Editorial
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
Table 1 Recommendations and suggestions on the incorporation of biomarkers and surveillance biopsies in kidney transplantation
Scenario A: Patients with acute kidney transplant dysfunction on whom a kidney transplant biopsy has been performed to exclude rejection
Recommendations
A1Diagnose 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
A2Quantify BK viremiaa and BK virus (BKV) nephropathy by specific staining
A3Detect anti-HLA antibodies/DSAd and define their immunoglobulin class, complement fixing capacities and titres through dilutions
Suggestions
A4Bank serum, plasma, urine, peripheral blood mononuclear cells (PBMC) and kidney transplant tissue for future biomarker researchc
A5Exclude active infection by cytomegalovirus (CMV) and Epstein-Barr virus (EBV)a
A6Generate a data base with detailed clinical and immunological variables, ideally, using a standardized data base from a consortium or a large multicentre/multinational collaboration
A7Test 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
A8Perform 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
B1Quantify BK viremiaa
B2Detect 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
B3Use validated disease classifiers and archetypes (if available) to enhance to pre-test probability for rejection, and perform a kidney transplant biopsy if positive
B4If a kidney transplant biopsy is performed, consider the recommendations and suggestions for Scenario A
Suggestions
B4Bank serum, plasma, urine and PBMC for future biomarker researchc
B5Exclude CMV and EBV infectiona
B6Generate a data base with detailed clinical and immunological variables, ideally, using a standardized data base from a consortium or a large multicentre/multinational collaboration
B7Test 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
C1Detect 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
C2Perform 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
C3In case of kidney dysfunction, consider the recommendations and suggestions for Scenarios A or B
Suggestions
C4Test 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
C5Consider 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
C6Detect 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
C7Bank serum, plasma, urine and PBMC at your pre-selected sampling time points and when kidney biopsies are performedc
C8Exclude CMV and EBV infectiona
C9Perform 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
D1Ensure adequate levels of immunosuppression and prevent non-compliance with treatmente
D2Perform 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
D3Monitor 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]
D4Detect 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
D5Perform 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
D6Perform a biomarker-driven biopsy if your chosen validated biomarker for rejection (or any other anomaly) turns positive, and bank tissue for further biomarker research
D7In case of kidney dysfunction, we recommend to perform a kidney transplant biopsy and to consider the recommendations and suggestions for Scenario A
Suggestions
D8Test 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
D9Bank serum, plasma, urine and PBMC at your pre-selected sampling time points and when kidney biopsies are performedc
D10Exclude 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
E1Ensure adequate levels of immunosuppression and prevent non-compliance with treatmente
E2Detect 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]
E3Detect 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
E4Perform 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
E5In 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
E6Test 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
E7Suggest 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
E8Bank serum, plasma, urine and PBMC at your pre-selected sampling time points and when kidney biopsies are performedc
E9Exclude CMV and EBV infectiona
E10Perform 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
F1Follow our recommendations and suggestions for Scenarios D and E
Scenario G: Patients with delayed graft function (DGF)
Recommendations
G1Perform 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]
G2Detect 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
G3Perform 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
G4Define 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]
G5Bank serum, plasma, urine and PBMC at the protocolised sampling time points and when kidney biopsies are performedc
G6Bank kidney transplant tissue for biomarker research whenever a biopsy is performedc
G7Test any experimental biomarker(s) of your choice at protocolised time points and correlate it/them with standard clinical variables and a detailed immune profilec
G8Perform a biomarker-driven biopsy if your chosen validated biomarker for rejection (or any other anomaly) turns positive, and bank tissue for further biomarker research
G9Exclude active CMV and EBV infectiona
Scenario H: Every kidney transplant patient included in a clinical trial
Recommendations
H1Bank serum, plasma, urine and PBMC at the protocolised sampling time points and when kidney biopsies are performedcf
H2Bank kidney transplant tissue for biomarker research whenever a biopsy is performedcf
H3Test any experimental biomarker(s) of your choice at the sampling points established by the trial designers and correlate it/them with
H4Consider 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