May 2019 Kidney Abstract Roundup

Acute Kidney Injury

Study Examines Risk Factors for Neonatal AKI

Clinical Journal of the American Society of Nephrology. 2019;14(2):183-195

Poor short- and long-term outcomes are associated with neonatal acute kidney injury (AKI). Jennifer R. Charlton, MD, and colleagues recently conducted a an international retrospective observational cohort study designed to examine the risk factors and outcomes of neonatal AKI in the first week of life.

AWAKEN (Assessment of Worldwide AKI Epidemiology in Neonates) included neonates admitted to the neonatal intensive care unit who received at least 48 hours of intravenous fluids. The study defined early AKI by the neonatal modification of Kidney Disease Improving Global Outcomes criteria: increase in serum creatinine >0.3 mg/dL or urine output <1 mL/kg per hour on postnatal days 2 to 7. The study  assessed the risk factors for AKI and the associations of AKI with death and duration of hospitalization.

Of the 2110 eligible neonates, 449 (21%) experienced early AKI. Following adjustment for neonatal and maternal factors and medication exposures, there was an association between early AKI and higher risk of death (adjusted odds ratio, 2.8; 95% confidence interval [CI], 1.7-4.7) and longer duration of hospitalization (parameter estimate: 7.3 days; 95% CI, 4.7 to 10.0).

Factors associated with increased risk of AKI were outborn delivery; resuscitation with epinephrine; admission diagnosis of hyperbilirubinemia, inborn errors of metabolism, or surgical need; frequent kidney function surveillance; and admission to a children’s hospital. Factors associated with a lower risk of AKI were multiple gestations, cesarean section, and exposures to antimicrobials, methylxanthines, diuretics, and vasopressors. There were variations in risk factors by gestational age strata.

“AKI in the first postnatal week is common and associated with death and longer duration of hospitalization. The AWAKEN study demonstrates a number of specific risk factors that should serve as ‘red flags’ for clinicians at the initiation of the neonatal intensive care unit course,” the researchers said.


Review of Mechanisms Associated with Progression of Renal Injury Progression Other than Cyst Formation

Nephrology Dialysis Transplantation. 2018;33(11):1887-1895

Common clinical manifestations in autosomal dominant polycystic disease (ADPKD) include hypertension and progressive decline in kidney function. Currently, the main pathogenic mechanism for the onset of those manifestations is considered to be cyst formation in patients with ADPKD. However, according to Vasileios Raptis, MD, and colleagues, the presence of polycystins in the vessels and cilia of the endothelial cells and vascular smooth muscle cells, as well as development of hypertension prior to decline in renal function and the prognostic implications for development of hypertension, may indicate that polycystins have a key role for endothelial damage in several vascular beds.

Pathologic polycystins induce abnormalities in intracellular calcium, which affect various cellular organelles and functions and may lead to several abnormal biochemical reactions within endothelial cells and to an imbalance between oxidant and antioxidant capacity. There are consequences to this process including accumulation of asymmetric-dimethylarginine, which is associated with progression of renal damage and interferes with the normal vascular response due to inhibition of nitric oxide. Long-term reduced nitric oxide bioavailability would result in relative vasoconstriction, impaired renal blood flow, and vascular remodeling.

Existing data from studies supporting the hypothesis that mechanisms other than cyst formation also contribute to the pathogenesis of hypertension and decline in renal function in patients with ADPKD are reported in this review.

Cardiovascular Complications

Transcatheter Valve Replacement versus SAVR in Patients with Renal Disease

American Journal of Cardiology.

Patients with reduced kidney function are at increased risk of developing aortic valve pathology. Yas Sanaiha, MD, and colleagues conducted an analysis to compare readmission performance between transcatheter and surgical aortic valve replacement (SAVR). Patients who underwent transcatheter or SAVR from 2011 to 2014 were identified using the Nationwide Readmissions Database; the data from nearly 50% of US hospitalizations were represented in the database.

Patients were stratified by chronic kidney disease (CKD) stage 1 to 5 and end-stage renal disease (ESRD) requiring dialysis. Predictors of readmission and costs were identified using Kaplan-Meier, Cox hazard, and multivariable regression models.

Of the 350,609 isolated aortic valve replacements, 4.7% of patients were diagnosed with CKD stages 1 to 5 or ESRD. Among the population with kidney disease (CKD or ESRD), patients who underwent transcatheter valve replacement were older (81.9 years vs 72.9 years; P<.001), and had a higher prevalence of heart failure (15.2% vs 4.3%; P=.04) and peripheral vascular disease (31.1% vs 22.8%; P<.0001) compared with those who underwent SAVR.

The rate of readmission due to heart failure and pacemaker replacement in patients with CKD stage 1 to 3 who underwent transcatheter valve replacement was higher than those who underwent SAVR. In the patients with CKD stage 1 to 3, there was an association between transcatheter aortic valve replacement and increased costs compared with SAVR for all renal failure patients.

The researchers said, “In conclusion, in the national cohort of chronic and end-stage renal disease patients, transcatheter aortic valve implementation was associated with increased mortality, readmissions for chronic kidney disease stages 1 to 3, and index hospitalization costs.”


Systematic Review to Identify Kidney Prediction Tool in Patients with Chronic Kidney Disease

Nephrology Dialysis Transplantation.

Researchers in The Netherlands, led by Chava L. Ramspek, PhD, conducted a systematic review of all available models predicting kidney failure in patients with chronic kidney disease. The researchers also sought to organize empirical evidence on the validity of the models to provide guidance in the interpretation and uptake of these tools.

The search for relevant articles was conducted in PubMed and EMBASE. Two independent investigators sequentially screened titles, abstracts, and full-text articles for inclusion in the review, and data on study design, model development, and performance were extracted. Recommendations on which models to use were based on assessments of the risk of bias and clinical usefulness.

A total of 2183 studies were screened. Of those, 42 were included in the review. Most had high discriminatory capacity and there was large overlap in the predictors. The overall risk of bias was high. Only 48% of the study included sufficient detail regarding use of the prediction tool in practice; few of the models were externally validated.

“The current systematic review may be used as a tool to select the most appropriate and robust prognostic model for various settings. Although some models showed great potential, many lacked clinical relevance due to being developed in a prevalent patient population with a wide range of disease severity. Future research efforts should focus on external validation and impact assessment in clinically relevant patient populations,” the researchers said.

Check out more Kidney Abstracts from April 2019