Abstract
α-Klotho is a known anti-aging protein that exerts diverse physiological effects, including phosphate homeostasis. Klotho expression occurs predominantly in the kidney and is significantly decreased in patients with chronic kidney disease. However, changes in serum klotho levels and impacts of klotho on outcomes among kidney transplant (KTx) recipients and kidney donors remain unclear. A literature search was conducted using MEDLINE, EMBASE, and Cochrane Database from inception through October 2019 to identify studies evaluating serum klotho levels and impacts of klotho on outcomes among KTx recipients and kidney donors. Study results were pooled and analyzed utilizing a random-effects model. Ten cohort studies with a total of 431 KTx recipients and 5 cohort studies with a total of 108 living kidney donors and were identified. After KTx, recipients had a significant increase in serum klotho levels (at 4 to 13 months post-KTx) with a mean difference (MD) of 243.11 pg/mL (three studies; 95% CI 67.41 to 418.81 pg/mL). Although KTx recipients had a lower serum klotho level with a MD of = −234.50 pg/mL (five studies; 95% CI −444.84 to −24.16 pg/mL) compared to healthy unmatched volunteers, one study demonstrated comparable klotho levels between KTx recipients and eGFR-matched controls. Among kidney donors, there was a significant decrease in serum klotho levels post-nephrectomy (day 3 to day 5) with a mean difference (MD) of −232.24 pg/mL (three studies; 95% CI –299.41 to −165.07 pg/mL). At one year following kidney donation, serum klotho levels remained lower than baseline before nephrectomy with a MD of = −110.80 pg/mL (two studies; 95% CI 166.35 to 55.24 pg/mL). Compared to healthy volunteers, living kidney donors had lower serum klotho levels with a MD of = −92.41 pg/mL (two studies; 95% CI −180.53 to −4.29 pg/mL). There is a significant reduction in serum klotho levels after living kidney donation and an increase in serum klotho levels after KTx. Future prospective studies are needed to assess the impact of changes in klotho on clinical outcomes in KTx recipients and living kidney donors.
Highlights
Introduction αKlotho is a membrane protein that is highly expressed in the kidney, especially in the distal tubular epithelial cells [1,2,3,4,5,6,7,8,9,10]
Egger’s regression test demonstrated no significant publication bias in all analyses (p > 0.05). In this meta-analysis, we demonstrated that serum klotho levels were significantly increased after successful kidney transplant (KTx)
While KTx recipients had lower serum klotho levels compared to unmatched healthy volunteers, serum klotho levels in kidney transplant recipients were comparable to those in estimated glomerular filtration rate (eGFR)-matched controls
Summary
Introduction αKlotho (klotho) is a membrane protein that is highly expressed in the kidney, especially in the distal tubular epithelial cells [1,2,3,4,5,6,7,8,9,10]. Membrane-bound klotho regulates phosphate homeostasis by acting as a co-factor of fibroblast growth factor 23 (FGF23) [11,12,13,14]. Since klotho expression is the most abundant in the kidney [40], patients with kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD), are found to have a significant reduction in klotho expression and soluble levels [41,42,43,44,45,46,47,48,49,50,51]. Studies have demonstrated that serum klotho declines in progressive human CKD with the lowest serum klotho levels among patients with end-stage kidney disease (ESKD) on dialysis [41,48]. Low serum klotho is associated with increased mortality and cardiovascular events among patients with ESKD [52]
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