TABLE 5.
Summary of studies on outcome of treated and untreated subclinical.
| Study | Type of study | Total patients (n) | Time of biopsy | Total subclinical TCMR (n) or (%) | Treatment of subclinical TCMR | Outcome |
|---|---|---|---|---|---|---|
| Nankivell et al. [157] | Retrospective Single center | 961 | 1, 2 weeks 1, 3, 6, 12 months post-transplant Annually thereafter | 6.9% of all biopsies TCMR | Methylprednisolone in 22.9% of TCMR and 12.3% of B-TCMR | Biopsies taken >3 months post-transplant with subclinical TCMR associated with higher ci and ct scores at 1 year biopsy |
| 23.4% of all biopsies B-TCMR | Persistent TCMR associated with more significant decline in eGFR at 2 years | |||||
| Moreso et al. [158 ] | Retrospective Single center | 372 | Protocol biopsy during initial 6 months post-transplant “For cause” | 74 subclinical TCMR | None | 15 years DCGS lower in patients with CAN + TCMR compared to no rejection RR 1.86 (1.11–3.12) |
| 65 subclinical TCMR + CAN | ||||||
| Scholten et al. [159] | RCT | 126 1:1 TAC vs. CsA | Protocol biopsy at 6 and 12 months post-transplant | At 6 months: 7.4% TCMR and 23.4% B-TCMR | None | Less subclinical TCMR in TAC group |
| At graft dysfunction | At 12 months 14.3% TCMR 24.5% B-TCMR | Subclinical TCMR not associated with creatinin clearance at 2 years | ||||
| Kurtkoti et al. [160] | RCT | 102 | Protocol biopsy at 1, 3 months post-transplant vs. Indication only | Protocol biopsy group at 1, 3 months: 17.3%, 12% | Pulse steroids | Serum creatinin significantly higher at 6 and 12 months in control group vs. protocol biopsy group |
| 1:1 | At 6 months: 137 ± 35 μmol vs. 113 ± 29 μmol (p < 0.001) | |||||
| Protocol biopy vs. Only indication biopsy | At 12 months: 134 ± 36 μmol vs. 106 ± 29 μmol (p < 0.001) | |||||
| Rush et al. (1998) [161] | RCT | 72 | Protocol biopsy at 1, 2, 3, 6, 12 months vs. Protocol biopsy at 6, 12 months | In early biopsy group: Subclinical TCMR at 1, 2, 3, 6 months: 43%, 32%, 27%, 15% | Pulse steroids | Significantly higher amount of patients with ci + ct scores ≥2 in control group vs. early biopsy group 24% vs. 6% at 6 months (p < 0.04) |
| 1:1 | In late biopsy group: Subclinical TCMR at 6 months: 32% | Significantly higher creatinin at 2 years in control group vs. early biopsy group 183 ± 22 μmol/L vs. 133 ± 14 μmol/L (p < 0.05) | ||||
| early biopsies vs. later biopsy | ||||||
| Choi et al. [162] | Retrospective Single center | 304 | Day 14 Post-transplant | 40 | None | 10 years graft survival subclinical TCMR vs. no rejection: 62.3% vs. 96.2% (p < 0.05) |
| Rush et al. (2007) [164] | RCT | 218 | Protocol biopsy at 1, 2, 3, 6 months vs. Protocol biopsy at 6months | In early biopsy group: Subclinical TCMR at 1, 2, 3, 6 months: 5.7%, 0%, 8.1%, 8.9% | Pulse steroids | Significantly higher increase in ci + ct scores ≥2 at 6 months compared to baseline in early biopsy/treatment group vs. control group (1.12 ± 1.36 and 0.57 ± 1.02, p = 0.04) |
| 1:1 | In late biopsy group: Subclinical TCMR at 6 months: 6.0% | No significant difference in creatinin clearance or proteinuria at 6 months between groups | ||||
| early (<6 months) biopsies/treatmentvs no biopsy | ||||||
| Loupy et al. [57] | Retrospective Single center + External validation | 1,001 | Protocol biopsy at 1 year | 132 | Pulse steroids | No significant difference in 8 years allograft survival or 8 years eGFR between subclinical TCMR vs. no rejection |
| Seifert et al. [165] | Retrospective Single center | 103 | Protocol biopsy at 3, 6 months | 37 | Increased maintenance immunosuppression, pulse steroids or thymoglobulin at discretion of physician | Significantly higher 5 years freedom from composite endpoint of acute clinical rejection or allograft loss in no rejection vs. untreated subclinical B-TCMR (p < 0.001) |
| No significant difference in 5 years composite endpoint between treated subclinical B-TCMR vs. no rejection | ||||||
| Significantly higher 5 years composite endpoint in no rejection vs. treated subclinical TCMR | ||||||
| Hoffman et al. [166] | Retrospective Single center | 192 | Protocol biopsy at 3, 12 months | 56 | Pulse steroids (Banff 1A/B) or thymoglobulin (Banff ≥ 2A) | No significant difference in delta creatinin between 3 and 24 months or odds of 50% decline in eGFR between 3 months and final follow up between subclinical TCMR vs. no rejection |
TCMR CAN, Chronic allograft nephropathy; ci, Interstitial fibrosis; ct, Tubular atrophy; CsA, Ciclosporin; DCGS, Death-censored graft survival; RCT, Randomized controlled trial; TAC, Tacrolimus; TCMR, T-cell mediated rejection; B-TCMR, Borderline TCMR.