Biomarker may detect RCC 5 years before clinical diagnosis

September 6, 2018

The protein Kidney Injury Molecule 1 shows promise as a blood-based biomarker for renal cell carcinoma diagnosis and for predicting overall survival after RCC diagnosis.

The protein Kidney Injury Molecule 1 (KIM-1) shows promise as a blood-based biomarker for renal cell carcinoma (RCC) diagnosis and for predicting overall survival after RCC diagnosis, according to findings of a recently published study.

Analyzing data obtained from participants in the European Prospective Investigation into Cancer and Nutrition (EPIC), a population-based, prospective cohort study, the research found a strong significant association between pre-diagnostic plasma concentration of KIM-1 and the risk of being diagnosed with RCC in the following 5 years. Furthermore, incorporating information about KIM-1 concentration approximately doubled the sensitivity of a model for predicting RCC risk.

In addition, the study, which was published in Clinical Cancer Research (July 23, 2018 [epub ahead of print]), found an association between elevated pre-diagnostic plasma KIM-1 concentration and risk of death among RCC cases.

“Nephron-sparing nephrectomy is associated with high cure rates for patients diagnosed with localized RCC, but the prognosis remains poor for patients with more advanced disease. Identifying a sensitive and specific biomarker for detecting RCC at an early stage could improve overall survival,” said study author Rupal S. Bhatt, MD, PhD, of Harvard Medical School and Beth Israel Deaconess Medical Center, Boston.

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“We have shown that plasma concentrations of KIM-1 are predictive of RCC up to 5 years prior to diagnosis, even among patients with a good prognosis. Thus, KIM-1 might increase the proportion of cases diagnosed with localized, curable disease. Now, further studies are needed, including research to determine when plasma KIM-1 becomes elevated prior to RCC diagnosis and if it is elevated before initial neoplastic changes occur,” Dr. Bhatt added.

Interest in the potential role of KIM-1 as a sensitive and specific blood biomarker for RCC diagnosis arose from previous studies showing that its plasma concentration was high in patients with clear cell RCC at the time of diagnosis, decreased significantly following nephrectomy, and accurately discriminated the RCC cases from healthy controls.

“It was not known, however, whether the plasma concentration of KIM-1 was elevated prior to RCC diagnosis,” said Dr. Bhatt.

To answer that question, the authors analyzed KIM-1 concentrations measured in plasma samples from 190 RCC cases and 190 controls. The selected cases had entered EPIC and donated blood up to 5 years prior to having a histologically confirmed diagnosis of RCC. Each case was matched to a control based on date of birth, date of blood donation, sex, and country of residence as matching criteria. Selected controls were cancer-free except for non-melanoma skin cancer.

Next: Median KIM-1 concentration 2.5-fold higher in the cases compared with the controlsKIM-1 was detectable in the plasma samples from 93% of the cases and 70% of the controls. The median KIM-1 concentration was 2.5-fold higher in the cases compared with the controls (149 pg/mL vs. 59 pg/mL).

Associations between plasma KIM-1 concentrations and RCC risk and survival were analyzed using conditional logistic regression and flexible parametric survival models. The results showed each doubling in KIM-1 concentration corresponded to a 1.71 incidence rate ratio of RCC. The increase in risk associated with an elevated KIM-1 concentration was similarly high whether considering cases diagnosed within 2 years of the plasma draw or those diagnosed 2 to 5 years thereafter. It also persisted in an analysis that included only RCC cases with good prognosis, suggesting the potential utility of KIM-1 concentration for predicting early-stage RCC.

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The authors noted that because the risk of RCC in the general population is low, an assay for plasma KIM-1 probably does not have a role as a screening test. Additionally, KIM-1 is elevated in patients with benign kidney disease, so this needs to be taken into consideration.

“More likely, it might be applied in high-risk populations or used as an adjunct to other diagnostics, Dr. Bhatt said.

 

In addition to Dr. Bhatt, co-authors include co-first authors David Muller, PhD, and Ghislaine Scelo, PhD, as well as Venkata Sabbisetti, PhD, and Joseph V. Bonventre, MD, PhD.