Effects of preoperative high-oral protein loading on short- and long-term renal outcomes following cardiac surgery: a cohort study.

BACKGROUND: Post-cardiac surgery acute kidney injury (AKI) is associated with increased mortality. A high-protein meal enhances the renal blood flow and glomerular filtration rate (GFR) and might protect the kidneys from acute ischemic insults. Hence, we assessed the effect of a preoperative high-oral protein load on post-cardiac surgery renal function and used experimental models to elucidate mechanisms by which protein might stimulate kidney-protective effects. METHODS: The prospective "Preoperative Renal Functional Reserve Predicts Risk of AKI after Cardiac Operation" study follow-up was extended to postoperative 12 months for 109 patients. A 1:2 ratio propensity score matching method was used to identify a control group (n = 214) to comparatively evaluate the effects of a preoperative protein load and standard care. The primary endpoints were AKI development and postoperative estimated GFR (eGFR) loss at 3 and 12 months. We also assessed the secretion of tissue inhibitor of metalloproteases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), biomarkers implicated in mediating kidney-protective mechanisms in human kidney tubular cells that we exposed to varying protein concentrations. RESULTS: The AKI rate did not differ between the protein loading and control groups (13.6 vs. 12.3%; p = 0.5). However, the mean eGFR loss was lower in the former after 3 months (0.1 [95% CI - 1.4, - 1.7] vs. - 3.3 [95% CI - 4.4, - 2.2] ml/min/1.73 m2) and 12 months (- 2.7 [95% CI - 4.2, - 1.2] vs - 10.2 [95% CI - 11.3, - 9.1] ml/min/1.73 m2; p < 0.001 for both). On stratification based on AKI development, the eGFR loss after 12 months was also found to be lower in the former (- 8.0 [95% CI - 14.1, - 1.9] vs. - 18.6 [95% CI - 23.3, - 14.0] ml/min/1.73 m2; p = 0.008). A dose-response analysis of the protein treatment of the primary human proximal and distal tubule epithelial cells in culture showed significantly increased IGFBP7 and TIMP-2 expression. CONCLUSIONS: A preoperative high-oral protein load did not reduce AKI development but was associated with greater renal function preservation in patients with and without AKI at 12 months post-cardiac surgery. The potential mechanisms of action by which protein loading may induce a kidney-protective response might include cell cycle inhibition of renal tubular epithelial cells. Clinical trial registration ClinicalTrials.gov: NCT03102541 (retrospectively registered on April 5, 2017) and ClinicalTrials.gov: NCT03092947 (retrospectively registered on March 28, 2017).

Acute kidney disease predicts chronic kidney disease in pediatric non-kidney solid organ transplant patients.

BACKGROUND: Acute kidney disease (AKD) is defined as impaired kidney function present for <90 days with or without an acute kidney injury (AKI) event. Adults with AKD have an increased risk for progression to chronic kidney disease (CKD) and mortality. There are no data on the epidemiology of AKD in children after transplant. The aim of this study was to evaluate the incidence and risk factors for AKI, AKD, and CKD in children after transplantation. METHODS: This is a retrospective cohort study of all children undergoing non-kidney solid organ transplant between 2011 and 2019 at UPMC Children's Hospital of Pittsburgh. AKI and AKD were defined using the Kidney Disease Improving Global Outcomes criteria. Patients with a new estimated glomerular filtration rate <60 ml/min/1.73m2 persisting for >3 months met criteria for new CKD. Variables associated with AKI, AKD, and CKD were analyzed. RESULTS: Among 338 patients, 37.9% met criteria for severe AKI, 13% for AKD, and 8% for a new diagnosis of CKD. Stage 3 AKI was independently associated with AKD (OR: 5.35; 95% CI: 2.23-12.86). Severe AKI was not associated with new-onset CKD, whereas AKD was associated with new-onset CKD (OR: 29.74; CI: 11.22-78.82). CONCLUSION: AKD may be superior to AKI in predicting risk of CKD in children after non-kidney solid organ transplantation.

Outcomes of adults with congenital heart disease that experience acute kidney injury in the intensive care unit.

BACKGROUND: Young adults with congenital heart disease (CHD) are increasing in number with an increased risk for acute kidney injury. Little is known concerning the impact of non-recovery of kidney function for these patients. Therefore, we sought to explore the rates of acute kidney disease, persistent renal dysfunction, and their associations with adverse outcomes in young adults with CHD. METHODS: This is a single-centre retrospective study including all patients at the ages of 18-40 with CHD who were admitted to an intensive care unit between 2010 and 2014. Patients with a creatinine ≥ 1.5 times the baseline at the time of hospital discharge were deemed to have persistent renal dysfunction, while acute kidney disease was defined as a creatinine ≥ 1.5 times the baseline 7-28 days after a diagnosis of acute kidney injury. Outcomes of death at 5 years and length of hospital stay were examined using multivariable logistic regression and negative binomial regression, respectively. RESULTS: Of the (89/195) 45.6% of patients with acute kidney injury, 33.7% had persistent renal dysfunction and 23.6% met the criteria for acute kidney disease. Persistent renal dysfunction [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.15-9.29] and acute kidney disease (OR: 11.79; 95% CI: 3.75-39.09) were independently associated with mortality at 5 years. Persistent renal dysfunction was associated with a longer duration of hospital stay (Incidence Rate Ratio: 1.96; 95% CI: 1.53-2.51). CONCLUSIONS: In young adults with CHD, acute kidney injury was common and persistent renal dysfunction, as well as acute kidney disease, were associated with increased mortality and length of hospitalisation.

The use of urinary biomarkers to predict acute kidney injury in children after liver transplant.

BACKGROUND: AKI after pediatric liver transplantation is associated with increased morbidity and mortality. The role of urinary biomarkers for the prediction of AKI in pediatric patients after liver transplantation has not been previously reported. The primary objective of this prospective pilot study was to determine the predictive capabilities of urinary KIM-1, NGAL, TIMP-2, and IGFBP7 for diagnosing AKI. METHODS: Sixteen children undergoing liver transplantation were enrolled in the study over a 19-month time period. The Kidney Disease Improving Outcomes criteria for urine output and serum creatinine were used to define AKI. Predictive ability was evaluated using the area under the curve obtained by ROC analysis. RESULTS: AKI occurred in 6 (37.5%) of the patients between 2 and 4 days after transplant. There were no differences in any of the biomarkers prior to transplant. When obtained within 6 hours after transplant, the area under the ROC curve for predicting AKI was 0.758 (95% CI: 0.458-1.00) for KIM-1, 0.900 (95% CI: 0.724-1.00) for NGAL, and 0.933 (95% CI: 0.812-1.00) for the product of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]). CONCLUSIONS: Our results show that both NGAL and [TIMP-2]·[IGFBP7] provide significant discrimination for AKI risk following liver transplant in children. Larger studies are needed to determine the optimal time point for measuring these biomarkers and to validate our findings.

Postoperative Acute Kidney Injury in Young Adults With Congenital Heart Disease.

BACKGROUND: There is an increasing number of young adults living with congenital heart disease (CHD). The goal of this study was to ascertain the frequency of acute kidney injury (AKI) as well as the risk factors and outcomes associated with AKI in young adults with CHD after a surgical procedure. METHODS: This was a single-center retrospective cohort study including all patients 18 to 40 years of age with a diagnosis of CHD admitted to a quaternary care children's hospital cardiac intensive care unit postoperatively from 2004 to 2015. We defined AKI using the Kidney Disease Improving Global Outcomes criteria for serum creatinine. We explored potential susceptibilities and exposures for AKI using multivariable logistic regression and determined the association of AKI with duration of mechanical ventilation and length of stay using Poisson regression. RESULTS: In 699 consecutively admitted patients AKI occurred in 13.2%. Suspected sepsis (odds ratio [OR], 2.87; 95% confidence interval [CI], 1.17 to 7.05), exposure to calcineurin inhibitors (OR, 5.80; 95% CI, 1.06 to 31.59), vancomycin (OR, 3.35; 95% CI, 1.11 to 10.14), and piperacillin-tazobactam (OR, 4.12; 95% CI, 1.23 to 13.78) increased the odds of AKI even after controlling for age, ejection fraction, recent cardiac catheterization, repeat cardiopulmonary bypass, bypass time, cross-clamp time, and other potential nephrotoxic medications. AKI was associated with a longer duration of mechanical ventilation (OR, 1.47; 95% CI, 1.15 to 1.89) and intensive care unit length of stay (OR, 1.50; 95% CI, 1.30 to 1.72). CONCLUSIONS: AKI is common in young adults with CHD postoperatively and is associated with negative outcomes. The results highlight the importance future research and clinical efforts aimed at prevention and improved management of AKI in this patient group.

Renal Response to a Protein Load in Healthy Young Adults as Determined by Iohexol Infusion Clearance, Cimetidine-Inhibited Creatinine Clearance, and Cystatin C Estimated Glomerular Filtration Rate.

OBJECTIVE: Renal reserve (RR) measures the increase in glomerular filtration rate (GFR) in response to a protein load; lack of RR could indicate subclinical kidney disease but such a test is not routinely used in clinical practice. The purpose of this study was to compare a meat versus liquid protein load in a cystatin C-based (Cys-C) RR test using cimetidine-inhibited creatinine clearance (Cr Cl) and iohexol infusion clearance (Io Cl) for validation. The design was cross-sectional analysis and the setting was a Clinical Research Center. SUBJECTS: Participants (N = 16), mean (standard deviation [SD]) age 22 (2) years, had normal health and blood pressure without proteinuria. INTERVENTION: Participants 1 to 8 received a beef burger (1 g/kg protein) and participants 9 to 16 received a ProCel shake (1-1.5 g/kg protein). MAIN OUTCOME MEASURE: RR defined as the difference in stimulated versus baseline GFR. RESULTS: Baseline GFR (SD) in mL/minute/1.73 m2 averaged 103.0 (15.6) for Cr Cl, 94.8 (7.9) for Io Cl, and 117.0 (6.0) for Cys-C estimated GFR (eGFR). Mean RR (SD) for the burger group (N = 8, mL/minute/1.73 m2) was 16.6 (12.3) for Cr Cl (P = .006); 7.2 (3.7) for Io Cl (P < .001), and 4.9 (2.6) for Cys-C eGFR (P = .001). Mean RR for the shake group (N = 8) was 15.8 (5.8) for Cr Cl (P < .001), 10.1 (7.8) for Io Cl (P = .008), and 2.4 (2.9) for Cys-C eGFR (P = .05). CONCLUSION: Protein loading stimulates Io Cl and Cr Cl after a beef or milk-based protein load. The change in Cys-C eGFR is significant but smaller for the shake and burger group, which may be due to the dilutional effect of water loading or the length of Cys-C half-life in the blood.

Epidemiology and pathophysiology of cardiac surgery-associated acute kidney injury.

PURPOSE OF REVIEW: Acute kidney injury (AKI) remains a serious complication of cardiac surgery. An understanding of the epidemiology and pathophysiology of AKI in cardiac surgery patients is crucial to early recognition and proper management. RECENT FINDINGS: The article will review the current criteria used for defining AKI and the most recently published incidence rates of AKI in the cardiac surgery population. Variables associated with AKI will be reviewed. The cause of cardiac surgery-associated AKI is multifactorial involving genetic factors as well as insults because of nephrotoxins, ischemia and reperfusion, cardiac dysfunction, venous congestion, inflammation, and oxidative stress. SUMMARY: Investigators should aim to use consistent criteria for defining AKI in future studies. Efforts should be taken to use actual measurements rather than estimated values of baseline serum creatinine whenever possible. Further study of the more recently proposed pathophysiologic factors contributing to cardiac surgery-associated AKI, such as circulating damage-associated molecular patterns, venous congestion, and genetic predisposition, are warranted.

Rapid assessment of renal reserve in young adults by cystatin C.

BACKGROUND: The kidney can increase glomerular filtration rate (GFR) in response to a protein load (renal reserve). In a pilot study of healthy young adults we examined renal reserve using changes in serum cystatin C (cysC). METHODS: Glomerular filtration rate was obtained using iohexol single slope plasma disappearance. To stimulate GFR, subjects ingested a beefburger containing 60 grams of protein. CysC was measured by immunonephelometry before and 125-141 minutes after protein loading. RESULTS: All subjects were found to have a normal iohexol plasma disappearance GFR with a mean of 104.6 ± 9.9 mL/min per 1.73 m(2). CysC decreased in each subject after the meat meal. Baseline cysC-based estimated GFR was 98.1 ± 9.1 mL/min per 1.73 m(2) with a mean increase of 12.0 ± 5.2 (p = 0.0003). CONCLUSIONS: Our study showed a consistent decrease in serum cysC and increase in cysC-based estimated GFR following a protein load in young adults. Further studies are needed using renal clearance methods to confirm that cysC accurately determines renal reserve in patients with and without chronic kidney disease.