Soluble Klotho Levels Predictive of Kidney Failure in Type 2 Diabetes

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Soluble Klotho is a novel biomarker of renal dysfunction and potential treatment target for renoprotection in type 2 diabetes.
Soluble Klotho is a novel biomarker of renal dysfunction and potential treatment target for renoprotection in type 2 diabetes.

In patients with type 2 diabetes, decreased levels of soluble Klotho (sKlotho) can predict renal function decline, and do so independently of traditional risk markers, according to research published in the Journal of Clinical Endocrinology & Metabolism.

More specifically, in patients with relatively preserved renal function, sKlotho was predictive of a 50% or greater decline in estimated glomerular filtration rate (eGFR), independent of FGF-23, calcium, and phosphate levels.

Klotho is an antiaging gene that encodes a single-pass transmembrane protein and is expressed primarily in the kidney. Previous studies have suggested that reduced levels of sKlotho are predictive of renal function decline and cardiovascular mortality in elderly persons without diabetes, as well as those receiving hemodialysis.

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Experimental research also supports the hypothesis that Klotho may be not only a biomarker but also a pathogenic factor in the progression of chronic kidney disease and cardiovascular complications.

The current single-center, observational follow-up study included 101 patients with type 2 diabetes and eGFR >45 mL/minute (91% on renin angiotensin system blockade) who were followed for a median of 9 (range, 2-13) years. The primary outcome was a >50% decline in eGFR.

A total of 21% of the cohort reached the primary outcome. Patients in the lower quartile of sKlotho levels had a more rapid decrease in their eGFR vs those in the higher quartile (median, −3.3 [interquartile range, −4.48 to −1.73] mL/minute/year vs −1.43 [interquartile range, −2.8 to 0.01] mL/minute/year; P =.01).

A 10% higher sKlotho level was associated with a 12% reduction in the incidence of the primary outcome (hazard ratio, 0.27; 95% CI, 0.15-0.52; P <.001), whereas those with sKlotho levels that fell below the median of 204.4 pg/mL had nearly a 4-fold higher cumulative incidence of the primary outcome vs patients who remained above the median (24% vs 6.2%; P =.01).

"Our results complement the animal and in-vitro data that indicate sKlotho may be a potential treatment target to delay progression of renal dysfunction and support the emerging role of sKlotho as a potential novel bio-marker and predictor of renal disease in diabetes," write the authors.

Reference

Fountoulakis N, Maltese G, Gnudi L, Karalliedde J. Reduced levels of anti-ageing hormone klotho predict renal function decline in type 2 diabetes [published online March 2, 2018]. J Clin Endocrinol Metab. doi: 10.1210/jc.2018-00004

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