A2/A2B to B Renal Transplantation: Past,Present, and Future Directions

One component of the new national kidney allocation system (KAS) in the United States that was implemented on December 4, 2014, was the allocation of kidneys from A₂ and A₂B (A, non‐A₁ and AB, non‐A₁B) deceased donors into blood group B candidates (A₂/A₂B → B). In so far as this is an important component of the new KAS that has the potential to further increase the access to transplantation for blood group B candidates on the waiting list, most of whom are minority candidates, we will review the body of evidence and historical perspectives that led to its inclusion in the new KAS. This review will also describe prospects for more widespread use of A₂/A₂B → B transplantation and a novel mechanism of humoral immunosuppression in B patients before and after transplantation with an A₂ or A₂B kidney.     

Exogenous Lipocalin 2 Ameliorates Acute Rejection in a Mouse Model of Renal Transplantation

Lipocalin 2 (Lcn2) is rapidly produced by damaged nephron epithelia and is one of the most promising new markers of renal injury, delayed graft function and acute allograft rejection (AR); however, the functional importance of Lcn2 in renal transplantation is largely unknown. To understand the role of Lcn2 in renal AR, kidneys from Balb/c mice were transplanted into C57Bl/6 mice and vice versa and analyzed for morphological and physiological outcomes of AR at posttransplantation days 3, 5, and 7. The allografts showed a steady increase in intensity of interstitial infiltration, tubulitis and periarterial aggregation of lymphocytes associated with a substantial elevation in serum levels of creatinine, urea and Lcn2. Perioperative administration of recombinant Lcn2:siderophore:Fe complex (rLcn2) to recipients resulted in functional and morphological amelioration of the allograft at day 7 almost as efficiently as daily immunosuppression with cyclosporine A (CsA). No significant differences were observed in various donor–recipient combinations (C57Bl/6 wild‐type and Lcn2^?/?, Balb/c donors and recipients). Histochemical analyses of the allografts showed reduced cell death in recipients treated with rLcn2 or CsA. These results demonstrate that Lcn2 plays an important role in reducing the extent of kidney AR and indicate the therapeutic potential of Lcn2 in transplantation.

     

TCC in Transplant Ureter—When and When Not to Preserve the Transplant Kidney

We present four cases of transitional cell carcinoma of the transplant ureter (TCCtu). In three cases, localized tumor resection and a variety of reconstructive techniques were possible. Transplant nephrectomy with cystectomy was performed as a secondary treatment in one locally excised case. Transplant nephroureterectomy was performed as primary treatment in one case. The role of oncogenic viruses and genetic fingerprinting to determine the origin of TCCtu are described. Our cases and a systematic literature review illustrate the surgical, nephrological, and oncological challenges of this uncommon but important condition.     

Identifying Subphenotypes of Antibody‐Mediated Rejection in Kidney Transplants

The key lesions in antibody‐mediated kidney transplant rejection (ABMR) are microcirculation inflammation (peritubular capillaritis and/or glomerulitis lesions, abbreviated “pg”) and glomerular double contours (cg lesions). We used these features to explore subphenotypes in 164 indication biopsies with ABMR‐related diagnoses: 137 ABMR (109 pure and 28 mixed with T cell–mediated rejection [TCMR]) and 27 transplant glomerulopathy (TG), identified from prospective multicenter studies. The lesions indicated three ABMR subphenotypes: pgABMR, cgABMR, and pgcgABMR. Principal component analysis confirmed these subphenotypes and showed that TG can be reclassified as pgcgABMR (n = 17) or cgABMR (n = 10). ABMR‐related biopsies included 45 pgABMR, 90 pgcgABMR, and 25 cgABMR, with four unclassifiable. Dominating all time intervals was the subphenotype pgcgABMR. The pgABMR subphenotype presented earliest (median <2 years), frequently mixed with TCMR, and was most associated with nonadherence. The cgABMR subphenotype presented late (median 9 years). Subphenotypes differed in their molecular changes, with pgABMR having the most histologic–molecular discrepancies (i.e. potential errors). Donor‐specific antibody (DSA) was not identified in 29% of pgcgABMR and 46% of cgABMR, but failure rates and molecular findings were similar to cases where DSA was known to be positive. Thus, ABMR presents distinct subphenotypes, early pg‐dominant, late cg‐dominant, and combined pgcg phenotype, differing in time, molecular features, accompanying TCMR, HLA antibody, and probability of nonadherence.     

Estimated GFR for Living Kidney Donor Evaluation

All living kidney donor candidates undergo evaluation of GFR. Guidelines recommend measured GFR (mGFR), using either an endogenous filtration marker or creatinine clearance, rather than estimated GFR (eGFR), but measurement methods are difficult, time consuming and costly. We investigated whether GFR estimated from serum creatinine (eGFRcr) with or without sequential cystatin C is sufficiently accurate to identify donor candidates with high probability that mGFR is above or below thresholds for clinical decision making. We combined the pretest probability for mGFR thresholds <60, <70, ≥80, and ≥90 mL/min per 1.73 m² based on demographic characteristics (from the National Health and Nutrition Examination Survey) with test performance of eGFR (categorical likelihood ratios from the Chronic Kidney Disease Epidemiology Collaboration) to compute posttest probabilities. Using data from the Scientific Registry of Transplant Recipients, 53% of recent living donors had predonation eGFRcr high enough to ensure ≥95% probability that predonation mGFR was ≥90 mL/min per 1.73 m², suggesting that mGFR may not be necessary in a large proportion of donor candidates. We developed a Web‐based application to compute the probability, based on eGFR, that mGFR for a donor candidate is above or below a range of thresholds useful in living donor evaluation and selection.     

A Smartphone App for Increasing Live Organ Donation

The incidence of live donor transplantation has declined over the past decade, and waitlisted candidates report substantial barriers to identifying a live donor. Since asking someone to donate feels awkward and unfamiliar, candidates are hesitant to ask directly and may be more comfortable with a passive approach. In collaboration with Facebook leadership (Facebook Inc., Menlo Park, CA), we developed a mobile application—an app—that enables waitlisted candidates to create a Facebook post about their experience with organ failure and their need for a live donor. We conducted a single‐center prospective cohort study of 54 adult kidney‐only and liver‐only waitlisted candidates using the Facebook app. Cox proportional hazards models were used to describe donor referral on behalf of candidates using the app compared with matched controls. The majority of candidates who used the app reported it to be “good” or “excellent” with regard to the installation process (82.9%), readability (88.6%), simplicity (70.6%), clarity (87.5%) and the information provided (85.3%). Compared with controls, candidates using the Facebook app were _2.436.61_17.98 times more likely to have a donor come forward on their behalf (p < 0.001). The Facebook app is an easy‐to‐use instrument that enables waitlisted candidates to passively communicate with their social network about their need for a live donor.     

De Novo Belatacept in a Human Immunodeficiency Virus–Positive Kidney Transplant Recipient

Benefits of belatacept‐based immunosuppressive regimens in human immunodeficiency virus (HIV)–positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new‐onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV‐positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV‐positive renal transplant recipient.