Tubulointerstitial disease: role of ischemia and microvascular disease.
OBJECTIVE
Tubulointerstitial injury is characteristic of aging-associated renal injury and progressive renal disease. Salt-sensitive hypertension is also associated with tubulointerstitial inflammation, especially when accompanied by microvascular disease. Here we summarize recent studies on the pathogenesis and consequences of tubulointerstitial disease, emphasizing the role of ischemia and the microvasculature.


RESULTS
Tubulointerstitial injury occurs via several mechanisms of which one of the most important is chronic ischemia. Recent studies suggest that chronic vasoconstriction may contribute to the renal injury associated with angiotensin II, catecholamines, nitric oxide inhibition, hypokalemia, hyperuricemia, and cyclosporine nephropathy. Salt-sensitivity may result as a consequence of the tubulointerstitial inflammatory response to these conditions, and this appears to be perpetuated by the development of preglomerular vascular disease. With progression of tubulointerstitial disease there is also a loss of peritubular capillaries, and stimulating microvascular growth with angiogenic factors can stabilize renal function in these models.


CONCLUSIONS
Ischemia secondary to vasoconstriction or to structural changes of the renal vasculature may have important consequences both in terms of mediating salt-sensitive hypertension and renal progression. Angiogenic factors may have potential benefit in preventing or treating these conditions.
Nakagawa
Takahiko
T
Division of Nephrology, Baylor College of Medicine, Houston, Texas 77030, USA. takahiko@bcm.tmc.edu
Kang
Duk-Hee
DH
Ohashi
Ryuji
R
Suga
Shin-ichi
S
Herrera-Acosta
Jaime
J
Rodriguez-Iturbe
Bernardo
B
Johnson
Richard J
RJ
D000818:Animals; D006801:Humans; D007511:Ischemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D009395:Nephritis, Interstitial / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D014652:Vascular Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D014661:Vasoconstriction