Longitudinal analysis of living donor kidney transplant rates in pediatric candidates in the United States.

Among adults, living donor kidney transplant rates began declining in the United States after 2004 but whether a similar decline is occurring in the pediatric candidates has not been well studied. Share 35, a change in allocation rules implemented in October of 2005, may also have influenced rates of living donation. We sought to determine whether a decline in rates was occurring in pediatric candidates and whether the Share 35 program was the cause of the decline. All children listed for a kidney transplant or transplanted with a living donor without listing between 1996 and 2011 were identified in the United States (N=14 911) of which 6046 had received a living donor transplant during follow-up. Kaplan-Meier analysis showed a decline in living donor rates in candidates listed after 2001. Logistic regression analysis for living donor kidney transplantation confirmed the timing of the drop but also showed that changes in candidate demographics and center listing practices were impacting rates. A large drop in parental donation was the main cause for the drop. The rate of living donor transplant among pediatric candidates declined after 2001 predating by 4 years the implementation of Share 35, suggesting that factors other than changes in allocation rules are responsible for the decline.

Therapeutic apheresis in renal transplantation; current practices.

Apheresis is an important treatment modality for the removal of pathologic antibodies and circulating proteins in kidney transplantation. The use of apheresis has been shown to be a necessary preconditioning component in ABO incompatible kidney transplant. Removal of pathologic anti-A and anti-B antibodies has been accomplished with a variety of apheresis modalities including plasma exchange, fractional plasma exchange, and immunoabsorption techniques. Using these modalities in conjunction with potent modern immunosuppression, ABO incompatible kidney transplants have achieved graft and patient survivals similar to that seen in ABO compatible transplants. Apheresis has also been an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both for the purposes of desensitization and treatment of antibody mediated rejection of the kidney. Although good randomized controlled trials are lacking in the treatment of acute antibody mediated rejection, most treatment regimens include the use of apheresis as an essential component for reduction of anti-HLA antibody titers. Similarly, a variety of desensitization protocols have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted in the presence of donor-specific HLA antibodies. Most of these protocols involve apheresis to improve the removal of pathologic antibodies. Finally, aphereis has been used with mixed success for the treatment of recurrent focal segmental glomerulosclerosis. Evidence indicates that in some cases a circulating factor exists which apheresis can remove and ameliorate the nephrotic proteinuria.

Mechanical Preservation and Delayed Graft Function and Hospital Length of Stay as Deployed in the United States: Analysis of the Last Decade.

BACKGROUND Mechanical preservation (MP) of deceased donor kidney transplants showed a 30% to 50% reduction in delayed graft function (DGF) as defined by dialysis in the first week, when compared with cold storage. DGF is associated with longer hospital stays and increased costs. In this study, we sought to understand the impact of MP on rates of DGF and length of hospital stays in a contemporary cohort of deceased donor kidney transplants in the United States. MATERIAL AND METHODS All single deceased donor kidney transplants performed between January 1, 2010, and September 2, 2020, were identified in the Scientific Registry of Transplant Recipients database. Donor kidneys were considered pumped if the transplant center received the kidney on the pump. RESULTS Multivariate logistic regression showed that MP had similar odds of reduction of DGF for all subsets of donors. The unadjusted rate of DGF for pumped brain-dead standard criteria donor (BDSCD) recipients was similar to that of donors stored on ice. The rate of DGF for expanded criteria donors (ECD) and donors after cardiac death (DCD) was lower in the recipients who received MP. The similar DGF rates in BDSCD donor recipients were due to longer cold ischemia times in MP kidneys. The lower DGF rates seen in ECD and DCD recipients of pumped kidneys did not translate into a shortened length of hospitalization after transplant. CONCLUSIONS As currently deployed, only DCD and ECD donor recipients of MP kidneys experienced a lower DGF rate. In all subsets of patients, MP did not appreciably shorten the hospital length of stay.

Parsing the 100% calculated panel reactive antibody kidney transplant candidates: Who gets transplanted?

The new kidney allocation system in the United States has improved deceased donor transplant rates among candidates with high calculated panel reactive antibodies (CPRAs). Probability analysis predicts a very low transplant rate as the CPRA approaches 100%. This study sought to determine if the rate of deceased donor kidney transplant based on the actual CPRA in the cohort of 100% qualifying candidates behaved as predicted by probability analysis. Nine thousand two hundred and twenty eight patients were identified on the waiting list on or after December 2014 that had at least one CPRA greater than or equal to 99.5%. The distribution of the 100% CPRA group was highly skewed toward 100% (Median CPRA 99.98%). The decile group within the 100% CPRA qualifying population was by far the most important factor determining kidney transplantation. The highest two deciles of CPRA had a very low rate of transplantation. Options to improve the prospects of deceased donor transplant include intelligently lowering the CPRA by reducing unacceptable antigens, expanding the donor pool by listing candidates for higher risk donors, or through desensitization. The CPRA calculator should display the non-integer CPRA out to several decimal points so that informed decisions can be made for these candidates regarding their prospects of receiving a deceased donor offer.

Impact of comorbidities on mortality in managed care patients with CKD.

BACKGROUND: Our previous work showed that patients with chronic kidney disease (CKD) were 10 times more likely to die than progress to end-stage renal disease. This study examines the impact of comorbidities on mortality risk in a cohort with CKD at 3 levels of progression and a sex- and age-matched comparison group. METHODS: In a historical, prospective, cohort study, we selected electronic medical record data for health maintenance organization (HMO) members with an index and repeated glomerular filtration rate (GFR) in the range of 15 to 90 mL/min/1.73 m(2) (0.25 to 1.50 mL/s/1.73 m(2)) in 1996 who were followed up for at least 54 months or died during this period. These were matched for birth year and sex with HMO members not meeting GFR criteria, but with the same follow-up criteria. Major comorbid chronic conditions also were identified based on International Classification of Diseases, Ninth Revision, diagnostic codes in the electronic medical record. Conditional logistic regression was used to estimate the relative risk for mortality versus comparison subjects as a function of GFR, age, and other chronic conditions. RESULTS: In the final sample of 19,945 pairs, we found that risk for mortality increases as GFR decreases, but also that both age and other chronic conditions are significant risk factors for mortality. CONCLUSION: Baseline levels of estimated GFR and other major chronic disorders all contributed negatively to survival. The relative impact of these comorbidities was greatest among younger (<60 years) patients with CKD, and their relative effect diminished with age.

Approach to the Highly Sensitized Kidney Transplant Candidate.

For patients with ESRD, kidney transplant offers significant survival and quality-of-life advantages compared with dialysis. But for patients seeking transplant who are highly sensitized, wait times have traditionally been long and options limited. The approach to the highly sensitized candidate for kidney transplant has changed substantially over time owing to new advances in desensitization, options for paired donor exchange (PDE), and changes to the deceased-donor allocation system. Initial evaluation should focus on determining living-donor availability because a compatible living donor is always the best option. However, for most highly sensitized candidates this scenario is unlikely. For candidates with an incompatible donor, PDE can improve the prospects of finding a compatible living donor but for many highly sensitized patients the probability of finding a match in the relatively small pools of donors in PDE programs is limited. Desensitization of a living donor/recipient pair with low levels of incompatibility is another reasonable approach. But for pairs with high levels of pathologic HLA antibodies, outcomes after desensitization for the patient and allograft are less optimal. Determining the degree of sensitization by calculated panel-reactive antibody (cPRA) is critical in counseling the highly sensitized patient on expected wait times to deceased-donor transplant. For candidates with a high likelihood of finding a compatible deceased donor in a reasonable time frame, waiting for a kidney is a good strategy. For the candidate without a living donor and with a low probability of finding a deceased-donor match, desensitization on the waiting list can be considered. The approach to the highly sensitized kidney transplant candidate must be individualized and requires careful discussion among the transplant center, patient, and referring nephrologist.

Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization.

BACKGROUND: Chronic kidney disease is the primary cause of end-stage renal disease in the United States. The purpose of this study was to understand the natural history of chronic kidney disease with regard to progression to renal replacement therapy (transplant or dialysis) and death in a representative patient population. METHODS: In 1996 we identified 27 998 patients in our health plan who had estimated glomerular filtration rates of less than 90 mL/min per 1.73 m(2) on 2 separate measurements at least 90 days apart. We followed up patients from the index date of the first glomerular filtration rates of less than 90 mL/min per 1.73 m(2) until renal replacement therapy, death, disenrollment from the health plan, or June 30, 2001. We extracted from the computerized medical records the prevalence of the following comorbidities at the index date and end point: hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, hyperlipidemia, and renal anemia. RESULTS: Our data showed that the rate of renal replacement therapy over the 5-year observation period was 1.1%, 1.3%, and 19.9%, respectively, for the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) stages 2, 3, and 4, but that the mortality rate was 19.5%, 24.3%, and 45.7%. Thus, death was far more common than dialysis at all stages. In addition, congestive heart failure, coronary artery disease, diabetes, and anemia were more prevalent in the patients who died but hypertension prevalence was similar across all stages. CONCLUSION: Our data suggest that efforts to reduce mortality in this population should be focused on treatment and prevention of coronary artery disease, congestive heart failure, diabetes mellitus, and anemia.

Infectious complications in living-donor kidney transplant recipients undergoing multi-modal desensitization.

BACKGROUND: Pre-existing humoral barriers challenge the transplantation of living donor kidneys (LDK) into highly sensitized ABO- and human leukocyte antigen (HLA)-incompatible recipients. Conditioning these LDK recipients' immune systems is required before they undergo transplantation. We hypothesized that medical desensitization would yield higher post-transplantation rates of infection. METHODS: We conducted a study in which matched controls consisting of non-desensitized (NDS) LDK recipients were compared with desensitized (DS) receipients. Pre-transplantation desensitization included treatment with rituximab and mycophenolate mofetil followed by intravenous immunoglobulin (IVIg) and plasmapheresis. All participants in the study underwent induction therapy and maintenance immunosuppression. Primary outcomes included infection (opportunistic, local, systemic) within 12 mo after transplantation. RESULTS: Twenty-five patients underwent desensitization and LDK transplantation. Graft survival in the DS and NDS groups of patients was 96% and 98%, respectively. The mean 3- and 12-mo serum creatinine concentrations in the DS and NDS groups were 1.1±0.2 mg/dL and 1.2±0.3 mg/dL and 0.95±0.4 mg/dL and 0.73±0.8 mg/dL (p=0.3 and p=0.01), respectively. Thirty-six percent of the patients in the DS group had one or more infections, vs. 28% of those in the NDS group (p=0.1). No difference was observed in the frequency of opportunistic or systemic infections in the two groups. Local infections were statistically significantly more frequent in the DS group (60% vs. 30%, respectively; p=0.02). CONCLUSION: Pre-operative desensitization in highly sensitized LDK recipients is followed by a similar incidence of opportunistic and systemic infections as in NDS patients. Local infections were significantly more frequent in the DS than in the NDS patients in the study. With careful monitoring of infectious complications, pre-transplant desensitization permits LDK transplantation into highly sensitized patients.

Duration of dialysis pretransplantation is an important risk factor for delayed recovery of renal function following deceased donor kidney transplantation.

Delayed graft function (DGF) is a common problem in kidney transplantation and is associated with adverse graft outcomes and increased cost of care. The purpose of this study was to determine if the duration of dialysis increases the risk of DGF. All primary deceased donor renal transplants between January 2000 and December 2003 were identified in the Organ Procurement and Transplant Network database. Two separate definitions of DGF were used: dialysis in the first week post-transplant (DPT) and creatinine drop of < 25% in the first 24 h or slow graft function (SGF). The rate of DPT and SGF increased from 5.7% and 34.4%, respectively, for pre-emptively transplanted patients, to 32% and 49.9% for patients who had been on dialysis for 6 or more years. When compared to pre-emptive transplantation, increasing duration of dialysis increased the adjusted risk of both DPT and SGF (OR 6.64 (95% CI 5.49-8.03) and OR 1.76 (95% CI 1.56-2.00) for patients on dialysis for 6 or more years, for DPT and SGF, respectively. A strong association between duration of dialysis and DGF exists, and investigations into the mechanisms by which dialysis influences DGF may lead to useful interventions to limit this complication.

Recipient age and risk of chronic allograft nephropathy in primary deceased donor kidney transplant.

Single center and registry data studies have had conflicting results regarding the impact of recipient age on chronic allograft nephropathy (CAN). We tested the hypothesis that advanced recipient age is a risk factor for graft failure due to CAN. All patients who underwent primary deceased donor kidney transplant between January 1, 1995 and December 31, 2000 recorded in the United Network of Organ Sharing (UNOS) database were analyzed for the occurrence of death censored graft loss and by two different definitions of graft loss due to CAN. Kaplan-Meier analysis based on the recipient age, and Cox proportional hazard regression was used to estimate the independent effect of recipient age on the three endpoints of interest. For all endpoints, after age of 9 years, the risk of graft loss declined with each successive decade increase in age. This pattern of risk was similar for both Caucasian and African-American recipients, although for any given age the risk of graft loss was always higher in African-American recipients. Analysis of UNOS data does not support the hypothesis that advanced recipient age is a risk factor for CAN.

Factors associated with improvement in deceased donor renal allograft function in the 1990s.

The decade of the 1990s saw an improvement in cadaveric renal graft function and dramatic reduction in the acute rejection (AR) rate. The purpose of this study was to determine whether the reduction in rejection rate was the primary cause of the improvement in graft function seen and whether this improved long-term graft survival. All adult patients who received a cadaver renal transplant between 1991 and 2000 and had graft survival of at least 6 mo and complete data for creatinine at 6 mo, HLA mismatch, delayed graft function, and acute rejection (AR) were identified in the United Network for Organ Sharing database. A total of 40,164 cases that met the inclusion criteria were identified. The mean Modification of Diet in Renal Disease GFR at 6 mo improved from 49.94 ml/min per 1.73 m2 in 1991 to 54.59 ml/min per 1.73 m2 in 2000 (P < 0.001). The improvement in GFR was not gradual but occurred over a 4-yr period between 1994 and 1997, coinciding with the introduction of new immunosuppressive agents mycophenolate mofetil and tacrolimus into maintenance immunosuppression regimens. The improvement was seen in all subgroups of patients, even patients without clinical AR or delayed graft function. The magnitude of improvement in patients without clinical AR was similar to that seen in patients with AR. The drop in clinical AR rate accounted for a minority of the improvement in graft function in the 1990s. Other factors, such as reduced drug toxicity and improved control of subclinical rejection, seem to account for the majority of the improvement. This improvement in graft function at 6 mo did not translate into improved long-term graft survival, however.

Effect of donor recipient age match on survival after first deceased donor renal transplantation.

Donor-recipient age matching has been proposed as a means of improving overall outcomes in deceased donor renal transplantation. It was hypothesized that donor-recipient age matching would improve patient survival time in younger recipients while not adversely affecting patient survivals in older recipients because they seldom outlive their grafts. By use of data from United Network of Organ Sharing Standard Transplant and Analysis and Research Files 50,320 patients were identified who underwent a first deceased donor renal transplantation between January 1, 1990, and December 31, 1997. Adjusted patient survival and death-with-graft function patient survival were analyzed from the date of transplantation. Patient survival was affected by donor age for all recipient age groups, including recipients older than 55 yr. The effect of donor age on patient survival is greater than that seen with HLA matching. The effect of donor age on patient survival persisted even when censoring recipients in whom grafts failed before death, suggesting that both longevity and quality of graft function are important in patient survival. Donor-recipient age matching is occurring to a limited degree in this population. Donor-recipient age matching would improve survival in younger recipients but would adversely affect survival in older patients by reducing the availability of younger donor kidneys for this group. The issue of donor-recipient age matching needs to be debated among the public and transplantation community so that a logical and just system can be developed.