Capillary rarefaction: a missing link in renal and cardiovascular disease?

Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular morbidity and mortality. Capillary rarefaction may be both one of the causes as well as a consequence of CKD and cardiovascular disease. We reviewed the published literature on human biopsy studies and conclude that renal capillary rarefaction occurs independently of the cause of renal function decline. Moreover, glomerular hypertrophy may be an early sign of generalized endothelial dysfunction, while peritubular capillary loss occurs in advanced renal disease. Recent studies with non-invasive measurements show that capillary rarefaction is detected systemically (e.g., in the skin) in individuals with albuminuria, as sign of early CKD and/or generalized endothelial dysfunction. Decreased capillary density is found in omental fat, muscle and heart biopsies of patients with advanced CKD as well as in skin, fat, muscle, brain and heart biopsies of individuals with cardiovascular risk factors. No biopsy studies have yet been performed on capillary rarefaction in individuals with early CKD. At present it is unknown whether individuals with CKD and cardiovascular disease merely share the same risk factors for capillary rarefaction, or whether there is a causal relationship between rarefaction in renal and systemic capillaries. Further studies on renal and systemic capillary rarefaction, including their temporal relationship and underlying mechanisms are needed. This review stresses the importance of preserving and maintaining capillary integrity and homeostasis in the prevention and management of renal and cardiovascular disease.

Immunosuppressive regimen and interstitial fibrosis and tubules atrophy at 12 months postrenal transplant.

BACKGROUND AND OBJECTIVES: Chronic renal transplant dysfunction is histopathologically characterized by interstitial fibrosis and tubular atrophy. This study investigated the relative contribution of baseline donor, recipient, and transplant characteristics to interstitial fibrosis and tubular atrophy score at month 12 after renal transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective study includes all 109 consecutive recipients with adequate implantation and month 12 biopsies transplanted between April of 2003 and February of 2007. Immunosuppression regimen was tacrolimus and steroids (10 days) plus either sirolimus or mycophenolate mofetil. RESULTS: Average interstitial fibrosis and tubular atrophy score increased from 0.70 to 1.65 (P<0.001). In an adjusted multiple linear regression analysis, interstitial fibrosis and tubular atrophy score at month 12 was significantly related to donor type (donors after cardiac death versus living donor had interstitial fibrosis and tubular atrophy score+0.41, 95% confidence interval=0.05-0.76, P=0.02), baseline interstitial fibrosis and tubular atrophy, and immunosuppression regimen. Because of interaction between the latter two variables (P=0.002), results are given separately: recipients with a baseline interstitial fibrosis and tubular atrophy score of zero had a 0.60 higher score at month 12 (95% confidence interval=0.09-1.10, P=0.02) when mycophenolate mofetil-treated, whereas recipients with a baseline interstitial fibrosis and tubular atrophy score more than zero had a 0.38 higher score at month 12 (95% confidence interval=0.01-0.74, P=0.04) when sirolimus-treated. A higher score at month 12 correlated with a lower estimated GFR (ρ=-0.45, P<0.001). CONCLUSIONS: These findings suggest that histologic assessment of a preimplantation biopsy may guide choice of immunosuppresion to maximize transplant survival and its interaction with type of immunosuppression.