Plasma Mucin-1 (CA15-3) Levels in Autosomal Dominant Tubulointerstitial Kidney Disease due to MUC1 Mutations

Abstract

<b><i>Introduction:</i></b> Patients with ADTKD-<i>MUC1</i> have one allele producing normal mucin-1 (MUC1) and one allele producing mutant MUC1, which remains intracellular. We hypothesized that ADTKD-<i>MUC1</i> patients, who have only 1 secretory-competent wild-type <i>MUC1</i> allele, should exhibit decreased plasma mucin-1 (MUC1) levels. To test this hypothesis, we repurposed the serum CA15-3 assay used to measure MUC1 in breast cancer to measure plasma MUC1 levels in ADTKD-<i>MUC1</i>. <b><i>Methods:</i></b> This cross-sectional study analyzed CA15-3 levels in a reference population of 6,850 individuals, in 85 individuals with ADTKD-<i>MUC1</i>, and in a control population including 135 individuals with ADTKD-<i>UMOD</i> and 114 healthy individuals. <b><i>Results:</i></b> Plasma CA15-3 levels (mean ± standard deviation) were 8.6 ± 4.3 U/mL in individuals with ADTKD-<i>MUC1</i> and 14.6 ± 5.6 U/mL in controls (<i>p</i> &#x3c; 0.001). While there was a significant difference in mean CA15-3 levels, there was substantial overlap between the 2 groups. Plasma CA15-3 levels were &#x3c;5 U/mL in 22% of ADTKD-<i>MUC1</i> patients, in 0/249 controls, and in 1% of the reference population. Plasma CA15-3 levels were &#x3e;20 U/mL in 1/85 ADTKD-<i>MUC1</i> patients, in 18% of control individuals, and in 25% of the reference population. Segregation of plasma CA15-3 levels by the rs4072037 genotype did not significantly improve differentiation between affected and unaffected individuals. CA15-3 levels were minimally affected by gender and estimated glomerular filtration rate. <b><i>Discussion/Conclusions:</i></b> Plasma CA15-3 levels in ADTKD-<i>MUC1</i> patients are approximately 40% lower than levels in healthy individuals, though there is significant overlap between groups. Further investigations need to be performed to see if plasma CA15-3 levels would be useful in diagnosis, prognosis, or assessing response to new therapies in this disorder.