Abstract
Several investigators have reported chymase-positive mast cells in tubulointerstitial damage. However, the significance of the presence of chymase in the pathophysiology of renal diseases is unclear. We investigated relationships among chymase, renal damage, and intra-renal circulation. The participant pool consisted of 52 patients with immunoglobulin A (IgA) nephropathy who underwent renal biopsy. Of these, 18 were examined before and 2 months after the initiation of treatment with prednisolone alone (n=9) or combined with the angiotensin II receptor blocker valsartan (n=9). Biopsied renal specimens were evaluated, and the degree of renal circulation (resistive index; RI) was calculated by measuring flow velocity using Doppler sonography. The number of chymase-positive mast cells as visualized by immunohistochemical staining correlated significantly with both tubulointerstitial damage (ρ = 0.69, p < 0.001) and RI (r = 0.52, p<0.001). Treatment with prednisolone combined with valsartan effectively decreased both chymase-positive mast cells and RI, displaying a significant correlation between these biomarkers (ρ = 0.85, p = 0.016). However, no such effect was observed with prednisolone alone. The severity of tubulointerstitial damage and the degree of proteinuria were similar in both treatment groups throughout the study term. We concluded that the presence of chymase-positive mast cells and the associated decrease in renal circulation corresponded to disease progression in IgA nephropathy. Combination therapy using prednisolone and valsartan may lead to improvements in intra-renal circulation and to interference in the recruitment of chymasepositive mast cells.
Similar content being viewed by others
Article PDF
References
Ruger BM, Hasan Q, Greenhill NS, avis PF, Dunbar PR, Neale TJ : Mast cells and type VIII collagen in human diabetic nephropathy. Diabetologia 1996; 39: 1215–1222.
Ehara T, Shigematsu H : Contribution of mast cells to the tubulointerstitial lesions in IgA nephritis. Kidney Int 1998; 54: 1675–1683.
Hiromura K, Kurosawa M, Yano S, Naruse T : Tubulointerstitial mast cell infiltration in glomerulonephritis. Am J Kidney Dis 1998; 32: 593–599.
Toth T, Toth-Jakatics R, Jimi S, Ihara M, Urata H, Takebayashi S : Mast cells in rapidly progressive glomerulonephritis. J Am Soc Nephrol 1999; 10: 1498–1505.
Yamada M, Ueda M, Naruko T, et al: Mast cell chymase expression and mast cell phenotypes in human rejected kidneys. Kidney Int 2001; 59: 1374–1381.
Tokuyama H, Hayashi K, Matsuda H, et al: Differential regulation of elevated renal angiotensin II in chronic renal ischemia. Hypertension 2002; 40: 34–40.
Morikawa T, Imanishi M, Suzuki H, et al: Mast cell chymase in the ischemic kidney of severe unilateral renovascular hypertension. Am J Kidney Dis 2005; 45: e45–e50.
Fine LG, Bandyopadhay D, Norman JT : Is there a common mechanism for the progression of different types of renal diseases other than proteinuria? Towards the unifying theme of chronic hypoxia. Kidney Int Suppl 2000; 75: S22–S26.
Thomas SE, Anderson S, Gordon KL, Oyama TT, Shankland SJ, Johnson RJ : Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia. J Am Soc Nephrol 1998; 9: 231–242.
Jacobson HR : Chronic renal failure: pathophysiology. Lancet 1991; 338: 419–423.
Bohle A, Muller GA, Wehrmann M, Mackensen-Haen S, Xiao JC : Pathogenesis of chronic renal failure in the primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides. Kidney Int Suppl 1996; 54: S2–S9.
Konishi Y, Morikawa T, Yasu T, et al: Blunted response of the renin-angiotensin system and nitric oxide synthesis related to sodium sensitivity in immunoglobulin A nephropathy. Hypertens Res 2004; 27: 7–13.
Tublin ME, Bude RO, Platt JF : The resistive index in renal Doppler sonography: where do we stand? AJR Am J Roentgenol 2003; 180: 885–892 ( Review).
Mostbeck GH, Kain R, Mallek R, et al: Duplex Doppler sonography in renal parenchymal disease. Histopathologic correlation. J Ultrasound Med 1991; 10: 189–194.
Huang XR, Chen WY, Truong LD, Lan HY : Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II–mediated diabetic renal and vascular disease. J Am Soc Nephrol 2003; 14: 1738–1747.
Murphy ME, Tublin ME : Understanding the Doppler RI: impact of renal arterial distensibility on the RI in a hydronephrotic ex vivo rabbit kidney model. J Ultrasound Med 2000; 19: 303–314.
Church MK, Levi-Schaffer F : The human mast cell. J Allergy Clin Immunol 1997; 99: 155–160.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Konishi, Y., Morikawa, T., Okada, N. et al. Evidence for Abundant Presence of Chymase-Positive Mast Cells in the Kidneys of Patients with Immunoglobulin A Nephropathy: Effect of Combination Therapy with Prednisolone and Angiotensin II Receptor Blocker Valsartan. Hypertens Res 31, 1517–1524 (2008). https://doi.org/10.1291/hypres.31.1517
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1291/hypres.31.1517