Acute Changes In Renal Function Research Articles

#1413 High performance of ACLARA calculator of rat creatinine clearance for the chronic follow up of renal function

Abstract Background and Aims A neural network-based calculator to estimate rat creatinine clearance (ClCr), as a measurement of the glomerular filtration rate (GFR), from paired plasma creatinine concentration and body weight data has been recently developed [1]. Like human GFR estimating formulae, ACLARA averts long experimental procedures and reduces animal stress (by obviating the use of individual isolation in metabolic cages). This tool is publicly available for free use among the scientific community (https://idal.uv.es/aclara/). When collated with experimentally measured ClCr, ACLARA performs very well at comparing experiments in the whole, showing almost identical behavior of all experimental groups and conditions. Yet, ACLARA was trained mostly with data from short experiments involving acute changes in renal function, and from young rats. Fewer data from older animals was included in the development of the calculator. Thus, its field performance on longer evolution of renal function in adult rats has not yet been sufficiently validated. Accordingly, the aim of this work was to deepen in the assessment of ACLARA in the long-term evolution of rat ClCr. Method The evolution of measured (mClCr) versus ACLARA-estimated ClCr (eClCr) was compared at different time points over a period of 3 months in 20 male Wistar rats with chronic renal damage and 8 age-matched controls. In total, 176 data pairs of mClCr and eClCr were obtained. On the one hand, mClCr was determined by the usual experimental procedure [2]. Briefly, rats were allocated in metabolic cages to obtain 24-hour urine samples and urine flow (UF). Creatinine concentration was measured in the urine (Cru) and plasma (Crp) by a colorimetric assay based on the Jaffe's reaction, and mCrCl was then calculated as Cru x UF / Crp. On the other hand, eClCr was estimated with the ACLARA calculator from the corresponding Crp and body weight data. A Pearson's correlation study between mClCr and eClCr was carried out. Results Our results reveal that the information provided by the 90-day evolution of mClCr and eClCr is virtually identical at the whole experiment level (see Fig. 1). Furthermore, ACLARA seems to provide slightly more coherent and homogeneous information, as the considerable experimental error introduced by urine collection is averted in eClCr but present in mClCr. At the individual data level, ACLARA-estimated values are slightly lower than the corresponding measurements. The correlation between mClCr and eClCr was highly significant (r Pearson= 0.83; p < 0.0001). Conclusion ACLARA shows high performance at estimating CrCl in rats of growing age. Our results support its use also in chronic studies in which renal function must be evaluated. Funding This research was funded by grants from Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación (PI21/01226 and PI21/00548 co-funded by the European Union; and RICORS2040, RD21/0005/0004, co-funded by the European Union – NextGenerationEU, Mecanismo para la Recuperación y la Resiliencia (MRR)) and from Consejería de Educación, Junta de Castilla y León (IES160P20), co-funded by FEDER funds. Joana Mercado-Hernández is recipient of a predoctoral fellowship from the Junta de Castilla y Leon (Spain) and the European Social Fund from the European Commission.

1565. Antiretroviral Stewardship: Protocol Development and Implementation at an Academic Medical Center.

Abstract Background 1.2 million people are living with HIV (PLWH) in the USA. As this population grows older (47% of PLWH were over age 50 in 2018) and more medically complex, the risk of medication errors increases. This population has not been prioritized for stewardship efforts, but experts have called for ARV stewardship programs to be developed. We developed a protocol to systematically review patients on ARVs during inpatient admissions to reduce and prevent medication errors, improve patient safety, and improve equity of care for PLWH. Methods We implemented a pharmacist-driven intervention over a 3-month period and compared it to usual practice in the 3 months prior to launch. Patients with active ARV prescriptions were identified using a novel automated patient report generated within the EMR. Then, a pharmacist reviewed the ARV regimen and opportunistic infection prophylaxis for accuracy, completeness, potential DDIs or administration issues. A standardized consult note was developed to communicate pharmacist recommendations to the care team. We evaluated qualitative features of the ARV-related interventions and calculated the proportion of hospital days with and without medication errors. Results The baseline period included 52 patients with an average age of 52 years and LOS of 6.6 days. The intervention period included 60 patients with an average age of 53 years and LOS of 5.4 days. During the intervention, automated pharmacy review led to medication intervention on 49% of patients, compared with 36% of patients in the baseline period. Similarly, the average time to pharmacy intervention decreased from 3 days after admission in the baseline period to 2.5 days in the intervention period. The most common interventions were resuming an ARV regimen and management of DDIs. The most common clinical rationales for interventions were DDIs, acute changes in renal function, and non-formulary medication restrictions. Automated patient identification and pharmacist review reduced the prevalence of medication errors related to ART from 17% of inpatient days to 2% of inpatient days. Conclusion There is a need for ARV stewardship. Expanding, automating, and standardizing these capabilities improved patient safety by reducing medication errors and improving continuity of care in the inpatient setting. Disclosures All Authors: No reported disclosures

The effect of acute changes in glomerular filtration rate on common biochemical tests

ObjectivesTo characterise the effect of acute kidney injury on the concentration of common biochemical analytes. Designand methods: Pairs of serum or plasma samples from the same patients routinely submitted to the laboratory were subject to further analysis based on changes in serum creatinine within 72 h. Samples collected from patients on dialysis were excluded. Samples were measured for 28 biochemical analytes including electrolytes, liver function tests, iron studies, creatine kinase, amylase, lipase, parathyroid hormone, troponin T and troponin I, B-natriuretic peptide and NT pro B-natriuretic peptide. Results148 sample pairs were included with 99 having a rise in serum creatinine >50%, 18 with a fall of >50% and 31 with smaller changes. Acute changes in renal function were associated with changes in the concentration of several analytes, with the changes of the greatest magnitude observed in urea, phosphate, urate, parathyroid hormone, troponin T, BNP and NT-ProBNP. The remaining analytes did not show significant changes with changes in renal function. ConclusionAcute changes in renal function are associated with significant changes in concentration of some serum/plasma biochemical analytes but not others. Expected changes in analyte concentration must be considered in the setting of acute kidney injury to avoid misinterpretation of blood test results.

MO146: Effects of High-Intensity Exercise on Renal and Endothelial Function of Crossfit Athletes

Abstract BACKGROUND AND AIMS High-intensity exercise modalities such as Crossfit have increased the number of practitioners due to the benefits such as weight loss. However, high-intensity exercise can induce renal and endothelial damage. The objective was to verify the main acute effects of high-intensity exercise on renal and endothelial function of Crossfit athletes. METHOD The study was conducted by evaluating 10 high-performance Crossfit athletes, performing pre- and 24-h post-competition test collection. The athletes were evaluated using biomarkers for kidney injury, such as lipocalin associated with neutrophil gelatinase (NGAL), creatine kinase (CK), albumin, creatinine and estimated glomerular filtration rate (eGFR). Endothelial damage was evaluated using serum enzymatic markers, intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and Syndecan-1. In addition, athletes' physical and social evaluation questionnaires measuring body composition data and socioeconomic conditions were used. Statistical analysis was performed with Shapiro-Wilk and Student t test for parametric values and Wilcoxon for non-parametric data. Pearson and Spearman tests were used for data with normality and non-normality, respectively. RESULTS There was a significant increase in creatinine (1.03 ± 0.24 versus 1.36 ± 0.34 mg/ dL, P = .001) and CK [median 302.40 (115.75–474.00) versus 2048.80 (542.75–3391.25) U/L, P = .005] 24 h after the activity, and reduced eGFR (91.55 ± 21.15 versus 66.45 ± 20.6 mL/min/1.73 m², P = .000). The values of ICAM-1, VCAM-1, Syndecan-1 and NGAL did not show statistically significant variations. There was a strong positive correlation between syndecan-1 and CK (P = .000, r = 0.953). CONCLUSION The study showed that high performance exercise performed by athletes does not cause significant acute changes in renal function, but its intensity was able to cause muscle damage and endothelial changes in the participants.

Long-term effects of hyperproteic diet on functional renal reserve and natriuresis

Introduction: A hyperproteic diet normally results in acute changes in renal function evidenced by increases of natriuresis and glomerular filtration rate (renal functional reserve).Objectives: To assess the changes in natriuresis and creatinine clearance during 12 weeks on hyperproteic and hypersodic diet. Materials and Methods: Eighteen adults male Holtzman rats were included and the follow-up period was 12 weeks. The rats were initially distributed into three groups; hyperproteic diet (30%) from an animal source (n = 6), hyperproteic diet (30%) from a plant source (n = 6) and normoproteic diet (18%) from an animal source (n = 6). The diets were isocaloric, normosodic (0.25%). From week 8, each group was divided into three rats each and received a high-sodium (1.5%) and normosodic diet (0.25%) respectively. Results: The hyperproteic diet group (animal or plant vegetal source) had higher creatinine clearance than normoproteic diet (P < 0.05). The hyperproteic vegetal diet group had a peak with an increased renal functional reserve in 21% (P = 0.04). The natriuresis increased in the group on the animal-source diet during the first 2 weeks (P = 0.03). The group plant-source diet did not have significant change at the first week (P = 0.50); however, there was a subsequent decrease in the level of natriuresis between weeks 3 to 8. When the groups were exposed to a hypersodic diet, there was not difference in the natriuretic response between the groups (P > 0.05). Conclusion: A hyperproteic vegetal diet increased renal functional reserve but not natriuresis during an acute or long-term period; however, the natriuretic response was not impaired when a hypersodic diet was added, though hyperfiltration was present.

Prospective pediatric study comparing glomerular filtration rate estimates based on motion-robust dynamic contrast-enhanced magnetic resonance imaging and serum creatinine (eGFR) to 99mTc DTPA

Current methods to estimate glomerular filtration rate (GFR) have shortcomings. Estimates based on serum creatinine are known to be inaccurate in the chronically ill and during acute changes in renal function. Gold standard methods such as inulin and 99mTc diethylenetriamine pentaacetic acid (DTPA) require blood or urine sampling and thus can be difficult to perform in children. Motion-robust radial volumetric interpolated breath-hold examination (VIBE) dynamic contrast-enhanced MRI represents a novel tool for estimating GFR that has not been validated in children. The purpose of our study was to determine the feasibility and accuracy of GFR measured by motion-robust radial VIBE dynamic contrast-enhanced MRI compared to estimates by serum creatinine (eGFR) and 99mTc DTPA in children. We enrolled children, 0-18years of age, who were undergoing both a contrast-enhanced MRI and nuclear medicine 99mTc DTPA glomerular filtration rate (NM-GFR) within 2weeks of each other. Enrolled children consented to an additional 6-min dynamic contrast-enhanced MRI scan using the motion-robust high spatiotemporal resolution prototype dynamic radial VIBE sequence (Siemens, Erlangen, Germany) at 3tesla (T). The images were reconstructed offline with high temporal resolution (~3s/volume) using compressed sensing image reconstruction including regularization in temporal dimension to improve image quality and reduce streaking artifacts. Images were then automatically post-processed using in-house-developed software. Post-processing steps included automatic segmentation of kidney parenchyma and aorta using convolutional neural network techniques and tracer kinetic model fitting using the Sourbron two-compartment model to calculate the MR-based GFR (MR-GFR). The NM-GFR was compared to MR-GFR and estimated GFR based on serum creatinine (eGFR) using Pearson correlation coefficient and Bland-Altman analysis. Twenty-one children (7 female, 14 male) were enrolled between February 2017 and May 2018. Data from six of these children were not further analyzed because of deviations from the MRI protocol. Fifteen patients were analyzed (5 female, 10 male; average age 5.9years); the method was technically feasible in all children. The results showed that the MR-GFR correlated with NM-GFR with a Pearson correlation coefficient (r-value) of 0.98. Bland-Altman analysis (i.e. difference of MR-GFR and NM-GFR versus mean of NM-GFR and MR-GFR) showed a mean difference of -0.32 and reproducibility coefficient of 18 with 95% confidence interval, and the coefficient of variation of 6.7% with values between -19 (-1.96 standard deviation) and 18 (+1.96 standard deviation). In contrast, serum creatinine compared with NM-GFR yielded an r-value of 0.73. Bland-Altman analysis (i.e. difference of eGFR and NM-GFR versus mean of NM-GFR and eGFR) showed a mean difference of 2.9 and reproducibility coefficient of 70 with 95% confidence interval, and the coefficient of variation of 25% with values between -67 (-1.96 standard deviation) and 73 (+1.96 standard deviation). MR-GFR is a technically feasible and reliable method of measuring GFR when compared to the reference standard, NM-GFR by serum 99mTc DTPA, and MR-GFR is more reliable than estimates based on serum creatinine.

Protocol Development for Preventing Contrast-Induced Nephropathy

Contrast-induced nephropathy (CIN) is related to substantial economic and clinical consequences, including extended hospitalization, the necessity for dialysis, and an amplified risk of death. As radiographic diagnostic testing becomes commonplace, a significant concern among practitioners is the prevention of radiographic contrast-induced nephropathy. Radiographic contrast agents are used most often in tests such as coronary angiography, percutaneous coronary angioplasty, atherectomy, and stent placement, computer-aided tomography (CAT) scanning, and magnetic resonance imaging (MRI). 1 Administration of these contrast agents often cause acute changes in renal function ranging from an acute reduction of renal function to the transient need for hemodialysis. Early studies assessing the renal effects of radiocontrast administration in dogs proved a reduction in renal perfusion lasting up to 20 hours after radiocontrast administration. 8 Although no randomized controlled trial (RCT) has studied the benefits of hydration alone, it appears reasonable that sufficient hydration may offset some of the presumed hemodynamic effects that could lead to contrast-induced nephropathy. Various preventative strategies have been studied with mixed results. This paper constitutes reviewing current and old practices and developing a tentative simple protocol for prevention of Contrast induced nephropathy in nearby hospitals.

Echocardiographic predictors of change in renal function with intravenous diuresis for decompensated heart failure

AimsThe aim of this study was to identify echocardiographic predictors of improved or worsening renal function during intravenous diuresis for decompensated heart failure. Secondary aim included defining the incidence and clinical risk factors for acute changes in renal function with decongestion.Methods and resultsA retrospective review of 363 patients admitted to a single centre for decompensated heart failure who underwent intravenous diuresis and transthoracic echocardiography was conducted. Clinical, echocardiographic, and renal function data were retrospectively collected. A multinomial logistic regression model was created to determine relative risk ratios for improved renal function (IRF) or worsening renal function (WRF). Within this cohort, 36% of patients experienced WRF, 35% had stable renal function, and 29% had IRF. Patients with WRF were more likely to have a preserved left ventricular ejection fraction compared with those with stable renal function or IRF (P = 0.02). Patients with IRF were more likely to have a dilated, hypokinetic right ventricle compared with those with stable renal function or WRF (P ≤ 0.01), although this was not significant after adjustment for baseline characteristics. Left atrial size, left ventricular linear dimensions, and diastolic function did not significantly predict change in renal function.ConclusionsAn acute change in renal function occurred in 65% of patients admitted with decompensated heart failure. WRF was statistically more likely in patients with a preserved left ventricular ejection fraction. A trend towards IRF was noted in patients with global right ventricular dysfunction.

NEW DEFINITION OF CI-AKI:COMBINED SERUM CREATININE AND CYSTATIN C

Background: Contrast-induced acute kidney injury (CI-AKI) was traditionally defined as an increase of serum creatinine (sCr) after contrast media (CM) exposure. Recently, serum cystatin C (sCyC) has been proposed as an alternative to sCr to detect acute changes in renal function. The clinical

Use of Both Serum Cystatin C and Creatinine as Diagnostic Criteria for Contrast-Induced Acute Kidney Injury and Its Clinical Implications.

BackgroundContrast‐induced acute kidney injury (CI‐AKI) was traditionally defined as an increase in serum creatinine (sCr) after contrast media exposure. Recently, serum cystatin C (sCyC) has been proposed as an alternative to detect acute changes in renal function. The clinical implications of combining sCyC and sCr to diagnose CI‐AKI remain unknown.Methods and ResultsOne thousand seventy‐one consecutive patients undergoing coronary angiography/intervention were prospectively enrolled. SCyC and sCr were assessed at baseline and 24 to 48 hours after contrast media exposure. CI‐AKI determined by sCr (CI‐AKI sCr) was defined as an sCr increase greater than 0.3 mg/dL or 50% from baseline. Major adverse events at 12 months were assessed. CI‐AKI sCr developed in 25 patients (2.3%). Twelve‐month follow‐up was available for 1063 patients; major adverse events occurred in 61 patients (5.7%). By receiver operating characteristic curve analysis, an sCyC increase of greater than 15% was the optimal cutoff for CI‐AKI sCr detection, which occurred in 187 patients (17.4%). To evaluate the use of both sCyC and sCr as CI‐AKI diagnostic criteria, we stratified patients into 3 groups: no CI‐AKI, CI‐AKI detected by a single marker, and CI‐AKI detected by both markers. Multivariable logistic regression revealed that the predictability of major adverse events increased in a stepwise fashion in the 3 groups (no‐CI‐AKI group as the reference, CI‐AKI detected by a single marker: odds ratio=2.25, 95% CI: 1.24–4.10, P<0.01; CI‐AKI detected by both markers: odds ratio=10.00, 95% CI: 3.13–31.91, P<0.001).ConclusionsCombining sCyC and sCr to diagnose CI‐AKI would be beneficial for risk stratification and prognosis in patients after contrast media exposure.

Effects of Serum Uric Acid on Estimated GFR in Cardiac Surgery Patients: A Pilot Study

Background: The aim of the study was to investigate the effects of serum uric acid (SUA) on acute kidney injury (AKI) in patients undergoing cardiac surgery. Methods: Prospectively collected data from a previous study were analyzed to investigate the relationship between SUA and AKI as assessed by neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine (SCr) and kinetic estimated glomerular filtration rate (KeGFR). Results: Patients undergoing cardiovascular surgery (n = 37) were included. SUA was measured at postoperative 1 h. Statistically significant correlations were present between SUA and NGAL measured at postoperative 1 h (r = 0.39, p = 0.008), 6 h (r = 0.31, p = 0.029) and 24 h (r = 0.31, p < 0.001), respectively. Significant correlations were also noted between SUA and SCr measured on postoperative day 1 (r = 0.41, p = 0.006), day 2 (r = 0.29, p = 0.042) and day 3 (r = 0.42, p = 0.009). Negative correlations were demonstrated between SUA and day 1 (r = -0.44, p = 0.007), day 2 (r = -0.43, p = 0.007), day 3 (r = -0.44, p = 0.006 and day 4 KeGFR (r = -0.35, p = 0.035). The inverse relationship of SUA and KeGFR was also demonstrated with a different method (Jelliffe) of measurement. Conclusions: A reduction in glomerular filtration rate (GFR) can lead to a rise in SUA. However, in this study, we are able to show that SUA at 1 h (maximal dilution time) effectively predicts subsequent changes in urinary NGAL, SCr, KeGFR, and the development of AKI. Thus, these findings suggest that uric acid precedes and predicts acute changes in renal function and cannot be ascribed to a simple relationship in which a reduced GFR raises SUA.

Association of Intraoperative Hypotension with Postoperative Acute Kidney and Myocardial Injuries in Noncardiac Surgery Patients

In an observational study including 33,330 noncardiac surgeries performed in 27,381 patients with detailed intraoperative blood pressures, Walsh et al.1 showed that intraoperative mean arterial pressure less than 55 mmHg was associated with the development of postoperative acute kidney and myocardial injuries. This study makes an important contribution to the effort to define risk factors for acute vital organ injury after surgery. Strengths of this study include the large sample of patients and adjust for most of the known risk factors that can affect acute kidney and myocardial injuries after surgery. Furthermore, the authors openly discuss the limitations of their work. However, in our view, there are several aspects of this study design that should be discussed and clarified.First, the body mass index and ethnicity were not included in the basic demographic data of patients for analysis and adjustment. It has been shown that in the noncardiac surgery patients, body mass index is independently associated with risk for postoperative acute kidney injury (AKI).2,3 Furthermore, obesity is an independent predictor of perioperative cardiac adverse events.4 In a retrospective study including 975,825 patients undergoing colorectal surgery, Masoomi et al.5 find that black race is associated with higher risk of postoperative AKI. Their trial design did also not include the detail about anesthesia techniques and intraoperative managements. Consequently, it is difficult to estimate the extent to which interventions by anesthesiologists might have influenced outcomes. A retrospective analysis including 9,171 patients undergoing joint-replacement operations shows that use of general anesthesia is independently associated with risk for postoperative AKI.2 Besides the transfusion volume adjusted by this study, other intraoperative managements, such as total vasopressor dose administered, use of a vasopressor infusion, and diuretic administration, have been shown to be independent predictors of postoperative AKI.3 In addition, intraoperative hypoxemia, tachycardia, and hypertension are associated independently with increased risk of myocardial injury after noncardiac surgery.6,7 Thus, we cannot exclude the possibility that the above confounding factors would have contributed to final analysis of their results.Second, this study assessed occurrence of acute kidney and myocardial injuries within 7 days after surgery. However, the authors did not mention specific measurement times of serum creatinine, troponin T, and creatinine kinase-MB after surgery. In addition, the study design did not include the detail about postoperative recovery and managements of patients. Thus, this study cannot provide enough evidence to support that all kidney and myocardial injuries occurred within 7 days after surgery are attributed to intraoperative hypotension. Actually, serum troponin appears at 30 min to 6 h after myocardial injury.8 Although serum creatinine lags behind acute changes in renal function, but AKI (defined by a 50% or more increase in serum creatinine) by intraoperative causes can be often detected between 1 and 3 days after surgery.9 For early detection of the potential kidney and myocardial injuries by intraoperative factors, we would suggest that the related serum biomarkers be measured as soon as possible after surgery, especially for patients who are at high risk of kidney and myocardial injuries. To prevent new kidney and myocardial injuries or avoid aggravation of existing organ injury by postoperative low perfusion, we emphasize that perioperative hemodynamic optimization of noncardiac surgery patients should be continued to the postoperative period, modifying prognosis of patients.Finally, 506 patients (1.5%) died within 30 days of surgery in this study. The authors should provide the detailed reasons of all death cases through analyzing death certificates, medical records, and autopsy reports, as described in previous studies.7,10 We would like to know how many of patients with postoperative AKI received kidney-replacement treatment, and how many of deaths are directly related to postoperative acute kidney and myocardial injuries. In addition, the authors should assess association between severity of postoperative acute vital organ and 30-day mortality. All these will help explore whether there is a causal relationship between postoperative acute vital organ injury and mortality or whether acute vital organ injury merely indicates a worse outcome.The authors declare no competing interests.

GRP-100 Incidence of Errors in Drug Dosage According to Kidney Function-Estimating Equations in Medical Inpatients

BackgroundInpatients frequently require dose adjustments of medicines due to acute changes in renal function. The FDA recommend adjusting medicines according to the estimated glomerular filtration obtained with the Cockcroft-Gault formula....

Assessment and Diagnosis of Renal Dysfunction in the ICU

Identifying patients with impaired renal function is crucial in the setting of critical illness. Serum creatinine serves as the gold standard for assessing steady-state renal function, helping to define those with chronic kidney disease (CKD). Although these baseline creatinine values are often not available in the setting of critical illness, CKD, whether defined by serum creatinine or proteinuria, increases the risk of developing acute kidney injury (AKI). Despite delays in elevations following renal insults, serum creatinine remains the standard for assessing acute changes in renal function. Standardized definitions of AKI, using changes in serum creatinine and urine output, have informed the epidemiology of ICU-acquired AKI and have helped define the long-term outcomes in patients who experience AKI. A complex cyclical interplay exists between AKI and CKD, in which CKD predisposes patients to an increased risk of AKI, whereas those with AKI, regardless of baseline renal function, are more likely to suffer from post-AKI CKD. The clarification of the AKI-CKD dynamic remains a work in progress and will be aided by the implementation of novel measures of renal function. Several novel biomarkers of renal function have been proposed to augment serum creatinine in the diagnosis of AKI and CKD. These biomarkers, taken with recent clinical investigations, have laid the groundwork for the impending paradigm shift in risk stratifying and in diagnosing changes in renal function in the ICU.

Cardio-Renal Syndrome: New Perspective in Diagnostics

Chronic heart failure and chronic renal failure are at epidemic proportions. These patients have significantly altered cardiac, renal, and all-cause outcomes. Much of the current research has focused on treating these individual organs in isolation. Although there are positive data on outcomes with neurohormonal modulation, they, however, remain underused. At present, data lacks for novel treatment options, while evidence continues to point at significantly worsened prognosis. Current diagnostic tools that detect acute changes in renal function or renal injury appear retrospective, which often hinder meaningful diagnostic and therapeutic decisions. This review is aimed at exploring the importance of accurate assessment of renal function for the heart failure patient by providing a synopsis on cardio-renal physiology and establishing the possibility of novel approaches in bridging the divide.

Relationship of Loop Diuretic Dosing and Acute Changes in Renal Function during Hospitalization for Heart Failure

Worsening renal function (WRF) during heart failure (HF) hospitalization is an accepted correlate of poor prognosis. Loop diuretics are increasingly being considered as a potential cause of worsened HF outcomes, perhaps via WRF. However, the magnitude of worsening in renal function attributable to loop diuretics has not been quantified. This was a retrospective cohort study of patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between Jan 1, 2000 and June 30, 2008. Patients with preexisting end-stage renal disease were excluded. Daily creatinine (Cr) measurements, furosemide dosing (only loop diuretic on hospital formulary), and radiocontrast dye studies were collected using administrative data. Day-to-day changes in Cr and MDRD estimated glomerular filtration (eGFR) were calculated. The first Cr or eGFR value during hospitalization or in the emergency department was considered baseline. Generalized estimating equations were used to test the association furosemide exposure over previous 2 days to the daily change in Cr and eGFR. Covariates included undergoing radiocontrast study, age, race, gender, and baseline Cr or eGFR. Among 6071 patients who met inclusion criteria there were a total of 20,645 observations. This cohort was 51% female, 68% African American, and baseline Cr was 1.36 mg/dl. Furosemide exposure was associated with an average daily increase in Cr of 0.021 mg/dL and decrease in eGFR of 0.72 ml/min/1.73m2 (per 100 mg furosemide daily, both p<0.001). Over a typical length of stay of 5 days this would amount to a Cr increase of 0.11 mg/dL or decrease in eGFR of 3.6 ml/min/1.73m2. Furosemide exposure accounted for only 0.4% and 0.1% of the variation in Cr and eGFR changes, respectively. Undergoing radiocontrast study, African American race, and higher age were associated with day-to-day creatinine increases (all p<0.01). Reanaysis after classifying furosemide exposure into low (<40mg/day), medium (40-100mg/day), and high (>100mg/day) and censoring patients-days after radiocontrast exposure did not significantly affect the magnitude of the worsening renal function. While loop diuretic exposure is statistically associated with WRF among hospitalized HF patients, the associated magnitude of renal function change is very small, and loop diuretics explain little of the variability in renal function during hospitalization. More important explanatory factors likely exist but remain unidentified.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Cystatin C and Contrast-Induced Acute Kidney Injury

Cystatin C (CyC) is more sensitive than serum creatinine (sCr) to rapidly detect acute changes in renal function. We measured CyC together with sCr in 410 consecutive patients with chronic kidney disease undergoing either coronary and/or peripheral angiography and/or angioplasty. sCr was assessed at baseline and 24 and 48 hours after contrast media exposure. CyC was assessed at baseline and at 24 hours. Major adverse events (including death of any cause and dialysis) at 12 months were assessed. At 48 hours after contrast media exposure, contrast-induced acute kidney injury (defined as a sCr increase > or =0.3 mg/dL) occurred in 34 patients (8.2%). A CyC increase concentration > or =10% at 24 hours after contrast media exposure was detected in 87 patients (21.2%). This was the best CyC cutoff for the early identification of patients at risk for contrast-induced acute kidney injury (negative predictive value=100%; positive predictive value=39.1%). According to the defined cutoffs (that is, increase in CyC > or =10% and sCr > or =0.3 mg/dL), major adverse events occurred in 16 of 297 patients (5.4%) without any cutoffs satisfied (group 1), in 9 of 49 patients (18.4%) with only a CyC increase > or =10% (group 2), and in 9 of 31 patients (29%) with both cutoffs satisfied (group 3). By logistic regression analysis, the independent predictors of major adverse events at 1 year were group 2 (odds ratio=2.52; 95% confidence interval, 1.17 to 5.41; P=0.02), group 3 (odds ratio=4.45; 95% confidence interval, 1.72 to 11.54; P=0.002), and baseline glomerular filtration rate (odds ratio=0.91; 95% confidence interval, 0.88 to 0.95; P<0.001). In patients with chronic kidney disease, CyC seems to be a reliable marker for the early diagnosis and prognosis of contrast-induced acute kidney injury.

The Impact of Pre- and Postoperative Renal Dysfunction on Outcome of Patients Undergoing Coronary Artery Bypass Grafting (CABG)

Acute changes in renal function after elective coronary bypass surgery represent a challenging clinical problem. In this study, we evaluated perioperative risk factors for the development of postoperative renal dysfunction (PRD), and the impact of such an event on the perioperative course. Additionally, we investigated the influence of preoperatively mildly increased serum creatinine on perioperative mortality and morbidity. We retrospectively analyzed data of 2511 patients undergoing isolated CABG between 2004 and 2007 with a preoperative serum creatinine < or = 2.2 mg/dL. There were 592 patients with a preoperative serum creatinine of between 1.4 and 2.2 mg/dl (mild renal dysfunction group) and 1919 patients with a serum creatinine < 1.4 mg/dl. Perioperative risk factors for PRD were analyzed by multivariate regression analysis. Global in-hospital mortality was 3.1 %.The incidence of PRD was 6.2 %. Mortality for patients who had PRD was 7.8 vs. 2.9 % for patients who did not ( P < 0.05). PRD increased the length of hospital stay by 3.7 days (12.2 vs. 15.9; P < 0.05). Multivariate logistic regression identified the following variables as independent predictors of PRD: age, angina class III/IV, diabetes mellitus, prolonged cardiopulmonary bypass time, and preoperative serum creatinine. With regard to preoperative renal function, we found that operative mortality was higher in the mild renal dysfunction group (5.7 % vs. 2.5 %; P < 0.05). New dialysis/hemofiltration (5.1 % vs. 1.2 %; P < 0.05) and postoperative stroke (5.1 % vs. 1.6 %; P < 0.05) were also more common in these patients. Mild renal dysfunction preoperatively is an important predictor of outcome after CABG. In these patients, PRD dramatically increases mortality, morbidity and length of hospital stay.

Pharmacist-Driven Aminoglycoside Quality Improvement Program

Our objective was to determine the impact of a pharmacist-driven aminoglycoside quality improvement program on the dosing methods of aminoglycosides at our institution. We assessed our current quality through retrospective review of all patients receiving aminoglycosides during a 5-month period. We then developed and implemented a pharmacist-driven aminoglycoside dosing program and prospectively assessed patients during a matched 5-month period. Two hundred and sixteen patients were evaluated, 87 pre-program and 129 post-program. Prior to standardized pharmacist intervention, 44% of patients achieved optimal therapy. Post implementation, patients achieving optimal therapy increased to 80% (p < 0.001). Patients in the pre-program group had a higher rate of acute changes in renal function compared to the post-pro-gram group (14.9% versus 6.2% [p <0.05]). This pharmacist-driven aminoglycoside dosing quality improvement program increased the frequency of optimal dosing of aminoglycosides and reduced the incidence of nephrotoxicity at our institution.