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Pulmonary Hypertension in CKD: A New Problem Child

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Cardio-Renal Clinical Challenges

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Abstract

Pulmonary hypertension (PH) is prevalent in chronic kidney disease (CKD) patients, particularly in those on chronic hemodialysis treatment. Concomitant diseases and several CKD-specific risk factors, including the presence of artero-venous fistula, fluid overload, sleep breathing disorders and the exposure to dialysis membranes, can be implicated at various level in the genesis of PH in the CKD population. PH in CKD is a potentially reversible process because it may regress after kidney transplantation. In small cohort studies on stage 5 CKD pre-dialysis and dialysis patients, PH was associated with a higher risk of death. Large prospective studies adopting well standardized criteria of pulmonary artery pressure measurement, such as right heart catheterization, are needed to clarify the risk of PH in earlier CKD stages. Clinical trials are eagerly awaited to define the optimal therapeutic management of CKD patients with PH.

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References

  1. Naeije R. Physiology of the pulmonary circulation and the right heart. Curr Hypertens Rep. 2013;15(6):623–31.

    Article  CAS  PubMed  Google Scholar 

  2. Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, et al. Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S55–66.

    Article  PubMed  Google Scholar 

  3. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr. 2010;23(7):685–713; quiz 86–8.

    Article  PubMed  Google Scholar 

  4. Berger M, Haimowitz A, Van Tosh A, Berdoff RL, Goldberg E. Quantitative assessment of pulmonary hypertension in patients with tricuspid regurgitation using continuous wave Doppler ultrasound. J Am Coll Cardiol. 1985;6(2):359–65.

    Article  CAS  PubMed  Google Scholar 

  5. Himelman RB, Struve SN, Brown JK, Namnum P, Schiller NB. Improved recognition of cor pulmonale in patients with severe chronic obstructive pulmonary disease. Am J Med. 1988;84(5):891–8.

    Article  CAS  PubMed  Google Scholar 

  6. Fisher MR, Forfia PR, Chamera E, Housten-Harris T, Champion HC, Girgis RE, et al. Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension. Am J Respir Crit Care Med. 2009;179(7):615–21.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S43–54.

    Article  PubMed  Google Scholar 

  8. McGlothlin D. Classification of pulmonary hypertension. Heart Fail Clin. 2012;8(3):301–17.

    Article  PubMed  Google Scholar 

  9. Lam CS, Borlaug BA, Kane GC, Enders FT, Rodeheffer RJ, Redfield MM. Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation. 2009;119(20):2663–70.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Friedman WF. Proceedings of National Heart, Lung, and Blood Institute pediatric cardiology workshop: pulmonary hypertension. Pediatr Res. 1986;20(9):811–24.

    Article  CAS  PubMed  Google Scholar 

  11. Kessler R, Chaouat A, Weitzenblum E, Oswald M, Ehrhart M, Apprill M, et al. Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences. Eur Respir J. 1996;9(4):787–94.

    Article  CAS  PubMed  Google Scholar 

  12. Hachulla E, Gressin V, Guillevin L, Carpentier P, Diot E, Sibilia J, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52(12):3792–800.

    Article  PubMed  Google Scholar 

  13. Mukerjee D, St George D, Coleiro B, Knight C, Denton CP, Davar J, et al. Prevalence and outcome in systemic sclerosis associated pulmonary arterial hypertension: application of a registry approach. Ann Rheum Dis. 2003;62(11):1088–93.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Hadengue A, Benhayoun MK, Lebrec D, Benhamou JP. Pulmonary hypertension complicating portal hypertension: prevalence and relation to splanchnic hemodynamics. Gastroenterology. 1991;100(2):520–8.

    CAS  PubMed  Google Scholar 

  15. Krowka MJ, Swanson KL, Frantz RP, McGoon MD, Wiesner RH. Portopulmonary hypertension: results from a 10-year screening algorithm. Hepatology. 2006;44(6):1502–10.

    Article  PubMed  Google Scholar 

  16. Pabst S, Hammerstingl C, Hundt F, Gerhardt T, Grohe C, Nickenig G, et al. Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study. PLoS One. 2012;7(4):e35310.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Yigla M, Fruchter O, Aharonson D, Yanay N, Reisner SA, Lewin M, et al. Pulmonary hypertension is an independent predictor of mortality in hemodialysis patients. Kidney Int. 2009;75(9):969–75.

    Article  PubMed  Google Scholar 

  18. Nakhoul F, Yigla M, Gilman R, Reisner SA, Abassi Z. The pathogenesis of pulmonary hypertension in haemodialysis patients via arterio-venous access. Nephrol Dial Transplant. 2005;20(8):1686–92.

    Article  CAS  PubMed  Google Scholar 

  19. Issa N, Krowka MJ, Griffin MD, Hickson LJ, Stegall MD, Cosio FG. Pulmonary hypertension is associated with reduced patient survival after kidney transplantation. Transplantation. 2008;86(10):1384–8.

    Article  PubMed  Google Scholar 

  20. Abdelwhab S, Elshinnawy S. Pulmonary hypertension in chronic renal failure patients. Am J Nephrol. 2008;28(6):990–7.

    Article  CAS  PubMed  Google Scholar 

  21. Yigla M, Nakhoul F, Sabag A, Tov N, Gorevich B, Abassi Z, et al. Pulmonary hypertension in patients with end-stage renal disease. Chest. 2003;123(5):1577–82.

    Article  PubMed  Google Scholar 

  22. Havlucu Y, Kursat S, Ekmekci C, Celik P, Serter S, Bayturan O, et al. Pulmonary hypertension in patients with chronic renal failure. Respiration. 2007;74(5):503–10.

    Article  CAS  PubMed  Google Scholar 

  23. Bozbas SS, Akcay S, Altin C, Bozbas H, Karacaglar E, Kanyilmaz S, et al. Pulmonary hypertension in patients with end-stage renal disease undergoing renal transplantation. Transplant Proc. 2009;41(7):2753–6.

    Article  CAS  PubMed  Google Scholar 

  24. Yigla M, Keidar Z, Safadi I, Tov N, Reisner SA, Nakhoul F. Pulmonary calcification in hemodialysis patients: correlation with pulmonary artery pressure values. Kidney Int. 2004;66(2):806–10.

    Article  PubMed  Google Scholar 

  25. Amin M, Fawzy A, Hamid MA, Elhendy A. Pulmonary hypertension in patients with chronic renal failure: role of parathyroid hormone and pulmonary artery calcifications. Chest. 2003;124(6):2093–7.

    Article  PubMed  Google Scholar 

  26. Tarrass F, Benjelloun M, Medkouri G, Hachim K, Benghanem MG, Ramdani B. Doppler echocardiograph evaluation of pulmonary hypertension in patients undergoing hemodialysis. Hemodial Int. 2006;10(4):356–9.

    Article  PubMed  Google Scholar 

  27. Mahdavi-Mazdeh M, Alijavad-Mousavi S, Yahyazadeh H, Azadi M, Yoosefnejad H, Ataiipoor Y. Pulmonary hypertension in hemodialysis patients. Saudi J Kidney Dis Transpl. 2008;19(2):189–93.

    PubMed  Google Scholar 

  28. Etemadi J, Zolfaghari H, Firoozi R, Ardalan MR, Toufan M, Shoja MM, et al. Unexplained pulmonary hypertension in peritoneal dialysis and hemodialysis patients. Rev Port Pneumol. 2012;18(1):10–4.

    Article  CAS  PubMed  Google Scholar 

  29. Unal A, Sipahioglu M, Oguz F, Kaya M, Kucuk H, Tokgoz B, et al. Pulmonary hypertension in peritoneal dialysis patients: prevalence and risk factors. Perit Dial Int. 2009;29(2):191–8.

    PubMed  Google Scholar 

  30. Casas-Aparicio G, Castillo-Martinez L, Orea-Tejeda A, Abasta-Jimenez M, Keirns-Davies C, Rebollar-Gonzalez V. The effect of successful kidney transplantation on ventricular dysfunction and pulmonary hypertension. Transplant Proc. 2010;42(9):3524–8.

    Article  CAS  PubMed  Google Scholar 

  31. Fabbian F, Cantelli S, Molino C, Pala M, Longhini C, Portaluppi F. Pulmonary hypertension in dialysis patients: a cross-sectional Italian study. Int J Nephrol. 2011;2011:283475.

    Article  PubMed Central  Google Scholar 

  32. Zlotnick DM, Axelrod DA, Chobanian MC, Friedman S, Brown J, Catherwood E, et al. Non-invasive detection of pulmonary hypertension prior to renal transplantation is a predictor of increased risk for early graft dysfunction. Nephrol Dial Transplant. 2010;25(9):3090–6.

    Article  PubMed  Google Scholar 

  33. Kumbar L, Fein PA, Rafiq MA, Borawski C, Chattopadhyay J, Avram MM. Pulmonary hypertension in peritoneal dialysis patients. Adv Perit Dial. 2007;23:127–31.

    CAS  PubMed  Google Scholar 

  34. Agarwal R. Prevalence, determinants and prognosis of pulmonary hypertension among hemodialysis patients. Nephrol Dial Transplant. 2012;27(10):3908–14.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Kiykim AA, Horoz M, Ozcan T, Yildiz I, Sari S, Genctoy G. Pulmonary hypertension in hemodialysis patients without arteriovenous fistula: the effect of dialyzer composition. Ren Fail. 2010;32(10):1148–52.

    Article  CAS  PubMed  Google Scholar 

  36. Li Z, Liu S, Liang X, Wang W, Fei H, Hu P, et al. Pulmonary hypertension as an independent predictor of cardiovascular mortality and events in hemodialysis patients. Int Urol Nephrol. 2014;46(1):141–9.

    Article  PubMed  Google Scholar 

  37. Ramasubbu K, Deswal A, Herdejurgen C, Aguilar D, Frost AE. A prospective echocardiographic evaluation of pulmonary hypertension in chronic hemodialysis patients in the United States: prevalence and clinical significance. Int J Gen Med. 2010;3:279–86.

    PubMed Central  PubMed  Google Scholar 

  38. Abassi Z, Nakhoul F, Khankin E, Reisner SA, Yigla M. Pulmonary hypertension in chronic dialysis patients with arteriovenous fistula: pathogenesis and therapeutic prospective. Curr Opin Nephrol Hypertens. 2006;15(4):353–60.

    Article  CAS  PubMed  Google Scholar 

  39. Clarkson MR, Giblin L, Brown A, Little D, Donohoe J. Reversal of pulmonary hypertension after ligation of a brachiocephalic arteriovenous fistula. Am J Kidney Dis. 2002;40(3):E8.

    Article  PubMed  Google Scholar 

  40. Giaid A. Nitric oxide and endothelin-1 in pulmonary hypertension. Chest. 1998;114(3 Suppl):208S–12.

    Article  CAS  PubMed  Google Scholar 

  41. Zoccali C. The endothelium as a target in renal diseases. J Nephrol. 2007;20 Suppl 12:S39–44.

    CAS  PubMed  Google Scholar 

  42. Arrigoni FI, Vallance P, Haworth SG, Leiper JM. Metabolism of asymmetric dimethylarginines is regulated in the lung developmentally and with pulmonary hypertension induced by hypobaric hypoxia. Circulation. 2003;107(8):1195–201.

    Article  CAS  PubMed  Google Scholar 

  43. Sasaki A, Doi S, Mizutani S, Azuma H. Roles of accumulated endogenous nitric oxide synthase inhibitors, enhanced arginase activity, and attenuated nitric oxide synthase activity in endothelial cells for pulmonary hypertension in rats. Am J Physiol Lung Cell Mol Physiol. 2007;292(6):L1480. 7.

    Article  CAS  PubMed  Google Scholar 

  44. Kielstein JT, Bode-Boger SM, Hesse G, Martens-Lobenhoffer J, Takacs A, Fliser D, et al. Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol. 2005;25(7):1414–8.

    Article  CAS  PubMed  Google Scholar 

  45. Zoccali C, Bode-Boger S, Mallamaci F, Benedetto F, Tripepi G, Malatino L, et al. Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study. Lancet. 2001;358(9299):2113–7.

    Article  CAS  PubMed  Google Scholar 

  46. Sakaguchi Y, Shoji T, Kawabata H, Niihata K, Suzuki A, Kaneko T, et al. High prevalence of obstructive sleep apnea and its association with renal function among nondialysis chronic kidney disease patients in Japan: a cross-sectional study. Clin J Am Soc Nephrol. 2011;6(5):995–1000.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Zoccali C, Mallamaci F, Tripepi G. Nocturnal hypoxemia predicts incident cardiovascular complications in dialysis patients. J Am Soc Nephrol. 2002;13(3):729–33.

    PubMed  Google Scholar 

  48. Ressl J, Urbanova D, Widimsky J, Ostadal B, Pelouch V, Prochazka J. Reversibility of pulmonary hypertension and right ventricular hypertrophy induced by intermittent high altitude hypoxia in rats. Respiration. 1974;31(1):38–46.

    Article  CAS  PubMed  Google Scholar 

  49. Ward JP, McMurtry IF. Mechanisms of hypoxic pulmonary vasoconstriction and their roles in pulmonary hypertension: new findings for an old problem. Curr Opin Pharmacol. 2009;9(3):287–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Sica AL, Greenberg HE, Ruggiero DA, Scharf SM. Chronic-intermittent hypoxia: a model of sympathetic activation in the rat. Respir Physiol. 2000;121(2–3):173–84.

    Article  CAS  PubMed  Google Scholar 

  51. Barcelo A, de la Pena M, Ayllon O, Vega-Agapito MV, Pierola J, Perez G, et al. Increased plasma levels of asymmetric dimethylarginine and soluble CD40 ligand in patients with sleep apnea. Respiration. 2009;77(1):85–90.

    Article  CAS  PubMed  Google Scholar 

  52. Grassi G, Seravalle G, Ghiadoni L, Tripepi G, Bruno RM, Mancia G, et al. Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(11):2620–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Mallamaci F, Tripepi G, Maas R, Malatino L, Boger R, Zoccali C. Analysis of the relationship between norepinephrine and asymmetric dimethyl arginine levels among patients with end-stage renal disease. J Am Soc Nephrol. 2004;15(2):435–41.

    Article  CAS  PubMed  Google Scholar 

  54. Tripepi G, Mattace Raso F, Sijbrands E, Seck MS, Maas R, Boger R, et al. Inflammation and asymmetric dimethylarginine for predicting death and cardiovascular events in ESRD patients. Clin J Am Soc Nephrol. 2011;6(7):1714–21.

    Article  CAS  PubMed  Google Scholar 

  55. Craddock PR, Fehr J, Brigham KL, Kronenberg RS, Jacob HS. Complement and leukocyte-mediated pulmonary dysfunction in hemodialysis. N Engl J Med. 1977;296(14):769–74.

    Article  CAS  PubMed  Google Scholar 

  56. Yigla M, Abassi Z, Reisner SA, Nakhoul F. Pulmonary hypertension in hemodialysis patients: an unrecognized threat. Semin Dial. 2006;19(5):353–7.

    Article  PubMed  Google Scholar 

  57. Buemi M, Senatore M, Gallo GC, Crasci E, Campo S, Sturiale A, et al. Pulmonary hypertension and erythropoietin. Kidney Blood Press Res. 2007;30(4):248–52.

    Article  CAS  PubMed  Google Scholar 

  58. Nitta K, Akiba T, Uchida K, Kawashima A, Yumura W, Kabaya T, et al. The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. Am J Kidney Dis. 2003;42(2):303–9.

    Article  CAS  PubMed  Google Scholar 

  59. Akmal M, Barndt RR, Ansari AN, Mohler JG, Massry SG. Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy. Kidney Int. 1995;47(1):158–63.

    Article  CAS  PubMed  Google Scholar 

  60. Hyduk A, Croft JB, Ayala C, Zheng K, Zheng ZJ, Mensah GA. Pulmonary hypertension surveillance–United States, 1980–2002. Morb Mortal Wkly Rep Surveill Summ. 2005;54(5):1–28.

    Google Scholar 

  61. Shah SJ, Thenappan T, Rich S, Tian L, Archer SL, Gomberg-Maitland M. Association of serum creatinine with abnormal hemodynamics and mortality in pulmonary arterial hypertension. Circulation. 2008;117(19):2475–83.

    Article  CAS  PubMed  Google Scholar 

  62. Fares WH, Trow TK. Targeted approaches to the treatment of pulmonary hypertension. Ther Adv Respir Dis. 2012;6(3):147–59.

    Article  CAS  PubMed  Google Scholar 

  63. Barst RJ, Gibbs JS, Ghofrani HA, Hoeper MM, McLaughlin VV, Rubin LJ, et al. Updated evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54(1 Suppl):S78–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Redolfi S, Arnulf I, Pottier M, Bradley TD, Similowski T. Effects of venous compression of the legs on overnight rostral fluid shift and obstructive sleep apnea. Respir Physiol Neurobiol. 2011;175(3):390–3.

    Article  PubMed  Google Scholar 

  65. Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;344(2):102–7.

    Article  CAS  PubMed  Google Scholar 

  66. Tang SC, Lam B, Lai AS, Pang CB, Tso WK, Khong PL, et al. Improvement in sleep apnea during nocturnal peritoneal dialysis is associated with reduced airway congestion and better uremic clearance. Clin J Am Soc Nephrol. 2009;4(2):410–8.

    Article  PubMed Central  PubMed  Google Scholar 

  67. Califf RM, Adams KF, McKenna WJ, Gheorghiade M, Uretsky BF, McNulty SE, et al. A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST). Am Heart J. 1997;134(1):44–54.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. CNR, Institute of Clinical Physiology, c/o Ospedali Riuniti, Via Vallone Petrara SNC, 89100, Reggio Calabria, Italy

    Davide Bolignano MD

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Correspondence to Davide Bolignano MD .

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  1. Renal and Transplantation Department, Guy's Hospital, London, United Kingdom

    David Goldsmith

  2. Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania

    Adrian Covic

  3. Karolinska Institutet Danderyd University Hospital, Stockholm, Sweden

    Jonas Spaak

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Bolignano, D. (2015). Pulmonary Hypertension in CKD: A New Problem Child. In: Goldsmith, D., Covic, A., Spaak, J. (eds) Cardio-Renal Clinical Challenges. Springer, Cham. https://doi.org/10.1007/978-3-319-09162-4_14

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