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Endurance Exercise Intervention Is Beneficial to Kidney Function in a Rat Model of Isolated Abdominal Venous Congestion: a Pilot Study

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Abstract

In this study, the effects of moderate intense endurance exercise on heart and kidney function and morphology were studied in a thoracic inferior vena cava constricted (IVCc) rat model of abdominal venous congestion. After IVC surgical constriction, eight sedentary male Sprague-Dawley IVCc rats (IVCc-SED) were compared to eight IVCc rats subjected to moderate intense endurance exercise (IVCc-MOD). Heart and kidney function was examined and renal functional reserve (RFR) was investigated by administering a high protein diet (HPD). After 12 weeks of exercise training, abdominal venous pressure, indices of body fat content, plasma cystatin C levels, and post-HPD urinary KIM-1 levels were all significantly lower in IVCc-MOD versus IVCc-SED rats (P < 0.05). RFR did not differ between both groups. The implementation of moderate intense endurance exercise in the IVCc model reduces abdominal venous pressure and is beneficial to kidney function.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

ATIIT1R:

Angiotensin II type 1 receptor

ATP:

Adenosine triphosphate

AWT:

Anterior wall thickness

BSA:

Bovine serum albumin

CO:

Cardiac output

CRP:

C-reactive protein

CVP:

Central venous pressure

EDV:

End-diastolic volume

EF:

Ejection fraction

ESV:

End-systolic volume

FENa :

Fractional excretion of sodium

G:

Gauge (needle diameter)

GFR:

Glomerular filtration rate

HPD:

High protein diet

HR:

Heart rate

IVCc:

Inferior vena cava constriction

IVCc-MOD:

IVCc rats subjected to moderate intense endurance exercise

IVCc-SED :

Sedentary IVCc rats

KIM-1:

Kidney injury molecule 1

LVEDD:

Left ventricular end-diastolic diameter

LVEDP:

Left ventricular end-diastolic pressure

LVESD:

Left ventricular end-systolic diameter

LVP:

Left ventricular pressure

NO:

Nitric oxide

PWT:

Posterior wall thickness

RFR:

Renal functional reserve

TBS-T:

Tris-buffered solution containing 0.1% Tween-20

References

  1. Adams Jr., K. F., Fonarow, G. C., Emerman, C. L., LeJemtel, T. H., Costanzo, M. R., Abraham, W. T., Berkowitz, R. L., Galvao, M., & Horton, D. P. (2005). Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). American Heart Journal, 149, 209–216.

    Article  Google Scholar 

  2. Baker, J. S., McCormick, M. C., & Robergs, R. A. (2010). Interaction among skeletal muscle metabolic energy systems during intense exercise. J Nutr Metab, 2010, 905612.

    Article  Google Scholar 

  3. Baxmann, A. C., Ahmed, M. S., Marques, N. C., Menon, V. B., Pereira, A. B., Kirsztajn, G. M., & Heilberg, I. P. (2008). Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clinical Journal of the American Society of Nephrology, 3, 348–354.

    Article  CAS  Google Scholar 

  4. Beavers, K. M., Brinkley, T. E., & Nicklas, B. J. (2010). Effect of exercise training on chronic inflammation. Clinica Chimica Acta, 411, 785–793.

    Article  CAS  Google Scholar 

  5. Cao, G., González, J., Müller, A., Ottaviano, G., Ambrosio, G., Toblli, J. E., & Milei, J. (2016). Beneficial effect of moderate exercise in kidney of rat after chronic consumption of cola drinks. PLoS One, 11, e0152461.

    Article  Google Scholar 

  6. Cops, J., Mullens, W., Verbrugge, F. H., Swennen, Q., De Moor, B., Reynders, C., Penders, J., Achten, R., Driessen, A., Dendooven, A., Rigo, J.-M., & Hansen, D. (2018a). Selective abdominal venous congestion induces adverse renal and hepatic morphological and functional alterations despite a preserved cardiac function. Scientific Reports, 8, 17757.

    Article  CAS  Google Scholar 

  7. Cops, J., Mullens, W., Verbrugge, F. H., Swennen, Q., Reynders, C., Penders, J., Rigo, J. M., & Hansen, D. (2018b). Selective abdominal venous congestion to investigate cardiorenal interactions in a rat model. PLoS One, 13, e0197687.

    Article  Google Scholar 

  8. Cops, J., Haesen, S., De Moor, B., Mullens, W., & Hansen, D. (2019a). Current animal models for the study of congestion in heart failure: an overview. Heart Failure Reviews.

  9. Cops, J., Haesen, S., De Moor, B., Mullens, W., & Hansen, D. (2019b). Exercise intervention in hospitalized heart failure patients, with emphasis on congestion-related complications: a review. Heart Failure Reviews.

  10. Damman, K., Voors, A. A., Hillege, H. L., Navis, G., Lechat, P., van Veldhuisen, D. J., & Dargie, H. J. (2010). Congestion in chronic systolic heart failure is related to renal dysfunction and increased mortality. European Journal of Heart Failure, 12, 974–982.

    Article  Google Scholar 

  11. Dupont, M., Mullens, W., & Tang, W. H. (2011). Impact of systemic venous congestion in heart failure. Current Heart Failure Reports, 8, 233–241.

    Article  Google Scholar 

  12. Erdem, A., Gundogan, N. U., Usubutun, A., Kilinc, K., Erdem, S. R., Kara, A., & Bozkurt, A. (2000). The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats. Nephrology, Dialysis, Transplantation, 15, 1175–1182.

    Article  CAS  Google Scholar 

  13. Forestieri, P., Guizilini, S., Peres, M., Bublitz, C., Bolzan, D. W., Rocco, I. S., Santos, V. B., Moreira, R. S., Breda, J. R., de Almeida, D. R., Carvalho, A. C., Arena, R., & Gomes, W. J. (2016). A cycle ergometer exercise program improves exercise capacity and inspiratory muscle function in hospitalized patients awaiting heart transplantation: a pilot study. Brazilian Journal of Cardiovascular Surgery, 31, 389–395.

    PubMed  PubMed Central  Google Scholar 

  14. Groehs, R. V., Antunes-Correa, L. M., Nobre, T. S., Alves, M. J., Rondon, M. U., Barreto, A. C., & Negrao, C. E. (2016). Muscle electrical stimulation improves neurovascular control and exercise tolerance in hospitalised advanced heart failure patients. European Journal of Preventive Cardiology, 23, 1599–1608.

    Article  Google Scholar 

  15. Heaps, C. L., & Parker, J. L. (2011). Effects of exercise training on coronary collateralization and control of collateral resistance. Journal of Applied Physiology (1985), 111, 587–598.

    Article  Google Scholar 

  16. Hedman, K., Nylander, E., Henriksson, J., Bjarnegard, N., Brudin, L., & Tamas, E. (2016). Echocardiographic characterization of the inferior vena cava in trained and untrained females. Ultrasound in Medicine and Biology, 42, 2794–2802.

    Article  Google Scholar 

  17. Howden, E. J., Fassett, R. G., Isbel, N. M., & Coombes, J. S. (2012). Exercise training in chronic kidney disease patients. Sports Medicine, 42, 473–488.

    Article  Google Scholar 

  18. Ichinose, F., Bloch, K. D., Wu, J. C., Hataishi, R., Aretz, H. T., Picard, M. H., & Scherrer-Crosbie, M. (2004). Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency. American Journal of Physiology: Heart and Circulatory Physiology, 286, H1070–H1075.

    CAS  PubMed  Google Scholar 

  19. Johansen, K. L. (2007). Exercise in the end-stage renal disease population. Journal of the American Society of Nephrology, 18, 1845–1854.

    Article  CAS  Google Scholar 

  20. Kasai, H., Tanabe, N., Koshikawa, K., Hirasawa, Y., Sugiura, T., Sakao, S., & Tatsumi, K. (2017). The development of marked collateral circulation due to inferior vena cava filter occlusion in a patient with chronic thromboembolic pulmonary hypertension complicated with anti-phospholipid syndrome. Internal Medicine, 56, 931–936.

    Article  Google Scholar 

  21. Kemi, O. J., Haram, P. M., Loennechen, J. P., Osnes, J. B., Skomedal, T., Wisloff, U., & Ellingsen, O. (2005). Moderate vs. high exercise intensity: differential effects on aerobic fitness, cardiomyocyte contractility, and endothelial function. Cardiovascular Research, 67, 161–172.

    Article  CAS  Google Scholar 

  22. Kurishima, C., Saiki, H., Masutani, S., & Senzaki, H. (2015). Tailored therapy for aggressive dilatation of systemic veins and arteries may result in improved long-term Fontan circulation. Journal of Thoracic and Cardiovascular Surgery, 150, 1367–1370.

    Article  Google Scholar 

  23. Lewinter, C., Doherty, P., Gale, C. P., Crouch, S., Stirk, L., Lewin, R. J., LeWinter, M. M., Ades, P. A., Kober, L., & Bland, J. M. (2015). Exercise-based cardiac rehabilitation in patients with heart failure: a meta-analysis of randomised controlled trials between 1999 and 2013. European Journal of Preventive Cardiology, 22, 1504–1512.

    Article  Google Scholar 

  24. Li, X., & Wang, K. (2017). Effects of moderate-intensity endurance exercise on angiotensin II and angiotensin II type I receptors in the rat heart. Molecular Medicine Reports, 16, 2439–2444.

    Article  CAS  Google Scholar 

  25. Martens, P., & Mullens, W. (2018). How to tackle congestion in acute heart failure. Korean Journal of Internal Medicine, 33, 462–473.

    Article  CAS  Google Scholar 

  26. Mingels, A., Jacobs, L., Kleijnen, V., Wodzig, W., & Dieijen-Visser, M. (2009). Cystatin C a marker for renal function after exercise. International Journal of Sports Medicine, 30, 668–671.

    Article  CAS  Google Scholar 

  27. Mullens, W., Abrahams, Z., Francis, G. S., Sokos, G., Taylor, D. O., Starling, R. C., Young, J. B., & Tang, W. H. (2009). Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. Journal of the American College of Cardiology, 53, 589–596.

    Article  Google Scholar 

  28. Nijst, P., & Mullens, W. (2014). The acute cardiorenal syndrome: burden and mechanisms of disease. Current Heart Failure Reports, 11, 453–462.

    Article  Google Scholar 

  29. O'Connor, C. M., Whellan, D. J., Lee, K. L., Keteyian, S. J., Cooper, L. S., Ellis, S. J., Leifer, E. S., Kraus, W. E., Kitzman, D. W., Blumenthal, J. A., Rendall, D. S., Miller, N. H., Fleg, J. L., Schulman, K. A., McKelvie, R. S., Zannad, F., & Pina, I. L. (2009). Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA, 301, 1439–1450.

    Article  CAS  Google Scholar 

  30. Rafiq, K., Noma, T., Fujisawa, Y., Ishihara, Y., Arai, Y., Nabi, A. H., Suzuki, F., Nagai, Y., Nakano, D., Hitomi, H., Kitada, K., Urushihara, M., Kobori, H., Kohno, M., & Nishiyama, A. (2012). Renal sympathetic denervation suppresses de novo podocyte injury and albuminuria in rats with aortic regurgitation. Circulation, 125, 1402–1413.

    Article  CAS  Google Scholar 

  31. Sabbisetti, V. S., Waikar, S. S., Antoine, D. J., Smiles, A., Wang, C., Ravisankar, A., Ito, K., Sharma, S., Ramadesikan, S., Lee, M., Briskin, R., De Jager, P. L., Ngo, T. T., Radlinski, M., Dear, J. W., Park, K. B., Betensky, R., Krolewski, A. S., & Bonventre, J. V. (2014). Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. Journal of the American Society of Nephrology, 25, 2177–2186.

    Article  CAS  Google Scholar 

  32. Siddiqui, A. (2011). Effects of vasodilation and arterial resistance on cardiac output. Journal of Clinical & Experimental Cardiology, 2.

  33. Smart, N. A., King, N., McFarlane, J. R., Graham, P. L., & Dieberg, G. (2018). Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: a systematic review and meta-analysis. British Journal of Sports Medicine, 52, 834–843.

    Article  CAS  Google Scholar 

  34. Spinelli, A., Sharma, A., Villa, G., Samoni, S., Ramponi, F., Brocca, A., Brendolan, A., Chiaramonte, S., Castellano, G., Gesualdo, L., & Ronco, C. (2017). Rationale for the evaluation of renal functional reserve in living kidney donors and recipients: a pilot study. Nephron, 135, 268–276.

    Article  CAS  Google Scholar 

  35. Stuewe, S. R., Gwirtz, P. A., & Mallet, R. T. (2001). Exercise training increases creatine kinase capacity in canine myocardium. Medicine and Science in Sports and Exercise, 33, 92–98.

    Article  CAS  Google Scholar 

  36. Tsukiyama, Y., Ito, T., Nagaoka, K., Eguchi, E., & Ogino, K. (2017). Effects of exercise training on nitric oxide, blood pressure and antioxidant enzymes. Journal of Clinical Biochemistry and Nutrition, 60, 180–186.

    Article  CAS  Google Scholar 

  37. Vaidya, V. S., Ozer, J. S., Dieterle, F., Collings, F. B., Ramirez, V., Troth, S., Muniappa, N., Thudium, D., Gerhold, D., Holder, D. J., Bobadilla, N. A., Marrer, E., Perentes, E., Cordier, A., Vonderscher, J., Maurer, G., Goering, P. L., Sistare, F. D., & Bonventre, J. V. (2010). Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nature Biotechnology, 28, 478–485.

    Article  CAS  Google Scholar 

  38. Verbrugge, F. H., Grieten, L., & Mullens, W. (2014). New insights into combinational drug therapy to manage congestion in heart failure. Current Heart Failure Reports, 11, 1–9.

    Article  CAS  Google Scholar 

  39. Wang, J., Lu, L., Wang, Y., Wu, Y., Han, J., Wang, W., Li, C., & Tu, P. (2015). Qishenyiqi dropping pill attenuates myocardial fibrosis in rats by inhibiting RAAS-mediated arachidonic acid inflammation. Journal of Ethnopharmacology, 176, 375–384.

    Article  Google Scholar 

  40. Wens I, Broekmans T, Hendriks JJA, Savelberg HH, Hesseling MK & BO E (2015). Effects of exercise intensity in experimental autoimmune encephalomyelitis. J Mult Scler 2.

  41. Zhao, Z., Liao, G., Zhou, Q., Lv, D., Holthfer, H., & Zou, H. (2016). Sulforaphane attenuates contrast-induced nephropathy in rats via Nrf2/HO-1 pathway. Oxidative Medicine and Cellular Longevity, 2016, 9825623.

    PubMed  PubMed Central  Google Scholar 

  42. Zheng, H., Li, Y. F., Zucker, I. H., & Patel, K. P. (2006). Exercise training improves renal excretory responses to acute volume expansion in rats with heart failure. American Journal of Physiology: Renal Physiology, 291, F1148–F1156.

    Article  CAS  Google Scholar 

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Acknowledgments

The authors thank Jeanine Santermans and Marc Jans for embedding tissues is paraffin and Petra Bex and Rosette Beenaerts for their skillful assistance.

Funding

J.C. is supported by BOF funding from UHasselt/BIOMED.

Author information

Author notes

  1. Wilfried Mullens and Dominique Hansen contributed equally to this work.

Authors and Affiliations

  1. BIOMED, UHasselt – Universiteit Hasselt, Agoralaan, 3590, Diepenbeek, Belgium

    Jirka Cops, Bart De Moor, Sibren Haesen, Lien Lijnen, Lieselotte Lemoine, Joris Penders, Ivo Lambrichts, Wilfried Mullens & Dominique Hansen

  2. Faculty of Medicine and Life Sciences, UHasselt – Universiteit Hasselt, Agoralaan, 3590, Diepenbeek, Belgium

    Jirka Cops & Sibren Haesen

  3. Department of Nephrology, Jessa Ziekenhuis, 3500, Hasselt, Belgium

    Bart De Moor

  4. Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, 2000, Antwerp, Belgium

    Inez Wens

  5. Department of Surgical Oncology, Ziekenhuis Oost-Limburg, 3600, Genk, Belgium

    Lieselotte Lemoine

  6. Clinical Laboratory, Ziekenhuis Oost-Limburg, 3600, Genk, Belgium

    Carmen Reynders & Joris Penders

  7. Department of Cardiology, Ziekenhuis Oost-Limburg, 3600, Genk, Belgium

    Wilfried Mullens

  8. REVAL, UHasselt – Universiteit Hasselt, Agoralaan, 3590, Diepenbeek, Belgium

    Dominique Hansen

  9. Heart Centre, Jessa Ziekenhuis, 3500, Hasselt, Belgium

    Dominique Hansen

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  1. Jirka Cops
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Corresponding author

Correspondence to Jirka Cops.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This study conforms to the EU Directive 2010/63/EU for animal experiments and was approved by the Ethical Committee for Animal Experiments of Hasselt University, Belgium (protocol number: 201757).

This article does not contain any studies with human participants.

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Associate Editor Domingo A. Pascual-Figal oversaw the review of this article

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Statement clinical relevance

This study provides relevant insight concerning the impact of moderate intense endurance exercise training on the development of abdominal venous congestion and the progression of kidney dysfunction.

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Cops, J., De Moor, B., Haesen, S. et al. Endurance Exercise Intervention Is Beneficial to Kidney Function in a Rat Model of Isolated Abdominal Venous Congestion: a Pilot Study. J. of Cardiovasc. Trans. Res. 13, 769–782 (2020). https://doi.org/10.1007/s12265-019-09947-5

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