APSH-OP-4: HISTOLOGICAL MEASURES OF STRUCTURAL KIDNEY DAMAGE ARE ASSOCIATED WITH SHORTENING OF KIDNEY TELOMERE LENGTH

Abstract

Objective: Telomeres shorten with each cell division and serve as markers of cell senescence. The rate of telomere attrition varies across tissues within the same individual. Telomere attrition and dysfunction has been associated with various disease states. Studies have shown that leukocyte telomere length (LTL) may be predictive of telomere length in other tissues of the body. Several histological changes occur in the kidney before functional impairment becomes evident. It is unclear if telomeres are associated with these early changes. We sought to (i) investigate whether LTL is a proxy of kidney telomere length (KTL), and (ii) estimate the extent to which both measures of biological ageing associate with histological markers of kidney damage. Design and Methods: Study group consisted of 200 participants (Female 38% and Male 62%) from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study. Participants had no personal history of primary nephropathy and were eligible for unilateral elective nephrectomy because of sporadic non-invasive renal cancer. Kidney tissue samples were collected from the healthy (unaffected by cancer) pole immediately after nephrectomy and fixed in 10% formalin, then embedded in paraffin blocks. The extent of kidney histological damage was assessed using a semi-quantitative method of kidney slide evaluation. LTL and KTL were quantified using quantitative polymerase chain reaction. Results: There was a significant negative correlation between KTL and age (r = -0.287, P < 0.001). The correlation between LTL and age showed directionally consistent, but non-significant pattern (r = -0.135, P = 0.063). Unadjusted and adjusted analysis showed insignificant association between LTL and KTL (r = 0.042, P = 0.575). However, both KTL and LTL correlated with tubular atrophy (r = -0.28, -0.16; P < 0.001, 0.05, respectively). Each increased unit of both KTL and LTL also associated with a decrease of 61.3% and 47.4%, respectively in likelihood of developing tubular atrophy (Table 1). Shorter KTL was associated with increased odds of developing interstitial fibrosis, interstitial inflammation, and Bowmans capsule thickening (Table 1). KTL also associated with percentage of Bowmans capsule thickening (β = -0.214, P = 0.027), percentage of sclerosed glomeruli (β = -0.227, P = 0.017), and Remuzzi score (β = -0.280, P = 0.001). In contrast, LTL did not show an association with any other kidney histology variables, except with tubular atrophy in adjusted analysis. Conclusions: LTL shows only a weak association with tubular atrophy and KTL is a much more accurate measure of histologically confirmed structural kidney damage than LTL. LTL cannot be used as a proxy of KTL or the extent of kidney damage.