HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients.

Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.

Prozone rates in the solid-phase platelet crossmatch assay and correlation with class I HLA antibody levels.

BACKGROUND: Solid-phase platelet crossmatch (PXM) testing is used to help manage patients with platelet transfusion-refractoriness. Recently, we published the first report of false-negative PXM results from prozone effect that was mitigated using sample dilution. This study aimed to describe the prevalence of PXM prozone effect and the levels of class I HLA antibodies (HLA-Abs) associated with positive PXM results and with false-negative PXM results from prozone effect. STUDY DESIGN AND METHODS: A cross-sectional study of patients undergoing PXM testing from July 2019 through December 2020 was performed. All PXM tests were run simultaneously using undiluted and 1:4 diluted patient plasma. Prozone effect was defined as a negative PXM result using undiluted patient plasma but a positive PXM result using 1:4 diluted patient plasma. RESULTS: Among 59 patients, 830 individual ABO-compatible PXM results yielded an overall positivity rate of 25.8% (214/830) and a false-negative rate from prozone effect of 4.7% (10/214). Among the 28 patients with class I HLA-Ab testing and no other anti-platelet antibodies, maximum HLA-Ab mean fluorescence intensity (MFI) was significantly associated with a positive PXM result (p < .0001; AUC approx. 0.9) and categorized into negative (<3700), indeterminate (3700-10300), and positive (>10300) maximum HLA-Ab MFI zones. Maximum HLA-Ab MFI, however, was not associated with prozone effect (p = .17; AUC approx. 0.6). DISCUSSION: While there is a strong predictive association between class I HLA-Ab levels and positive PXM results, PXM prozone effect is a common occurrence not associated with class I HLA-Ab levels, so additional testing with diluted samples should be considered.

Daratumumab interference in flow cytometric anti-granulocyte antibody testing can be overcome using non-human blocking antibodies.

BACKGROUND: Daratumumab (DARA), a human IgG1K monoclonal antibody targeting CD38, is used to treat refractory multiple myeloma patients. CD38 is expressed on many cell types (RBCs, granulocytes, lymphocytes, etc.), and thus, DARA can interfere with serological tests. Information regarding how DARA affects anti-granulocyte antibody (AGA) testing and optimal neutralization of DARA will help laboratories perform accurate testing. METHODS: Screening of AGA was performed by the granulocyte agglutination test (GAT) and the flow cytometric granulocyte immunofluorescence test (Flow-GIFT). Samples were tested from patients on DARA (n = 7), non-transfused blood donors (healthy controls, n = 7) and AGA reactive samples (positive controls, n = 5). Two neutralization experiments, CD38 removal with DTT and DARA epitope blockage with mouse anti-CD38, were evaluated. RESULTS: Positive reactivity of human IgG binding was observed in 5/7 DARA cases when tested by Flow-GIFT; however, all 7 cases had negative GAT agglutination results. Further studies by Flow-GIFT revealed DARA concentrations >0·63 µg/ml bound to granulocytes. DARA binding was negated by DTT though a reduced Flow-GIFT sensitivity was observed in positive control samples due to increased background detection of human IgG. Mouse anti-CD38 neutralized the detection of human IgG observed in DARA-treated patient serum without effecting controls. CONCLUSION: We established that DARA can interfere with AGA testing, leading to false positive Flow-GIFT results without causing GAT agglutination. DTT treatment increased background binding of secondary antibodies causing a decrease in Flow-GIFT sensitivity. In comparison, blockage of the DARA binding epitope using mouse anti-CD38 antibody was effective in neutralizing DARA interference while maintaining Flow-GIFT sensitivity.

Development and performance characteristics of Platelet Virtual Crossmatch (PLT VXM), a software application for the evaluation and management of platelet transfusion-refractory patients.

BACKGROUND: Platelet (PLT) transfusion refractoriness increases bleeding complications, hospital stays, and PLT inventory usage. Immune-mediated refractoriness can be evaluated for using a physical PLT crossmatch with ABO-compatible inventory and, if positive, managed with HLA-compatible PLT inventory and donors. Manual completion of these complex tasks can be time-consuming and potentially error-prone. This study was conducted to determine if a Web-based software application could improve process efficiency and accuracy. STUDY DESIGN AND METHODS: Workflow analysis was performed to identify process, data, and analytic requirements for a software application for three PLT transfusion-refractoriness associated tasks: (a) physical PLT crossmatch inventory selection, (b) HLA-compatible inventory selection, and (c) HLA-compatible donor selection. After software application development, a comparison study was performed over 10 consecutive days, with each task performed manually and with the software application (Platelet Virtual Crossmatch [PLT VXM]) for a different unique immune-mediated PLT transfusion-refractory recipient. Task completion time, number of incompatible units/donors presented, and number of documentation errors were compared. RESULTS: PLT VXM is a Web-based software application developed using R and the Shiny Web application framework. PLT VXM significantly reduced median task completion times by 4.5 (49%), 11.2 (79%), and 59.1 minutes (94%), respectively. PLT VXM did not present any incompatible PLT units or donors for user consideration. PLT VXM also had a lower number of documentation errors than the manual process, and none of these documentation errors were software generated. CONCLUSION: Computer-aided evaluation and management of immune-mediated PLT transfusion-refractory recipients can significantly improve workflow and reduce manual errors in this complex process.

False-negative solid-phase platelet crossmatch results due to prozone phenomenon.

Prozone is a known phenomenon affecting immunoassays causing falsely low or negative results when excess target is present in the test system. For assays used to evaluate immune-mediated platelet (PLT) transfusion refractoriness, prozone-like phenomenon has been described in solid-phase human leukocyte antigen (HLA) antibody testing and can be mitigated by diluting samples or pretreating samples with ethylenediaminetetraacetic acid (EDTA) or dithiothreitol. Prozone phenomenon has not yet been described in solid-phase red blood cell (RBC) adherence PLT crossmatch assays. CASE REPORT: A 40-year-old female with myeloid sarcoma and PLT transfusion refractoriness underwent repeated solid-phase PLT crossmatches; however, crossmatch-compatible PLTs units did not yield adequate PLT count responses. Class I HLA antibody testing with neat, diluted, and EDTA-pretreated serum demonstrated significant prozone-like effect and the presence of numerous high strength HLA antibodies. Based on this HLA antibody profile, HLA antigen-negative PLTs gave an adequate PLT count response. It was noted that the HLA types of her crossmatch-compatible PLTs were incompatible with her HLA antibody profile (eg, HLA-A2). With ABO-identical, HLA-A2-positive PLT units, a solid-phase PLT crossmatch was repeated using undiluted and diluted EDTA plasma. Undiluted EDTA plasma demonstrated negative or weakly positive PLT crossmatches while the diluted EDTA plasma demonstrated strongly positive PLT crossmatches. CONCLUSION: The prozone phenomenon can cause false-negative results in solid-phase RBC adherence PLT crossmatch assays, which can be mitigated with sample dilution. In immune-mediated PLT transfusion-refractory patients with high-strength HLA antibodies, sample dilution should be considered to correctly identify compatible PLT inventory.

Variations in hemoglobin measurement and eligibility criteria across blood donation services are associated with differing low-hemoglobin deferral rates: a BEST Collaborative study.

BACKGROUND: Determination of blood donor hemoglobin (Hb) levels is a pre-requisite to ensure donor safety and blood product quality. We aimed to identify Hb measurement practices across blood donation services and to what extent differences associate with low-Hb deferral rates. METHODS: An online survey was performed among Biomedical Excellence for Safer Transfusion (BEST) Collaborative members, extended with published data. Multivariable negative-binomial regression models were built to estimate adjusted associations of minimum donation intervals, Hb cut-offs (high, ≥13.5 g/dL in men or ≥ 12.5 g/dL in women, vs. lower values), iron monitoring (yes/no), providing or prescribing iron supplementation (yes/no), post-versus pre-donation Hb measurement and geographical location (Asian vs. rest), with low-Hb deferral rates. RESULTS: Data were included from 38 blood services. Low-Hb deferral rates varied from 0.11% to 8.81% among men and 0.84% to 31.85% among women. Services with longer minimum donation intervals had significantly lower deferral rates among both women (rate ratio, RR 0.53, 95%CI 0.33-0.84) and men (RR 0.53, 95%CI 0.31-0.90). In women, iron supplementation was associated with lower Hb deferral rates (RR 0.47, 95%CI 0.23-0.94). Finally, being located in Asia was associated with higher low-Hb deferral rates; RR 9.10 (95%CI 3.89-21.27) for women and 6.76 (95%CI 2.45-18.68) for men. CONCLUSION: Differences in Hb measurement and eligibility criteria, particularly longer donation intervals and iron supplementation in women, are associated with variations in low-Hb deferral rates. These insights could help improve both blood donation service efficiency and donor care.

Long-term outcomes of eculizumab-treated positive crossmatch recipients: Allograft survival, histologic findings, and natural history of the donor-specific antibodies.

We aimed to determine the long-term outcomes of eculizumab-treated, positive crossmatch (+XM) kidney transplant recipients compared with +XM and age-matched negative crossmatch (-XM) controls. We performed an observational retrospective study and examined allograft survival, histologic findings, long-term B-cell flow cytometric XM (BFXM), and allograft-loss-associated factors. The mean (SD) posttransplant follow-up was 6.3 (2.5) years in the eculizumab group; 7.6 (3.5), +XM control group; 7.9 (2.5), -XM control group. The overall and death-censored allograft survival rates were similar in +XM groups (P = .73, P = .48) but reduced compared with -XM control patients (P < .001, P < .001). In the eculizumab-treated group, 57.9% (11/19) of the allografts had chronic antibody-mediated rejection, but death-censored allograft survival was 76.6%, 5 years; 75.4%, 7 years. Baseline IgG3 positivity and BFXM ≥300 were associated with allograft loss. C1q positivity was also associated with allograft loss but did not reach statistical significance. Donor-specific antibodies appeared to decrease in eculizumab-treated patients. After excluding patients with posttransplant plasmapheresis, 42.3% (9/21) had negative BFXMs; 31.8% (7/22), completely negative single-antigen beads 1 year posttransplant. Eculizumab-treated +XM patients had reduced allograft survival compared with -XM controls but similar survival to +XM controls. BFXM and complement-activating donor-specific antibodies (by IgG3 and C1q testing) may be used for risk stratification in +XM transplantation.

Karyomegalic interstitial nephritis in a renal allograft.

Karyomegalic interstitial nephritis (KIN) is a rare renal interstitial disease entity characterized by large tubular nuclei, accompanied by interstitial inflammation, tubular atrophy, and interstitial fibrosis. Approximately 50 cases of KIN have been described in the native kidney. In this case study, we describe the first case of KIN in a kidney allograft. A 41-year-old man presented with declining kidney function and a serum creatinine of 2.7 mg/dL. The native kidney biopsy showed large pleomorphic nuclei in the proximal and distal tubular epithelial cells, which was associated with interstitial inflammation, and extensive interstitial fibrosis and tubular atrophy. Immunohistochemistry for cytomegalovirus, adenovirus, and simian virus 40 were negative. A diagnosis of KIN was rendered. The patient received a living-related kidney transplant from his sister. At 4-, 12-, and 24-months posttransplant, protocol allograft biopsies showed KIN with large pleomorphic nuclei in the proximal and distal tubules with mild interstitial inflammation, minimal tubular atrophy, and interstitial fibrosis. At 24.7 months of follow-up, the patient has stable renal function with a serum creatinine of 1.6 mg/dL. The KIN may represent recurrent KIN or donor-associated KIN. Recognition of this rare disease entity is important as it can be mistaken for a viral infection.

Extracorporeal Photopheresis Improves Survival in Hematopoietic Cell Transplant Patients with Bronchiolitis Obliterans Syndrome without Significantly Impacting Measured Pulmonary Functions.

We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non-ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV1 percentage predicted (FEV1PP) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV1PP before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non-ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, -9.5 versus -1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.

De novo donor-specific antibody following BK nephropathy: The incidence and association with antibody-mediated rejection.

BACKGROUND AND OBJECTIVES: The risk of de novo donor-specific antibody (dnDSA) development following BK viremia (BKV) or nephropathy (BKN) after kidney transplant remains unclear. We aimed to evaluate the relationships among dnDSA, BKV (BK blood PCR > 15 000 copies), BKN, antibody-mediated rejection (AMR), and allograft loss. PATIENTS AND METHODS: We performed a retrospective cohort study of 904 solitary kidney transplant recipients transplanted between 10/2007 and 5/2014. Cox proportional hazards regression with time-dependent covariates were used to assess the relationships among BKN, isolated BKV, dnDSA, and the subsequent risk of AMR and allograft loss. RESULTS: In multivariate analysis, we observed that BKN, but not BKV was a risk factor for dnDSA (HR, 3.18, P = .008). Of the patients with BK nephropathy, 14.0% (6/43) developed dnDSA, which occurred within 14 months of BK diagnosis. DnDSA in this setting remains a risk factor for subsequent AMR (HR 4.75, P = .0001) and allograft loss (HR 2.63, P = .018). CONCLUSIONS: BKN is an independent risk factor for development of dnDSA. Improved understanding of the characteristics of patients with BKN who are at highest risk for development of dnDSA would be valuable to customize immunosuppression reduction in this population.

A brief overview of clinical significance of blood group antibodies.

CONCLUSIONS: This review was derived from a presentation made on September 2, 2016 for the first Academy Day presented by the Working Party on Immunohematology at the International Society of Blood Transfusion (ISBT) Congress in Dubai. The focus of this review is to provide a brief overview of the clinical significance of blood group antibodies. Blood group antibodies can be naturally occurring (e.g., anti-A and anti-B through exposure to naturally occurring red blood cell [RBC] antigen-like substances) or can occur via exposure to foreign (donor) RBC antigens through previous transfusions, transplants, or exposure to fetal RBCs during or after pregnancy. However, not all blood group antibodies are clinically significant. Clinically significant blood group antibodies can cause adverse events after blood component transfusion or transplantation and/or can cause hemolytic disease of the fetus and newborn.

How do I manage the platelet transfusion-refractory patient?

BACKGROUND: Platelet transfusion-refractoriness is a challenging and expensive clinical scenario seen most often in patients with hematologic malignancies. Although the majority of platelet transfusion-refractory cases are due to nonimmune causes, a significant minority are caused by alloimmunization against Class I human leukocyte antigens (HLAs) or human platelet antigens (HPAs). Such platelet transfusion-refractory patients can be effectively managed with appropriate antigen-negative products. STUDY DESIGN AND METHODS: Our institution has developed a diagnostic and management algorithm for the platelet transfusion-refractory patient with an early focus on identifying those cases caused by immune-mediated factors. Using physical platelet cross-matches to initially classify platelet transfusion-refractory patients as immune-mediated or not, cross-match-compatible inventory is then provided to immune-mediated patients, whereas subsequent HLA (with or without HPA) testing is performed. RESULTS: Our blood donor program performs Class I HLA typing of all repeat platelet donors to facilitate the identification of antigen-negative platelet units (virtual cross-matching) as well as the recruitment of HLA-matched donors. The platelet transfusion-refractoriness algorithm realizes an initial net cost savings once two apheresis platelets are saved from use for each newly identified, immune-mediated platelet transfusion-refractory patient. CONCLUSION: An algorithm utilizing physical platelet cross-matches, Class I HLA and HPA antibody testing, and upfront Class I HLA typing of platelet donors leads to overall resource savings and improved clinical management for platelet transfusion-refractory patients.

Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant.

OBJECTIVE: HLA-DPB1 matching may impact allogeneic hematopoietic stem cell transplantation (ASCT) outcomes; however, this locus is not in linkage disequilibrium with the remainder of the HLA genes. After classifying HLA-DPB1 mismatches based on T-cell epitope, avoiding non-permissive mismatches may impact survival. We tested this hypothesis at a single academic institution. METHODS: Retrospective HLA-DPB1 genotyping was performed on 153 adult patients who underwent ASCT and unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 loci (10/10). Using the ImMunoGeneTics/HLA T-cell epitope matching algorithm, mismatch status was classified as permissive or non-permissive. RESULTS: Of 153 donor-recipient pairs, 22 (14.4%) were HLA-DPB1 matches, 64 (42.8%) permissive mismatches, and 67 (43.8%) non-permissive mismatches. DPB1 mismatch increased risk of chronic graft-versus-host disease (cGVHD; RR 2.89 [1.19-9.53], P=.016) compared with DPB1-matched transplants, but there were no differences in overall mortality, risk of relapse, or acute GVHD (aGVHD). Combining matches and permissive mismatches and comparing to non-permissive mismatches, there was no significant difference in overall survival or relapse; however, patients receiving non-permissive mismatched transplants experienced greater risk of aGVHD overall and severe aGVHD (RR 1.66 [1.13-2.44], P=.010 and RR 1.97 [1.10-3.59], P=.024, respectively). CONCLUSION: In this single-center study, HLA-DPB1 matching influenced outcomes of patients undergoing ASCT for hematologic malignancy.

Comparison of two double red cell collection settings on Fenwal Alyx apheresis instrument.

The Fenwal Alyx for collecting double red cell products has two red cell volume collection settings: fixed collection target of 360 ml (180 ml/unit) and a variable target of collecting either 400 or 360 ml (200 or 180 ml/unit), where the machine aims for the higher possible collection target. We retrospectively compared the two collection targets for the RBC content, donor time, technician time, and collection efficiency. We compared 18 fixed (F) target collections to 40 variable (V) target collections. All collections were performed as per the manufacturer's recommendations on Alyx and donors met the manufacturer's eligibility criteria. There was no significant difference in average whole blood processed (F: 963 ml, V: 1,000 ml); donor time (F: 43 min, V: 45 min) or technician time (F: 64 min, V: 64 min). There was a significant difference in unit volume (F: 283 ml, V: 300 ml); grams Hb/unit (F: 53 g, V: 57 g); ml RBC/unit (F: 157 ml, V: 167 ml); and RBC recovery (F: 87.8%, V: 88.9%). The fixed target had a significantly lower frequency of products with ≥51 g Hb (80.6%) than variable target (96.3%) and ≥153 ml RBC/unit (F: 55.6%, V: 96.3%). In conclusion, the variable target efficiently allows collections of products with higher red cell volume and hemoglobin without a significant increase in collection and processing time.

Hemovigilance and the Notify Library.

CONCLUSIONS: Hemovigilance systems allow reporting of adverse occurrences associated with blood transfusion to a central database where events can be reviewed and analyzed for the benefit of patients and donors. Hemolytic and serologic transfusion reactions are among the many types of reactions reported to these systems. The Notify Library, a database of adverse events associated with medical products of human origin, has incorporated hemovigilance into its didactic resources. Students and practitioners are encouraged to use the electronic library and to further enhance this resource through review and recommendation of additional publications in the area of immunohematology.

Double red blood cell collection: comparison of three apheresis systems.

BACKGROUND: We compared three instruments for double red blood cell (DRBC) collection to efficiently optimize our RBC inventory. STUDY DESIGN AND METHODS: Instruments compared were the TerumoBCT Trima Accel (Trima), the Fenwal Alyx (Alyx), and the Haemonetics MCS+ 8150 (MCS+). Forty consecutive collections (80 products) per instrument were evaluated for hemoglobin (Hb) content, leukoreduction, collection time, instrument efficiency, donor acceptance, and reactions. The total number of whole blood donors who could be eligible for DRBC collection was analyzed. All collections were as per the manufacturer recommendations with target volume of 360 or 400mL. Leukoreduction was integral to the collection procedure for the Alyx and Trima, while it was a separate process for the MCS+. RESULTS: The total numbers of whole blood donors who could be eligible for DRBC collection were 10,116 for the MCS+, 9378 for the Alyx, and 8573 for the Trima. All units collected had more than 42.5 g of Hb. Mean Hb levels were as follows: Trima, 59.2 g; Alyx, 56.8 g; and MCS+, 51.5 g. Donor times for the Trima, Alyx, and MCS+ were 52, 45, and 52 minutes, respectively. Technician times for the Trima, Alyx, and MCS+ (without filtration) were 87, 73, and 64 minutes. All collected products had fewer than 5 × 10(6) white blood cells. CONCLUSIONS: All three instruments would be capable of collecting an acceptable leukoreduced DRBC product. The Alyx was most portable, with the shortest donor time and total technician time (considering filtration time) and highest collection efficiency and would collect from more donors than the Trima. We thus chose the Alyx as it best fits the specific needs of our center.

Recipient clinical risk factors predominate in possible transfusion-related acute lung injury.

BACKGROUND: Possible transfusion-related acute lung injury (pTRALI) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome (ARDS). We questioned whether transfusion factors are important for the development of pTRALI. STUDY DESIGN AND METHODS: In this nested case-control study, we prospectively identified 145 consecutive patients with pTRALI and randomly selected 163 transfused controls over a 4-year period at the University of California at San Francisco and the Mayo Clinic (Rochester, Minnesota). RESULTS: For pTRALI, we found evidence against transfusion being important: receipt of plasma from female donors (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.29-2.3; p = 0.70), total number of units transfused (OR, 0.99; 95% CI, 0.89-1.10; p = 0.86), and number of red blood cell and whole blood units transfused (OR, 0.78; 95% CI, 0.59-1.03; p = 0.079). In contrast, we found that risk for pTRALI was associated with additional recipient factors: chronic alcohol abuse (OR, 12.5; 95% CI, 2.8-55; p < 0.001), current smoker (OR, 4.2; 95% CI, 1.67-10.8; p = 0.0024), shock before transfusion (OR, 4.6; 95% CI, 2.0-10.7; p < 0.001), and positive fluid balance before transfusion (OR, 1.32/L; 95% CI, 1.20-1.44; p < 0.001). CONCLUSION: Recipient risk factors for ARDS rather than transfusion risk factors predominate in pTRALI.

Clinical findings, pathology, and outcomes of C3GN after kidney transplantation.

C3 glomerulonephritis (C3GN) results from abnormalities in the alternative pathway of complement, and it is characterized by deposition of C3 with absent or scant Ig deposition. In many patients, C3GN progresses to ESRD. The clinical features, pathology, and outcomes of patients with C3GN receiving kidney transplantation are unknown. Between 1996 and 2010, we identified 21 patients at our institution who received a kidney transplant because of ESRD from C3GN. The median age at the time of initial diagnosis of C3GN at kidney biopsy was 20.8 years. The median time from native kidney biopsy to dialysis or transplantation was 42.3 months. Of 21 patients, 14 (66.7%) patients developed recurrent C3GN in the allograft. The median time to recurrence of disease was 28 months. Graft failure occurred in 50% of patients with recurrent C3GN, with a median time of 77 months to graft failure post-transplantation. The remaining 50% of patients had functioning grafts, with a median follow-up of 73.9 months. The majority of patients had hematuria and proteinuria at time of recurrence. Three (21%) patients were positive for monoclonal gammopathy and had a faster rate of recurrence and graft loss. Kidney biopsy at the time of recurrence showed mesangial proliferative GN in eight patients and membranoproliferative GN in six patients. All allograft kidney biopsies showed bright C3 staining (2-3+), with six biopsies also showing trace/1+ staining for IgM and/or IgG. To summarize, C3GN recurs in 66.7% of patients, and one half of the patients experience graft failure caused by recurrence.