Citations

ABSTRACTThis single‐center retrospective study investigated subclinical rejection prevalence and significance in simultaneous pancreas and kidney transplant (SPKT) recipients. We analyzed 352 SPKT recipients from July 2003 to April 2022. Our protocol included pancreas allograft surveillance biopsies at 1, 4, and 12months post‐transplant. After excluding 153 patients unable to undergo pancreas biopsy, our study cohort comprised 199 recipients. Among the 199 patients with protocol pancreas biopsies, 107 had multiple protocol pancreas biopsies in the first year, totaling 323. Subclinical rejection was identified in 132 episodes (41%). Of these, 72% were Grade 1, 20% were indeterminate, and 8% were Banff Grade 2 or higher. All episodes of subclinical rejection were treated. Rates of pancreas graft loss (10% vs. 7%) and clinical rejection (21% vs. 20%) at 3 years were similar between those with and without subclinical rejection. Subclinical rejection Banff Grade 2 or more was associated with poor pancreas graft survival HR of 5.5 (95% CI: 1.24–24.37, p = 0.025). Of 236 simultaneous protocol kidney and pancreas biopsies, 102 (43%) showed pancreas subclinical rejection, while only 17% had concurrent kidney subclinical rejection. Our findings suggest limited predictive value of pancreatic enzymes and euglycemia in detecting pancreas rejection. Furthermore, poor concordance existed between pancreas and kidney subclinical rejection.

The Hispanic population of the United States is the second largest racial or ethnic group, comprising 18.7% of the population. However, this population is incredibly heterogeneous differing in genetic traits, cultural upbringing, educational backgrounds, and financial status. The impact of this heterogeneity on the prevalence and outcomes of renal disease and kidney transplantation is understudied compared with non-Hispanic White and Black populations. What is known appears to be underrecognized. This review aims to critically assess current medical literature on Hispanic individuals, focusing on etiological factors, disease progression, and outcomes related to CKD and kidney transplantation. By doing so, we aim to underscore key areas for further in-depth investigation.

The value of the crossmatch test in assessing pretransplant immunological risk is vital for clinical decisions, ranging from the indication of the transplant to the guidance of induction protocols and treatment with immunosuppressants. The crossmatch tests in transplantation can be physical or virtual, each with its advantages and limitations. Currently, the virtual crossmatch stands out for its sensitivity and specificity compared to the physical tests. Additionally, the virtual crossmatch can be performed in less time, allowing for a reduction in cold ischemia time. It shows a good correlation with the results of physical tests and does not negatively impact graft survival. Proper communication between clinicians and the transplant immunology laboratory will lead to a deeper understanding of each patient’s immunological profile, better donor–recipient selection, and improved graft survival.

Background. The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods. A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results. We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]‚ respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion. Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.

Many clinical laboratories supporting solid organ transplant programs use multiple HLA genotyping technologies, depending on individual laboratory needs. Sequence‐specific primers and quantitative polymerase chain reaction (qPCR) serve the rapid turnaround necessary for deceased donor workup, while sequence‐specific oligonucleotide probe (SSOP) technology is widely employed for higher volumes. When clinical need mandates high‐resolution data, Sanger sequencing‐based typing (SBT) has been the “gold standard.” However, all those methods commonly yield ambiguous typing results that utilize valuable laboratory resources when resolution is required. In solid organ transplantation, high‐resolution typing may provide critical information for highly sensitized patients with donor‐specific anti‐HLA antibodies (DSA), particularly when DSA involve HLA alleles not discriminated by SSOP typing. Arguments against routine use of SBT include assay complexity, long turnaround times (TAT), and increased costs. Here, we compare a next generation sequencing (NGS) technology with SSOP for accuracy, effort, turnaround time, and level of resolution for genotyping of 11 HLA loci among 289 specimens from five clinical laboratories. Results were concordant except for SSOP misassignments in eight specimens and 21 novel sequences uniquely identified by NGS. With few exceptions, SSOP generated ambiguous results while NGS provided unambiguous three‐field allele assignments. For complete HLA genotyping of up to 24 samples by either SSOP or NGS, bench work was completed on day 1 and typing results were available on day 2. This study provides compelling evidence that, although not viable for STAT typing of deceased donors, a single‐pass NGS HLA typing method has direct application for solid organ transplantation.

The lymphocyte crossmatch is currently the only cell‐based compatibility assay performed by histocompatibility laboratories for transplant purposes. While in many transplant programs the complement‐dependent cytotoxicity crossmatch (CDCXM) remains in use, when available, the flow cytometry crossmatch (FCXM) is the method of choice because of its superior sensitivity and specificity. Unfortunately, the maintenance and cost of a flow cytometer is a considerable limitation for small histocompatibility laboratories. Therefore, in this study, we evaluated the use of the Cellometer Vision CBA image cytometer (Nexcelom Bioscience LLC, Lawrence, Massachusetts) as an alternative instrument to perform the crossmatch assay. The 3‐color FCXM protocol was modified into two separate 2‐color panel image cytometry crossmatches (IXMs), one for T cells and one for B cells. After initial serum and cell incubation, a cocktail consisting of PE/Cy5‐conjugated anti‐human CD3 or CD19 and PE‐conjugated anti‐human IgG F(ab′)2was added to the T cell and B cell panels, respectively. The final cell preparation was added to a separate counting chamber. Images were captured using the Cellometer Vision CBA, an image cytometer designed for cell counting, size analysis and fluorescence intensity measurement. Thirty‐nine IXMs were performed and compared with the FCXM. We obtained a concordance sensitivity of 94.1% and 100% and specificity of 100% and 88.9% for T cells and B cells, respectively. The linearity of the system was verified using dilutions of a sample containing known donor‐specific anti‐HLA antibodies (DSA) against the target cells. This feasibility study demonstrates that the FCXM test could be easily adapted to the Cellometer Vision CBA image cytometer without compromising specificity and sensitivity. The low instrumentation cost, minimal maintenance, and simple operation allow for efficient implementation or transition from the FCXM to the IXM method.

AbstractBackgroundBefore the 2014 policy change pertaining to infectious disease screening, many organ procurement organizations (OPOs) were supplementing serologic screening of deceased organ donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV‐1), hepatitis B virus (HBV), and hepatitis C virus (HCV). The number of seronegative,NAT‐positive donors has not been directly measured.MethodsHIV,HBV, andHCVscreening results of 11 229 donor referrals evaluated from 2010 to 2013 were obtained from 3OPO‐affiliated laboratories, capturing 35% of all donors in the United States. Laboratories used either polymerase chain reaction assay or transcription‐mediated amplification assay to test 9643 deceased donors byNAT.ResultsTheNATresults were positive in 21 (0.2%), 1 (0.02%), and 11 (0.1%) donors who were seronegative forHIV,HBV, andHCV, respectively. All discordantHIV‐1 results were from one laboratory using a polymrease chain reaction assay. Thirteen of the reactiveHIV NATresults in seronegative referrals were repeated and were non‐reproducibly positive (NRP). Ten (0.1%), 452 (7.8%), and 197 (2.2%) ofHIV‐,HBV‐, andHCV‐seropositive donors, respectively, were negative byNAT.ConclusionsThis study highlights the importance of robust quality assurance to minimizeNRP NATresults.NATmay allow for increased utilization of organs fromHBV‐ andHCV‐seropositive,NAT‐negative donors.