• Proteins in the Wnt signaling pathway help drive kidney scarring that can lead to chronic kidney disease.

Washington, DC (July 23, 2015) -- Chronic diseases such as diabetes and hypertension cause injury to the kidneys, which can lead to scarring and the development of chronic kidney disease. By identifying proteins important to this scarring process, researchers now point to a new strategy for possibly preventing kidney failure and the need for dialysis or transplantation in many patients. The findings appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN).

When Benjamin Humphreys MD, PhD (Washington University School of Medicine) and his colleagues examined the complex process of scarring, or fibrosis, in failing kidneys, they discovered that proteins in the Wnt signaling pathway play a critical role in the crosstalk between cells as scarring occurs. Wnt proteins are important in development but are normally turned off in healthy kidneys. When the researchers boosted expression of Wnt proteins in the kidneys of healthy mice, the organs developed fibrosis. "This means that drugs targeting Wnts might be an effective strategy for humans with chronic kidney disease," said Dr. Humphreys.

The investigators were surprised to find that Wnt proteins cause kidney fibrosis without inflammation. "In the models we typically use to study in the laboratory, and also in human fibrosis, there is always some degree of inflammation, so to not find any was unexpected," explained Dr. Humphreys. "We conclude that inflammation is not required for the development of kidney fibrosis, and this suggests that purely anti-inflammatory drugs may not be as effective at treating chronic kidney disease.

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Study co-authors include Omar Maarouf, MD, Anusha Aravamudhan, BS, Deepika Rangarajan, BS, Tetsuro Kusaba, MD, Victor Zhang, Jeremy Welborn, Daniel Gauvin, BS, Xiuyun Hou, PhD, and Rafael Kramann, MD.

Disclosures: Dr. Humphreys has received research support in the past from Evotec AG for the study of kidney fibrosis, but those funds did not support this project. The authors reported no other financial disclosures.

The article, entitled "Paracrine Wnt1 Drives Interstitial Fibrosis without Inflammation by Tubulointerstitial Cross-Talk," will appear online at http://jasn.asnjournals.org/ on July 23, 2015.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

Founded in 1966, and with more than 15,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.

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Detection of occult bone metastases can be critical in determining the management of patients with renal cell carcinoma, especially when standard of care imaging techniques test negative.

¹⁸F-NaF PET/CT is significantly more sensitive at detecting renal cell carcinoma (RCC) skeletal metastases than conventional than bone scintigraphy or computed tomography (CT), according to an article published online ahead of print in the Annals of Oncology.

Researchers assessed the sensitivity of 18F-labelled sodium fluoride in conjunction with positron emission tomography/computed tomography (18F-NaF PET/CT) for detecting bone metastases compared to imaging with bone scinigraphy or CT.

They used an adaptive two-stage trial design, which was stopped after the first stage because of statistical efficacy.

Ten patients with stage 4 RCC and bone metastases were imaged with ¹⁸F-NaF PET/CT and ^99mTc-labelled methylene diphosphonate (^99mTc-MDP) bone scintigraphy, including pelvic single photon (SPECT).

A total of 77 lesions were diagnosed as malignant: 100% were identified by ¹⁸F-NaF PET/CT, 46% by CT, and 28% by bone scintigraphy/SPECT.

Standard-of-care imaging with CT and bone scintigraphy identified 65% of the metastases reported by ¹⁸F-NaF PET/CT.

Reference

1. Gerety EL, Lawrence EM, Wason J, et al. Prospective study evaluating the relative sensitivity of ¹⁸F-NaF PET/CT for detecting skeletal metastases from renal cell carcinoma in comparison to multidetector CT and ^99mTc-MDP bone scintigraphy, using an adaptive trial design. Annals of Oncol.2015. [epub ahead of print]. doi: 10.1093/annonc/mdv289.

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