Sub-classification of borderline changes into diffuse or focal and its impact on long-term renal transplant outcomes.

BACKGROUND: Borderline changes (BL) with stable renal function is a controversial category in renal transplantation, given its contradictory outcomes. The aim of this study was to compare the clinical outcomes of BL in patients with stable renal function classified as focal and diffuse according to the extent of tubulitis. METHODS: Patients with no history of rejection with a surveillance graft biopsy at 3 or 12 months showing BL (n = 40), acute cellular rejection (n = 20) or normal biopsies (n = 20), were included in this study. Biopsies with BL were divided into diffuse BL (BLD) and focal BL (BLF) according to the extent of tubulitis. Because of the low frequency of subclinical ACR (ACRND) (n = 12), biopsies with ACR and graft dysfunction (ACRD) (n = 8) were also included. A composite outcome that included the presence of rejection in subsequent biopsies, graft loss, patient death, decrease in GFR ≥30% or presence of de novo DSA (dnDSA) during the first year of follow-up was evaluated. RESULTS: The primary composite outcome occurred in five patients of each of the Normal, BLF and ACRND, eight patients with BLD and six patients with ACRD (p = 0.105). A trend towards more rejection episodes was observed in the ACRND and ACRD. Also, a shorter time to rejection in the BLD, ACRND and ACRD groups compared to BLF and Normal groups (p = 0.039) was observed. During the first year of follow-up, no patient in the ACRND group developed dnDSA, compared to 15-25% in the other groups. The median time of dnDSA development in the BLF group was 45 months, and in the BLD group was 10 months (p = 0.020). CONCLUSION: Classifying BL biopsies with stable renal function into focal and diffuse categories, is a simple and feasible strategy that helps to differentiate between BLD with a phenotype that shows a trend towards worse outcomes, and BLF that behaves more similar to normal biopsies.

Incidence of cervical intraepithelial lesions and human papilloma virus infection in female renal transplant recipients.

BACKGROUND: Female renal transplant recipients (RTR) are at high risk of human papillomavirus (HPV)-related anogenital premalignancies and cancer. The aim of this study was to estimate the incidence of cervical intraepithelial lesions (IL) and HPV infection, and their associated factors, in Mexican RTR. METHODS: This is a prospective cohort study conducted between January 2011 and December 2017. Demographic, clinical, and gynecological data were collected using a previously designed questionnaire. Gynecological examination, cervical cytology, and detection of high- and low-risk HPV DNA were undertaken prior to and after the renal transplant (RT). Colposcopically guided biopsies were obtained from patients who presented high grade squamous intraepithelial lesions (HSIL) during the follow-up period. Diagnoses were established according to the Bethesda system. RESULTS: Among 130 RTR, 62 were eligible for our study. The overall incidence of IL was 17.7% (95% CI, 8% to 27%), (11/62 patients), at 25.6 ± 10.7 months post-RT. Nine out of the eleven affected patients had low-grade squamous intraepithelial lesions (81.8%) and only two had HSIL (18.2%). The incidence of HPV infection, determined in a subgroup of 30 RTR, was 53.3% (95% CI, 35% to 71%), (16 out of 30 patients), at 18.3 ± 8.9 months post-RT. High-risk HPV genotypes were present in 62.5% of HPV positive cases (10/16). In 11 patients (36.6%), HPV infection was not associated to IL. CONCLUSIONS: HPV infection and cervical IL are common in the early posttransplant period. Our findings support the need of screening for cervical cancer to detect precancerous changes in RTR and the need of strengthening the knowledge of medical personnel on this issue.

A potential role of neutrophil extracellular traps (NETs) in kidney acute antibody mediated rejection.

BACKGROUND: The aim of this study was to evaluate neutrophil extracellular traps (NETs) in kidney transplant recipients (KTR) and their potential involvement in acute antibody-mediated rejection (AAMR). METHODS: We studied 3 groups: KTR with AAMR (KTR-Cases, n = 14); KTR without any immunologic event (KTR-Controls, n = 14) and donors (n = 12). Spontaneous and lipopolysaccharide-induced NETosis were evaluated by immunofluorescence indirect (IFI) (NET/cells ratio). Plasmatic cH3-DNA complexes were evaluated by ELISA, (Optic Density Index - ODI). The expression of MPO and citrullinated histone 4 (cH4) was evaluated in renal biopsies. RESULTS: We found an enhanced spontaneous NETosis in KTR regardless of whether they had rejection. The Nets/cells ratio in spontaneous NETosis was 0.203 (IQR 0.12-0.34) in Total-KTR and 0.094 (IQR 0.01-0.17) in donors, p = .011. Likewise, the ODI of cH3-DNA was 1.41 (IQR 0.94-1.72) in Total-KTR, and 0.95 (IQR 0.83-1.27) in donors, p = .019. KTR-Cases had the higher amount of NETs 1.70 (IQR 1.19-1.91). In two KTR-Cases, expression of MPO and cH4 was found in biopsies. CONCLUSIONS: KTR show enhanced NETosis. This may indicate a permanent activation of neutrophils. Although more studies are needed, the higher amount of NETs and netting neutrophils in biopsies of KTR-Cases suggest a role of NETosis in AAMR.

A urine score for noninvasive accurate diagnosis and prediction of kidney transplant rejection.

Accurate and noninvasive monitoring of renal allograft posttransplant is essential for early detection of acute rejection (AR) and to affect the long-term survival of the transplant. We present the development and validation of a noninvasive, spot urine-based diagnostic assay based on measurements of six urinary DNA, protein, and metabolic biomarkers. The performance of this assay for detecting kidney injury in both native kidneys and renal allografts is presented on a cohort of 601 distinct urine samples. The urinary composite score enables diagnosis of AR, with a receiver-operator characteristic curve area under the curve of 0.99 and an accuracy of 96%. In addition, we demonstrate the clinical utility of this assay for predicting AR before a rise in the serum creatinine, enabling earlier detection of rejection than currently possible by standard of care tests. This noninvasive, sensitive, and quantitative approach is a robust and informative method for the rapid and routine monitoring of renal allografts.

Use of the Tissue Common Rejection Module Score in Kidney Transplant as an Objective Measure of Allograft Inflammation.

Long-term kidney transplant (KT) allograft outcomes have not improved as expected despite a better understanding of rejection and improved immunosuppression. Previous work had validated a computed rejection score, the tissue common rejection module (tCRM), measured by amplification-based assessment of 11 genes from formalin-fixed paraffin-embedded (FFPE) biopsy specimens, which allows for quantitative, unbiased assessment of immune injury. We applied tCRM in a prospective trial of 124 KT recipients, and contrasted assessment by tCRM and histology reads from 2 independent pathologists on protocol and cause biopsies post-transplant. Four 10-µm shaves from FFPE biopsy specimens were used for RNA extraction and amplification by qPCR of the 11 tCRM genes, from which the tCRM score was calculated. Biopsy diagnoses of either acute rejection (AR) or borderline rejection (BL) were considered to have inflammation present, while stable biopsies had no inflammation. Of the 77 biopsies that were read by both pathologists, a total of 40 mismatches in the diagnosis were present. The median tCRM scores for AR, BL, and stable diagnoses were 4.87, 1.85, and 1.27, respectively, with an overall significant difference among all histologic groups (Kruskal-Wallis, p < 0.0001). There were significant differences in tCRM scores between pathologists both finding inflammation vs. disagreement (p = 0.003), and both finding inflammation vs. both finding no inflammation (p < 0.001), along with overall significance between all scores (Kruskal-Wallis, p < 0.001). A logistic regression model predicting graft inflammation using various clinical predictor variables and tCRM revealed the tCRM score as the only significant predictor of graft inflammation (OR: 1.90, 95% CI: 1.40-2.68, p < 0.0001). Accurate, quantitative, and unbiased assessment of rejection of the clinical sample is critical. Given the discrepant diagnoses between pathologists on the same samples, individuals could utilize the tCRM score as a tiebreaker in unclear situations. We propose that the tCRM quantitative score can provide unbiased quantification of graft inflammation, and its rapid evaluation by PCR on the FFPE shave can become a critical adjunct to help drive clinical decision making and immunosuppression delivery.

Changes in the commercial brand of tacrolimus lead to subtherapeutic trough levels and acute rejection in renal transplant recipients.

BACKGROUND: The vigilance of tacrolimus (TAC) trough levels is an essential part of renal transplant follow up. Reduced TAC trough levels and high variability are related to adverse outcomes. The aim of this study was to evaluate the impact of brand changes on tacrolimus (TAC) subtherapeutic (SubT) trough levels, acute rejection (AR), and kidney function. METHODS: This is a prospective, observational cohort study of renal transplant recipients, between January 2016 and October 2018. Tacrolimus trough levels and brand used by the patient were both registered at every consult. Tacrolimus values ≤3.5 ng/mL were considered SubT. RESULTS: 445 patients were included. The median number of TAC brand changes was 2 (IQR, 1-4). Patients were grouped according to the number of brand changes: Group 1 = 0 (n = 107), Group 2 = 1-4 (n = 236), and Group 3 = ≥5 (n = 102). Patients with the greatest number of brand changes had a greater proportion and number of SubT TAC trough levels (Group 1 = 36.4%, average 0.53; Group 2 = 39.8%, average 0.65, Group 3 = 59.8%, average 1.17, P < .001) and AR (Group 1 = 0.9%, Group 2 = 11%, Group 3 = 14.7%, P < .001). On multivariate analysis, SubT levels and the number of brand changes were related to AR. CONCLUSIONS: In Mexico, changes in TAC brand are associated with an elevated frequency of SubT levels. Brand changes and SubT levels are independently associated with acute rejection. The supply policies on TAC brands in Mexico require revision to avoid changing brands as much as possible.

"Expanding the limits". Three-year follow-up of renal transplant recipients from a deceased donor with creatinine greater than 5 mg/dl. Report of three cases.

Due the shortage of organ donors and the increase in the waiting list of kidney transplant recipients (KTR), alternative strategies have been considered with the aim of increasing the number of organs available. The use of kidneys from donors with acute renal failure and elevated serum creatinine has been considered as a way to increase the number of donors. The objective of this work is to report the 3-year follow-up of three KTR patients of a deceased donor with serum creatinine greater than or equal to 5 mg/dL.

Ante la escasez de donadores de órganos y el incremento en la lista de espera de receptores de trasplante renal (RTR) se han considerado medidas alternativas con el objetivo de aumentar el número de órganos disponibles. El uso de riñones de donadores con insuficiencia renal aguda y creatinina sérica terminal elevada se ha considerado un camino para incrementar el número de donadores. El objetivo de este trabajo es notificar el seguimiento a tres años de tres pacientes RTR de donador fallecido con creatinina sérica ≥ 5 mg/dl.

TREATMENT STRATEGIES AND OUTCOME OF PARVOVIRUS B19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS: A CASE SERIES AND LITERATURE REVIEW OF 128 PATIENTS.

BACKGROUND: There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. OBJECTIVE: The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. METHODS: We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. RESULTS: In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. CONCLUSIONS: In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Reporte de la primera cadena de trasplante renal en México / First kidney domino transplant in Mexico

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Treatment strategies and outcome of parvovirus b19 infection in kidney transplant recipients: a case series and literature review of 128 patients.

Abstract Background There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. Objective The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. Methods We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. Results In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. Conclusions In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

Intellectual performance of kidney transplant recipients' offspring: a cross-sectional, multicenter study.

OBJECTIVE: The number of successful pregnancies in kidney transplant (KT) recipients has increased in recent years. Little evidence is available about the risk of in utero immunosuppressive exposure for long-term cognitive consequences. The aim of this study was to evaluate the impact of immunosuppression during pregnancy on intellectual performance of children born to KT recipients. METHODS: Using a cross-sectional design, women who had undergone KT and their children (aged 4+ years) were recruited at the outpatient follow-up in five transplant centers. Women who did not receive immunosuppression during pregnancy with similar distributions of socioeconomic status and length of gestation and their children were also recruited. Children were assessed with Wechsler Intelligence Scales. RESULTS: The study sample included 50 exposed and 50 unexposed children. No differences between groups in all the proposed confounding factors were found. Full-scale IQ did not differ significantly between both groups. Also, significant differences in any index or subscale score were not observed, with the exception of time required to complete the Wechsler preschool and primary scale of intelligence (WPPSI) Zoo locations subtest, which was done quicker in the unexposed group (p = .007). Exposure to immunosuppression during pregnancy was not a significant predictor of low IQ in logistic regression after adjustment for other factors. CONCLUSIONS: Immunosuppression therapy during pregnancy of KT women did not affect global intellectual performance of their offspring, except maybe for visuospatial working memory in preschool children.

Pretransplant angiotensin II type 1-receptor antibodies point to an increase in renal graft sub-intimal fibrosis in living- donor kidney transplant recipients.

The association between anti-AT1Rabs and microvascular injury observed in antibody-mediated rejection has been described in kidney graft Biopsies (KGBx). METHODS: We herein describe the histopathologic findings of KGBx performed during the first year of transplantation (Tx) in 134 patients tested for pre-Tx anti-AT1Rabs in cryopreserved sera (04/2009 to 09/2013). Protocol KGBx before implantation (time-zero), 1 year after Tx and for cause KGBx were included. 21/134 Tx patients were anti-AT1Rab positive (≥17 U/mL); 7/21 experienced acute rejection. For comparison a control group with anti-AT1Rabs <17 U/mL, with (n = 16) and without (n = 31) acute rejection was included. RESULTS: Preimplantation KGBx showed no differences in inflammatory and chronic findings, nor in subintimal fibrosis (25 vs 12.8%, p = .42) between patients with anti-AT1Rabs ≥17 U/mL and those with <17 U/mL. Follow-up KGBx revealed a significantly greater proportion of arterial sub-intimal fibrosis (52.3 vs. 27.6%, p = .049) and extension (15.7 vs. 5.3, p = .015) in anti-AT1Rabs ≥17 U/mL compared to anti-AT1Rabs <17 U/mL KGBx. No differences were observed in microcirculation inflammation, nor in interstitial fibrosis or tubular atrophy between groups. Also, anti-AT1Rabs ≥17 U/mL (ß 10.1, 2.3 to 17.8, p = .012) and more importantly anti-AT1Rabs ≥ 30 U/mL (ß12.1, 3.1 to 20.9, p < .01), were independent risk factors associated with vascular occlusion resulting from sub-intimal fibrosis. CONCLUSION: Our study findings have shown that anti-AT1Rab values ≥17 U/mL are significantly associated to sub-intimal fibrosis and a greater percentage of vessel occlusion in kidney graft biopsies obtained during the first year posttransplant, particularly in coexistence with inflammation and de novo DSA.

Fosfomycin trometamol in the prophylaxis of post-kidney transplant urinary tract infection: A controlled, randomized clinical trial.

BACKGROUND: The aim of this controlled clinical trial was to evaluate the efficacy and safety of fosfomycin trometamol (FOS) in urinary tract infection (UTI) prophylaxis during the first 6 months after renal transplant (RT). METHODS: The intervention group received 3 g of FOS PO every 10 days and trimethoprim-sulfamethoxazole (TMP-SMX, 160/800 mg) three times per week (Group 1), whereas the control group received TMP-SMX (160/800 mg) daily (Group 2). The outcomes were the time until the first UTI (symptomatic infection or asymptomatic bacteriuria (>105  CFU/mL)) and the incidence of UTI during the first 6 months post RT. Intermediate analysis was conducted after one-half of the estimated sample size of patients was enrolled. RESULTS: The recruitment of patients was stopped after the intermediate analysis due showed no emerging trends or reasonable chance of demonstrating benefit. Sixty-seven patients were included (32 in Group 1 and 35 in Group 2). The UTI incidence (40.6% vs 42.8%, P = 0.85) and time until the first episode were similar between the groups (log rank, P = 0.862). UTI due to Klebsiella spp. was observed in both groups at equal rates (25% vs 20%, P = 0.62), episodes due to Escherichia coli were less frequent in Group 1 (12.5% vs 34.2%, P = 0.04), and Enterococcus faecalis infection only occurred in Group 2 (n = 4). Resistance to FOS was observed for Klebsiella spp.; in contrast, E. coli and E. faecalis were susceptible. CONCLUSIONS: The addition of FOS to TMP-SMX was not beneficial for the prevention of UTI after RT in our setting. (ClinicalTrials.gov, NCT01820897).

Value of C3d assay and IgG subclass in the prediction of the flow cytometry cross-match result for renal transplantation.

The aim of this study is to compare the association and the predictive capacity of DSA MFI, complement fixing capacity (C3d assay) and IgG subclasses determination in the prediction of FCxM result. METHODS: We used cryopreserved (70C) sera from potential renal transplant recipients, containing DSA against their respective potential donors. All patients showed negative AHG-CDC CxM and either positive or negative FCxM. Class I and Class II HLA-DSA were determined by Luminex SAB. C3d were detected by Luminex (Lifecodes®Immucor), DSA IgG 1-4 subclasses were evaluated using monoclonal antibodies specific for IgG subclasses (Luminex). RESULTS: 93 donor/recipient tests were evaluated; 32 (35.9%) patients presented at least one C3d + Ab, of which only 11 (11.8%) were donor specific. At least one IgG subclass was identified in 45 samples (48.3%). Twenty-seven FCxM tests (29%) were positive. On multivariate analysis HLA mismatches, the IgG subclass detection, DSA MFI and class II PRA remain associated to FCxM whereas C3d + Ab was not associated. For the FCxM prediction, the IgG subclass detection in combination with the DSA-MFI > 2800, had the best negative predictive value 93.9 (CI 95%, 84.2-100). CONCLUSION: Neither the C3d assay nor the IgG subclasses detection alone had an adequate predictive capacity for the FCxM. In the absence of IgG subclass detection and DSA-MFI < 2000, the probability of a negative FCxM was near 94%.

Graft immunologic events in deceased donor kidney transplant recipients with preformed HLA-donor specific antibodies.

INTRODUCTION: Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center. PATIENTS AND METHODS: 246 KT were performed at our center between 01/2012 and 12/2015 and 100 KTR obtained from a DD were analyzed; 24% harbored DSA by SAB assay, MFI values >500 were considered positive. All recipients received thymoglobulin induction and generic tacrolimus-based maintenance therapy. Graft biopsies were performed by protocol on months 3 and 12 as well as per indication. The incidence of AMR and ACR was correlated with the existence of pretransplant DSA. RESULTS: Overall, 34% of patients developed an acute rejection episode, 54.2% in the DSA group versus 27.6% in the non-DSA group (p=0.032), and most of these events were detected as subclinical conditions in protocol biopsies. AMR events developed in 33.3% and 19.7% (p=0.176) in the DSA and the non-DSA groups, respectively. ACR events were found in 16.6% and 6.6% (p=0.127) in the DSA and non-DSA groups, respectively. Graft function was similar between groups at the end of the 1st year posttransplant and no immunological graft loss occurred. CONCLUSION: Despite the use of depleting induction therapy and adequate tacrolimus trough levels along with MMF and steroids, a high rate of rejection events was observed during the first year post-transplantation.

KDIGO clinical practice guideline on the evaluation and care of living kidney donors

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.

KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors is intended to assist medical professionals who evaluate living kidney donor candidates and provide care before, during and after donation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach and guideline recommendations are based on systematic reviews of relevant studies that included critical appraisal of the quality of the evidence and the strength of recommendations. However, many recommendations, for which there was no evidence or no systematic search for evidence was undertaken by the Evidence Review Team, were issued as ungraded expert opinion recommendations. The guideline work group concluded that a comprehensive approach to risk assessment should replace decisions based on assessments of single risk factors in isolation. Original data analyses were undertaken to produce a "proof-in-concept" risk-prediction model for kidney failure to support a framework for quantitative risk assessment in the donor candidate evaluation and defensible shared decision making. This framework is grounded in the simultaneous consideration of each candidate's profile of demographic and health characteristics. The processes and framework for the donor candidate evaluation are presented, along with recommendations for optimal care before, during, and after donation. Limitations of the evidence are discussed, especially regarding the lack of definitive prospective studies and clinical outcome trials. Suggestions for future research, including the need for continued refinement of long-term risk prediction and novel approaches to estimating donation-attributable risks, are also provided.In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) Living Kidney Donor Work Group. KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors. Transplantation. 2017;101(Suppl 8S):S1-S109.

Summary of Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.

Kidney Disease: Improving Global Outcomes (KDIGO) engaged an evidence review team and convened a work group to produce a guideline to evaluate and manage candidates for living kidney donation. The evidence for most guideline recommendations is sparse and many "ungraded" expert consensus recommendations were made to guide the donor candidate evaluation and care before, during, and after donation. The guideline advocates for replacing decisions based on assessments of single risk factors in isolation with a comprehensive approach to risk assessment using the best available evidence. The approach to simultaneous consideration of each candidate's profile of demographic and health characteristics advances a new framework for assessing donor candidate risk and for defensible shared decision making.

Anti-HLA-DQ antibodies are highly and independently related to the C1q-binding capacity of HLA antibodies.

The complement-binding capacity of anti-HLA antibodies (HLAabs) is recognized as a key pathogenic factor. The aim of this study is to describe the patient characteristics associated to the presence of C1q+ as well as those of the Abs per se when associated to C1q binding. METHODOLOGY: This is a cross-sectional, observational, descriptive study of patients with previous sensitizing factors and awaiting a kidney transplant (KT). We determined anti-HLA antibodies and their C1q binding capacity with the C1q assay. RESULTS: Among the 55 included patients, 26 (47.2%) had at least one C1q+ anti-HLAab. A previous transplant history, a greater number of HLAabs, a greater % of class I or class II PRA, the average MFI of all HLAabs, the MFI of the dominant HLAab and the HLAab antigenic specificities against HLA-B, -C and -DQ, all proved to be risk factors associated to the presence of C1q binding HLAabs (C1q+). In the total population, were detected 1268 HLAabs, 230 (18.1%) of which were C1q+. On multivariate analysis, both HLAabs against the HLA-DQ antigenic specificity (OR 9.82 95% CI 5.4-17.6, p<0.001) and the MFI documented by LABScreen®SAB (OR 1.2% CI 1.22-1.3, p<0.001), proved to be risk factors. CONCLUSION: Anti-HLA-DQ antibodies and the MFI (LABScreen®SAB) are highly and independently related to the C1q-binding capacity of HLA antibodies.