Variations in Creatinine Generation Among Patients With Glomerular Disease: Evidence From the NEPTUNE and CureGN Studies.

RATIONALE & OBJECTIVE: Estimation of glomerular filtration rate (GFR) assumes that creatinine generation (crG) is relatively stable. This study identified factors associated with crG variability and its impact on serum creatinine changes ( Scr) among patients with glomerular disease.

STUDY DESIGN

An observational cohort study.

SETTING & PARTICIPANTS: Nephrotic Syndrome Study Network and Cure Glomerulonephropathy adult and pediatric participants with at least one crG measurement.

PREDICTORS

Potential predictors of crG levels included age, sex, disease diagnosis, weight status, estimated GFR (eGFR), urine protein, steroid use, and nonsteroid immunosuppressant use. crG change ( crG) was then used as an exposure to assess impacts on Scr.

OUTCOMES

crG levels and Scr.

ANALYTICAL APPROACH

The intraclass correlation coefficient illustrated crG variability within individuals. Multivariable linear mixed models identified factors associated with crG levels. Among those with 2+ crG measurements, multivariable linear mixed models estimated the association between crG and Scr.

RESULTS

Among 4,626 crG measurements from 1,081 participants, there was only moderate correlation between measurements within individuals (intraclass correlation coefficient = 0.517, 95% CI, 0.482-0.548) overall. For pediatric participants, factors significantly associated with crG included age, sex, weight status, and urine protein. Among adults, significant factors were age, sex, disease diagnosis, weight status, eGFR, steroid use, and nonsteroid immunosuppressant use.

LIMITATIONS

The 24-hour urine collections may have collection error, measured GFR was unavailable, and edema status was unavailable.

CONCLUSIONS

crG was highly dynamic within individuals over time and varied with glomerular disease activity and treatments. The impact of crG on Scr -and subsequently on estimation of kidney function-is potentially large. Accounting for these changes or development of alternative kidney function measures are needed among glomerular disease patients.