Early loss of peritubular capillaries after kidney transplantation

Abstract

Inflammation, interstitial fibrosis (IF), and tubular atrophy (TA) precede chronic transplant dysfunction, which is a major cause of renal allograft loss. There is an association between IF/TA and loss of peritubular capillaries (PTCs) in advanced renal disease, but whether PTC loss occurs in an early stage of chronic transplant dysfunction is unknown. Here, we studied PTC number, IF/TA, inflammation, and renal function in 48 patients who underwent protocol biopsies. Compared with before transplantation, there was a statistically significant loss of PTCs by 3 months after transplantation. Fewer PTCs in the 3-month biopsy correlated with high IF/TA and inflammation scores and predicted lower renal function at 1 year. Predictors of PTC loss during the first 3 months after transplantation included donor type, rejection, donor age, and the number of PTCs at the time of implantation. In conclusion, PTC loss occurs during the first 3 months after renal transplantation, associates with increased IF and TA, and predicts reduced renal function.

Figure 1.

Loss of PTCs occurs within the first 3 months after transplantation (P < 0.001, paired samples t test). DCD and DBD renal allografts show a significant loss of PTCs within the first 3 months after transplantation (respective P < 0.001, n = 19; P = 0.004, n = 12). LD renal allografts showed a trend toward PTC loss in the first 3 months (P = 0.061, n = 17) (paired samples t test per group). Immunohistochemical quantification of a (B through D) LD and (E through G) DCD kidney. Panels H and I are enlargements of respective figures F and G. In preimplantation biopsies, PTCs are evenly distributed (B, E), whereas after (C, F) 3 and (D, G) 12 months, areas can occur without PTCs (asterisks) even when no IF/TA is present (D). In areas with inflammation (F, H), and with IF/TA (G, I), a lower number of PTCs is observed. Arrowhead denotes PTC; arrow denotes tubule.

Figure 2.

Relationship between number of PTCs at 3 months and (A) MDRD and (D) IF/TA after 12 months and with (B) inflammation and (C) PTCitis after 3 months. A low number of PTCs at 3 months is significantly correlated with a low MDRD score (r = 0.424, P = 0.003). Number of PTCs at 3 months is significantly negatively rank correlated with (B) total inflammation (ρ = −0.469, P = 0.001) and (C) PTCitis score (ρ = −0.469, P = 0.001) at 3 months and with (D) IF/TA score at 12 months (ρ = −0.377, P = 0.008).