Varicella zoster virus serostatus before and after kidney transplantation, and vaccination of adult kidney transplant candidates

In recent years we observed 3 lethal primary varicella infections in adult kidney transplant recipients. Therefore, we wondered how many of our adult renal transplant patients were not protected against varicella zoster virus (VZV), and therefore were at risk for such a primary infection. We also studied the prevalence of VZV seronegativity in the adult patients on our waitlist for kidney transplantation. Finally, we vaccinated these seronegative patients with an attenuated live vaccine. Sera were obtained from 854 transplanted patients, and from 286 candidates on the waitlist for kidney transplantation. We observed that 2.1% of our renal transplant recipients and 3.2% of the patients on the waitlist were seronegative for VZV. We vaccinated 11 seronegative patients on the waitlist twice without side effects. In 7 of 11 patients this resulted in a positive serologic response. In conclusion, the prevalence of VZV seronegativity was low both in renal transplant recipients (2%) and in patients on the waitlist (3%). Vaccination of transplant candidates resulted in a moderate efficiency of 64%.     

Immune status assessment in adult lung transplant candidates

BackgroundLung transplant recipients have an increased susceptibility to a variety of infections due to immunosuppressive therapy. Current guidelines recommend pneumococcal and other vaccinations, prior to lung transplantation to protect against post-transplant infections, but measurement of the antibody response to vaccination is not advised. Immune status investigation in lung transplant candidates, including the response to pneumococcal polysaccharide vaccination, has not been described.MethodsImmune status investigation, including measurement of immunoglobulins, complement and the response to 23-valent pneumococcal polysaccharide vaccination (23vPPV) was performed in 81 adult lung transplant candidates.ResultsEighteen patients had low IgG levels and 32 patients had low IgG1 and/or IgG2 levels. After vaccination with 23vPPV the median antibody concentration of all serotypes increased significantly. Fifty-two patients had protective IgG-post-vaccination antibody levels to at least 10 serotypes. Twenty-nine patients had an impaired response to 23vPPV.ConclusionsIn conclusion, a significant proportion of our cohort of lung transplant candidates had one or more abnormalities in the immune status. It is likely that these patients have an increased risk for infections after transplantation. Revaccination, including measurement of antibody response, and possibly antibody replacement therapy should be considered to minimize infection risk.     

The impact of multi-organ transplant allocation priority on waitlisted kidney transplant candidates

Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas–kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the “next-sequential KAT candidate” who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.     

Immunoadsorption of sensitized kidney transplant candidates immediately prior to surgery

Patients with anti-human leucocyte antigen (HLA) antibodies from previous transplantation, blood transfusion are highly sensitized and at risk to hyperacute renal graft loss. As these antibodies are identified to be of pathogenic importance, an effective removal may allow successful transplantation. Six 'high risk patients' [panel-reactive antibodies (PRA) >30% or retransplanted patients with an acutely rejected first graft within 6 months from surgery] were treated by protein A immunoadsorption (IA) immediately prior to transplantation. We treated the calculated plasma volume one to three times prior to surgery: mean 4600 mL (range 2100-10 200 mL). After transplantation we repeated the sessions according to antibody (Ab) recurrence, graft function and signs of rejection. The panel reactive Ab were reduced from mean 65% pre-IA (range 35-85) to lowest 15% (range 0-55). After the course they reappeared to 30% (range 0-90). Five of the six patients had no clinical signs of vascular rejection. At a follow-up of mean 54 months (+/-14) four grafts still function with a mean serum creatinine of 172 micromol/L (+/-57). Protein A IA is a safe and effective adjunct in the treatment of highly sensitized patients awaiting renal transplantation. The treatment immediately prior to operation can prevent hyperacute rejection and increases the graft survival in these patients.     

Limited health literacy and adverse outcomes among kidney transplant candidates

More than one‐third of US adults have limited health literacy, putting them at risk of adverse clinical outcomes. We evaluated the prevalence of limited health literacy among 1578 adult kidney transplant (KT) candidates (May 2014‐November 2017) and examined its association with listing for transplant and waitlist mortality in this pilot study. Limited health literacy was assessed at KT evaluation by using a standard cutoff score ≤5 on the Brief Health Literacy Screen (score range 0‐12, lower scores indicate worse health literacy). We used logistic regression and adjusted Cox proportional hazards models to identify risk factors for limited health literacy and to quantify its association with listing and waitlist mortality. We found that 8.9% of candidates had limited health literacy; risk factors included less than college education (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI]:1.86‐4.43), frailty (aOR = 1.85, 95% CI:1.22‐2.80), comorbidity (Charlson comorbidity index [1‐point increase] aOR = 1.12, 95% CI: 1.04‐1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20‐5.41) after adjusting for age, sex, race, and income. Candidates with limited health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54‐0.91) decreased likelihood of listing and a 2.42‐fold (95% CI: 1.16‐ to 5.05‐fold) increased risk of waitlist mortality. Limited health literacy may be a salient mechanism in access to KT; programs to aid candidates with limited health literacy may improve outcomes and reduce disparities.     

Risk-stratified screening for ischemic heart disease in kidney transplant candidates

BACKGROUND: Few studies have examined the effectiveness of a risk-stratified approach to screening kidney transplantation candidates for ischemic heart disease (IHD). METHODS: We retrospectively reviewed records from all adult patients (n = 514) placed on the deceased donor kidney transplantation waiting list at a single center between January 1992 and June 2000. During this time there was a consistent policy for high-risk patients to undergo noninvasive stress testing and/or coronary angiography. We examined screening tests, the resulting interventions, and the incidence of subsequent IHD events (myocardial infarction, angioplasty, bypass surgery, or IHD death) among those screened and not screened. RESULTS: For 224 (43.6%) low-risk patients who were not screened, the actuarial incidence of an IHD event after listing (before or after transplantation) was only 0.5% at 1 year, 3.5% at 3 years, and 5.3% at 5 years. Screening 290 (56.4%) high-risk patients resulted in prophylactic angioplasty in 18 (6.2%), and bypass surgery in 8 (2.8%) before listing. After listing, 61 patients were screened, resulting in angioplasty in 6 (9.8%) and bypass surgery in 1 (1.6%). Of the 68 patients who ultimately had an IHD event after being placed on the waiting list, only 13 (19.4%) had not been screened. CONCLUSIONS: A risk-stratified screening strategy effectively avoided unnecessary testing in 43.6%. However, the relatively low proportion of screened patients who underwent prophylactic angioplasty or bypass grafting raises the question of whether screening was effective in preventing IHD events.     

Evaluation of candidates for living donor kidney transplantation

Living donor kidney transplantation has become the option of preference for the treatment of endstage renal disease, whenever its performance is possible. The advantages of patient and graft survival should be balanced with risks associated with donation. Therefore, the evaluation of candidates for living donor kidney transplantation is mainly the comprehensive evaluation of these risks: medical, psychological, social and economic. Evaluating risks implies we are treating a controversial process, the medical progress, which is modifiable with time, even in the family and/or social environment of the donor-receptor couple. Short and long-term safety of living donor nephrectomy is directly engaged to the existence of a healthy donor. This he is the main objective of standard evaluation of candidates. Currently, with a growing demand of this option, minor abnormalities or risk factors detected during evaluation do not always become a formal contraindication, but we should try to establish a most objective threshold for the acceptance of donors in all evaluated spheres, for surgical risks and others directly related or not with renal mass reduction, and even for those engaged to the existence of a genetic link between donor and receptor, which might determine the presence of any future primary renal disease. As for other donation types, the process of evaluation should also ensure minimal risks for the receptor, with the same safety criteria applied to cadaver donors. We can conclude that careful evaluation of candidates for living kidney donation is the best guarantee for their safety and transplant success, and, in our opinion, it is the best instrument to offer an adequate informed consent.     

Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates

Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3⁺, CD3⁺/CD4⁺, CD3⁺/CD8⁺ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.     

Evaluation of proteinuria in healthy living kidney donor candidates

BACKGROUND: Evaluation of living kidney donor candidates includes careful assessment for the presence or absence of kidney disease. Kidney donation has been considered to be at least relatively contraindicated if urinary total protein excretion is above the normal range. However, at the present time, there is no uniformly accepted level of urine total protein excretion that would exclude donation. Albumin excretion instead of total protein excretion as a criterion has not previously been evaluated. MATERIALS AND METHODS: This was a prospective observational study over a 3-year period in a single tertiary care center designed to assess current selection criteria for kidney donation with respect to urine total protein and albumin excretion. RESULTS: Twenty four percent (25 of 105) of healthy adult kidney donor candidates had elevated urinary total protein excretion rates (150 to 292 mg/24 h). Of these 105 candidates, 39 had simultaneous measurements of both urinary total protein and albumin. Although one-third (13/39) had elevated 24-hour urine total protein values, none had elevated urine albumin excretion. CONCLUSION: Measurement of albumin, the most common single protein found in urine, appears to be helpful in the evaluation of proteinuria in donor candidates. Many healthy adult kidney donor candidates have mildly elevated total protein excretion but normal albumin excretion. We believe that such patients should not be excluded from donation.     

Use of direct‐acting agents for hepatitis C virus‐positive kidney transplant candidates and kidney transplant recipients

In some parts of the world, hepatitis C virus (HCV) infection remains a huge problem for kidney transplant candidates and kidney transplant (KT) recipients. Until 2 years ago, anti‐HCV treatment for the general population relied on pegylated alpha‐interferon plus ribavirin, but led to a sustained viral response (SVR) in <50% of cases. This treatment was contraindicated in KT patients because of acute‐rejection issues and was poorly tolerated in patients with end‐stage renal disease (ESRD). Over the last year, direct‐acting antiviral agents (DAAs) have entered the market and are associated in the general population with a SVR of >90%, whatever the patient's HCV genotype. In KT patients, sofosbuvir‐based therapy is associated with a SVR at nearly 100% in patients with a HCV genotype‐1 infection, with almost no side effects and only mild interference with immunosuppressive drugs. Most HCV(+) patients with ESRD are genotype 1: in that setting, a recent study reported that the association of grazoprevir/elbasvir 100/50 mg/day led to a SVR of nearly 95% with very few side effects. Thus, it is concluded that DAAs can be safely used and lead to results in KT candidates and KT patients that are as good as those observed in the nonrenal population.     

Effect of high-dose intravenous immunoglobulin on anti-HLA antibodies in sensitized kidney transplant candidates

Limited data exist on the effect of intravenous immunoglobulin (IVIg) on anti-HLA antibodies as determined by solid-phase assays. We reviewed our experience treating sensitized wait-listed kidney transplant recipients with IVIg as a method for desensitization and report our results utilizing Luminex single antigen (LSA) bead assay to quantify antibody reactivity (MFI). Fifteen patients with a cPRA > 40% received 2 g/kg IVIg per month for four months or until transplanted. LSA testing was performed before and after IVIg. Median MFI for anti-class I antibodies fell in 11 (73%) and increased in 4 (27%) patients after IVIg. Similar significant changes in MFI for anti-class II antibodies were observed in 10 patients (66%). Administration of IVIg was associated with a modest decrease in reactivity to both class I and II HLA antigens (median MFI change 493 and 1110, respectively; p < 0.0001) but did not significantly alter mean cPRA (85% before IVIg vs. 80% after IVIg; p = 0.1). Our data suggest a smaller effect of IVIg on HLA antibody reactivity than previously described, leading us to question how best to measure the efficacy of a desensitization protocol in current practice.     

Anesthetic management of infants receiving an adult kidney transplant

Renal transplantation in infants has been associated with a high incidence of acute tubular necrosis and of renal artery thrombosis. Since 1978, 24 infants who received an adult kidney transplant at the University of Minnesota have had aggressive administration of intravenous colloids to increase the central venous pressure to 16-20 mm Hg before renal reperfusion. Acute tubular necrosis developed in only two infants, and there were no cases of renal artery thrombosis. Chest radiographic evidence of pulmonary edema was present in the recovery room in seven patients (29%) and within the first four postoperative days in five patients (21%). Yet, only two infants (8.3%) required postoperative mechanical ventilation beyond 24 h to manage fluid overload. With aggressive intravenous colloid administration, infants in renal failure can receive an adult kidney transplant with a low incidence of active tubular necrosis or renal artery thrombosis, but pulmonary edema may develop requiring ventilatory support.     

Dramatic secular changes in prognosis for kidney transplant candidates in the United States

Over recent decades, numerous clinical advances and policy changes have affected outcomes for candidates of kidney transplantation in the United States. We examined the national Scientific Registry for Transplant Recipients for adult (18+) solitary kidney transplant candidates placed on the waiting list for primary listing from 2001 to 2015. We evaluated rates of mortality, transplantation, and waitlist removal. Among 340 115 candidates there were significant declines in mortality (52 deaths/1000 patient years in 2001‐04 vs 38 deaths/1000 patient years in 2012‐15) and transplant rates (304 transplants/1000 patient years in 2001‐04 vs 212 transplants/1000 patient years in 2012‐15) and increases in waitlist removals (15 removals/1000 patient years in 2001‐04 vs 25/1000 patient years in 2012‐15) within the first year after listing. At 5 years an estimated 37% of candidates listed in 2012‐15 were alive without transplant as compared to 22% in 2001‐04. Declines in mortality over time were significantly more pronounced among African Americans, candidates with longer dialysis duration, and those with diabetes (P < .001). Cumulatively, results indicate dramatic changes in prognoses for adult kidney transplant candidates, likely impacted by selection criteria, donor availability, regulatory oversight, and clinical care. These trends are important considerations for prospective policy development and research, clinical and patient decision‐making, and evaluating the impact on access to care.