lrHA-AKI) compared with early referral patients (erHA-AKI) with respect to renal function recovery, renal replacement therapy (RRT) requirement, and in-hospital mortality of HA-AKI.

Design, setting, participants, & measurements

Noncritically ill patients admitted to the tertiary care academic center of Lausanne, Switzerland, between 2004 and 2008 in the medical and surgical services were included. Acute kidney injury was defined using the Acute Kidney Injury Network (AKIN) classification.

Results

During 5 years, 4296 patients (4.12% of admissions) experienced 4727 episodes of HA-AKI during their hospital stay. The mean ± SD age of the patients was 61 ± 15 years with a 55% male predominance. There were 958 patients with nrHA-AKI (22.3%) and 2504 patients with lrHA-AKI (58.3%). RRT was required in 31% of the patients with lrHA-AKI compared with 24% of the patients with erHA-AKI. In the multiple risk factor analysis, compared with erHA-AKI, nrHA-AKI and lrHA-AKI were significantly associated with worse renal outcome and higher in-hospital mortality.

Conclusions

These data suggest that HA-AKI is frequent and the patients with nrHA-AKI or lrHA-AKI are at increased risk for in-hospital morbidity and mortality.     

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.     

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

Background and objectives

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

Design, setting, participants, & measurements

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

Results

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

Conclusions

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

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

Background and objectives

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

Design, setting, participants, & measurements

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

Results

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

Conclusions

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

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.     

The outcome of tuberculosis treatment in subjects with chronic kidney disease in Brazil: a multinomial analysis

OBJECTIVE:

To analyze the association between clinical/epidemiological characteristics and outcomes of tuberculosis treatment in patients with concomitant tuberculosis and chronic kidney disease (CKD) in Brazil.

METHODS:

We used the Brazilian Ministry of Health National Case Registry Database to identify patients with tuberculosis and CKD, treated between 2007 and 2011. The tuberculosis treatment outcomes were compared with epidemiological and clinical characteristics of the subjects using a hierarchical multinomial logistic regression model, in which cure was the reference outcome.

RESULTS:

The prevalence of CKD among patients with tuberculosis was 0.4% (95% CI: 0.37-0.42%). The sample comprised 1,077 subjects. The outcomes were cure, in 58%; treatment abandonment, in 7%; death from tuberculosis, in 13%; and death from other causes, in 22%. The characteristics that differentiated the ORs for treatment abandonment or death were age; alcoholism; AIDS; previous noncompliance with treatment; transfer to another facility; suspected tuberculosis on chest X-ray; positive results in the first smear microscopy; and indications for/use of directly observed treatment, short-course strategy.

CONCLUSIONS:

Our data indicate the importance of sociodemographic characteristics for the diagnosis of tuberculosis in patients with CKD and underscore the need for tuberculosis control strategies targeting patients with chronic noncommunicable diseases, such as CKD.     

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.     

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.     

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.     

Preoperative Hemoglobin and Outcomes in Patients with CKD Undergoing Cardiac Surgery

Background and objectives

Preoperative anemia adversely affects outcomes of cardiothoracic surgery. However, in patients with CKD, treating anemia to a target of normal hemoglobin has been associated with increased risk of adverse cardiac and cerebrovascular events. We investigated the association between preoperative hemoglobin and outcomes of cardiac surgery in patients with CKD and assessed whether there was a level of preoperative hemoglobin below which the incidence of adverse surgical outcomes increases.

Design, setting, participants, & measurements

This prospective observational study included adult patients with CKD stages 3–5 (eGFR<60 ml/min per 1.73 m²) undergoing cardiac surgery from February 2000 to January 2010. Patients were classified into four groups stratified by preoperative hemoglobin level: <10, 10–11.9, 12–13.9, and ≥14 g/dl. The outcomes were postoperative AKI requiring dialysis, sepsis, cerebrovascular accident, and mortality.

Results

In total, 788 patients with a mean eGFR of 43.5±13.7 ml/min per 1.73 m² were evaluated, of whom 22.5% had preoperative hemoglobin within the normal range (men: 14–18 g/dl; women: 12–16 g/dl). Univariate analysis revealed an inverse relationship between the incidence of all adverse postoperative outcomes and hemoglobin level. Using hemoglobin as a continuous variable, multivariate logistic regression analysis showed a proportionally greater frequency of all adverse postoperative outcomes per 1-g/dl decrement of preoperative hemoglobin (mortality: odds ratio, 1.38; 95% confidence interval, 1.23 to 1.57; P<0.001; sepsis: odds ratio, 1.31; 95% confidence interval, 1.14 to 1.49; P<0.001; cerebrovascular accident: odds ratio, 1.31; 95% confidence interval, 1.00 to 1.67; P=0.03; postoperative hemodialysis: odds ratio, 1.38; 95% confidence interval, 1.11 to 1.75; P<0.01). Moreover, preoperative hemoglobin<12 g/dl was an independent risk factor for postoperative mortality (odds ratio, 2.6; 95% confidence interval, 1.1 to 7.3; P=0.04).

Conclusions

Similar to the general population, preoperative anemia is associated with adverse postoperative outcomes in patients with CKD. Whether outcomes could be improved by therapeutically targeting higher preoperative hemoglobin levels before cardiac surgery in patients with underlying CKD remains to be determined.     

Chronic kidney disease: an independent risk factor of all-cause mortality for elderly Chinese patients with chronic heart failure

Objective

To evaluate the prognostic value of chronic kidney disease (CKD) in elderly Chinese patients with chronic heart failure (CHF).

Methods

The study consisted of 327 elderly patients with CHF. All-cause mortality was chosen as an endpoint over the median follow-up period of 345 days. Cox regression analysis was used to identify the risk factors of mortality.

Results

The median age of the entire cohort was 85 years (60–100 years). The mortality for 168 elderly patients with CHF and CKD (51.4% of entire cohort) was 39.9% (67 deaths), which was higher than the mortality for CHF patients without CKD [25.2% (40/159 deaths)] and the mortality for entire cohort with CHF [32.7% (107/327 deaths)]. The Cox regression analysis showed that old age [hazard ratio (HR): 1.033; 95% confidence interval (95% CI): 1.004–1.064], CKD (HR: 1.705; 95% CI: 1.132–2.567), CHF New York Heart Association (NYHA) class IV (HR: 1.913; 95% CI: 1.284–2.851), acute myocardial infarction (AMI) (HR: 1.696; 95% CI: 1.036–2.777), elevated resting heart rate (HR: 1.021; 95% CI: 1.009–1.033), and decreased plasma albumin (HR: 0.883; 95% CI: 0.843–0.925) were independent risk factors of mortality for elderly patients with CHF.

Conclusions

CKD was an independent risk factor of mortality for elderly Chinese patients with CHF.     

CKD and Hypertension during Long-Term Follow-Up in Children and Adolescents Previously Treated with Extracorporeal Membrane Oxygenation

Background and objectives

Many children receiving extracorporeal membrane oxygenation develop AKI. If AKI leads to permanent nephron loss, it may increase the risk of developing CKD. The prevalence of CKD and hypertension and its predictive factors during long-term follow-up of children and adolescents previously treated with neonatal extracorporeal membrane oxygenation were determined.

Design, setting, participants, & measurements

Between November of 2010 and February of 2014, neonatal survivors of extracorporeal membrane oxygenation who visited the prospective follow-up program at 1, 2, 5, 8, 12, and 18 years of age were screened for CKD and hypertension (BP≥95th percentile of reference values). CKD was suspected in children with either an eGFR<90 ml/min per 1.73 m² or proteinuria (urinary protein-to-creatinine ratio >0.50 for children ages ≤24 months and >0.20 at >24 months). The RIFLE classification (risk, injury, or failure as 150%, 200%, or 300% of serum creatinine reference values) was used to define AKI during extracorporeal membrane oxygenation without preemptive hemofiltration.

Results

Median follow-up of 169 screened participants was 8.2 years (interquartile range=5.2–12.1 years). Nine children had a lower eGFR, but all rates were >60 ml/min per 1.73 m². Proteinuria was observed in 20 children (median=0.26 mg protein/mg creatinine; interquartile range=0.23–0.32 mg protein/mg creatinine), and 32 children had hypertension. Only history of AKI was associated with CKD (P=0.004). Children with RIFLE scores injury and failure had 4.3 times higher odds of CKD signs or hypertension than those without AKI (95% confidence interval, 1.6 to 12.1; P=0.004).

Conclusions

Altogether, 54 participants (32%) had at least one sign of CKD and/or hypertension. However, most values were marginally abnormal, with no immediate consequences for clinical care. Nevertheless, a prevalence of 32% clearly indicates that survivors of neonatal extracorporeal membrane oxygenation, especially those with AKI, are at risk of a more rapid decline of kidney function with increasing age. Therefore, screening for CKD development in adulthood is recommended.     

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.     

Circulating Follistatin in Patients with Chronic Kidney Disease: Implications for Muscle Strength,Bone Mineral Density,Inflammation, and Survival

Summary

Background and objectives

Follistatin mediates muscle growth and bone mineralization. At present, it is unknown whether circulating follistatin levels are altered in chronic kidney disease (CKD) or links to CKD risk factors and outcomes.

Design, setting, participants, & measurements

Plasma follistatin levels were cross-sectionally analyzed in relation to protein-energy wasting (PEW), handgrip strength (HGS), bone mineral density (BMD), and inflammatory markers in 280 CKD stage 5 patients, 32 CKD stage 4 patients, 16 CKD stage 3 patients, and 32 control subjects. In CKD stage 5 patients survival was prospectively investigated during a follow-up period of up to 5 years.

Results

The plasma follistatin concentration was not higher in CKD stage 5 patients than in other CKD stages or controls. In CKD stage 5 patients, circulating follistatin positively correlated with age, high-sensitivity C-reactive protein (hsCRP), and IL-6; negatively correlated with HGS, serum creatinine, and BMD; and was increased in patients with PEW. In a multivariate logistic regression model, lower HGS, lower BMD, and higher hsCRP independently correlated with higher follistatin levels. In a Cox regression model, follistatin levels were not associated with all-cause mortality.

Conclusions

Circulating follistatin levels were neither elevated nor predicted outcome in patients with CKD. However, increased follistatin levels occurred together with increased inflammation, reduced muscle strength, and low BMD, suggesting an involvement of a mechanism including follistatin in the uremic wasting process.     

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.     

Chronic Kidney Disease Stage Progression in Liver Transplant Recipients

Summary

Background and objectives

There is little information on chronic kidney disease (CKD) stage progression rates and outcomes in liver transplant recipients. Identifying modifiable risk factors may help prevent CKD progression in liver transplant recipients.

Design, setting, participants, & measurements

We performed a retrospective review of 1151 adult, deceased-donor, single-organ primary liver transplants between July 1984 and December 2007 and analyzed kidney outcomes and risk factors for CKD stage progression. Seven hundred twenty-nine patients had an available estimated GFR at 1 year posttransplant to establish a baseline stage. The primary end point was the CKD progression from one stage to a higher stage (lower GFR).

Results

Kaplan–Meier estimates of patient survival were 91%, 74%, and 64% at 5, 10, and 15 years, respectively. Estimates of liver allograft survival were 89%, 71%, and 60% at the same time points. At 1 year, 7%, 34%, 56%, 3%, and 1% of patients were in CKD stages 1, 2, 3, 4, and 5. The incidence of stage progression was 28%, 40%, and 53% at 3, 5, and 10 years. The incidence of ESRD was 2.6%, 7.5%, and 18% at 5, 10, and 20 years. Multivariable Cox regression analyses demonstrated that CKD stage at 1 year, pretransplant diabetes and urinary tract infections/hypercholesterolemia in the first year proved to be independent risk factors for stage progression (hazard ratio 1.9, 0.28, 1.39, and 1.46, respectively, P < 0.05).

Conclusions

Future studies will determine whether treatment of risk factors in the first posttransplant year prevent CKD progression in liver transplant recipients.     

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.