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Acute and chronic kidney injury on the same thread: but biomarkers do not point directions unambiguously

According to the United States Centers for Disease Control and Prevention, an estimated 37 million people are living with chronic kidney disease (CKD) in the US, and more than 850 million individuals worldwide, making it the 8th leading cause of death. Acute kidney injury (AKI) occurs when kidneys stop working properly, which can cause toxins to build up in the blood, making it hard for the body to balance fluids. AKI complicates the course of illness in approximately 20% of hospitalized patients. Once viewed as a self-limited and reversible condition, AKI is now increasingly recognized as a significant risk factor for longterm cardiovascular and kidney complications. Hospitalized individuals with AKI have three to eight-fold increased risks for developing incident CKD. Previous studies used cross-sectional measurements of biomarkers to evaluate kidney injury, inflammation and tubular health in patients with AKI.

However, biomarker measurements at singular timepoint may not sufficiently capture the evolution of these biological processes over time. Although treatable, AKI could lead to CKD, a much more severe and potentially fatal condition, and other heart problems. AKI is most commonly seen in hospitalized patients whose kidneys are affected by medical and surgical stress and complications, potentially resulting in a longer recovery process and prolonged harm to the kidneys. In a new study looking at the long-term effects of hospitalized patients who have AKI, Johns Hopkins Medicine researchers found that higher levels of certain biomarkers in urine and blood can predict a patient’s risk of developing CKD. researchers measured seven urine and two plasma biomarkers of kidney injury, inflammation and tubular health at multiple timepoints over the course of a year after diagnosis, in a cohort of 656 hospitalized patients with AKI.

The goal was to determine the associations of longitudinal changes in these biomarkers with progression of kidney disease after AKI. The researchers found that for each deviation increase in change of the biomarker KIM-1, MCP-1 in urine and TNFRI in plasma from baseline to 12 months was associated with a two- to three-fold increased risk for CKD. Scientists said that these findings suggest that sustained tissue injury and inflammation, as well as slower restoration of tubular health, are associated with higher risk of kidney disease progression. However, they also observed that the increase in the urine biomarker Uromodulin was associated with a 40% reduced risk for CKD. The findings, published in the Journal of Clinical Investigation Insight, could help doctors better understand whether or not the body is healing properly, after someone sustains kidney damage, and potentially prevent the progression of AKI to CKD.

Doctor Chirag Parikh, PhD, director of the Division of Nephrology at the Johns Hopkins University School of Medicine and senior author, stated: “About 20% of hospitalized patients develop AKI and have a three- to eight-fold increased risk of developing chronic kidney disease later on in life. AKI incidence in the hospital continues to rise, so we set out to understand how and why AKI progresses to CKD, and if monitoring these patients over time can give us clues to kidney disease progression. Longitudinal measurement of some of these proteins have the potential to guide management of patients with AKI after discharge, which includes follow-up with a nephrologist; optimizing diabetes and cardiac medications; and accurate dosing of all medications with reduced kidney function”.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Wen Y, Xu L et al. JCI Insight. 2023 Mar 23:e167731.

Conway BR et al. J Amer Soc Nephrol. 2020; 31(12):2833.

Chawla LS et al. New Engl J Med. 2014; 371(1):58–66.

Coca SG et al. Amer J Kidney Dis. 2009; 53(6):961–973.

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