Quantifying Change in Proteinuria After Acute Kidney Injury Among Patients With Chronic Kidney Disease: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

TL;DR

This study found that acute kidney injury in patients with chronic kidney disease is linked to a small but significant increase in urine protein levels, possibly indicating lasting kidney damage.

Contribution

The study provides new evidence that AKI independently increases proteinuria in CKD patients, beyond changes in blood pressure or medication use.

Findings

Each AKI episode was associated with a 3% increase in urinary protein-creatinine ratio.

Most AKI episodes were stage 1, and the increase in proteinuria was small but statistically significant.

The findings suggest residual structural kidney damage may occur after AKI in CKD patients.

Abstract

Quantifying the change in proteinuria after acute kidney injury (AKI) may shed light on the pathway through which AKI contributes to kidney disease progression.

Prospective cohort study of patients with chronic kidney disease (CKD).

3,197 participants who were enrolled in the multicenter, prospective Chronic Renal Insufficiency Cohort between January 7, 2013, and January 12, 2021.

AKI was defined as ≥1.5 peak to nadir inpatient serum creatinine ascertained during a hospital admission.

Natural log-transformed urinary protein-creatinine ratio (UPCR) ascertained at annual Chronic Renal Insufficiency Cohort research study visits.

Mixed-effects regression.

Among 3,197 participants, the mean age was 65 years, 44% were women, and 42% self-identified as non-Hispanic Black. The median baseline estimated glomerular filtration rate was 52 mL/min/1.73 m2 and UPCR was 0.14 g/g. 560 patients experienced 861 episodes of AKI over a median period of 6 years, with most being stage 1 (68%). In the multivariable model that adjusted for blood pressure and renin-angiotensin system inhibitor use, each AKI episode was associated with a 3% increase in UPCR (relative change ratio, 1.03; 95% CI, 1.01-1.05; P < 0.01).

Hospitalized AKI with baseline CKD only, predominance of stage 1 AKI, timing of proteinuria collection was limited to annual visits, residual confounding.

Among CKD patients, AKI was independently associated with worsening proteinuria (independent of changes in blood pressure or renin-angiotensin system inhibitor use) and may reflect residual structural damage to the kidneys. However, the increase in proteinuria among patients with CKD after AKI was small.

The amount of protein in the urine is a key clinical metric used in daily practice to assess kidney health. Currently, the risk of chronic kidney disease progression is defined by the crosstabulation of glomerular filtration rate and protein in the urine. We studied 3,197 patients with chronic kidney disease and found that acute kidney injury events in the hospital were associated with an increase in urine protein levels, which may reflect residual kidney damage. Although the degree of worsening of urine protein levels was small (∼3%), these findings may guide future studies on the testing and management of urine protein after acute kidney injury.