Association between multimorbidity and discordance between creatinine- and cystatin C-based eGFR

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Abstract
Background and hypothesis: Large differences between glomerular filtration rate estimated with creatinine and cystatin C—termed estimated glomerular filtration rate (eGFR) discordance—have important implications for health. Several demographic factors and individual long-term conditions (LTCs) are associated with eGFR discordance. We hypothesize that the presence of multiple LTCs, i.e. multimorbidity is likely to be associated with eGFR discordance. Methods: Differences between creatinine-based and cystatin C-based eGFR [eGFR using serum creatinine (eGFRcr) and eGFR using serum cystatin C (eGFRcys), respectively] using European Kidney Function Consortium equations were calculated in over 400 000 UK Biobank participants. Large negative eGFR difference was defined as an eGFRcys >30% lower than eGFRcr, i.e. ([eGFRcys − eGFRcr]/eGFRcr) < −30%. Self-reported LTCs were counted and analysed overall and by type of multimorbidity (cardiometabolic, non-cardiometabolic, mixed mental and physical). Proportions of participants with large negative eGFR differences were cross-tabulated at different chronic kidney disease (CKD) stages and according to number of LTCs. The association between number of LTCs and eGFR discordance was assessed in logistic regression models adjusted for age, sex, body mass index, smoking status, and thyroid disease. Results: Multimorbidity (two or more LTCs of any type) was observed in 33% of the overall cohort and 63% of those with large negative eGFR differences. When CKD stage was assigned based on eGFRcr and then reassigned using eGFRcys, 15% of the cohort were reclassified to a more advanced CKD stage with frequency of reclassification increasing progressively with increasing counts of LTCs. Individuals with four or more LTCs of any type were more than four-fold more likely to have a large negative eGFR difference (adjusted odds ratio 4.64, 95% confidence interval 4.13–5.21) compared to individuals with no LTCs. Conclusion: Discordance between creatinine-based and cystatin C-based eGFR increased substantially with multimorbidity. Cystatin C testing should be considered (alongside creatinine) in individuals with multimorbidity to refine estimation of kidney function and risk stratification.
Funding Information
  • Wellcome Trust (223499/Z/21/Z)
  • Wellcome Early-Career Award (301005/Z/23/Z)

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