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Abstract: FR-PO938

Variations in Creatinine Generation among Patients with Glomerular Diseases

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Ramachandra, Shalini S., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Chiang, Melody, University of Michigan Department of Internal Medicine, Ann Arbor, Michigan, United States
  • Arbit, Michael, University of Michigan Department of Internal Medicine, Ann Arbor, Michigan, United States
  • Glenn, Dorey A., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States
  • Mariani, Laura H., University of Michigan Department of Internal Medicine, Ann Arbor, Michigan, United States
  • Zee, Jarcy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
Background

Estimation of glomerular filtration rate (eGFR) assumes that creatinine generation (CrG) is relatively stable, but the relationship between CrG variability and glomerular disease activity is unknown.

Methods

CrG was calculated using 24-hour timed urine collections from children and adults with MCD, FSGS, MN, IgAN, or non-biopsied pediatric nephrotic syndrome enrolled in the NEPTUNE and CureGN cohort studies. Intraclass correlation coefficients (ICC) were used to estimate CrG variability within individuals over time. Multivariable linear mixed models were used to identify: (1) factors associated with CrG and (2) the impact of change in CrG (ΔCrG) on changes in serum creatinine (ΔSCr), adjusting for simulated true GFR.

Results

A sample of 4626 CrG measurements were analyzed from 1081 study participants (26.7%<18 years). A moderate correlation between intra-individual measurements overall (ICC = 0.517, 95% CI: 0.482, 0.548), and a weak correlation among non-biopsied pediatric participants (ICC = 0.241 (95% CI: 0.000, 0.558) were observed. Among all pediatric participants, factors significantly associated with CrG included age, sex, weight status, and urine protein [Figure 1A]. Among adults, age, sex, disease diagnosis, weight status, eGFR, steroid use, and non-steroid immunosuppressant (IST) use were significantly associated with CrG [Figure 1B]. After adjustment for simulated true GFR (based on ρ=0.512 correlation with ΔCrG and ρ=-0.835 correlation with ΔSCr) and other covariates, every 10 mg/kg/day increase in ΔCrG was associated with a 0.48 mg/dL increase in ΔSCr (p < 0.001).

Conclusion

Creatinine generation was highly dynamic within individuals over time and varied with glomerular disease activity and treatments. The impact of changes in creatinine generation on estimation of kidney functions is potentially large. Accounting for these changes and/or routine use of other markers to measure kidney function may be beneficial for patients with glomerular disease.

Funding

  • NIDDK Support