PuSH - Publikationsserver des Helmholtz Zentrums München: Pro-neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease.

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Tönjes, A.* ; Hoffmann, A.* ; Kralisch, S.* ; Qureshi, A.R.* ; Klöting, N.* ; Scholz, M.* ; Schleinitz, D.* ; Bachmann, A.* ; Kratzsch, J.* ; Nowicki, M.* ; Paeschke, S.* ; Wirkner, K.* ; Enzenbach, C.* ; Baber, R.* ; Beige, J.* ; Anders, M.* ; Bast, I.* ; Blüher, M. ; Kovacs, P.* ; Löffler, M.* ; Zhang, M.Z.* ; Harris, R.C.* ; Stenvinkel, P.* ; Stumvoll, M.* ; Fasshauer, M.* ; Ebert, T.*

Pro-neurotensin depends on renal function and is related to all-cause mortality in chronic kidney disease.

Eur. J. Endocrinol. 183, 233-244 (2020)

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Background: Patients with chronic kidney disease (CKD) have a high risk of premature cardiovascular diseases (CVD) and show increased mortality. Pro-neurotensin (Pro-NT) was associated with metabolic diseases and predicted incident CVD and mortality. However, Pro-NT regulation in CKD and its potential role linking CKD and mortality have not been investigated, so far.Methods: In a central lab, circulating Pro-NT was quantified in three in dependent cohorts comprising 4715 participants (cohort 1: patients with CKD; cohort 2: general population study; and cohort 3: non-diabetic population study). Urinary Pro-NT was assessed in part of the patients from cohort 1. In a 4th independent cohort, serum Pro-NT was further related to mortality in patients with advanced CKD. Tissue-specific Nts expression was further investigated in two mouse models of diabetic CKD and compared to non-diabetic control mice.Results: Pro-NT significantly increased with deteriorating renal function (P < 0.001). In meta-analysis of cohorts 1-3, Pro-NT was significantly and independently associated with estimated glomerular filtration rate (P = 0.002). Patients in the middle/high Pro-NT tertiles at baseline had a higher all-cause mortality compared to the low Pro-NT tertile (Hazard ratio: 2.11, P = 0.046). Mice with severe diabetic CKD did not show increased Nts mRNA expression in different tissues compared to control animals.Conclusions: Circulating Pro-NT is associated with impaired renal function in independent cohorts comprising 4715 subjects and is related to all-cause mortality in patients with end-stage kidney disease. Our human and rodent data are in accordance with the hypotheses that Pro-NT is eliminated by the kidneys and could potentially contribute to increased mortality observed in patients with CKD.

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