Chronic allograft nephropathy (CAN) in protocol biop

The increase in the incidence of CAN between the 4th and 14th month is lower than the proportion of misclassified biopsies. Thus, monitoring the progression of CAN by means of two sequential biopsies at 4 and 14 months is inaccurate. We suggest that progression of scarring be monitored by means of a donor and a protocol biopsy performed during the first year evaluated with a quantitative approach.

Protocol biopsies may allow a reduction of sample size and especially the time of follow-up in a trial aimed to prevent CAN.

No abstract

Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

Aim: To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. Methods: A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/ artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Results: Chronic Banff scores increased during followup, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r Ω0.57, p ∞0.001), histocompatibility (r Ω0.38, p Ω 0.01) and serum cholesterol (r Ω0.31, p Ω0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r Ω0.44, p Ω0.004) and delayed graft function (p Ω0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. Conclusions: Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

These short-term results show that MMF introduction allows a CsA dose reduction, which improves renal function, reduces TGF-beta1 production, and improves the control of hypertension, without increasing the incidence of acute rejection.

The incidence of inflammatory lesions and transplant glomerulopathy is lower in patients treated with TAC than in patients treated with CsA. These data suggest that baseline immunosuppression could influence the severity of histological lesions in stable grafts.