The role of biomarkers in early identification of acute kidney injury among non-critically ill patients.

BACKGROUND: Prediction and/or early identification of acute kidney injury (AKI) and individuals at greater risk remains of great interest in clinical medicine. Acute kidney injury continues to be a common complication among hospitalized patients, with an incidence ranging from 6 to 58%, depending on the setting. Aim of this study was to determine the performance of Insulin-like growth factor binding protein-7 (IGFBP7), tissue metallopeptidase inhibitor 2 (TIMP2), and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in early detection of AKI among non-critically ill patients. METHODS: In this prospective observational study at Mayo Clinic Hospitals in Rochester, Minnesota, USA, non-critically ill patients admitted from the emergency department between October 31st, 2016 and May 1st, 2018, who had an acute kidney injury (AKI) probability of 5% or higher were included. Biomarkers were measured in residual urine samples collected in the emergency department. The primary outcome was biomarker performance in predicting AKI development within the first 72 h. RESULTS: Among 368 included patients, the mean age was 79 ± 12 years, and 160 (43%) were male. Acute kidney injury occurred in 62 (17%) patients; 11.5% stage 1, 2.5% stage 2, and 3% stage 3. Twelve patients (3%) died during hospitalization and 102 (28%) within nine months after admission. The median uNGAL and IGFBP7-TIMP2 were 57 [20-236 ng/ml], and 0.3 [0.1-0.8], respectively. The C-statistic of uNGAL and IGFBP7-TIMP2 of > 0.3 and > 2.0 for AKI prediction were 0.56, 0.54, and 0.53, respectively. In a model where one point is assigned to each marker of AKI (elevated serum creatinine, IGFBP7-TIMP2 > 0.3, and uNGAL), a higher score correlated with higher nine-month mortality [OR of 1.32 per point (95% CI 1.02-1.71)]. CONCLUSION: Among non-critically ill hospitalized patients, the performance of uNGAL and IGFBP7-TIMP2 for AKI prediction within 72 h of admission was modest. This suggests a limited role for these biomarkers in AKI risk stratification among non-critically ill patients. Key learning points What was known Acute kidney injury (AKI) is a common complication among hospitalized patients. It is associated with increased morbidity and mortality. Various clinical prediction models and biomarkers have been developed to identify patients in special populations (such as ICU and cardiac surgery) who are at risk of AKI and diagnose AKI early. This study adds The performance of the biomarkers uNGAL, TIMP-2, and IGFBP-7 in predicting AKI within 72 h of admission in non-critically ill patients was modest. However, these biomarkers were found to have a prognostic value for predicting 9-month mortality. One potential application of these biomarkers is identifying patients at higher AKI risk before exposing them to nephrotoxic agents. Potential impact This study provides evidence regarding the real-world performance of current FDA-approved biomarkers (uNGAL, TIMP-2, and IGFBP-7) for predicting acute kidney injury (AKI) within 72 h of hospital admission among noncritically ill patients. While the performance of these biomarkers for predicting short-term AKI was modest, they may have a prognostic value for predicting 9-month mortality.

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Characterising acute kidney injury: The complementary roles of biomarkers of renal stress and renal function.

PURPOSE: Although epidemiological studies have enhanced our understanding of acute kidney injury, defining the biologic processes corresponding to the clinical phenotype remains challenging. We have examined biomarkers associated with renal stress plus markers of glomerular function to assess whether this approach may aid prediction of AKI or other relevant endpoints. MATERIALS & METHODS: Urinary [TIMP-2]·[IGFBP7], serum creatinine, plasma cystatin C and plasma proenkephalin 119-159 2 were analyzed in patients enrolled in the prospective, international, Sapphire study. Heterogenous critically ill patients (n = 723) were examined with a primary endpoint of development of KDIGO stage 2-3 within 12 h and a secondary endpoint of major adverse kidney events at 30 days (MAKE30). RESULTS: 100 patients (14%) reached the primary endpoint. Markers of renal stress outperformed those associated with glomerular function. Combining [TIMP-2]•[IGFBP7] with serum creatinine, but not the other functional markers, significantly (p = 0.02) increased the area under the ROC curve (AUC) from 0.80 (0.76-0.84) to 0.85 (0.81-0.89). In patients who did not develop AKI, all markers of glomerular filtration, but not [TIMP-2]·[IGFBP7], were significantly elevated in patients with a history of CKD (p < 0.05). CONCLUSIONS: The combination of cell-cycle arrest biomarkers, TIMP-2 and IGFBP7, with serum creatinine but not cystatin C or PENK improved risk stratification for the development of stage 2 or 3 AKI over [TIMP-2]·[IGFBP7] alone.

Hospital-acquired serum phosphate derangements and their associated in-hospital mortality.

BACKGROUND: We aimed to report the incidence of hospital-acquired hypophosphataemia and hyperphosphataemia along with their associated in-hospital mortality. METHODS: We included 15 869 adult patients hospitalised at a tertiary medical referral centre from January 2009 to December 2013, who had normal serum phosphate levels at admission and at least two serum phosphate measurements during their hospitalisation. The normal range of serum phosphate was defined as 2.5-4.2 mg/dL. In-hospital serum phosphate levels were categorised based on the occurrence of hospital-acquired hypophosphataemia and hyperphosphataemia. We analysed the association of hospital-acquired hypophosphataemia and hyperphosphataemia with in-hospital mortality using multivariable logistic regression. RESULTS: Fifty-three per cent (n=8464) of the patients developed new serum phosphate derangements during their hospitalisation. The incidence of hospital-acquired hypophosphataemia and hyperphosphataemia was 35% and 27%, respectively. Hospital-acquired hypophosphataemia and hyperphosphataemia were associated with odds ratio (OR) of 1.56 and 2.60 for in-hospital mortality, respectively (p value<0.001 for both). Compared with patients with persistently normal in-hospital phosphate levels, patients with hospital-acquired hypophosphataemia only (OR 1.64), hospital-acquired hyperphosphataemia only (OR 2.74) and both hospital-acquired hypophosphataemia and hyperphosphataemia (ie, phosphate fluctuations; OR 4.00) were significantly associated with increased in-hospital mortality (all p values <0.001). CONCLUSION: Hospital-acquired serum phosphate derangements affect approximately half of the hospitalised patients and are associated with increased in-hospital mortality rate.

Prospective evaluation of high-dose methotrexate pharmacokinetics in adult patients with lymphoma using novel determinants of kidney function.

High-dose methotrexate (HDMTX) pharmacokinetics (PKs), including the best estimated glomerular filtration rate (eGFR) equation that reflects methotrexate (MTX) clearance, requires investigation. This prospective, observational, single-center study evaluated adult patients with lymphoma treated with HDMTX. Samples were collected at predefined time points up to 96 h postinfusion. MTX and 7-hydroxy-MTX PKs were estimated by standard noncompartmental analysis. Linear regression determined which serum creatinine- or cystatin C-based eGFR equation best predicted MTX clearance. The 80 included patients had a median (interquartile range [IQR]) age of 68.6 years (IQR 59.2-75.6), 54 (67.5%) were men, and 74 (92.5%) were White. The median (IQR) dose of MTX was 7.6 (IQR 4.8-11.3) grams. Median clearance was similar across three dosing levels at 4.5-5.6 L/h and was consistent with linear PKs. Liver function, weight, age, sex, concomitant chemotherapy, and number of previous MTX doses did not impact clearance. MTX area under the curve (AUC) values varied over a fourfold range and appeared to increase in proportion to the dose. The eGFRcys (ml/min) equation most closely correlated with MTX clearance in both the entire cohort and after excluding outlier MTX clearance values (r = 0.31 and 0.51, respectively). HDMTX as a 4-h infusion displays high interpatient pharmacokinetic variability. Population PK modeling to optimize MTX AUC attainment requires further evaluation. The cystatin C-based eGFR equation most closely estimated MTX clearance and should be investigated for dosing and monitoring in adults requiring MTX as part of lymphoma management.

Prolonged exposure to continuous renal replacement therapy in patients with acute kidney injury.

BACKGROUND: Little is known about the process of deciding to discontinue continuous renal replacement therapy (CRRT) in patients with acute kidney injury (AKI) and the impact of CRRT duration on outcomes. METHODS: We report the clinical parameters of prolonged CRRT exposure and predictors of doubling of serum creatinine or need for dialysis at 90 days after CRRT with propensity score matching, including covariates that were likely to influence patients in the prolonged CRRT group. RESULTS: Among 104 survey responders, most use urine output (87%) to guide CRRT discontinuation, 24% use improvement in clinical or hemodynamic status. In the cohort study, of 854 included patients, 465 participated in the assessment of kidney recovery. Patients with prolonged CRRT had higher SOFA scores (11.9 vs. 11.2) and were more likely to be mechanically ventilated (99% vs. 84%) at CRRT initiation compared to patients without prolonged CRRT, p-value < 0.05. In multivariable logistic regression, daily urine output and cumulative fluid balance leading to CRRT discontinuation or day seven were independently associated with lower [OR 0.87 per 200 ml/day increase] and higher odds [OR 1.03 per 1-L increase] of requiring prolonged CRRT, respectively. After propensity score matching, prolonged exposure to CRRT was independently associated with increased risk of doubling serum creatinine or dialysis at 90 days, OR 3.1 (95% CI 1.23-8.3 p = 0.017). CONCLUSIONS: Resolution of critical illness and signs of kidney recovery are important factors when considering CRRT discontinuation. Prolonged CRRT exposure may be associated with less chance of kidney recovery among survivors.

Ultrasonographic Assessment of Extravascular Lung Water in Hospitalized Patients Requiring Hemodialysis: A Prospective Observational Study.

INTRODUCTION: Sonographic technologies can estimate extravascular lung water (EVLW) in hemodialysis (HD) patients. This study investigated the suitability of a handheld scanner in contrast to a portable scanner for quantifying EVLW in hospitalized patients requiring HD. METHODS: In this prospective study, 54 hospitalized HD patients were enrolled. Bedside lung ultrasound was performed within 30 min before and after dialysis using handheld (phased array transducer, 1.7-3.8 MHz) and portable (curved probe, 5-2 MHz) ultrasound devices. Eight lung zones were scanned for total B-lines number (TBLN). The maximum diameter of inferior vena cava (IVC) was measured. We performed Passing-Bablok regression, Deming regression, Bland-Altman, and logistic regression analysis. RESULTS: The 2 devices did not differ in measuring TBLN and IVC (p > 0.05), showing a high correlation (r = 0.92 and r = 0.51, respectively). Passing-Bablok regression had a slope of 1.11 and an intercept of 0 for TBLN, and the slope of Deming regression was 1.02 within the CI bands of 0.94 and 1.11 in the full cohort. TBLN was logarithmically transformed for Bland-Altman analysis, showing a bias of 0.06 (TBLN = 1.2) between devices. The slope and intercept of the Deming regression in IVC measurements were 0.77 and 0.46, respectively; Bland-Altman plot showed a bias of -0.07. Compared with predialysis, TBLN significantly (p < 0.001) decreased after dialysis, while IVC was unchanged (p = 0.16). Univariate analysis showed that cardiovascular disease (odds ratio [OR] 8.94 [2.13-61.96], p = 0.002), smoking history (OR 5.75 [1.8-20.46], p = 0.003), and right pleural effusion (OR 5.0 [1.2-25.99], p = 0.03) were strong predictors of EVLW indicated by TBLN ≥ 4. CONCLUSION: The lung and IVC findings obtained from handheld and portable ultrasound scanners are comparable and concordant. Cardiovascular disease and smoking history were strong predictors of EVLW. The use of TBLN to assess EVLW in hospitalized HD patients is feasible. Further studies are needed to determine if TBLN can help guide volume removal in HD patients.

Kidney Recovery From Acute Kidney Injury After Hematopoietic Stem Cell Transplant: A Systematic Review and Meta-Analysis.

Patients with the recovery of kidney function after an episode of acute kidney injury (AKI) have better outcomes compared to those without recovery. The current systematic review is conducted to assess the rates of kidney function recovery among patients with AKI or severe AKI requiring kidney replacement therapy (KRT) within 100 days after hematopoietic stem cell transplant (HSCT). Methods The Ovid MEDLINE, EMBASE, and Cochrane databases were systemically searched from database inceptions through August 2019 to identify studies reporting the rates of recovery from AKI after HSCT. The random-effects and generic inverse variance methods of DerSimonian-Laird were used to combine the effect estimates obtained from individual studies. Results A total of 458 patients from eight cohort studies with AKI after HSCT were identified. Overall, the pooled estimated rates of AKI recovery among patients with AKI and severe AKI requiring KRT within 100 days were 58% (95%CI: 37%-78%) and 10% (95%CI: 2%-4%), respectively. Among patients with AKI recovery, the pooled estimated rates of complete and partial AKI recovery were 60% (95%CI: 39%-78%) and 29% (95%CI: 10%-61%), respectively. There was no clear correlation between study year and the rate of AKI recovery (p=0.26). Conclusion The rate of recovery from AKI after HSCT depends on the severity of AKI. While recovery is common, complete recovery is reported in about two-thirds of all AKI patients. The rate of recovery among those with AKI requiring renal replacement therapy (RRT) is substantially lower.

Clinician perspectives on inpatient cystatin C utilization: A qualitative case study at Mayo Clinic.

INTRODUCTION: Serum creatinine (SCr) testing has been the mainstay of kidney function assessment for decades despite known limitations. Cystatin C (CysC) is an alternative biomarker that is generally less affected than SCr by pertinent non-renal factors in hospitalized patients, such as muscle mass. Despite its potential advantages, the adoption of CysC for inpatient care is not widespread. At one hospital with CysC testing, we demonstrated a significant rise in non-protocolized use over the last decade. This study uses qualitative methods to provide the first report of how clinicians understand, approach, and apply CysC testing in inpatient care. METHODS: Fifteen clinicians from various disciplines were interviewed about their experience with inpatient CysC testing. The semi-structured interviews were audio-recorded, transcribed verbatim, and analyzed thematically using a phenomenological approach. RESULTS: Knowledge and confidence with CysC varied greatly. Clinicians reported first learning about the test from colleagues on consulting services or multidisciplinary teams. The majority believed CysC to provide a more accurate measure of kidney function than SCr. Common scenarios for CysC ordering included medication dosing, evaluation of acute kidney injury, and a thorough evaluation of kidney function in patients with risk factors for an altered SCr. Facilitators for ordering CysC included the availability of rapid results turnaround and the automated calculation of glomerular filtration rate based on the biomarker. Barriers to use included a lack of education about CysC, and the absence of an institutional protocol for use. DISCUSSION: Clinicians at our site decided independent of institutional guidance whether and when CysC added value to patient care. While the majority of study participants indicated advantages to rapid turnaround CysC testing, its use depended not just on the features of the specific case but on clinician familiarity and personal preference. Findings from this research can guide the implementation and expansion of CysC testing.

Prediction of Vancomycin Levels Using Cystatin C in Overweight and Obese Patients: a Retrospective Cohort Study of Hospitalized Patients.

The use of the kidney function biomarker cystatin C (cysC) can improve the accuracy of vancomycin dosing for target trough attainment in nonobese patients. It is unknown whether cysC can also improve vancomycin target trough attainment in overweight and obese patients. We conducted a retrospective observational study of overweight or obese hospitalized adults with stable renal function administered intravenous vancomycin between January 2011 and July 2019. Linear regression models were used to predict initial steady-state vancomycin troughs using several factors, including various cysC- and serum creatinine (SCr)-based estimates of kidney function. We compared the predicted proportion of patients within the target trough range (10 to 20 mg/liter) using the derived models to that observed from usual care. Of the 200 included patients, the mean trough level was 15 ± 6.3 mg/liter. The optimal model to predict the initial trough included both cysC and SCr (R2 = 0.48) rather than either biomarker alone. This model predicted that 79% (95% confidence interval [CI], 73% to 85%) of troughs could be between 10 and 20 mg/liter compared to the 62% observed in clinical practice (P < 0.001), a 1.3-fold increase. This study is the first to examine the role of cysC in predicting vancomycin levels in an exclusively overweight or obese population. While dosing models based on cysC appear promising in this setting, prospective validation is needed.

Artificial intelligence to guide management of acute kidney injury in the ICU: a narrative review.

PURPOSE OF REVIEW: Acute kidney injury (AKI) frequently complicates hospital admission, especially in the ICU or after major surgery, and is associated with high morbidity and mortality. The risk of developing AKI depends on the presence of preexisting comorbidities and the cause of the current disease. Besides, many other parameters affect the kidney function, such as the state of other vital organs, the host response, and the initiated treatment. Advancements in the field of informatics have led to the opportunity to store and utilize the patient-related data to train and validate models to detect specific patterns and, as such, predict disease states or outcomes. RECENT FINDINGS: Machine-learning techniques have also been applied to predict AKI, as well as the patients' outcomes related to their AKI, such as mortality or the need for kidney replacement therapy. Several models have recently been developed, but only a few of them have been validated in external cohorts. SUMMARY: In this article, we provide an overview of the machine-learning prediction models for AKI and its outcomes in critically ill patients and individuals undergoing major surgery. We also discuss the pitfalls and the opportunities related to the implementation of these models in clinical practices.

Characteristics and Outcomes of Kidney Transplant Recipients Requiring High-Acuity Care After Transplant Surgery: A 10-Year Single-Center Study.

OBJECTIVE: To study the characteristics and outcomes of a cohort of kidney transplant recipients who required high-acuity care after transplant surgery. PATIENTS AND METHODS: All adult (aged ≥18 years) solitary kidney transplant recipients from January 1, 2007, through December 31, 2016, were screened and those who required high-acuity care within the same hospitalization were enrolled. Patient demographic and clinical data were collected from the departmental database and electronic DataMart. RESULTS: Of 1525 patients, 266 (17.4%) required high-acuity care after the kidney transplant operation: 166 (62.4%) directly from the operating room and 100 (37.6%) after an interval during the same hospitalization. Overall, 2 main indications were hypotension (n=87; 32.7%) and cardiac rhythm disturbances (n=83; 31.2%). Recipients in the direct admission group had higher medium body mass index (31.0 [interquartile range, 26.6-36.0] vs 28.0 [interquartile range, 24.3-32.4] kg/m2; P<.001) and were more likely to have undergone a concomitant procedure with the transplant surgery. Overall, in-hospital mortality was 1.9% (n=5). CONCLUSION: In contemporary practice, patients with higher body mass index are more likely to require high-acuity care immediately after kidney transplant surgery. The most common reasons are hypotension and cardiac rhythm disorders. The overall intensive care unit mortality rate of these patients is low. However, these patients are at risk for graft loss and death in the long term compared with patients who do not require intensive care unit care after transplant surgery.

Timing of resumption of beta-blockers after discontinuation of vasopressors is not associated with post-operative atrial fibrillation in critically ill patients recovering from non-cardiac surgery: A retrospective cohort analysis.

BACKGROUND: Post-operative atrial fibrillation is a complication with high morbidity. In patients on prior-to-admission beta-blockers, early post-operative beta-blockade reduces atrial fibrillation risk; however, this benefit is not studied in hemodynamically unstable patients requiring vasopressors. METHODS: A retrospective analysis was performed at two high-volume centers of adult patients on home beta-blockers, undergoing non-cardiac surgery between 2005 and 2015, and who required post-operative vasopressors. Patients were divided into early beta-blockers (within 24 h) or delayed from vasopressor cessation. The primary outcome was the atrial fibrillation incidence. A propensity score was developed for early beta-blockers and used for adjustment. RESULTS: Eight-hundred seventy one patients required post-operative vasopressors; 423 in the early group and 448 in the delayed group. In the delayed beta-blocker group, intraoperative hypotension was more common (21.6% versus 24.1%, p < 0.001), APACHE III scores higher (56.6 versus 50.8, p < 0.001) and more post-operative norephinephrine use (56.7% veruss 30.3%, p < 0.001). Eighty eight patients developed atrial fibrillation: 40 in the early group, and 48 in the delayed group (p = 0.538). After adjustment, early beta-blockade was not associated with changed incidence of atrial fibrillation. CONCLUSIONS: In patients requiring postoperative vasopressors, early beta-blockade did not protect against postoperative atrial fibrillation.

Patterns of Cystatin C Uptake and Use Across and Within Hospitals.

OBJECTIVE: To characterize the use of cystatin C (cysC) across and within hospitals. PATIENTS AND METHODS: This 2-part study first evaluated access to cysC testing across 129 hospitals in the state of Minnesota, using a telephone-based survey. Second, granular data from a single center (Mayo Clinic) with on-site, rapid-turnaround testing (<1 day) and automated estimated glomerular filtration rate (eGFR) reporting was used to describe temporal patterns. The characteristics of hospitals that offered cysC testing and of patients who underwent rapid cysC testing at Mayo Clinic between January 1, 2011, and March 31, 2018, were described. Poisson regression analyzed temporal trends in cysC testing. RESULTS: Of the 114 hospitals (88%) that responded to the statewide survey, cysC was available in 91 (80%), but only 3 of 91 (3%) reported a turnaround time of <1 day. At Mayo Clinic, cysC use increased from 0.74 tests per 1000 patient-days in 2011 to 14 tests per 1000 patient-days in 2018 (P=.004). Of the 3774 patients with cysC tests, the mean first available eGFR was 46 mL/min per 1.73 m2 using cysC and 59 mL/min per 1.73 m2 using serum creatinine (P<.001). CysC testing was used across all intensities of care and was ordered by a variety of specialties. Nephrology was consulted in only 42% of cases. CONCLUSION: In the hospital, rapid-turnaround cysC testing is necessary for practical use but was not widely available in Minnesota. When available, a marked increase in cysC testing was observed over the study timeframe. Additional research is needed to determine optimal strategies for implementation of cysC within hospitals.

Assessment of muscle mass in critically ill patients: role of the sarcopenia index and images studies.

PURPOSE OF REVIEW: Sarcopenia is a progressive generalized decline in skeletal muscle mass, strength, and function. This condition is highly prevalent in critically ill patients and is associated with poor outcomes in the ICU. In this review, we describe the use, evidence, and limitations of the most common validated imaging studies used to assess muscle mass in ICU, and we provide an overview of the benefits of using the sarcopenia index [(serum creatinine/serum cystatin C) × 100]) in the ICU. RECENT FINDINGS: Currently, the determination of muscle mass using anthropometric measurements and serum biomarkers is unreliable. Several new techniques, including a dual-energy X-ray absorptiometry, computed tomography scan, ultrasonography, and bioimpedance analysis, have been studied and validated for the diagnosis and prognosis of sarcopenia in the ICU. However, these techniques are often not accessible for the majority of critically ill patients. The sarcopenia index constitutes an accurate method to diagnose sarcopenia, predict ICU outcomes, and nutritional status in critically ill patients. SUMMARY: Diagnosis of sarcopenia has substantial implications in ICU patients. Choosing the correct test to identify patients who may need preventive or therapeutic support for this condition will favorably impact ICU outcomes.

Predictors of Augmented Renal Clearance in a Heterogeneous ICU Population as Defined by Creatinine and Cystatin C.

INTRODUCTION: The incidence of augmented renal clearance (ARC) in the intensive care unit (ICU) is highly variable, and identification of these patients remains challenging. OBJECTIVE: The objective of this study was to define the incidence of ARC in a cohort of critically ill adults, using serum Cr and cystatin C, and to identify factors associated with its development. METHODS: This is a retrospective cohort study of critically ill patients without stage 2 or 3 acute kidney injury with both serum Cr and cystatin C available. The incidence of ARC was defined as a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)Cr-cystatin C-estimated glomerular filtration rate >130 mL/min. A multivariable logistic regression model using a penalized Lasso method was fit to identify independent predictors of ARC. RESULTS: Among the 368 patients included in the study, indication for ICU admission was nonoperative in 55% of patients, and 9% of patients were admitted for major trauma. The overall incidence of ARC was low at 4.1%. In a multivariable logistic regression model, Charlson comorbidity index, major trauma, intracerebral hemorrhage, age, and Sequential Organ Failure Assessment score were found to predict ARC. CONCLUSION: The incidence of ARC in this study was low, but prediction models identified several factors for early identification of patients with risk factors for or who develop ARC, particularly in a cohort with a low baseline risk of ARC. These factors could be used to help identify patients who may develop ARC.

Risk Factors for Acute Kidney Injury in Hospitalized Non-Critically Ill Patients: A Population-Based Study.

OBJECTIVE: To develop and validate an acute kidney injury (AKI) risk prediction model for hospitalized non-critically ill patients. PATIENTS AND METHODS: We retrospectively identified all Olmsted County, Minnesota, residents admitted to non-intensive care unit (ICU) wards at Mayo Clinic Hospital, Rochester, Minnesota, in 2013 and 2014. The cohort was divided into development and validation sets by year. The primary outcome was hospital-acquired AKI defined by Kidney Disease: Improving Global Outcomes criteria. Cox regression was used to analyze mortality data. Comorbid risk factors for AKI were identified, and a multivariable model was developed and validated. RESULTS: The development and validation cohorts included 3816 and 3232 adults, respectively. Approximately 10% of patients in both cohorts had AKI, and patients with AKI had an increased risk of death (hazard ratio, 3.62; 95% CI, 2.97-4.43; P<.001). Significant univariate determinants of AKI were preexisting kidney disease, diabetes mellitus, hypertension, heart failure, vascular disease, coagulopathy, pulmonary disease, coronary artery disease, cancer, obesity, liver disease, and weight loss (all P<.05). The final multivariable model included increased baseline serum creatinine value, admission to a medical service, pulmonary disease, diabetes mellitus, kidney disease, cancer, hypertension, and vascular disease. The area under the receiver operating characteristic curves for the development and validation cohorts were 0.71 (95% CI, 0.69-0.75) and 0.75 (95% CI, 0.72-0.78), respectively. CONCLUSION: Hospital-acquired AKI is common in non-ICU inpatients and is associated with worse outcomes. Patient data at admission can be used to identify increased risk; such patients may benefit from more intensive monitoring and earlier intervention and testing with emerging biomarkers.

Creatinine: From physiology to clinical application.

Estimating static kidney function accurately and detecting changes in kidney function in a timely fashion are challenging but critically important tasks. Serum creatinine is the most widely used functional biomarker of the kidney. However, its use is associated with substantial shortcomings. Understanding these shortcomings is critical in allowing accurate interpretation of creatinine values and translating them into changes in kidney function. In this review, the pathways involved in creatinine generation and metabolism as well as the techniques involved in measuring creatinine concentrations are discussed. This allows for the discussion of the value and pitfalls in using creatinine as a marker of kidney function. In addition, information regarding alternative functional biomarkers of the kidney is provided.