TABLE 4.
Summary of studies on subclinical DSA in renal transplant recipients.
| Study | Type of study | Total patients (n) | Total DSA+ | Biopsied patients with subclinical DSA (n) | dnDSA/preformed DSA | Time of biopsy | Subclinical aABMR (n) (%)* | Subclinical caABMR (n) (%)* | Subclinical cABMR (n) (%)* | Subclinical TCMR (n) (%)* | Subclinical mixed rejection (n) (%)* | No rejection (n) (%)* | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Wiebe et al. [22, 34] | Retrospective Single center | 508 | 64 | 45 | dnDSA | 6 months post-transplant At dnDSA detection Graft dysfunction | Not specified | Not specified | Not specified | Not specified | Not specified | Not specified | Time to 50% allograft loss in clinical dnDSA vs. subclinical dnDSA: 3.3 years vs. 8.8 years (p < 0.0001) |
| Significantly worse allograft survival in subclinical dnDSA vs. no dnDSA + no dysfunction | |||||||||||||
| Bertrand et al. [77] | Retrospective Multicenter | 123 | 123 | 123 | dnDSA | At dnDSA detection | 32 (26%) | 19 (15.5%) | Not specified | Not specified | Not specified | No ABMR: 72 (58.5%) | Significantly worse post-biopsy 8-years allograft survival and 5 years delta creatinine in subclinical aABMR and cABMR compared to dnDSA without rejection |
| Loupy et al. [57] | Retrospective Single center + external validation | 1,001 | 256 | 256 | Preformed DSA + dnDSA | 1 year post-transplant | With DSA: 142 (55%)* | With DSA: 17 (6.6%)* | Not specified | With DSA: 97 (38%)* | Significantly worse post-biopsy 8-years allograft survival and delta creatinine in subclinical ABMR compared to subclinical TCMR or no rejection | ||
| Total: 142 (14.2%)** | Total: 132 (13.2%)** | Total: 727 (72.6%)** | No significant difference between (treated) subclinical TCMR and no rejection in either allograft survival or delta creatinine | ||||||||||
| Coemans et al. [78] | Retrospective Single center | 1,000 | 155 | At 3 months: 60 | Preformed DSA (108) + dnDSA (47) | 3, 12, and 24 months post-transplant | At 3 months: 42.5% | Not specified | Not specified | Not specified | Not specified | No aABMR at 3 months: 57.5% | No analysis of effect of subclinical rejection vs. no rejection on transplant outcome |
| At 12 months: 37 | Additional protocol biopsy at either 3, 4 or 5 years post-transplant | At 1 year: 40.5% | At 12 months: 59.5% | ||||||||||
| At 24 months: 29 | Indication | At 2 years: 37.3% | At 24 months: 62.7% | ||||||||||
| At 60 months: 15 | At 5 years: 13.3% | At 5 years: 86.7% | |||||||||||
| Schinstock et al. [30] | Retrospective Single center | 771 | 54 | 40 biopsied at detection of DSA | dnDSA | 4, 12, 24, 60 months post-transplant at dnDSA detection Graft dysfunction | At dnDSA detection: 10 (25%) | Not specified | At dnDSA detection: 3 (7.5%) | At dnDSA detection: 8 (20%) | Not specified | Not specified | Only those with dnDSA + ABMR had evidence of graft loss at mean follow up of 3.2 ± 2.0 years |
| 34 biopsied 1 year post detection of DSA | 1 year post dnDSA detection 18 (53%) | 1 year post dnDSA detection 13 (38.2%) | 1 year post dnDSA detection 5 (14.7%) | 21.4% vs. 0% in dnDSA without AMR. (p < 0.01) | |||||||||
| Not all subclinical | No significant difference in composite endpoint of −50% eGFR or allograft loss between dnDSA without AMR vs. no dnDSA (p = 0.26) | ||||||||||||
| Yamamoto et al. [79] | Retrospective Single center | 899 | 95 | 43 | dnDSA | At dnDSA detection | 18 (42%) At rebiopsy 2 years post biopsy in those without ABMR: 0 (0%) | Not specified | Not specified | No ABMR: 25 (58%) | Only 1 of 11 patients at 2 years follow up without ABMR at initial biopsy had deteriorating creatinemia/proteinuria | ||
| At rebiopsy 2 years post biopsy in those without ABMR: 8 (100%) | |||||||||||||
| Parajuli et al. [80] | Retrospective Single center | 45 | 45 | 29 | dnDSA | At dnDSA detection “Other indications" | 9 (31%) | 3 (10%) | 3 (10%) | 14 (48%) | Significantly better 1 year post biopsy eGFR in patients with subclinical dnDSA vs. clinical dnDSA. | ||
| No statistical differences in allograft loss rate but low event rate | |||||||||||||
| Waldecker et al. [81] | Retrospective Single center | 865 | 132 | 34 | dnDSA | At dnDSA detection Graft dysfunction | 11 (26%) | 3 (9%) | 1 (3%) | 5 (15%) | 4 (12%) | 5 (15%) | No analysis of effect of subclinical rejection on transplant outcomes |
| Eskandary et al. [82] | Retrospective Single center | 861 | 86 | 86 | Preformed DSA + dnDSA | Cross-sectional screening | 44 (51%) | Not specified | Not specified | No ABMR 42 (49%) | Only patients with subclinical ABMR had evidence of graft loss | ||
| 5 vs. 0 without rejection during a median follow up of 20.5 months | |||||||||||||
| Cornell et al. [83] | Prospective trial cohort + historical retrospective matched cohort | 78 | 78 | 78 | Preformed DSA | 3–4, 12 and 24 months post-transplant | Overall: At 3–4 months: 41.8% | Not specified | Not specified | Overall: No ABMR at 3–4 months: 58.2% | No analysis of effect of subclinical rejection vs. no rejection on transplant outcome | ||
| At 1 year: 37% | At 1 year: 63% | ||||||||||||
| At 2 years: 20% | At 2 years: 80% | ||||||||||||
ABMR, antibody-mediated rejection; aABMR, active ABMR; cABMR, Chronic ABMR; caABMR, Chronic active ABMR; DSA, Donor specific antibody; TCMR, T-cell mediated rejection. *: Proportion of total subclinical DSA patients with a biopsy **: Proportion of total patients.