Keynote speaker addresses need for broader assessment of kidney health
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Having a broader assessment of kidney health will improve diagnostic accuracy and provide noninvasive methods to monitor changes without repeated biopsies, according to a speaker at the virtual National Kidney Foundation Spring Clinical Meetings.
“The severity of tubular interstitial fibrosis on biopsy is among the strongest risk markers for risk of loss of kidney function and end-stage renal disease,” Joachim Ix, MD, MAS, professor of medicine and chief of the division of nephrology-hypertension at the University of California, San Diego and Veterans Affairs San Diego Healthcare System, said in his presentation.
According to Ix, the keynote speaker and recipient of the NKF’s 2020 Shaul G. Massry Award, noninvasive kidney tubule health assessment might bring markers to predict loss of kidney function independent of glomerular markers, might predict chronic kidney disease-related complications independent of glomerular markers and may allow differentiation of different causes of creatinine rise.
“Perhaps it is time we move beyond serum creatinine and albuminuria and consider a broader assessment of kidney health,” Ix said.
Alpha 1-microglobulin and beta 2-microglobulin are two proteins in the bloodstream that have been studied because these are similar to creatinine but reabsorb the proximal tubule so as not to have high concentrations in an individual’s urine. Another protein Ix focused on was uromodulin, which is the most abundant protein in the urine of patients without proteinuria and glomerular disease.
Ix and colleagues conducted the SPRINT trial, which recruited 9,300 patients who were hypertensive with CKD and were randomized to either a group in which intensive blood pressure reduction was practiced (less than 120 mm Hg) vs. a control group in which a standard target of 140 mm Hg would prevent cardiovascular disease development.
Using these biomarkers for tubule function, researchers found higher urine concentrations of alpha 1-microglobulin were associated with a more rapid decline in kidney function and uromodulin was associated with kidney function loss.
Ix discussed studying whether having evidence of tubule cell injury or dysfunction at baseline would hint about the health of the kidney and if individuals had abnormalities, and whether they were at higher risk of acute kidney injury during SPRINT follow-up. The tubule cell injury biomarkers were not independently associated with AKI risk, but biomarkers that marked function of the kidneys rather than injury were strongly associated with AKI.
Among 2,500 patients in SPRINT with CKD, there were 305 CVD events during the 3.5 years of follow-up. There were no associations between the biomarkers for tubule cell injury and CVD risk but the two biomarkers for tubule cell function were associated with CVD risk.
To evaluate the effects of blood pressure lowering on kidney tubule injury in patients with CKD, researchers used 1,000 SPRINT participants with an eGFR less than 60 mL/min and repeated urine markers of tubule function and injury. During the first year, patients experienced a roughly 8 mL/min eGFR decline with intensive blood pressure lowering with a 30% reduction in albuminuria.
When individuals were characterized by eGFR decline in the first year, albumin to creatinine, alpha 1-microglobulin and beta 2-microglobulin had the largest eGFR decline. These individuals had the largest reductions in biomarker urine concentration suggesting hemodynamic effect.
Ix suggested not relying solely on eGFR and albuminuria in kidney biopsies and, instead, focusing on tubular interstitial damage, fibrosis and dysfunction because these have a strong association with CKD progression and CVD.
“I’m hopeful that we can ultimately have a broader assessment of kidney health that will help us improve diagnostic accuracy for the causes of AKI and CKD, might provide us noninvasive methods to improve prognosis and ultimately allow us to monitor changes in kidney health over time,” Ix said. – by Erin T. Welsh
Reference:
Ix J. Prognostic insights from non-invasive assessment of kidney tubule health. Presented at: National Kidney Foundation Spring Clinical Meetings; March 26-29, 2020 (virtual meeting).
Disclosure: Ix reports being a principal investigator of an Investigator Initiated Research Project supported by Baxter International.
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