Uroperitoneum in 32 Foals: Influence of Intravenous Fluid Therapy, Infection, and Sepsis

Clinical Implications

Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] Trial)

Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer-term outcomes among participants in PARADISE-MI. In this randomized, double-blind, active-controlled, event-driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run-in. The frequency of an initial pre-specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all-cause mortality, and longer-term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03-1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92-2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p-interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all-cause mortality, or differences in longer-term eGFR slope. Findings were similar across the randomized treatment arms (p-interaction >0.6 for all). Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer-term kidney function.

BK Viremia Was Not Associated with Acute Kidney Injury in Hematopoietic Cell Transplant Recipients

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To determine whether gadodiamide is a safe and useful angiographic contrast agent for help in diagnosis and percutaneous treatment of renal artery stenosis in patients with renal insufficiency. Diagnostic renal angiography and percutaneous renal interventions were performed by using gadodiamide (total dose, 0.3 mmol/kg) and CO2 as intraarterial contrast agents in 25 procedures in 24 patients with renal insufficiency. Serum creatinine levels were obtained within 24 hours before and at 24 and 48 hours after the procedure. Increases in serum creatinine of more than 44 mumol/L were considered clinically important. Gadodiamide-enhanced angiograms were compared with CO2-enhanced angiograms. In 23 (92%) of 25 procedures, there was no increase in serum creatinine level at 48 hours. One patient with acute and chronic rejection of a renal transplant and one with evidence of cholesterol embolization had a clinically important increase in serum creatinine level at 48 hours. No marked increase in creatinine level was observed in patients with relatively low baseline levels (n = 19). Gadodiamide-enhanced angiograms appeared to be better than CO2-enhanced angiograms for help in identifying renal artery occlusions, visualizing renal vessels incompletely filled with CO2, and determining the progress of intervention. Gadodiamide appears to be a safe and useful intraarterial contrast agent in patients with renal insufficiency and can be used to supplement or confirm CO2-enhanced angiographic findings.

314 Treatment With Intravenous Fluid Therapy Was Not Associated With Improved Survival Among Patients With Ebola Virus Disease: An International Multisite Cohort Study

Extensive tumor implants secondary to sarcoma, sarcomatosis, or mesothelioma in children is rare. We conducted the first phase 1 trial of escalating doses of cisplatin during hyperthermic intraperitoneal chemotherapy (HIPEC) in children with sarcomatosis. The most devastating complication of cisplatin therapy is nephrotoxicity. Here we present the anesthetic management and analysis of the impact of intraoperative fluid management on the incidence of renal failure. Of the 10 patients under 18 years of age who underwent HIPEC in the context of our phase 1 trial, six patients were under the age of 10 years. We reviewed the anesthetic management, intraoperative fluid and blood administration, and postoperative renal function in these patients. The average age and weight were 6 years and 20.9 kg, respectively. To avoid renal toxicity, urine output was maintained at an average of 3 ml/kg/h. Crystalloid and colloid were transfused at an average rate of 9 ml/kg/h. Percentage increase in creatinine postoperatively varied from 33 to 500 %. Volume of fluid administered did not correlate with percentage increase in creatinine. All patients had a temporary increase in their serum creatinine, but none required dialysis. Fluid administration at an average rate of 9 ml/kg/h was required to maintain satisfactory urine output. This rate of intraoperative fluid administration is similar to what is provided to adult HIPEC patients. There was no significant correlation in the volume or type of fluid delivered and the increase in serum creatinine. More studies are needed to determine optimal fluid management in children undergoing HIPEC with cisplatin.

Background. About 30–50% patients develop acute kidney injury (AKI) after cardiac surgery, which is still diagnosed by serum creatinine on clinic. However, the increase of serum creatinine is insensitive and delayed. The aim of this study is to test the hypothesis that neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) are early biomarkers for AKI in patients after cardiac surgery. Methods. Thirty-three cases undergoing cardiac surgery were classified into an AKI group and non-AKI group, according to the AKI definition (> 26.5 μmol/L increase of serum creatinine, more than or equal to 50% increase of serum creatinine within 48 h, or a reduction in urine output < 0.5 mL/Kg per hour for more than six hours). The concentrations of serum NGAL, urine NGAL, and urine IL-18 at different time-points were measured. Results. Nine cases (27.27%) developed postoperative AKI, but diagnosis with serum creatinine was 12–48 h postoperation. The concentrations of serum NGAL were not significantly increased postoperation. The concentrations of urine NGAL and IL-18 were significantly increased in the AKI group, which reached the peak at 2–4 h postoperation, and a more significant difference could be seen after correction for urine creatinine. The concentrations of urine NGAL and IL-18 2 h postoperation, either corrected for urine creatinine or not, showed good sensitivity and specificity. Increased levels of urine NGAL and IL-18 2 h postoperation were significantly correlated with increased level of serum creatinine 12 h postoperation. Logistic regression analysis showed that urine NGAL corrected for urine creatinine 2 h postoperation and urine IL-18 2 h postoperation emerged as powerful independent predictors of AKI after cardiac surgery. Conclusions. The concentrations of urine NGAL and IL-18 could be useful biomarkers for AKI in patients after cardiac surgery, especially after correction for urine creatinine.

Hypertriglyceridemia is common among patients infected with HIV and often requires treatment with a triglyceride-lowering medication, such as fenofibrate. Studies have shown that fenofibrate has the potential to increase serum creatinine, a phenomenon that seems to occur more in patients with baseline renal dysfunction or who are on medications that can affect renal hemodynamics. HIV-infected individuals are at an increased risk of developing renal problems and may be a target population for fenofibrate-induced increases in serum creatinine. The purpose of this report is to describe a case of an HIV-infected individual who experienced a considerable increase in serum creatinine after initiating fenofibrate, and to highlight this underreported yet important adverse effect. Additionally, we discuss the postulated mechanisms, relevant literature among HIV noninfected individuals, and potential risk factors.

Hemoglobin affinity for oxygen is altered by pH, temperature, and high altitude, making oxygen more readily available to the tissues. RSR13 (Allos Therapeutics, Denver, CO), an analog of the drugs clofibrate and bezofibrate, causes a dose-dependent, rightward shift of the oxygen dissociation curve in animals and humans. We tested the safety, pharmacodynamic, and pharmacokinetics of RSR13, an allosteric modifier of hemoglobin, in patients having general surgery in a prospective, randomized, double-blinded, placebo-controlled, dose-escalation clinical trial. After the induction of general anesthesia with endotracheal intubation, 26 patients who consented were randomly assigned to receive an infusion of RSR13 or placebo (2:1) in an ascending dose scheme. Doses studied were 10, 20, 30, 40, 50, 60, 75, and 100 mg/kg infused for 30--60 minutes. Samples were taken for determination of RSR13 concentration in plasma, red blood cells, and urine, as well as for determination of the p50 in blood by using three-point tonometry at frequent intervals after the infusion of the study drug. The RSR13 administration resulted in a dose-dependent rightward shift of the oxygen dissociation curve, with the target p50 shift of 10 mm Hg achieved at the 75- and 100-mg/kg doses. No differences were seen between RSR13 and placebo groups in laboratory or hemodynamic findings, with the exception of a transient, limited increase in serum creatinine in 3 patients who received RSR13. These increases peaked at 48 h (2.2, 3.5, and 4.5 mg/dL respectively), were not associated with oliguria, did not require treatment, and did not prolong hospitalization in any patient. The reasons for the unexplained increases in serum creatinine were not evident, but potentially included surgery itself (nephrectomy), patient condition, or the concomitant administration of renally cleared medications or drugs that affect renal blood flow. We studied the safety and tolerance of an investigational drug, RSR13 (Allos Therapeutics, Denver, CO), in general surgery patients. This drug, which increases the amount of oxygen available to the body, was well tolerated by the 17 patients who received it. There were clinically relevant increases in serum creatinine in 3 patients, indicating a decrease in renal function, but these increases were short-lived and resolved without treatment.

The renal safety of sevoflurane.

Background and Aims Acute kidney injury (AKI) is common after major surgery and is associated with increased mortality. Currently, the Kidney Disease: Improving Global Outcomes (KDIGO) criteria define AKI as an absolute creatinine increase ≥0.3 mg/dl within 48 hours, a relative creatinine increase ≥50% known or presumed to have occurred within 7 days, or a urine output &amp;lt;0.5 ml/kg/h for at least 6 hours. However, it remains contested whether small absolute creatinine increases should be viewed as equivalent to relative creatinine increases—especially for low baseline estimated glomerular filtration rate (eGFR) where such creatinine changes relate to smaller eGFR changes. Here, we used a multinational collaboration to investigate this uncertainty. Method We conducted a multinational population-based cohort study including adult patients from Denmark, Alberta (Canada), Grampian, and Tayside &amp; Fife (United Kingdom) undergoing major elective surgery. The inclusion of patients undergoing major elective surgery allowed for accurate assessment of baseline eGFR and postoperative changes in creatinine. This is because it is standard practice in all the included cohorts to have a recent outpatient creatinine measurement before surgery and to monitor creatinine levels in the days following surgery. We ascertained the most recent outpatient eGFR before surgery using the 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation. We determined both the highest relative increase in creatinine within 7 days and the highest absolute increase in creatinine within 2 days during the first 7 days after the day of surgery. The outcome of interest was death within 90 days after surgery. Logistic regressions were performed to construct heatmaps depicting age-, sex-, year-, and surgery type-standardized 90-day mortality according to absolute and relative creatinine increases across pre-operative baseline eGFR levels. Results We identified 314,136 surgical procedures (172,544 procedures from Denmark, 124,119 from Alberta, 9891 from Grampian, and 7582 from Tayside &amp; Fife) performed in 276,988 patients with 13,906 deaths within 90 days. Across the populations, the median age ranged from 66 to 70 years, and 40 to 44% were female. Absolute creatinine increases: Compared to no change in creatinine, an absolute increase of 0.3 mg/dl (26.5 µmol/l) within 2 days was associated with a consistent 2.5–3.5 percentage point (%p) absolute increase in mortality for eGFR between 15 and 90 ml/min/1.73 m2 (Figs 1 and 2). The increase in mortality was &amp;gt;3.5%p at eGFR &amp;gt;90 mL/min/1.73 m² and &amp;lt;2.5%p at eGFR &amp;lt;15 mL/min/1.73 m², although the precision of these estimates was low. These absolute increases in mortality corresponded to a relative increase in mortality of 25% for a baseline eGFR of 15 ml/min/1.73 m2, 160% for a baseline eGFR of 90 ml/min/1.73 m2, and 244% for an eGFR of 120 ml/min/1.73 m2. Relative creatinine increases: The absolute increases in mortality between a 50% relative creatinine increase and no change within 7 days decreased with eGFR from 9.6%p for a baseline eGFR of 15 ml/min/1.73 m2 to 3.5%p for a baseline eGFR of 90 ml/min/1.73 m2 (Figs 1 and 2). After this point, it increased to 5.3%p for a baseline eGFR of 120 ml/min/1.73 m2. The corresponding relative increases in mortality rose from 134% for a baseline eGFR of 15 ml/min/1.73 m2 to 255% for a baseline eGFR of 60 ml/min/1.73 m2, after which it remained at the same level. Conclusion Across baseline eGFR levels &amp;gt;15 ml/min/1.73 m2, both an absolute creatinine increase of 0.3 mg/dl and a relative increase of 50% were associated with a considerably higher mortality than no change. Yet, the magnitude of the increase in risk was substantially higher for a 50% increase compared with a 0.3 mg/dl increase at low baseline eGFR. This distinction should be emphasized in future guidelines to improve the consistency of clinical interpretations.

A disintegrin and metalloproteinase (ADAM) 17, also known as tumour necrosis factor α-converting enzyme (TACE), is a metalloproteinase that releases the ectodomains of most growth factors, cytokines, receptors and enzymes and has been associated with the presence of chronic kidney disease (CKD) and cardiovascular (CV) disease. The role of circulating ADAMs in the progression of renal function and CV events in CKD patients is unknown. A total of 2570 subjects from an observational and multicentre study with CKD Stages 3-5, CKD Stage 5D and controls without any history of CV disease were studied. Circulating ADAM activity was assessed using a fluorometric technique. Progression of renal disease was defined as a 30% increase in serum creatinine or dialysis requirement after 24 months of follow-up. CV outcomes were assessed after 48 months of follow-up. Patients with advanced CKD had higher ADAM activity as compared with patients with moderate CKD or controls. Male patients with progression of CKD had higher ADAM levels at baseline compared with patients with stable renal function {22.19 relative fluorescence units/μL/h [95% confidence interval (CI) 11.22-37.32] versus 12.15 (7.02-21.50)}. After multivariate adjustment, higher ADAM activity was identified as a risk factor for progression of CKD in male patients [30% increase in the creatinine odds ratio (OR) 2.72 (95% CI 1.58-4.68), P < 0.001; dialysis requirement OR 3.00 (95% CI 1.65-5.46), P < 0.001; dialysis requirement or 30% increase in the creatinine OR 3.15 (95% CI 2.06-4.81), P < 0.001]. ADAM activity was also identified as an independent risk factor for CV events [hazard ratio (HR) 1.68 (95% CI 1.20-2.36), P = 0.003]. High ADAMs activity levels are independently associated with CKD progression in males and with CV events in CKD patients.

Japanese patients with normal renal function were retrospectively analyzed to characterize increases in serum creatinine (SCr) observed following the use of a sulfamethoxazole-trimethoprim (SMX-TMP) combination product and identify factors affecting these increases. In the patients studied (n=49), an individual comparison was conducted for the three factors of age group [≤74 years (n=21) vs. ≥75 years (n=28)], sex [male (n=24) vs. female (n=25)], and total dose throughout the treatment period [≤7 g (n=24) vs. ≥8 g (n=25)] to determine the extent of SCr increase following SMX-TMP combination product use. SCr increased significantly following SMX-TMP combination product use in patients ≤74 years of age and ≥75 years of age, in both males and females, and in patients with a total dose of ≥8 g (8 to 96 g) (p<0.05). Multivariate logistic regression analysis was used to determine the independence of these factors. Total dose was identified as an independent factor and had an odds ratio of 6.571 [95% confidence interval=1.735-24.882, p=0.006]. Post-treatment percent increases in SCr were compared using pre-treatment levels as the baseline. The group with a total dose of ≥8 g (mean 29.8 g) had a significant SCr increase of 18.4% (p=0.002), while the increase in the ≤7 g (mean 5.3 g) group was only 4.5%. The data showed that SCr increased by about 20% when the total dose taken over the treatment period was around 30 g (about 2.4 g as TMP) and indicated that total dose contributes more than age and sex to the post-treatment increase in SCr.