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Variations in Creatinine Generation Among Patients With Glomerular Disease: Evidence From the NEPTUNE and CureGN
Shalini S Ramachandra1, Melody Chiang2, Michael Arbit2
1Division of Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Insights
Creatinine generation (crG) is highly variable in patients with glomerular disease, impacting serum creatinine (Scr) changes and kidney function estimation. Factors like age, sex, and disease activity influence crG, necessitating adjustments for accurate assessment.
Area of Science:
- Nephrology
- Renal Physiology
- Clinical Chemistry
Background:
- Glomerular filtration rate (GFR) estimation relies on stable creatinine generation (crG).
- Variability in crG can affect the accuracy of serum creatinine (Scr) as a marker of kidney function.
- Understanding factors influencing crG is crucial for patients with glomerular diseases.
Purpose of the Study:
- To identify factors associated with crG variability in patients with glomerular disease.
- To assess the impact of crG changes (ΔcrG) on serum creatinine changes (ΔScr).
- To highlight the implications for kidney function estimation in this population.
Main Methods:
- Observational cohort study of adult and pediatric participants from the Nephrotic Syndrome Study Network and Cure Glomerulonephropathy.
- Multivariable linear mixed models were used to identify predictors of crG levels and to estimate the association between ΔcrG and ΔScr.
- Analysis included 4,626 crG measurements from 1,081 participants.
Main Results:
- Moderate intra-individual correlation for crG measurements (ICC=0.517).
- Factors associated with crG in pediatric participants included age, sex, weight status, and urine protein.
- In adults, significant factors were age, sex, disease diagnosis, weight status, eGFR, and immunosuppressant use.
Conclusions:
- Creatinine generation is dynamic in glomerular disease patients, influenced by disease activity and treatment.
- Significant crG variability impacts ΔScr and kidney function estimation.
- There is a need to account for crG changes or develop alternative markers for kidney function assessment.
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.
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