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Capillary rarefaction: a missing link in renal and cardiovascular disease?

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Abstract

Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Capillary rarefaction may be both one of the causes as well as a consequence of CKD and cardiovascular disease. We reviewed the published literature on human biopsy studies and conclude that renal capillary rarefaction occurs independently of the cause of renal function decline. Moreover, glomerular hypertrophy may be an early sign of generalized endothelial dysfunction, while peritubular capillary loss occurs in advanced renal disease. Recent studies with non-invasive measurements show that capillary rarefaction is detected systemically (e.g., in the skin) in individuals with albuminuria, as sign of early CKD and/or generalized endothelial dysfunction. Decreased capillary density is found in omental fat, muscle and heart biopsies of patients with advanced CKD as well as in skin, fat, muscle, brain and heart biopsies of individuals with cardiovascular risk factors. No biopsy studies have yet been performed on capillary rarefaction in individuals with early CKD. At present it is unknown whether individuals with CKD and cardiovascular disease merely share the same risk factors for capillary rarefaction, or whether there is a causal relationship between rarefaction in renal and systemic capillaries. Further studies on renal and systemic capillary rarefaction, including their temporal relationship and underlying mechanisms are needed. This review stresses the importance of preserving and maintaining capillary integrity and homeostasis in the prevention and management of renal and cardiovascular disease.

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Funding

This work was partly financially supported by research grants from the Dutch Kidney Foundation (Grant DKF 13A1D303) and the “Profileringsfonds” of the Academic Hospital Maastricht (Grant PF292). Gert Jan Zonneveld (Audiovisual support of Maastricht UMC +) is thanked for design of Fig. 1.

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Authors and Affiliations

  1. Department of Pathology, Maastricht University Medical Centre+, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Floor M. E. G. Steegh, Anke A. Keijbeck & Carine J. Peutz-Kootstra

  2. Surgery, Maastricht University Medical Centre+, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Patrick A. de Hoogt

  3. Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands

    Timo Rademakers

  4. Internal Medicine, Maastricht University Medical Centre+, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Alfons J. H. M. Houben & Coen D. A. Stehouwer

  5. Biomedical Engineering, Maastricht University Medical Centre+, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands

    Koen D. Reesink

  6. Department of Pathology, UMC Amsterdam Cardiovascular Sciences, University of Amsterdam, Amsterdam, The Netherlands

    Mat J. A. P. Daemen

  7. Department of Pathology, Gelre Ziekenhuizen, Apeldoorn, The Netherlands

    Carine J. Peutz-Kootstra

  8. Porthoslaan 39, 6213 CN, Maastricht, The Netherlands

    Carine J. Peutz-Kootstra

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  1. Floor M. E. G. Steegh
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Contributions

FS, MD and CPK developed the concepts described in this review. AK, PH, TR, AH, KR, and CS further contributed to the concepts. FS and CPK performed literature research. All authors were involved in writing the paper and gave their final approval.

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Correspondence to Carine J. Peutz-Kootstra.

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Steegh, F.M.E.G., Keijbeck, A.A., de Hoogt, P.A. et al. Capillary rarefaction: a missing link in renal and cardiovascular disease?. Angiogenesis 27, 23–35 (2024). https://doi.org/10.1007/s10456-023-09883-8

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