Small Changes In Serum Creatinine Research Articles

MO424RENAL ANGINA: RISK OF ACUTE KIDNEY INJURY IN CRITICALLY ILL ADULTS IN FUNDACIÓN CARDIOINFANTIL IN BOGOTÁ USING CLINICAL RISK FACTORS AND CHANGES IN SERUM CREATININE

Background and AimsAcute Kidney Injury (AKI) has remarkable cardiovascular and mortality outcomes, both short and long term potentially preventable with adequate ICU support, thus, early diagnosis is mandatory. Full AKI diagnosis according to KDIGO criteria can result in delayed interventions at admission in ICU, giving potential benefits to alternatives in early diagnosis.Cruz and NEFROINT research group described a scale for prediction of severe AKI, based on risk factors and establishing creatinine cuts as markers of kidney distress.1Our aim is to describe the predictive capacity of small changes in serum creatinine correlating with clinical risk factors in adult critical care patients. 1. Clin J Am Soc Nephrol (2014) 9, 663-672.MethodWe retrospectively selected from our Critical Care Nephrology database adult patients admitted in any of our hospital`s ICU between February to August 2020, excluding those at admission with diagnosis of AKI, serum creatinine > 2.5 mg/dl, or those receiving dialysis (acute or chronic) or kidney transplantation. We defined AKI according to KDIGO criteria.We calculated Cruz et al scale of prediction of severe AKI. The minimally acceptable criteria for this test was a sensitivity of 95%. A point estimate and confidence intervals of sensitivity and specificity were derived from a contingency table.ResultsFrom 1204 new ICU patients, according to selection criteria we found 372 patients (women 40.3%), with mean age of 60.9 years (range 18-98), mainly hospitalized for medical conditions.Mean values of APACHE II was 22.9. Hemodynamic support was required in 41.1% of patients and mechanical ventilation in 58.6% of patients. (Table 1).AKI KDIGO 2-3 was diagnosed in 65 (26.8%) of patients.Creatinine at admission was statistically different in patients that developed AKI (CI 0.95 -0.51 - 0.15 mg/dl, p=0.0004). Requirement of hemodynamic (p = 0.003) and ventilatory support (p = 0.009), sepsis (p = 0.003), and diagnosis of COVID-19 (p = 0.03) were more frequent in patients who developed AKI.Clinical risk for severe AKI was present in 356 patients (95.7%): 66,5% at very high risk, 9,8% at high risk and 19,2% at moderate risk. Patients without risk criteria were classified as low risk (4,3%).In patients with risk factors for AKI, and a significative increase in creatinine adjusted to risks, diagnostic performance for predicting diagnosis of KDIGO 2-3 AKI had a sensitivity, specificity, positive and negative predictive value of 89% (CI95% 79 – 95%), 58% (CI95% 52 – 64%), 0.31 (CI95% 0.25 – 0.39) and 0.96 (CI95% 0.92 – 0.98) respectively (Figure).Renal replacement therapy was required in 39 (60%) of patients with severe AKI (incidence 10.5%). (Table 2)ConclusionRegardless of the risk stratification for AKI, the absence of significant early changes in serum creatinine rules out the possibility of progression to KDIGO 2-3 AKI in the first seven days after ICU admission.

A Simple Scoring Method for Predicting the Low Risk of Persistent Acute Kidney Injury in Critically Ill Adult Patients

The renal angina index has been proposed to identify patients at high risk of persistent AKI, based on slight changes in serum creatinine and patient conditions. However, a concise scoring method has only been proposed for pediatric patients, and not for adult patients yet. Here, we developed and validated a concise scoring method using data on patients admitted to ICUs in 21 Japanese hospitals from 2012 to 2014. We randomly assigned to either discovery or validation cohorts, identified the factors significantly associated with persistent AKI using a multivariable logistic regression model in the discovery cohort to establish a scoring system, and assessed the validity of the scoring in the validation cohort using receiver operating characteristic analysis and the calibration slope. Among 8,320 patients admitted to the ICUs, persistent AKI was present in 1,064 (12.8%) patients. In the discovery cohort (n = 4,151), ‘hyperbilirubinemia’, ‘sepsis’ and ‘ventilator and/or vasoactive’ with small changes in serum creatinine were selected to establish the scoring. In the validation cohort (n = 4,169), the predicting model based on this scoring had a c-statistic of 0.79 (95%CI, 0.77–0.81) and was well calibrated. In conclusion, we established a concise scoring method to identify potential patients with persistent AKI, which performed well in the validation cohort.

Guideline updates for definition, diagnosis and management of hepatorenal syndrome

Hepatorenal syndrome (HRS) is a unique form of acute kidney injury (AKI) developing in patients with end‐stage liver disease. AKI is a frequent complication in advanced cirrhosis patients which is associated with increased hospital admissions and decreased survival. The definition of AKI in cirrhosis has been recently modified and the new diagnostic criteria are based on small changes in serum creatinine with respect to previous values, occurring within a short period of time.
 Systemic circulatory dysfunction and marked kidney vasoconstriction play a key role in the development of HRS. The modification of the AKI definition has also led to a change in the diagnostic criteria of HRS. The new diagnostic criteria are based on AKI stages and there is no need to reach a specific serum creatinine threshold. The use of the new HRS definition may lead to an earlier identification of renal impairment and better prognostic stratification. According to these new criteria, treatment with vasoconstrictors and albumin for the management of HRS will be started at lower serum creatinine values, with expected higher response rates. There are consistent data showing that some urine biomarkers, particularly NGAL (neutrophil gelatinase‐associated lipocalin), may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis. Various HRS treatment regimens are available worldwide and all are designed to increase the mean arterial pressure by increasing the central blood volume and decreasing splanchnic vasodilation, and to serve as bridge to liver transplantation.

Hepatorenal syndrome in the era of acute kidney injury.

Acute kidney injury (AKI) is a frequent complication of patients with advanced cirrhosis that it is associated with increased hospital admissions and decreased survival. The definition of AKI in cirrhosis has been recently modified and the new diagnostic criteria are based on small changes in serum creatinine with respect to previous values, occurring within a short period of time. The use of this new definition may lead to an earlier identification of renal impairment and better prognostic stratification. Hepatorenal syndrome (HRS) is a unique form of AKI developing in patients with end-stage liver disease. Systemic circulatory dysfunction and marked kidney vasoconstriction play a key role in the development of HRS. The modification of the definition of AKI has also led to a change in the diagnostic criteria of HRS. The new diagnostic criteria are based on AKI stages and there is no need to reach a specific serum creatinine threshold. According to these new criteria, treatment with vasoconstrictors and albumin for the management of HRS will be started at lower serum creatinine values, with expected higher response rates. Finally, there are consistent data showing that some urine biomarkers, particularly NGAL (neutrophil gelatinase-associated lipocalin), may be useful in daily clinical practice for the differential diagnosis of the cause of AKI in cirrhosis.

Changes in Kidney Function Associated With Daily Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Preexposure Prophylaxis Use in the United States Demonstration Project.

HIV preexposure prophylaxis (PrEP) using daily oral tenofovir-disoproxil-fumarate/emtricitabine (TDF/FTC) is effective for preventing HIV acquisition, but concerns remain about its potential kidney toxicity. This study examined kidney function in individuals using PrEP in real-world clinical settings. Demonstration project in 2 sexually transmitted infection clinics and a community health center. We evaluated kidney function among men who have sex with men and transgender women taking tenofovir-disoproxil-fumarate/emtricitabine PrEP for up to 48 weeks. Serum creatinine and urine dipstick for protein were obtained at 12-week intervals. Kidney function was estimated using creatinine clearance (CrCl) (Cockcroft-Gault) and estimated glomerular filtration rate (eGFR) (CKD-EPI). From October 2012 to January 2014, we enrolled 557 participants (median age 33). Mean creatinine increased from baseline to week 12 by 0.03 mg/dL (4.6%) (P < 0.0001); mean CrCl decreased by 4.8 mL/min (3.0%) (P < 0.0001). These changes remained stable through week 48 (P = 0.81, P = 0.71 respectively). There were 75/478 (15.7%) participants who developed worsening proteinuria at week 12 compared with baseline (P < 0.0001), and this percent remained stable through week 48 (P = 0.73). Twenty-five participants (5.1%) developed new-onset eGFR <70 mL/min/1.73 m; independent predictors of this outcome were age ≥40 years (OR 3.79, 95% CI: 1.43 to 10.03) and baseline eGFR <90 mL/min/1.73 m (OR 9.59, 3.69-24.94). In a demonstration setting, daily tenofovir-disoproxil-fumarate/emtricitabine PrEP leads to reduced CrCl and eGFR; however, these eGFR changes are based on very small changes in serum creatinine and seem to be nonprogressive after the first 12 weeks. Future studies are needed to understand the prognostic significance of these small changes.

Acute kidney injury (AKI) in paediatric critical care

Abstract Incidence of acute kidney injury (AKI) is gradually increasing in children admitted to critical care units partly because of increased awareness of this entity. Though serum creatinine has been used in most definitions, its inability to accurately reflect kidney function has resulted in problems for clinical research in paediatric AKI. This has resulted in the use of more than 35 definitions of AKI in clinical studies, ranging from small changes in serum creatinine to requirement for dialysis. Therefore, comparisons among studies are difficult, resulting in a wide range of quoted epidemiology, morbidity, and mortality rates in the AKI paediatric literature. Acute kidney injury may be precipitated by critical illness, pre-existing medical conditions, and treatments received both before and during ICU admission. In this review we have attempted to outline the current definitions used for AKI, presence of AKI in various critical care conditions (bone marrow transplant, liver, sepsis, cardiac, primary renal conditions leading to glomerulonephritis) and outline the basic management.

Danno Renale Acuto da Mezzi Iodati di Contrasto. Fisiopatologia e Suggerimenti di Prevenzione

Abstract non disponibile

The Use of Automated Electronic Alerts in Studying Short-Term Outcomes Associated with Community-Acquired Acute Kidney Injury

Background/Aims: The use of electronic alerts (e-alerts) may increase the detection rate of acute kidney injury (AKI) since they are sensitive to small changes in serum creatinine. Our aim was to follow-up a cohort of patients presenting to hospital from the community with AKI (community-acquired AKI [c-AKI]), detected through the use of e-alerts, and describe their short-term outcomes regardless of whether they were subsequently admitted to hospital. Methods: Blood samples for all hospital attenders from the community either to the Accidents and Emergency department or one of the acute care areas of the hospital during a 6-month period (November 1, 2013-April 30, 2014) were screened for presence of c-AKI using a locally developed e-alerts system based on Kidney Disease: Improving Global Outcomes criteria. Follow-up data were obtained for a period of 3 months. Results: A total of 1,277 c-AKI episodes were identified in 1,185 patients (incidence 579 per 100,000 persons). Episodes that lead to hospitalization (n = 1,096 [86%]) were associated with a median length of hospital stay of 6.6 days; a graded increase in duration of stay was noted with increasing severity of AKI. Acute dialysis was needed during 21 (1.6%) episodes. For mortality rates, only the first AKI episode was considered. There were 298 deaths within 30 days of diagnosis irrespective of admissions status (30-day mortality rate: 25%). Conclusions: Using e-alerts in acute care settings to detect c-AKI is novel and may be used to stage and follow-up AKI using existing diagnostic criteria. c-AKI is relatively common and leads to significant mortality.

Diagnosis and Treatment of Acute Kidney Injury in Pediatrics

The term acute kidney injury (AKI) has replaced the outdated term acute renal failure throughout the literature and clinical practice. The term “injury” highlights the spectrum of organ injury that may occur and reflects the fact that even small changes in serum creatinine (rise of 0.3 mg/dL) can be associated with adverse outcomes. A major advance in the field of AKI research has been the development of standardized staged definitions of AKI that allow for comparison of incidence, prevalence, and outcomes across studies. The Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition represents the most recent consensus definition which is currently recommended for use in pediatric populations. Utilization of standard AKI definitions has made it clear that AKI occurs often in hospitalized patients and is associated with adverse short-term and long-term outcomes (hospital length of stay, mortality, subsequent chronic kidney disease). Awareness of the impact of AKI has resulted in increased efforts to understand, diagnose, prevent, and manage AKI earlier in the course of illness. While attempts at finding a treatment for AKI have been unsuccessful, largely due to the lack of sensitivity of the primary biomarker, serum creatinine, there have been many major advances in this field over the last 15 years. The development of novel biomarkers to predict the development of AKI in a timely manner and improve diagnostic accuracy is being pioneered by pediatric AKI researchers. The development of risk stratification scores (renal angina) and functional bedside tests (furosemide stress test) is enhancing our use of these biomarkers and our ability to predict those patients most likely to develop severe AKI. The recognition of the impact of fluid overload on mortality and hospital length of stay in patients with severe AKI has prompted more timely and frequent use of renal replacement therapy in critically ill children. Finally, we are recognizing that children who suffer AKI are at long-term risk for the development of chronic kidney disease and warrant follow-up.

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

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. 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. 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). 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.

Renal Replacement Therapy in Critically Ill: Current Trend and New Direction

Critically ill patients often present with renal dysfunction. Acute kidney injury (AKI) is common in intensive care unit (ICU) patients and is often a component of multiple organ dysfunction syndrome (MODS). Renal replacement therapy (RRT) plays a significant role in management of acute and chronic renal failure in ICU. During the last decade RRT has made remarkable progress in management of renal dysfunction of critically ill. The Acute Dialysis Quality Initiative conceived in 2002 proposed RIFLE classification for AKI (risk, injury, failure, loss, end-stage kidney disease) using serum creatinine and urine output in critically ill patients. More recently, the Acute Kidney Injury Network (AKIN) has been introduced for staging AKI. Studies have shown that mortality increases proportionately with increasing severity of AKI. In patients with severe AKI requiring RRT mortality is approximately 50% to 70% according to one study and even a small changes in serum creatinine are associated with increased mortality. The most common causes of AKI in ICU are sepsis, hypovolemia, low cardiac output and drugs. The various techniques of RRT used in ICU include intermittent hemodialysis (IHD), continuous RRT (CRRT), sustained low efficiency dialysis (SLED) and peritoneal dialysis (PD). It is preferable to use RRT at either RIFLE injury type or at AKIN stage II in critically ill patients. IHD is commonly used in hemodynamically stable ICU patients. Because of high dialysate (500ml/min) IHD may cause hypotension in some patients. Solute removal may be episodic and often result in inferior uraemic control and acid base control. CRRT is usually initiated with a blood flow of 100 to 200 ml/min. and thus hemodynamic instability associated with IHD is avoided. Major advantages of CRRT include continuous control of fluid status, hemodynamic stability and control of acid base status. It is expensive and there is high risk of bleeding because of use of high dose of IV heparin. SLED has been found to be safe and effective in critically ill patients with hemodynamic instability. It uses the same dialysis machine of IHD and combines the effectiveness of CRRT in unstable patients and easy operability of IHD. It is also cost effective. PD is initiated in ICU for AKI patients when bedside IHD is not available. It is good for hemodynamically unstable patients when IHD or CRRT is difficult. In patients on mechanical ventilator, PD interferes with function of diaphragm causing decrease in lung compliance. Early identification of AKI with bio markers is an important step in improving outcomes of AKI. These bio markers help early detection of AKI before the onset of rise in serum creatinine. Serum cystatin C is one of the sensitive bio markers of small changes in Glomerular filtration rate (GFR) and has been found to be useful. AKI in the ICU most commonly results from multiple insults. Therefore appropriate and early identification of patients at risk of AKI provides an opportunity to prevent subsequent renal insults. This strategy will influence overall ICU morbidity and mortality.Bangladesh Crit Care J March 2015; 3 (1): 17-21

Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury

Biomarker studies for early detection of acute kidney injury (AKI) have been limited by non-selective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), Interleukin-18 (IL-18), and Kidney Injury Moledule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category free net reclassification index improved with urine L-FABP [total net reclassification index for non-events 31.0%] and urine NGAL [total net reclassification index for events 33.3%]. However, only urine L-FABP significantly improved the integrated discriminative index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP providing independent and additive prognostic information when combined with clinical predictors.

Utilization of Small Changes in Serum Creatinine with Clinical Risk Factors to Assess the Risk of AKI in Critically lll Adults

Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patient's clinical course. We set out to assess the performance of this combination approach. A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1-0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit. Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for severe AKI was 92%, the specificity was 62%, the positive predictive value was 16%, and the negative predictive value was 99%. After adjustment for Sequential Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early creatinine elevation remained an independent predictor for severe AKI (adjusted relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early creatinine elevation to the best clinical model improved prediction of the primary outcome (area under the receiver operating characteristic curve increased from 0.75 to 0.83, P<0.001). Critically ill patients at high AKI risk, based on the combination of clinical factors and early creatinine elevation, are significantly more likely to develop severe AKI. As initially hypothesized, the high-risk combination group methodology can be used to identify patients at low risk for severe AKI in whom AKI biomarker testing may be expected to have low yield. The high risk combination group methodology could potentially allow clinicians to optimize biomarker use.

Adaptive Bayesian Analysis of Serum Creatinine as a Marker for Drug-Induced Renal Impairment in an Early-Phase Clinical Trial

A concern with using creatinine for the identification of drug-induced renal impairment is that small changes in serum creatinine (SCr) that frequently are perceived as measurement bias or imprecision translate into important changes in the glomerular filtration rate. Important drug-generated changes in creatinine are difficult to detect because they are frequently observed within the reference interval. The design of a crossover drug protocol is an opportunity to use study participants as their own control to identify these small but important changes. Twenty individuals participating in a phase I clinical trial were evaluated for SCr changes beyond those expected for biological variation according to individual Z scores derived from an adaptive Bayesian model. After 2 screening tests, participants were administered either drug (n = 11) or placebo (n = 9) during the first dosing interval. A washout period followed, and drug was then administered to the group that initially received placebo, and vice versa (10 visits total per participant). Although all creatinine values fell within the reference interval, 8 participants individually showed increased concentrations (Z scores >2.33). These 8 participants were confirmed at unblinding to have received the drug in the identified dosing period, with 1 exception. The ability to identify a drug effect on an individual-participant basis in early-phase studies permits drug developers to recognize issues early in development and rapidly engage in risk-benefit analysis. These results suggest that SCr monitoring is able to detect early kidney dysfunction when individual-based reference intervals are used.

The Meaning of Acute Kidney Injury and Its Relevance to Intensive Care and Anaesthesia

Acute kidney injury (AKI) is the new consensus term for acute renal failure. The term describes a continuum of kidney injury, a common condition in the critically ill and after major surgery, which is associated with increased mortality. The incidence of AKI in intensive care unit patients in Australia is >30% and sepsis is a major contributory factor. However, there is limited knowledge about its incidence after major surgery, except for cardiac surgery. The creation of staged AKI classification systems (RIFLE [Risk, Injury, Failure, Loss, End-stage], Acute Kidney Injury Network and the new Kidney Disease: Improving Global Outcomes criteria) has accelerated progress in critical care nephrology research by showing that even small changes in serum creatinine are associated with increased risk of death and that this risk increases progressively with severity of AKI. Recent thought and research has cast doubt over previously accepted pathophysiological views of AKI. Moreover, terms such as 'prerenal azotaemia' and 'acute tubular necrosis' are now being challenged as lacking validity, having little supportive evidence and carrying limited clinical utility. In this review, we explore the limitations of animal and human models of AKI and the implications of recent research on our current understanding of the pathophysiology of AKI. In addition, we describe conventional and novel diagnostic methods and therapies, and explore the clinical implications of the effect of fluid administration and perioperative management. Finally, we identify priorities for clinical investigations and future directions in AKI research.

Update on acute kidney injury after cardiac surgery

To review the current state of clinical practice and discuss recent advances in the diagnosis and management of acute kidney injury (AKI) in the context of cardiac surgery. A review of the published data pertaining to AKI in the setting of cardiac surgery and cardiothoracic surgical critical care medicine was conducted, and the relevant data were synthesized from appropriate interventional and observational study reports. Significant advances have occurred in the diagnosis of AKI, and consensus has been reported on a system of diagnosis using the serum creatinine and urine output. New biomarkers of injury and function are available that are likely to improve the interval to diagnosis of AKI after cardiac surgery. The adverse effect on outcome of small changes in serum creatinine is appreciated. Novel prevention and rescue therapies are now entering phase I and II studies. Urinary alkalinization was effective in a phase II blinded clinical trial and is now the subject of a multicenter, double-blind, randomized clinical trial of cardiac surgery patients. In 2011, the field of AKI could be emerging from a period of stagnation that has lasted more than 2 decades. The failure to translate successful animal model interventions to the clinic might have resulted from delays in diagnosis that might now be avoidable with the advent of novel diagnostic biomarkers.

Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies.

Renal angina: an emerging paradigm to identify children at risk for acute kidney injury

Acute kidney injury (AKI) leads to high rates of morbidity and independently increases mortality risk. Therapy for AKI is likely limited by the inability to reliably diagnose AKI in its early stages, and, importantly, small changes in serum creatinine may be associated with poor outcomes and severe AKI. Whereas AKI biomarker research seeks to identify more sensitive and timely indices of kidney dysfunction, AKI lacks physical signs and symptoms to trigger biomarker assessment in at-risk patients, limiting biomarker efficacy. Accurate models of AKI prediction are unavailable. Severity of illness (SOI) scoring systems and organ dysfunction scores (OD), which stratify patients by prediction of mortality risk, are AKI reactive, not predictive. Kidney-specific severity scores do not account for AKI progression, and stratification models of AKI severity are not predictive of AKI. Thus, there is a need for a kidney scoring system that can help predict the development of AKI. This review highlights the concept of renal angina, a combination of patient risk factors and subtle AKI, as a methodology to predict AKI progression. Fulfillment of renal angina criteria will improve the efficiency of AKI prediction by biomarkers, in turn expediting early therapy and assisting in creation of AKI-predictive scoring systems.

Serum Creatinine Measurement Immediately After Cardiac Surgery and Prediction of Acute Kidney Injury

After heart surgery, acute kidney injury (AKI) confers substantial long-term risk of death and chronic kidney disease. We hypothesized that small changes in serum creatinine (SCr) levels measured within a few hours of exit from the operating room could help discriminate those at low versus high risk of AKI. Prospective cohort of 350 elective cardiac surgery patients (valve or coronary artery bypass grafting) recruited in Winnipeg, Canada. Baseline SCr level was obtained at the preoperative visit 2 weeks before surgery. The postoperative SCr level was drawn within 6 hours of completion of surgery and then daily while the patient was in the hospital. Immediate (ie, <6 hours) postoperative SCr level change (ΔSCr), categorized as within 10% (reference), decrease >10%, or increase >10% relative to baseline. AKI, defined according to the new KDIGO (Kidney Disease: Improving Global Outcomes) consensus definition as an increase in SCr level >0.3 mg/dL within 48 hours or >1.5 times baseline within 1 week. We compared the C statistic of logistic models with and without inclusion of immediate postoperative ΔSCr. After surgery, 176 patients (52%) experienced a decrease >10% in SCr level, 26 (7.4%) experienced an increase >10%, and 143 had ΔSCr within ±10% of baseline. During hospitalization, 53 (14%) developed AKI. Bypass pump time, baseline estimated glomerular filtration rate, and European System for Cardiac Operative Risk Evaluation (euroSCORE) were associated with AKI in a parsimonious base logistic model. Added to the base model, immediate postoperative ΔSCr was associated strongly with subsequent AKI and significantly improved model discrimination over the base model (C statistic, 0.78 [95% CI, 0.71-0.85] vs 0.69 [95% CI, 0.62-0.77]; P < 0.001). A ≥10% SCr level decrease predicted significantly lower AKI risk (OR, 0.37; 95% CI, 0.18-0.76), whereas a ≥10% SCr level increase predicted significantly higher (OR, 6.38; 95% CI, 2.37-17.2) AKI risk compared with the reference category. We used a surrogate marker of AKI. External validation of our results is warranted. In elective cardiac surgery patients, measurement of immediate postoperative ΔSCr improves prediction of AKI.

Effects of intravenous ibandronate injection on renal function in women with postmenopausal osteoporosis at high risk for renal disease — The DIVINE study

The Designed for intravenous (IV) Ibandronate reNal safety Evaluation (DIVINE) study was a 1-year prospective, randomized, open label, multi-center study that evaluated the renal safety of quarterly (every 3months) ibandronate IV injection given over 15–30s compared with infusion given over 15min, and weekly oral alendronate, in women with postmenopausal osteoporosis (PMO) at increased risk for renal disease. Both injection and infusion of IV ibandronate showed comparable safety to alendronate, with only small changes in serum creatinine (sCr) for each treatment group, and AEs were generally comparable between groups. All three treatments had similar effects on renal function, measured by change in baseline of the glomerular filtration rate; the ibandronate IV injection group was noninferior to the ibandronate IV infusion and weekly oral alendronate groups at 9months, with similar results at 1year. The results of this study demonstrate the profile of IV ibandronate, which allows it to be dosed as an IV injection in the primary care setting without the need for an infusion, even in patients with pre-existing hypertension or diabetes mellitus.