Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients

Klont, Frank; Kieneker, Lyanne M.; Gomes-Neto, Antonio W.; Stam, Suzanne P.; ten Hacken, Nick H. T.; Kema, Ido P.; van Beek, André P.; van den Berg, Else; Horvatovich, Péter; Bischoff, Rainer; Bakker, Stephan J. L.

doi:10.3390/jcm9020293

Open AccessArticle

Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients

by

Frank Klont

^1,*

,

Lyanne M. Kieneker

²,

Antonio W. Gomes-Neto

²,

Suzanne P. Stam

²

,

Nick H. T. ten Hacken

³,

Ido P. Kema

⁴,

André P. van Beek

⁵

,

Else van den Berg

²,

Péter Horvatovich

¹

,

Rainer Bischoff

¹

and

Stephan J. L. Bakker

²

¹

Department of Analytical Biochemistry, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands

²

Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands

³

Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands

⁴

Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands

⁵

Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands

^*

Author to whom correspondence should be addressed.

J. Clin. Med. 2020, 9(2), 293; https://doi.org/10.3390/jcm9020293

Submission received: 19 December 2019 / Revised: 14 January 2020 / Accepted: 17 January 2020 / Published: 21 January 2020

(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)

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Abstract

Associations between insulin-like growth factor 1 (IGF1) and mortality have been reported to be female specific in mice and in human nonagenarians. Intervention in the growth hormone (GH)-IGF1 axis may particularly benefit patients with high risk of losing muscle mass, including renal transplant recipients (RTR). We investigated whether a potential association of circulating IGF1 with all-cause mortality in stable RTR could be female specific and mediated by variation in muscle mass. To this end, plasma IGF1 levels were measured in 277 female and 343 male RTR by mass spectrometry, and their association with mortality was assessed by Cox regression. During a median follow-up time of 5.4 years, 56 female and 77 male RTR died. In females, IGF1 was inversely associated with risk (hazard ratio (HR) per 1-unit increment in log2-transformed (doubling of) IGF1 levels, 95% confidence interval (CI)) of mortality (0.40, 0.24–0.65; p < 0.001), independent of age and the estimated Glomerular filtration rate (eGFR). In equivalent analyses, no significant association was observed for males (0.85, 0.56–1.29; p = 0.44), for which it should be noted that in males, age was negatively and strongly associated with IGF1 levels. The association for females remained materially unchanged upon adjustment for potential confounders and was furthermore found to be mediated for 39% by 24 h urinary creatinine excretion. In conclusion, low IGF1 levels associate with an increased risk of all-cause mortality in female RTR, which may link to conditions of low muscle mass that are known to be associated with poor outcomes in transplantation patients. For males, the strongly negative association of age with IGF1 levels may explain why low IGF1 levels were not found to be associated with an increased risk of all-cause mortality.

Keywords: insulin-like growth factor 1; growth hormone; muscle mass; patient survival; physical activity; renal transplant recipients

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MDPI and ACS Style

Klont, F.; Kieneker, L.M.; Gomes-Neto, A.W.; Stam, S.P.; ten Hacken, N.H.T.; Kema, I.P.; van Beek, A.P.; van den Berg, E.; Horvatovich, P.; Bischoff, R.; et al. Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients. J. Clin. Med. 2020, 9, 293. https://doi.org/10.3390/jcm9020293

AMA Style

Klont F, Kieneker LM, Gomes-Neto AW, Stam SP, ten Hacken NHT, Kema IP, van Beek AP, van den Berg E, Horvatovich P, Bischoff R, et al. Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients. Journal of Clinical Medicine. 2020; 9(2):293. https://doi.org/10.3390/jcm9020293

Chicago/Turabian Style

Klont, Frank, Lyanne M. Kieneker, Antonio W. Gomes-Neto, Suzanne P. Stam, Nick H. T. ten Hacken, Ido P. Kema, André P. van Beek, Else van den Berg, Péter Horvatovich, Rainer Bischoff, and et al. 2020. "Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients" Journal of Clinical Medicine 9, no. 2: 293. https://doi.org/10.3390/jcm9020293

APA Style

Klont, F., Kieneker, L. M., Gomes-Neto, A. W., Stam, S. P., ten Hacken, N. H. T., Kema, I. P., van Beek, A. P., van den Berg, E., Horvatovich, P., Bischoff, R., & Bakker, S. J. L. (2020). Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients. Journal of Clinical Medicine, 9(2), 293. https://doi.org/10.3390/jcm9020293

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Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients

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