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Proteinuria trajectories in chronic kidney disease (CKD) predict end-stage renal disease and mortality risk, as well as CKD progression over 2 years.

Repeat proteinuria measurements in patients with chronic kidney disease (CKD) are potential indicators of increased risk for end-stage kidney disease (ESKD) and death, regardless of known risk factors, according to results published in Kidney360.

While clinicians do collect repeat proteinuria measurements from patients with CKD, “clinicians may overlook the significance of temporal patterns of proteinuria,” Anand Srivastava, MD, MPH, and colleagues wrote.

“In addition, it is unclear whether proteinuria trajectories identify sub-populations with varying risks of adverse clinical outcomes,” they continued.

Dr. Srivastava and colleagues used group-based trajectory modeling to examine proteinuria trajectories based on annual urine protein-to-creatinine ratio (UPCR) measurements. The study included participants from the Chronic Renal Insufficiency Cohort Study who were alive and had not progressed to ESKD within 3 years of study entry. The researchers used multivariable-adjusted Cox proportional hazards models to assess associations of UPCR trajectories with ESKD and death in patients who were alive beyond the 3rd annual visit.

Rising Proteinuria & ESKD Risk

 The analysis included 3,209 participants. Trajectory analyses revealed four discrete groups based on annual UPCR measurements:

• Low-slowly rising (n=1,528);
• High-slowly rising (n=1,363);
• Regressing (n=114); and
• Rapidly rising (n=204).

Compared with patients in the low-slowly rising proteinuria trajectory group, participants in the other proteinuria trajectory groups had lower socioeconomic status, a higher prevalence of comorbid conditions, and lower estimated glomerular filtration rate.

Over a median follow-up of 8.6 years, 547 participants progressed to ESKD and 836 participants died, according to the study results. Compared with patients in the low-slowly rising group, all other proteinuria trajectory groups were associated with higher risks for subsequent ESKD. However, only the high-slowly rising group was associated with a higher mortality risk.

Additional Predictive Value of Proteinuria in CKD

 Prior research has indicated the predictive value of proteinuria measurements in CKD. A study published in the Journal of Clinical Medicine demonstrated that an elevated renal resistive index (RRI) and significant proteinuria were independent predictors of CKD progression over 2 years.

At the 2-year follow-up, 32% of patients met the endpoint of kidney function decline or new-onset ESKD. A multivariate logistic model in that study identified an elevated RRI and significant proteinuria as independent predictors. Odds ratios for meeting the combined endpoint were 4.28 with an elevated RRI and 3.59 with significant proteinuria.

The study also found that increased RRI and 24-hour urinary protein excretion were inversely and independently associated with the percent change in eGFR. Patients with elevated RRI and significant proteinuria had a higher percentage reduction at 2 years (-38.0% ± 20.4%) than patients with only proteinuria (-25.3% ± 19.0%) or patients without elevated RRI or proteinuria (-8.8% ± 25.1%). Patients with elevated RRI alone had a percentage change of -29.6% ± 21.0%.

“The apparent dominant role of the RRI as a marker of CKD progression independent of proteinuria suggests that it should be evaluated in all patients with CKD of unknown origin,” the researchers wrote.