Changes In Serum Creatinine Concentration Research Articles

Noninvasive and Invasive Renal Hypoxia Monitoring in a Porcine Model of Hemorrhagic Shock.

Up to 50% of patients with trauma develop acute kidney injury (AKI), in part due to poor renal perfusion after severe blood loss. AKI is currently diagnosed based on a change in serum creatinine concentration from baseline or prolonged periods of decreased urine output. Unfortunately, baseline serum creatinine concentration data is unavailable in most patients with trauma, and current estimation methods are inaccurate. In addition, serum creatinine concentration may not change until 24-48 h after the injury. Lastly, oliguria must persist for a minimum of 6 h to diagnose AKI, making it impractical for early diagnosis. AKI diagnostic approaches available today are not useful for predicting risk during the resuscitation of patients with trauma. Studies suggest that urinary partial pressure of oxygen (PuO2) may be useful for assessing renal hypoxia. A monitor that connects the urinary catheter and the urine collection bag was developed to measure PuO2 noninvasively. The device incorporates an optical oxygen sensor that estimates PuO2 based on luminescence quenching principles. In addition, the device measures urinary flow and temperature, the latter to adjust for confounding effects of temperature changes. Urinary flow is measured to compensate for the effects of oxygen ingress during periods of low urine flow. This article describes a porcine model of hemorrhagic shock to study the relationship between noninvasive PuO2, renal hypoxia, and AKI development. A key element of the model is the ultrasound-guided surgical placement in the renal medulla of an oxygen probe, which is based on an unsheathed optical microfiber. PuO2 will also be measured in the bladder and compared to the kidney and noninvasive PuO2 measurements. This model can be used to test PuO2 as an early marker of AKI and assess PuO2 as a resuscitative endpoint after hemorrhage that is indicative of end-organ rather than systemic oxygenation.

Doppler profiles of renal and hepatic hemodynamics in patients with cirrhosis of the liver

One in five individuals with cirrhosis of the liver may experience renal impairment, a frequent consequence that is linked to increased mortality and morbidity. Even before changes in serum creatinine concentration can be detected, renal hemodynamic alterations start to occur early in the course of functional kidney failure caused by liver disease. Studying the Doppler profiles of renal and hepatic hemodynamics in people with liver cirrhosis is the goal of this review article. People with liver cirrhosis, even before clinical signs of renal impairment appear. Doppler is a quick, reliable, and noninvasive technique that makes it possible to identify renal hemodynamic changes in individuals with liver cirrhosis even before they become clinically obvious.

Toxicity of zoledronic acid after intravenous administration: A retrospective study of 95 dogs.

BackgroundThere is a paucity of veterinary literature on the safety or outcome of zoledronic acid (ZA) use in dogs for either bone pain or hypercalcemia.Hypothesis/ObjectivesThe primary aim was to report the adverse events in dogs receiving intravenous administration of ZA.AnimalsNinety‐five dogs with ZA use.MethodsA retrospective cohort study was performed; all dogs that received at least 1 dose of ZA and had a serum biochemistry profile performed before and after treatment were reviewed. Diagnosis, indication for treatment, adverse events and survival times were recorded.ResultsNinety‐five dogs met the inclusion criteria. Thirty‐one (33%) received multiple intravenous infusions of ZA (range, 2‐7), making a total of 166 administrations in all dogs. The dose range was 0.13 to 0.32 mg/kg, given at intervals of 4 to 6 weeks. Thirteen adverse events were recorded in 10 dogs: azotemia (n = 8), vomiting (n = 2), pancreatitis (n = 1), cutaneous ulceration (n = 1), and diarrhea (n = 1). Zoledronic acid could not be confirmed as the cause of azotemia in any case. The change in serum creatinine concentration from dose to dose was not related to the total dose received (P = .46). Five dogs (5%) changed Veterinary Comparative Oncology Group Common Terminology Criteria (VCOG‐CTAE) renal/genitourinary grade after administration of ZA; their total dose 0.4 mg/kg (range, 0.26‐0.66) was not significantly different to the group which did not change VCOG‐CTAE renal/genitourinary grade 0.35 mg/kg (range, 0.2‐1.50; P = .93).Conclusions and Clinical ImportanceMultiple doses of ZA were well tolerated in dogs within this study. A small number of dogs developed progressive azotemia which was not associated with cumulative dose.

New Equations for Estimating Glomerular Filtration Rate.

The Chronic Kidney Disease Epidemiology (CKD-EPI) Collaboration has recently published new equations for calculating estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C (1). Implementation of these new equations for routine reporting of eGFR in adults is strongly recommended (2). For approximately 15 years, US clinical laboratories have been encouraged to report eGFR with creatinine measurements in adults (3). This recommendation was based on the relatively high prevalence of chronic kidney disease, which affects approximately 14% of the US adult population, and which often goes undetected in its early stages. Changes in serum creatinine concentration may not appear significant (e.g., 0.80 mg/dL vs 1.00 mg/dL) and may even be within the typical population-based reference interval and therefore not flagged on laboratory reports. But that change represents a nearly 25% difference in eGFR (in a 65-year-old female, 78 vs 59 mL/min/1.73m2) using the current CKD-EPI creatinine eGFR equation.

Potential role of imaging for assessing acute pancreatitis-induced acute kidney injury.

Acute kidney injury (AKI) is a common complication of acute pancreatitis (AP) that is associated with increased mortality. Conventional assessment of AKI is based on changes in serum creatinine concentration and urinary output. However, these examinations have limited accuracy and sensitivity for the diagnosis of early-stage AKI. This review summarizes current evidence on the use of advanced imaging approaches and artificial intelligence (AI) for the early prediction and diagnosis of AKI in patients with AP. CT scores, CT post-processing technology, Doppler ultrasound, and AI technology provide increasingly valuable information for the diagnosis of AP-induced AKI. Magnetic resonance imaging (MRI) also has potential for the evaluation of AP-induced AKI. For the accurate diagnosis of early-stage AP-induced AKI, more studies are needed that use these new techniques and that use AI in combination with advanced imaging technologies.

Efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli

BackgroundThe efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli have been poorly investigated in Japanese patients. This study was performed to investigate the efficacy and safety of colistin in Japanese patients by analyzing a considerable number of cases. Furthermore, we evaluated the relationship between the plasma concentration and efficacy and safety of colistin in some cases. MethodsA retrospective cohort study was conducted at Hokkaido University Hospital, analyzing patients treated with colistin (colistimethate sodium) during the period from January 2007 to December 2019. ResultsOverall, 42 cases were enrolled. Favorable clinical response was observed in 25 cases (59.5%), with an all-cause 30-day mortality of 33.3% (14/42 cases). Microbiological eradication was achieved in 18 cases (42.9%). Nephrotoxicity was observed in 20 cases (47.6%) and was mild and reversible in all cases. Plasma trough concentrations of colistin determined in nine patients correlated with changes in serum creatinine concentration (⊿) and creatinine clearance (%). The cutoff value of colistin trough concentration for nephrotoxicity was 2.02 μg/mL. ConclusionOur results showed approximately 60% clinical efficacy of colistin therapy against infections caused by multidrug-resistant gram-negative bacilli in the patients. Further studies with larger populations are needed to elucidate the efficacy and safety of colistin in Japanese patients.

Real-Time Prediction of Acute Kidney Injury in Hospitalized Adults: Implementation and Proof of Concept

Acute kidney injury (AKI) is diagnosed based on changes in serum creatinine concentration, a late marker of this syndrome. Algorithms that predict elevated risk for AKI are of great interest, but no studies have incorporated such an algorithm into the electronic health record to assist with clinical care. We describe the experience of implementing such an algorithm. Prospective observational cohort study. 2,856 hospitalized adults in a single urban tertiary-care hospital withan algorithm-predicted risk for AKI in the next 24 hours>15%. Alerts were also used to target a convenience sample of 100 patients for measurement of 16 urine and 6 blood biomarkers. Clinical characteristics at the time of pre-AKI alert. AKI within 24 hours of pre-AKI alert (AKI24). Descriptive statistics and univariable associations. At enrollment, mean predicted probability of AKI24 was 19.1%; 18.9% of patients went on to develop AKI24. Outcomes were generally poor among this population, with 29% inpatient mortality among those who developed AKI24 and 14% among those who did not (P<0.001). Systolic blood pressure<100mm Hg (28% of patients with AKI24 vs 18% without), heart rate>100 beats/min (32% of patients with AKI24 vs 24% without), and oxygen saturation<92% (15% of patients with AKI24 vs 6% without) were all more common among those who developed AKI24. Of all biomarkers measured, only hyaline casts on urine microscopy (72% of patients with AKI24 vs 25% without) and fractional excretion of urea nitrogen (20% [IQR, 12%-36%] among patients with AKI24 vs 34% [IQR, 25%-44%] without) differed between those who did and did not develop AKI24. Single-center study, reliance on serum creatinine level for AKI diagnosis, small number of patients undergoing biomarker evaluation. A real-time AKI risk model was successfully integrated into the EHR.

Comparison of Changes in Plasma Volume and Renal Function between Acetazolamide and Conventional Diuretics: Understanding the Mechanical Differences according to the “Chloride Theory”

Objective: We compared the effects of the chloride-regaining diuretic acetazolamide with those of conventional diuretics on plasma volume, serum electrolytes, and renal function in acutely decompensated heart failure (HF) patients. Methods: A retrospective analysis was performed on the data of 13 patients treated with acetazolamide (Group A) and 13 patients with conventional diuretics (Group B) matched based on diuresis-induced weight reduction (≥1 kg) during resolution of worsening HF. Changes in plasma volume (Strauss formula), renal function, and serum electrolytes under treatment were determined by peripheral blood tests. Results: Clinical characteristics at baseline were not different between groups A and B. After diuretic therapy, body weight reduction (–2.23 ± 1.11 vs. –2.22 ± 1.06 kg, p = 0.97) and the number of residual HF-related signs (0.31 ± 0.48 vs. 0.23 ± 0.44, p = 0.67) was not different between groups. After each treatment, the serum chloride concen­tration increased in Group A, but decreased in Group B (+5.31 ± 4.91 vs. – 4.54 ± 4.68 mEq/L, p < 0.0001). Plasma volume (0.63 ± 13.1 vs. –12.1 ± 10.5%, p < 0.01) and renal function determined by changes in serum creatinine concentration (0.048 ± 0.12 vs. 0.21 ± 0.24 mg/dL, p < 0.047) were preserved in Group A compared with Group B. Conclusions: While both groups exhibited equivalent body weight reduction and resolution of HF-related signs after each diuretic treatment, acetazolamide treatment preserved plasma volume and renal function compared to conventional diuretics.

Renin-Angiotensin System Blockade after Acute Kidney Injury (AKI) and Risk of Recurrent AKI.

How to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI. This is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders. Forty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m2 or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1-5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12). In this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.

Neutrophil Gelatinase-associated Lipocalin as a Marker of Postoperative Acute Kidney Injury Following Cardiac Surgery in Patients with Preoperative Kidney Impairment.

Acute kidney injury (AKI) is a serious complication of cardiac surgery. The current 'gold standard' for determining AKI is change in serum creatinine and urine output, however, this change occurs relatively late after the actual injury occurs. Identification of new biomarkers that detect early AKI is required. Recently, new biomarkers, such as the NephroCheck® Test and AKIRisk have also been tested and found to be good indicators of AKI. Neutrophil gelatinase-associated lipocalin (NGAL) has shown promise in paediatric patients but has displayed varied results in adult populations, particularly post cardiac surgery. The aim of this study was to assess the value of urinary NGAL as a biomarker of AKI in patients with pre-existing renal impairment (eGFR >15ml/min to eGFR<60ml/min). A post-hoc analysis of urinary NGAL concentrations from 125 patients with pre-existing kidney impairment, who participated in a randomised trial of haemofiltration during cardiac surgery, was undertaken. Urinary NGAL was measured using ELISA at baseline, post-operatively and 24 and 48 hours after surgery, and serum creatinine was measured pre and postoperatively and then at 24, 48, 72 and 96 hours as routine patient care. NGAL concentrations were compared in patients with and without AKI determined by changes in serum creatinine concentrations. A Kaplan-Meier plot compared survival for patients with or without AKI and a Cox proportional hazards analysis was performed to identify factors with the greatest influence on survival. Following surgery, 43% of patients developed AKI (based on KDIGO definition). Baseline urinary NGAL was not found to be significantly different between patients that did and did not develop AKI. Urinary NGAL concentration was increased in all patients following surgery, regardless of whether they developed AKI and was also significant between groups at 24 (p=0.003) and 48 hours (p<0.0001). Urinary NGAL concentrations at 48 hours correlated with serum creatinine concentrations at 48 hours (r=0.477, p<0.0001), 72 hours (r=0.488, p<0.0001) and 96 hours (r=0.463, p<0.0001). Urinary NGAL at 48 hours after surgery strongly predicted AKI (AUC=0.76; P=0.0001). A Kaplan- Meier plot showed that patients with postoperative AKI had a significantly lower 7-year survival compared with those without AKI. Postoperative urinary NGAL at 48 hours >156ng/mL also strongly predicted 7-year survival. However, additive EuroSCORE, age, current smoking and post-operative antibiotics usage were distinctly significantly more predictive of 7-year survival as compared with postoperative urinary NGAL at 48 hours >156ng/mL. Our study demonstrated that postoperative urinary NGAL levels at 48 hours postsurgery strongly predicts the onset or severity of postoperative AKI based on KDIGO classification in patients with preoperative kidney impairment and were also strongly related to 7-year survival.

Prevalence of acute kidney injury in a population of hospitalized horses.

BackgroundHospital‐acquired acute kidney injury (AKI) in humans and dogs increases morbidity and nonsurvival. Azotemia at presentation has been associated with a poor outcome in horses; however, prevalence and consequences of hospital‐acquired AKI are unreported.Hypothesis/ObjectivesTo evaluate the prevalence of AKI in hospitalized horses, risk factors associated with AKI, and the effect of AKI on short‐term survival. We hypothesized that the prevalence of AKI in horses is similar to that reported in other domestic mammalian species and would be associated with nonsurvival.AnimalsAdult horses hospitalized for >2 days from which a minimum of 2 measurements of serum creatinine concentration were available.MethodsRetrospective cohort study. Clinical records were reviewed and horses grouped according to their baseline serum creatinine concentration and change in serum creatinine concentration from baseline. The associations between signalment, diagnosis, and treatment variables, and the presence of azotemia or AKI were assessed using multinomial logistic regression. The relationship between these conditions and survival to discharge was evaluated.ResultsThree hundred twenty‐five horses were included; 4.3% (14/325) had azotemia at baseline and 14.8% (48/325) developed AKI. There were no significant associations between investigated risk factors and development of AKI. The presence of azotemia and AKI did not significantly affect survival to discharge (P = .08 and .81, respectively).Conclusions and Clinical ImportanceThe prevalence of AKI in this population of hospitalized horses is similar to that reported in dogs and humans; however, in this study population, there was less impact on morbidity and short‐term survival.

Comparison of five glomerular filtration rate estimating equations as predictors of acute kidney injury after cardiovascular surgery

We aimed to compare the ability of preoperative estimated glomerular filtration rate (eGFR), calculated using five different equations, to predict adverse renal outcomes after cardiovascular surgery. Cohorts of 4,125 adult patients undergoing elective cardiovascular surgery were evaluated. Preoperative eGFR was calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD) II, re-expressed MDRD II, Chronic Kidney Disease Epidemiology Collaboration, and Mayo quadratic (Mayo) equations. The primary outcome was postoperative acute kidney injury (AKI), defined by Kidney Disease: Improving Global Outcomes Definition and Staging criteria based on changes in serum creatinine concentrations within 7 days. The MDRD II and Cockcroft-Gault equations yielded the highest (88.1 ± 26.7 ml/min/1.73 m2) and lowest (79.6 ± 25.5 ml/min/1.73 m2) mean eGFR values, respectively. Multivariable analysis showed that a preoperative decrease in renal function according to all five equations was independently associated with an increased risk of postoperative AKI. The area under the receiver operating characteristics curve for predicting postoperative AKI was highest for the Mayo equation (0.713). Net improvements in reclassification and integrated discrimination were higher for the Mayo equation than for the other equations. The Mayo equation was the most accurate in predicting postoperative AKI in patients undergoing cardiovascular surgery.

Effect of Intraoperative Goal-directed Balanced Crystalloid versus Colloid Administration on Major Postoperative Morbidity: A Randomized Trial.

Crystalloid solutions leave the circulation quickly, whereas colloids remain for hours, thus promoting hemodynamic stability. However, colloids are expensive and promote renal toxicity in critical care patients. This study tested the hypothesis that goal-directed colloid administration during elective abdominal surgery decreases 30-day major complications more than goal-directed crystalloid administration. In this parallel-arm double-blinded multicenter randomized trial, adults having moderate- to high-risk open and laparoscopically assisted abdominal surgery with general anesthesia were randomly assigned to Doppler-guided intraoperative volume replacement with 6% hydroxyethyl starch 130/0.4 (n = 523) or lactated Ringer's solution (n = 534). The primary outcome was a composite of serious postoperative cardiac, pulmonary, infectious, gastrointestinal, renal, and coagulation complications that were assessed with a generalized estimating equation multivariate model. The primary safety outcome was a change in serum creatinine concentration up to 6 months postoperatively, compared to baseline concentrations. A total of 1,057 patients were included in the analysis. Patients assigned to crystalloid received a median [quartile 1, quartile 3] amount of 3.2 l [2.3, 4.4] of crystalloid, and patients assigned to colloid received 1.0 l [0.5, 1.5] of colloid and 1.8 l [1.2, 2.4] of crystalloid. The estimated intention-to-treat common effect relative risk for the primary composite was 0.90 for colloids versus crystalloids (95% CI: 0.65 to 1.23, P = 0.51), and 18% (91 of 523) of colloid patients and 20% (103 of 534) of crystalloid patients incurred at least one component of the primary outcome composite. There was no evidence of renal toxicity at any time. Doppler-guided intraoperative hydroxyethyl starch administration did not significantly reduce a composite of serious complications. However, there was also no indication of renal or other toxicity.

Early diagnosis of acute renal injury in patients with acute decompensation of chronic heart failure.

To study the possibilities of previously diagnosing acute renal damage in patients with acute decompensation of chronic heart failure with reduced systolic function using biomarkers of acute renal injury. The study included 60 patients (62.0±11.1 years) with HADS (BNP &gt;500 pg/ml) and a reduced left ventricular ejection fraction (LV 27.05% [23.25; 32.75], c FC III-IV NYHA). The level of creatinine, urea, uric acid, albumin in serum was determined in all patients, as well as a number of biomarkers: lipocalin associated with neutrophil gelatinase (NGAL) and cystatin C (CysC) in serum; kidney damage molecule-1 (KIM-1) and angiotensinogen (AGT) in the urine. AKI is determined based on changes in serum creatinine concentration or diuresis value. The results obtained indicate a high specificity and sensitivity of the use of biomarkers for the diagnosis of AKI in patients with ADHF. NGAL AUC - 0.833 (p&lt;0.001), Se - 82.8%, Sp - 4.2%. CysC AUC - 0.823 (p&lt;0.001), Se - 79.3%, Sp - 74.2%. KIM-1 AUC - 0.782 (p&lt;0.001), Se - 75.9%, Sp - 74.2%. AGT AUC - 0.829 (p&lt;0.001), Se - 82.8%, Sp - 77.4%. In a multifactorial regression analysis, it was found that with NGAL greater than 157.35 ng/ml, the risk of AKI increases 13.1 times (95% CI 1.365-126.431), with an increase in KIM-1, the risk of the development of AKI increases 20.6 times (95% CI 1.802-235.524), and with an increase in AGT more than 14.31 leng/ml, the risk of AKI increases 32.8 times (95% CI 2.752-390.110). Acute kidney injury develops in 48.3% of patients hospitalized with acute decompensation of chronic heart failure. Patients with acute decompensation of chronic heart failure and AKI have significantly higher serum NGAL and CysC, KIM-1 and AGT values in the urine compared with patients without impairing renal function. These biomarkers can serve both for the early diagnosis of acute kidney damage and the prediction of AKI in patients with acute decompensation of chronic heart failure.

Estimation of changes in serum creatinine and creatinine clearance caused by renal transporter inhibition in healthy subjects

Creatinine is excreted into urine by glomerular filtration and renal tubular secretion through drug transporters such as organic anion transporter 2 (OAT2), organic cation transporter 2 (OCT2), OCT3, multidrug and toxin extrusion protein 1 (MATE1), and MATE2-K. We aimed to investigate whether our method for estimating percentage changes in serum creatinine concentration (SCr) and creatinine clearance (CLcre) from the baseline is applicable for studying renal transporter inhibitors. We tested 14 compounds (cimetidine, cobicistat, dolutegravir, dronedarone, DX-619, famotidine, INCB039110, nizatidine, ondansetron, pyrimethamine, rabeprazole, ranolazine, trimethoprim, and vandetanib), which were reported to cause reversible changes in SCr and/or CLcre in healthy subjects excluding elderly. Percentage changes were estimated from the relative contributions of the forementioned transporters to CLcre and competitive inhibition by these compounds at their maximum plasma unbound concentrations. For 7 and 9 out of these compounds, changes in SCr and/or CLcre were estimated within 2- and 3-fold of observed values, respectively. Less than 10% changes in SCr and/or CLcre caused by cobicistat, dolutegravir, and rabeprazole were reproduced as such by our method. These findings suggest that our method can be used to estimate changes in SCr and CLcre caused by competitive inhibitions of renal drug transporters.

Use of therapeutic plasma exchange to treat nonsteroidal anti-inflammatory drug overdose in dogs.

BackgroundTherapeutic plasma exchange (TPE) may be an effective technique for treatment of accidental nonsteroidal anti‐inflammatory drug (NSAID) overdose, but information regarding the use of this technique in veterinary medicine is currently limited.ObjectivesTo evaluate the overall outcome for dogs with NSAID overdose treated with TPE and to determine if any presenting factors can predict or influence overall outcome. Secondary objectives included investigating TPE complications as well as the utility of other adjunctive treatments.AnimalsEleven client‐owned dogs presented for NSAID overdose that received TPE. All patients also received additional supportive treatment including IV lipid infusion.MethodsRetrospective review of medical records.ResultsEleven cases were included in the study. Of these, the NSAID ingested was ibuprofen in 6 (54.5%), naproxen in 4 (36.4%), and deracoxib in 1 (9.1%). All dogs survived to discharge with 3 (27.3%) developing acute kidney injury during hospitalization. A larger initial dose of NSAID ingested was associated with a higher maximum serum creatinine concentration during hospitalization (P = .04) and larger change in serum creatinine concentration from baseline (P = .02). Six dogs (54.5%) developed complications associated with TPE. The use of other treatments did not affect the overall outcome.Conclusions and Clinical ImportanceWe identified TPE as an effective treatment for NSAID overdose with good outcomes despite high doses of NSAID ingestion in dogs treated with a single TPE treatment. Complications were common but did not affect the final outcome. Therapeutic plasma exchange should be considered in patients presenting for high‐dose NSAID ingestion.

The role of the clinical laboratory in the detection and monitoring of acute kidney injury

Acute kidney injury (AKI) is a common syndrome presenting in multiple clinical settings and is frequently associated with serious short and long term adverse outcomes, which not only have impact on the patient but also on the health service increasing hospitalisation time and the costs related to the treatment. Early diagnosis and identification of the aetiology are essential for the management of the patients. During the last ten years, significant advances have been made towards the definition of this syndrome. The current consensus definitions of AKI include both changes in serum creatinine concentration and urine output. Although proposal have been made for the inclusion of novel biomarkers in the diagnostic workup of AKI as independent diagnostic markers these are not currently included in these definitions. In this review we will focus on these definitions and we will try to highlight their strengths and limitations in diagnosis and staging of AKI. Moreover, we will try to highlight the contribution of the clinical laboratory in AKI diagnosis in both the clinical and research settings.

Renoprotection by Direct Renin Inhibition: A Systematic Review and Meta- Analysis

Even mild abnormalities of the renal structure or function can increase the risk of mortality and complications in other organs. Therefore, safe and effective treatments are necessary in order to influence the progression of renal disease. We used 2 methods to assess the renoprotective effects of aliskiren: 1) a statistical analysis of clinical trials that investigated aliskiren-induced renoprotection, in terms of changes in serum creatinine concentration (sCr) or estimated glomerular filtration rate (eGFR), and, 2) clinical trials that investigated the renoprotective effects of aliskiren with respect to changes in albuminuria or proteinuria. In the forest plot, the overall risk ratio (%) for renal impairment with respect to changes in sCr or eGFR was 0.97 (0.88-1.06; overall p=0.48). The tabulation of data from clinical trials included 10 entries for monotherapy with aliskiren and 6 entries for add-on aliskiren. All of the clinical trials, except one, showed a decrease in proteinuria or albuminuria following aliskiren treatment. In conclusion, inhibiting renin and prorenin with aliskiren is a more promising renoprotective treatment compared with blocking the renin/prorenin receptors (RPR). One of the main mechanisms by which aliskiren may confer renoprotection is by decreasing albuminuria and proteinuria. However, it does not seem to change sCr and eGFR in patients at risk of developing renal disease. Furthermore, co-administration of an angiotensinconverting- enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) and aliskiren was shown to decrease albuminuria and proteinuria to a greater extent compared with monotherapy with these agents.

Longitudinal Estimated GFR Trajectories in Patients With and Without Type 2 Diabetes and Nephropathy

In clinical practice and clinical trials, changes in serum creatinine concentrations are used to evaluate changes in kidney function. It has been assumed that these changes follow a linear pattern when serum creatinine concentration is converted to estimated glomerular filtration rate (eGFR). However, the paradigm that kidney function declines linearly over time has been questioned by studies showing either linear or nonlinear patterns. To verify how this impacts on kidney end points in intervention trials, we analyzed eGFR trajectories in multiple clinical trials of patients with and without diabetes. Longitudinal observational study. 6 clinical trials with repeated measurements of serum creatinine. Patient demographic and clinical parameters. Probability of nonlinear eGFR function trajectory calculated for each patient from a Bayesian model of individual eGFR trajectories. The median probability of a nonlinear eGFR decline in all trials was 0.26 (interquartile range, 0.13-0.48). The median probability was 0.28 in diabetes versus 0.09 in nondiabetes trials (P<0.01). The percentage of patients with a >50% probability of nonlinear eGFR decline was generally low, ranging from 19.3% to 31.7% in the diabetes trials and from 15.1% to 21.2% in the nondiabetes trials. In the pooled data set, multivariable linear regression showed that higher baseline eGFR, male sex, diabetes status, steeper eGFR slope, and non-renin-angiotensin-aldosterone-system antihypertensives were independently associated with a greater probability of a nonlinear eGFR trajectory. Relatively short follow-up and no measured GFR. In both diabetes and nondiabetes trials, the majority of patients show a more or less linear eGFR decline. These data support the paradigm that in diabetic and nondiabetic kidney disease, eGFR decline progresses linearly over time during a clinical trial period. However, in diabetes, one should take the nonlinearity proportion into account in the design of a clinical trial.

Effects of Hydroxyethyl Starch 130/0.4 on Serum Creatinine Concentration and Development of Acute Kidney Injury in Nonazotemic Cats.

BackgroundHydroxyethyl‐starch (HES) solutions might have renal adverse effects in humans and dogs.ObjectiveTo determine if administration of 6% HES‐130/0.4 is associated with an increase in serum creatinine concentration and development of acute kidney injury (AKI) in nonazotemic cats.AnimalsA total of 62 critically ill cats; 26 HES exposed and 36 unexposed.MethodsRetrospective cohort study (2012–2015). Serum creatinine concentrations were recorded and changes in serum creatinine concentrations before exposure (baseline) and 2–10 and 11–90 days, respectively, were determined. Development of AKI was defined as a > 150% increase or >26 μmol/L increase in serum creatinine concentration from baseline. Risk factors, such as HES administration, cumulative volume of HES (mL/kg) and number of days of HES administration leading to development of AKI, and change in serum creatinine were analyzed.ResultsCats in the HES cohort received a mean volume of 98.5 ± 76.2 mL/kg (range, 8–278 mL/kg) HES over a median of 4 (range, 1–11) days, resulting in a median dose of 20.1 (range, 8–40.5) mL/kg per day. Short‐term %change in serum creatinine concentration (P = 0.40) and development of AKI (P = 0.32) were not significantly different between cohorts. Multivariable logistic regression did not identify HES dose in mL/kg (P = 0.33) and number of days of HES application (P = 0.49) as a risk factor for development of AKI.Conclusion and Clinical ImportanceHydroxyethyl‐starch administration to critically ill nonazotemic cats seems to be safe. A larger prospective study is required to determine the effect of HES administration at higher dosages and for prolonged time periods.