Tissue Histopathologic Injury in Renovascular Occlusive Disease

  • Monika L. GloviczkiEmail author
  • Stephen C. Textor


Many histopathologic findings within post-stenotic kidneys are nonspecific and represent conditions associated with aging, atherosclerosis and pre-existing hypertension. Two major abnormalities reported in patients with renovascular disease (RVD) are arteriolar nephrosclerosis and atheroembolic renal lesions. Other chronic renal “ischemia” markers include tubular atrophy, interstitial fibrosis and arteriolar sclerosis, but are less specific.

Recent data demonstrate that intra-renal oxygenation in renovascular disease (RVD) is affected in a patchy way and produces local alterations that can ultimately lead to irreversible tissue damage. Moreover, kidney injury has the tendency for progressive deterioration even after the primary causal factor is eliminated.

Transvenous or transjugular renal biopsy, requiring retrograde access through the venous system, was recently proposed as an alternative for patients with contraindications for percutaneous biopsy. This technique was used in a prospective study to examine histopathologic changes in biopsies from kidneys with moderate unilateral renal artery stenosis, compared with renal tissue specimens from normal kidney donors, and nephrectomy samples for total vascular occlusion. Tissue from affected kidneys has provided evidence for complex injury pathways in atherosclerotic RVD that include activation of Transforming Growth Factor-β (TGF- β) and accumulation of tissue macrophages in addition to progressive interstitial fibrosis. These data support a transition from a hemodynamic disorder to one with inflammatory and fibrotic injury that does not reverse entirely with restoration of blood flow alone.

Direct examination of kidney tissue obtained by biopsy might contribute to both understand the disease process and to identify those individuals likely to benefit (or not) from measures to restore blood flow or other treatment modalities.


Renovascular disease Kidney biopsy Ischemic nephropathy Arteriolar nephrosclerosis Atheroembolic renal lesions Tubular atrophy Interstitial fibrosis Arteriolar sclerosis 


  1. 1.
    Novick AC, Scoble JGH, editors. Renal vascular disease. London: WB Saunder Company Ltd; 1996.Google Scholar
  2. 2.
    Stewart BH, Dustan HP, Kiser WS, Meaney TF, Straffon RA, McCormack LJ. Correlation of angiography and natural history in evaluation of patients with renovascular hypertension. J Urol. 1970;104:231–8.PubMedGoogle Scholar
  3. 3.
    Schreiber MJ, Pohl MA, Novick AC. The natural history of atherosclerotic and fibrous renal artery disease. Urol Clin North Am. 1984;11:383–92.PubMedGoogle Scholar
  4. 4.
    Tollefson DF, Ernst CB. Natural history of atherosclerotic renal artery stenosis associated with aortic disease. J Vasc Surg. 1991;14:327–31.PubMedCrossRefGoogle Scholar
  5. 5.
    Zierler RE, Bergelin RO, Isaacson JA, Strandness Jr DE. Natural history of atherosclerotic renal artery stenosis: a prospective study with duplex ultrasonography. J Vasc Surg. 1994;19:250–7; discussion 7–8.PubMedCrossRefGoogle Scholar
  6. 6.
    de Mast Q, Beutler JJ. The prevalence of atherosclerotic renal artery stenosis in risk groups: a systematic literature review. J Hypertens. 2009;27:1333–40.PubMedCrossRefGoogle Scholar
  7. 7.
    Harding MB, Smith LR, Himmelstein SI, et al. Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization. J Am Soc Nephrol. 1992;2:1608–16.PubMedGoogle Scholar
  8. 8.
    Corradi B, Malberti F, Farina M, et al. Chronic renal failure due to atheromatous renovascular disease in the elderly. Contrib Nephrol. 1993;105:167–71.PubMedGoogle Scholar
  9. 9.
    Lerman LO, Textor SC, Grande JP. Mechanisms of tissue injury in renal artery stenosis: ischemia and beyond. Prog Cardiovasc Dis. 2009;52:196–203.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Novick AC, Ziegelbaum M, Vidt DG, Gifford Jr RW, Pohl MA, Goormastic M. Trends in surgical revascularization for renal artery disease. Ten years’ experience. JAMA. 1987;257:498–501.PubMedCrossRefGoogle Scholar
  11. 11.
    Zinman L, Libertino JA. Revascularization of the chronic totally occluded renal artery with restoration of renal function. J Urol. 1977;118:517–21.PubMedGoogle Scholar
  12. 12.
    Schefft P, Novick AC, Stewart BH, Straffon RA. Renal revascularization in patients with total occlusion of the renal artery. J Urol. 1980;124:184–6.PubMedGoogle Scholar
  13. 13.
    Dean RH, Tribble RW, Hansen KJ, O’Neil E, Craven TE, Redding 2nd JF. Evolution of renal insufficiency in ischemic nephropathy. Ann Surg. 1991;213:446–55; discussion 55–6.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Gloviczki ML, Lerman LO, Textor SC. Blood oxygen level-dependent (BOLD) MRI in renovascular hypertension. Curr Hypertens Rep. 2011;13:370–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Wright JR, Duggal A, Thomas R, Reeve R, Roberts IS, Kalra PA. Clinicopathological correlation in biopsy-proven atherosclerotic nephropathy: implications for renal functional outcome in atherosclerotic renovascular disease. Nephrol Dial Transplant. 2001;16:765–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Lopez-Novoa JM, Rodriguez-Pena AB, Ortiz A, Martinez-Salgado C, Lopez Hernandez FJ. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: clinical implications. J Transl Med. 2011;9:13.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Moran K, Mulhall J, Kelly D, et al. Morphological changes and alterations in regional intrarenal blood flow induced by graded renal ischemia. J Urol. 1992;148:463–6.PubMedGoogle Scholar
  18. 18.
    Eddy AA. Interstitial fibrosis in hypercholesterolemic rats: role of oxidation, matrix synthesis, and proteolytic cascades. Kidney Int. 1998;53:1182–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Wu XQ, Kong X, Zhou Y, Huang K, Yang JR, Li XL. Sesamin exerts renoprotective effects by enhancing NO bioactivity in renovascular hypertensive rats fed with high-fat-sucrose diet. Eur J Pharmacol. 2012;683:231–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Cheng J, Zhou W, Warner GM, et al. Temporal analysis of signaling pathways activated in a murine model of two-kidney, one-clip hypertension. Am J Physiol Renal Physiol. 2009;297:F1055–68.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Warner GM, Cheng J, Knudsen BE, et al. Genetic deficiency of Smad3 protects the kidneys from atrophy and interstitial fibrosis in 2K1C hypertension. Am J Physiol Renal Physiol. 2012;302:F1455–64.PubMedCentralPubMedCrossRefGoogle Scholar
  22. 22.
    Chade AR, Rodriguez-Porcel M, Grande JP, et al. Mechanisms of renal structural alterations in combined hypercholesterolemia and renal artery stenosis. Arterioscler Thromb Vasc Biol. 2003;23:1295–301.PubMedCrossRefGoogle Scholar
  23. 23.
    Chade AR, Rodriguez-Porcel M, Herrmann J, et al. Antioxidant intervention blunts renal injury in experimental renovascular disease. J Am Soc Nephrol. 2004;15:958–66.PubMedCrossRefGoogle Scholar
  24. 24.
    Favreau F, Zhu XY, Krier JD, et al. Revascularization of swine renal artery stenosis improves renal function but not the changes in vascular structure. Kidney Int. 2010;78:1110–8.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Keddis MT, Garovic VD, Bailey KR, Wood CM, Raissian Y, Grande JP. Ischaemic nephropathy secondary to atherosclerotic renal artery stenosis: clinical and histopathological correlates. Nephrol Dial Transplant. 2010;25:3615–22.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Silkensen JR, Kasiske BL, editors. Laboratory assessment of renal disease: clearance, urinalysis, and renal biopsy. 7th ed. Philadelphia: Saunders; 2004.Google Scholar
  27. 27.
    Voss DM, Lynn KL. Percutaneous renal biopsy: an audit of a 2 year experience with the Biopty gun. N Z Med J. 1995;108:8–10.PubMedGoogle Scholar
  28. 28.
    Fraser IR, Fairley KF. Renal biopsy as an outpatient procedure. Am J Kidney Dis. 1995;25:876–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Burstein DM, Schwartz MM, Korbet SM. Percutaneous renal biopsy with the use of real-time ultrasound. Am J Nephrol. 1991;11:195–200.PubMedCrossRefGoogle Scholar
  30. 30.
    Burstein DM, Korbet SM, Schwartz MM. The use of the automatic core biopsy system in percutaneous renal biopsies: a comparative study. Am J Kidney Dis. 1993;22:545–52.PubMedGoogle Scholar
  31. 31.
    Parrish AE. Complications of percutaneous renal biopsy: a review of 37 years’ experience. Clin Nephrol. 1992;38:135–41.PubMedGoogle Scholar
  32. 32.
    Mal F, Meyrier A, Callard P, et al. Transjugular renal biopsy. Lancet. 1990;335:1512–3.PubMedCrossRefGoogle Scholar
  33. 33.
    Lakin PC, Pavcnik D, Bloch RD, et al. Percutaneous transjugular kidney biopsy in swine with use of a side-cutting needle with a blunt-tipped stylet. J Vasc Interv Radiol. 1999;10:1229–32.PubMedCrossRefGoogle Scholar
  34. 34.
    Cluzel P, Martinez F, Bellin MF, et al. Transjugular versus percutaneous renal biopsy for the diagnosis of parenchymal disease: comparison of sampling effectiveness and complications. Radiology. 2000;215:689–93.PubMedCrossRefGoogle Scholar
  35. 35.
    Rychlik I, Petrtyl J, Tesar V, Stejskalova A, Zabka J, Bruha R. Transjugular renal biopsy. Our experience with 67 cases. Kidney Blood Press Res. 2001;24:207–12.PubMedCrossRefGoogle Scholar
  36. 36.
    Misra S, Gyamlani G, Swaminathan S, et al. Safety and diagnostic yield of transjugular renal biopsy. J Vasc Interv Radiol. 2008;19:546–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Levi IM, Ben-Dov IZ, Klimov A, Pizov G, Bloom AI. Transjugular kidney biopsy: enabling safe tissue diagnosis in high risk patients. Isr Med Assoc J. 2011;13:425–7.PubMedGoogle Scholar
  38. 38.
    Ahmed MS, Patel A, Borge MA, Picken MM, Leehey DJ. Simultaneous transjugular renal biopsy and hemodialysis catheter placement in patients with ARF. Am J Kidney Dis. 2004;44:429–36.PubMedCrossRefGoogle Scholar
  39. 39.
    Lefaucheur C, Nochy D, Bariety J. Renal biopsy: procedures, contraindications, complications. Nephrol Ther. 2009;5:331–9.PubMedCrossRefGoogle Scholar
  40. 40.
    See TC, Thompson BC, Howie AJ, et al. Transjugular renal biopsy: our experience and technical considerations. Cardiovasc Intervent Radiol. 2008;31:906–18.PubMedCrossRefGoogle Scholar
  41. 41.
    Sarabu N, Maddukuri G, Munikrishnappa D, et al. Safety and efficacy of transjugular renal biopsy performed by interventional nephrologists. Semin Dial. 2011;24:343–8.PubMedCrossRefGoogle Scholar
  42. 42.
    Wickre CG, Major JL, Wolfson M. Perinephric abscess: an unusual late infectious complication of renal biopsy. Ann Clin Lab Sci. 1982;12:453–4.PubMedGoogle Scholar
  43. 43.
    Ginsburg JC, Fransman SL, Singer MA, Cohanim M, Morrin PA. Use of computerized tomography to evaluate bleeding after renal biopsy. Nephron. 1980;26:240–3.PubMedCrossRefGoogle Scholar
  44. 44.
    Alter AJ, Zimmerman S, Kirachaiwanich C. Computerized tomographic assessment of retroperitoneal hemorrhage after percutaneous renal biopsy. Arch Intern Med. 1980;140:1323–6.PubMedCrossRefGoogle Scholar
  45. 45.
    Gloviczki ML, Glockner JF, Lerman LO, et al. Preserved oxygenation despite reduced blood flow in poststenotic kidneys in human atherosclerotic renal artery stenosis. Hypertension. 2010;55:961–6.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Gloviczki ML, Glockner JF, Crane JA, et al. Blood oxygen level-dependent magnetic resonance imaging identifies cortical hypoxia in severe renovascular disease. Hypertension. 2011;58:1066–72.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Gloviczki ML, Keddis MT, Garovic VD, et al. TGF expression and macrophage accumulation in atherosclerotic renal artery stenosis. Clin J Am Soc Nephrol. 2013;8(4):546–53.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Eirin A, Gloviczki ML, Tang H, et al. Inflammatory and injury signals released from the post-stenotic human kidney. Eur Heart J. 2013;34:540–8a.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2014

Authors and Affiliations

  1. 1.Division of Nephrology and HypertensionMayo ClinicRochesterUSA
  2. 2.Division of Nephrology and HypertensionMayo Clinic College of MedicineRochesterUSA

Personalised recommendations