Copyright
©The Author(s) 2017.
World J Transplant. Dec 24, 2017; 7(6): 276-284
Published online Dec 24, 2017. doi: 10.5500/wjt.v7.i6.276
Published online Dec 24, 2017. doi: 10.5500/wjt.v7.i6.276
Scenario A: Patients with acute kidney transplant dysfunction on whom a kidney transplant biopsy has been performed to exclude rejection | ||
Recommendations | ||
A1 | Diagnose rejection if present in kidney transplant biopsies according to the Banff classification (using the most current update; now the 2015 update), and report it in a systematic way | |
A2 | Quantify BK viremiaa and BK virus (BKV) nephropathy by specific staining | |
A3 | Detect anti-HLA antibodies/DSAd and define their immunoglobulin class, complement fixing capacities and titres through dilutions | |
Suggestions | ||
A4 | Bank serum, plasma, urine, peripheral blood mononuclear cells (PBMC) and kidney transplant tissue for future biomarker researchc | |
A5 | Exclude active infection by cytomegalovirus (CMV) and Epstein-Barr virus (EBV)a | |
A6 | Generate a data base with detailed clinical and immunological variables, ideally, using a standardized data base from a consortium or a large multicentre/multinational collaboration | |
A7 | Test any experimental biomarker(s) of your choice and correlate it/them with standard clinical variables and a detailed immune profile. The use of validated disease classifiers and archetypes appears to have more diagnostic accuracy than the use of single biomarkers | |
A8 | Perform a surveillance biopsy if kidney function and other clinical or laboratory parameters do not improve as expected after treatment to exclude persisting rejection or transformation to another type of rejectionb | |
Scenario B: Patients with acute kidney transplant dysfunction on whom a kidney transplant biopsy is being considered to exclude rejection | ||
Recommendations | ||
B1 | Quantify BK viremiaa | |
B2 | Detect anti-HLA antibodies/DSAd and define their immunoglobulin class, complement fixing capacities and titres through dilutions; and perform a kidney transplant biopsy if DSA are detected | |
B3 | Use validated disease classifiers and archetypes (if available) to enhance to pre-test probability for rejection, and perform a kidney transplant biopsy if positive | |
B4 | If a kidney transplant biopsy is performed, consider the recommendations and suggestions for Scenario A | |
Suggestions | ||
B4 | Bank serum, plasma, urine and PBMC for future biomarker researchc | |
B5 | Exclude CMV and EBV infectiona | |
B6 | Generate a data base with detailed clinical and immunological variables, ideally, using a standardized data base from a consortium or a large multicentre/multinational collaboration | |
B7 | Test any experimental biomarker(s) of your choice and correlate it/them with standard clinical variables and a detailed immune profile. The use of validated disease classifiers and archetypes appears to have more diagnostic accuracy than the use of single biomarkers | |
Scenario C: Patients with: (1) stable kidney function; (2) low immunological risk for ABMR with lack of preformed DSA; and (3) low immunological risk for TCMR or for the synthesis of de novo DSA due to no or low degree of HLA mismatch[16-18] | ||
Recommendations | ||
C1 | Detect anti-HLA antibodies/DSAd after a sensitization event (transfusions, pregnancies or other transplants e.g., pancreas after kidney transplantation) and define their immunoglobulin class, complement fixing capacities and titres through dilutions | |
C2 | Perform a kidney transplant biopsy if DSA are detected, diagnose it according to the Banff classification 2015 update and exclude intra-graft BKV infection by specific staining | |
C3 | In case of kidney dysfunction, consider the recommendations and suggestions for Scenarios A or B | |
Suggestions | ||
C4 | Test any experimental biomarker(s) of your choice at pre-selected time points and correlate it/them with standard clinical variables and a detailed immune profile. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry | |
C5 | Consider surveillance biopsies that exclude subclinical rejection and banking of kidney transplant tissue for biomarker researchc. Recommendation to select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry | |
C6 | Detect anti-HLA antibodies/DSAd at your pre-selected time points, to define their immunoglobulin class, complement fixing capacities and titres through dilutions, and correlate them with standard clinical variables and a detailed immune profile. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry. There are published consensus guidelines[19], but their recommendations are relatively arbitrary as well | |
C7 | Bank serum, plasma, urine and PBMC at your pre-selected sampling time points and when kidney biopsies are performedc | |
C8 | Exclude CMV and EBV infectiona | |
C9 | Perform a biomarker-driven biopsy if your chosen validated biomarker for rejection (or any other anomaly) turns positive, and bank tissue for further biomarker research | |
Scenario D: Patients with: (1) stable kidney function; and (2) high immunological risk for ABMR due to preformed DSA (desensitized or not) | ||
Recommendations | ||
D1 | Ensure adequate levels of immunosuppression and prevent non-compliance with treatmente | |
D2 | Perform surveillance biopsies to exclude subclinical rejection and banking of kidney transplant tissue for biomarker researchc. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry, but available guidelines[19] recommend them within the first 3 (or 6) mo post-transplantation | |
D3 | Monitor anti-HLA antibodies/DSAd and define their immunoglobulin class, complement fixing capacities and titres through dilutions at your pre-selected time points and correlate them with standard clinical variables and a detailed immune profile. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry; although there are published consensus guidelines[19] | |
D4 | Detect anti-HLA antibodies/DSAd after a sensitization event (transfusions, pregnancies or other transplants, e.g., pancreas after kidneytransplantation) and define their immunoglobulin class, complement fixing capacities and titres through dilutions | |
D5 | Perform a kidney transplant biopsy if DSA are detected, to diagnose it according to the Banff classification 2015 update and exclude intra-graft BKV infection by specific staining | |
D6 | Perform a biomarker-driven biopsy if your chosen validated biomarker for rejection (or any other anomaly) turns positive, and bank tissue for further biomarker research | |
D7 | In case of kidney dysfunction, we recommend to perform a kidney transplant biopsy and to consider the recommendations and suggestions for Scenario A | |
Suggestions | ||
D8 | Test any experimental biomarker(s) of your choice at pre-selected time points and correlate it/them with standard clinical variables and a detailed immune profile. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry | |
D9 | Bank serum, plasma, urine and PBMC at your pre-selected sampling time points and when kidney biopsies are performedc | |
D10 | Exclude CMV and EBV infectiona | |
Scenario E: Patients with: (1) stable kidney function; (2) high immunological risk for TCMR and for the synthesis of de novo DSA due to high degree HLA mismatch[16-18]; and (3) without preformed DSA | ||
Recommendations | ||
E1 | Ensure adequate levels of immunosuppression and prevent non-compliance with treatmente | |
E2 | Detect anti-HLA antibodies/DSAd, especially in those with HLA-B and HLA-DRB1 mismatches, thought to be more immunogenic[16], at your pre-selected time points and correlate them with standard clinical variables and a detailed immune profile. Define immunoglobulin class, complement fixing capacities and titres through dilutions. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry, although there are published consensus guidelines[19] | |
E3 | Detect anti-HLA antibodies/DSAd after a sensitization event (transfusions, pregnancies or other transplants, e.g., pancreas after kidneytransplantation) and define their immunoglobulin class, complement fixing capacities and titres through dilutions | |
E4 | Perform a kidney transplant biopsy if DSA are detected, diagnose according to the Banff classification 2015 update and exclude intra-graft BKV infection by specific staining | |
E5 | In case of kidney dysfunction, perform a kidney transplant biopsy, especially in those with HLA-B and HLA-DRB1 mismatches, thought to be more immunogenic, and consider the recommendations and suggestions for Scenario A | |
Suggestions | ||
E6 | Test any experimental biomarker(s) of your choice at pre-selected time points and correlate it/them with standard clinical variables and a detailed immune profile. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry | |
E7 | Suggest surveillance biopsies exclude subclinical rejection and banking of kidney transplant tissue for biomarker researchc. Select time points based on the modal distribution of rejection in a specific population of patients with similar immunological risk, ideally derived from your own registry | |
E8 | Bank serum, plasma, urine and PBMC at your pre-selected sampling time points and when kidney biopsies are performedc | |
E9 | Exclude CMV and EBV infectiona | |
E10 | Perform a biomarker-driven biopsy if your chosen validated biomarker for rejection (or any other anomaly) turns positive, and bank tissue for further biomarker research | |
Scenario F: Patients with: (1) stable kidney function; (2) high immunological risk for ABMR due to preformed DSA; and (3) high immunological risk for TCMR and for the synthesis of de novo DSA due to high degree HLA mismatch[16-18] | ||
Recommendation | ||
F1 | Follow our recommendations and suggestions for Scenarios D and E | |
Scenario G: Patients with delayed graft function (DGF) | ||
Recommendations | ||
G1 | Perform a kidney transplant biopsy if DGF extends beyond the first week post-transplantation without an obvious explanation, and subsequently every 7-10 d if DGF persists[14] | |
G2 | Detect anti-HLA antibodies/DSAd if DGF extends beyond the first week post-transplantation without an obvious explanation, and subsequently every 7-10 d if DGF persists, and define their immunoglobulin class, complement fixing capacities and titres through dilutions | |
G3 | Perform a kidney transplant biopsy if DSA are detected, to diagnose it according to the Banff classification 2015 update and exclude intra-graft BKV infection by specific staining | |
Suggestions | ||
G4 | Define lower threshold for performing a kidney transplant biopsy in patients with DGF and pre-formed DSA or with HLA-B and HLA-DRB1 mismatches thought to be more immunogenic[16] | |
G5 | Bank serum, plasma, urine and PBMC at the protocolised sampling time points and when kidney biopsies are performedc | |
G6 | Bank kidney transplant tissue for biomarker research whenever a biopsy is performedc | |
G7 | Test any experimental biomarker(s) of your choice at protocolised time points and correlate it/them with standard clinical variables and a detailed immune profilec | |
G8 | Perform a biomarker-driven biopsy if your chosen validated biomarker for rejection (or any other anomaly) turns positive, and bank tissue for further biomarker research | |
G9 | Exclude active CMV and EBV infectiona | |
Scenario H: Every kidney transplant patient included in a clinical trial | ||
Recommendations | ||
H1 | Bank serum, plasma, urine and PBMC at the protocolised sampling time points and when kidney biopsies are performedcf | |
H2 | Bank kidney transplant tissue for biomarker research whenever a biopsy is performedcf | |
H3 | Test any experimental biomarker(s) of your choice at the sampling points established by the trial designers and correlate it/them with | |
H4 | Consider performing surveillance biopsies at important assessment points as per trial protocol (which can help to exclude subclinical rejection and to assess histopathological response to interventions) and banking of kidney transplant tissue for biomarker researchc |
- Citation: Salcido-Ochoa F, Allen Jr JC. Biomarkers and a tailored approach for immune monitoring in kidney transplantation. World J Transplant 2017; 7(6): 276-284
- URL: https://www.wjgnet.com/2220-3230/full/v7/i6/276.htm
- DOI: https://dx.doi.org/10.5500/wjt.v7.i6.276