Patients with chronic kidney disease (CKD) accompanied by high levels of certain urinary markers of kidney tubule cell injury have more rapid kidney function decline, new study findings suggest.

Estimated glomerular filtration rate (eGFR) and albuminuria primarily reflect glomerular function and injury. Tubule cell atrophy and interstitial fibrosis, however, provide additional important information on progression risk, according to Rakesh Malhotra, MD, of the University of California San Diego, and colleagues.

In their analysis of 2428 SPRINT trial participants (mean age 73 years; 60% male; 66% white) with nondiabetic CKD (mean baseline eGFR 46 mL/min/1.73 m2), 87 cases of the kidney composite outcome (a 50% decline in eGFR, end-stage kidney disease requiring dialysis, or kidney transplantation) occurred over a median of 3.8 years.

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Urinary biomarkers of severe kidney injury, inflammation, and repair identified a subset of patients with CKD at risk for more rapid progression, the investigators reported in the Clinical Journal of the American Society of Nephrology. Patients in the highest quartile of kidney injury molecule-1 (KIM-1; more than 1596 pg/mL) had a significant 2.8-fold higher risk for the composite outcome. Similarly, patients with the highest quartile of monocyte chemoattractant protein-1 (MCP-1; more than 327 pg/mL), a marker of inflammation, had a significant 2.4-fold higher risk. Those with the highest levels of human cartilage glycoprotein-40 (YKL-40; more than 50 pg/mL), a marker of kidney repair, had a significant 1.9-fold increased risk. The investigators adjusted their models for baseline eGFR, urinary albumin, blood pressure, antihypertensive medications, and other CKD risk factors.

In linear analysis, the highest quartile of urinary interleukin-18 (IL-18; more than 57 pg/mL) was the only factor that significantly correlated with eGFR decline (-0.91 mL/min/1.73 m2 per year). The association appeared stronger among SPRINT participants randomized to standard vs intensive blood pressure control, suggesting that IL-18 reflects true eGFR decline rather than hemodynamic fluctuations.

According to Dr Malhotra’s team, “extremes of urinary KIM-1, MCP-1, and YKL-40 may mark risk for subsequent large eGFR declines. In contrast, urinary IL-18 may help to distinguish subtler changes in eGFR. Overall, these data demonstrate that markers of tubule cell injury provide information on risk of CKD progression independent of the glomerular markers of kidney health (eGFR and urine albumin).”

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Malhotra R, Katz R, Jotwani V, et al. Urine markers of kidney tubule cell injury and kidney function decline in SPRINT trial participants with CKD. Clin J Am Soc Nephrol. 15:349–358. doi: 10.2215/CJN.02780319