Consensus conference on best practices in live kidney donation: recommendations to optimize education, access, and care.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5-6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

A web-based application for initial screening of living kidney donors: development, implementation and evaluation.

Most centers utilize phone or written surveys to screen candidates who self-refer to be living kidney donors. To increase efficiency and reduce resource utilization, we developed a web-based application to screen kidney donor candidates. The aim of this study was to evaluate the use of this web-based application. Method and time of referral were tabulated and descriptive statistics summarized demographic characteristics. Time series analyses evaluated use over time. Between January 1, 2011 and March 31, 2012, 1200 candidates self-referred to be living kidney donors at our center. Eight hundred one candidates (67%) completed the web-based survey and 399 (33%) completed a phone survey. Thirty-nine percent of donors accessed the application on nights and weekends. Postimplementation of the web-based application, there was a statistically significant increase (p < 0.001) in the number of self-referrals via the web-based application as opposed to telephone contact. Also, there was a significant increase (p = 0.025) in the total number of self-referrals post-implementation from 61 to 116 per month. An interactive web-based application is an effective strategy for the initial screening of donor candidates. The web-based application increased the ability to interface with donors, process them efficiently and ultimately increased donor self-referral at our center.

Dynamic challenges inhibiting optimal adoption of kidney paired donation: findings of a consensus conference.

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.

Call to develop a standard acquisition charge model for kidney paired donation.

We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.

Economic cost of expanded criteria donors in cadaveric renal transplantation: analysis of Medicare payments.

BACKGROUND: The use of expanded criteria donors (ECDs) in cadaveric renal transplantation is increasing in the US. We assess the economic impact of the use of ECDs to the Medicare end stage renal disease program. METHODS: The United Nations for Organ Sharing renal transplant registry was merged to Medicare claims data for 42,868 cadaveric renal transplants performed between 1991-1996 using USRDS identifiers. Only recipients for whom Medicare was the primary payer were considered, leaving 34,534 transplants. An ECD was defined as (1) age < or =5 or > or =55 years, (2) nonheart-beating donors, donor history of (3) hypertension or (4) diabetes. High-risk recipients (HRR) were age >60 years, or a retransplant. Medicare payments from the pretransplant dialysis period were projected forward to provide a financial "breakeven point" with transplantation. RESULTS: There were 25,600 non-HRR transplants, with 5,718 (22%) using ECDs, and 8,934 HRR transplants, of which 2,200 (25%) used ECDs. The 5-year present value of payments for non-ECD/non-HRR donor/recipient pairings was $121,698 vs. $143,329 for ECD/non-HRR pairings (P<0.0001) and, similarly was $134,185 for non-ECD/HRR pairings vs. $165,716 for ECD/HRR pairings (P<0.0001). The break even point with hemodialysis ranged from 4.4 years for non-ECD/ non-HRR pairings to 13 years for the ECD/HRR combinations but was sensitive to small changes in graft survival. Transplantation was always less expensive than hemodialysis in the long run. CONCLUSIONS: The impact of ECDs on Medicare payments is most pronounced in high-risk recipients. Cadaveric renal transplantation is a cost-saving treatment strategy for the Medicare ESRD program regardless of recipient risk status or the use of ECDs.

Morphology of hydrogel implants used for refractive keratoplasty.

The pathology of 14 keratophakia procedures in nine nonhuman primates using various hydrogel lenses as donor lenticles is presented. The lenses were treated as if they were human donor corneas using currently practiced keratophakia procedures. This included microkeratome resection of the recipient cornea, staining of the lenses before cryolathing and, in most instances, lathing according to a modified computer program after which the lenses were inserted into the previously dissected recipient lamellar bed. There was no histologic evidence of an inflammatory reaction to the hydrogels. The major pathologic feature was the presence of activated keratocytes lining the dissected intrastromal pockets.

Why do some epikeratoplasties fail?

We performed a morphologic analysis of nine epikeratoplasty lenticules that were removed due to nonhealing epithelial defects, interface opacity, and/or haze of the donor lenticule. Structural abnormalities were found in all layers of the donor lenticules, with the major changes being present in the surface epithelium and Bowman's layer. Significant changes in the stromal collagen were documented. Similar changes were found in a previous analysis of never-used, factory-prepared lenticules that had been prepared following the use of a corneal press and a lyophilization process. This study suggests that the presently used process of tissue preparation may be deleterious to the structure of the donor lenticule and may adversely affect surface reepithelialization. The placement of the lenticule above the recipient's Bowman layer may be an additional retardant to postoperative reepithelialization.

The pathologic findings of epithelial ingrowth.

A case of postcataract epithelial ingrowth that occurred when a chronic fistula was produced after a discussion of a secondary membrane is reported. The ingrowth was examined preoperatively with the specular microscope, and the excised anterior segment was examined with correlative microscopy. The patient recovered 6/18 (20/60) visual acuity after a subsequent penetrating keratoplasty. The characteristics of the epithelial ingrowth consisted of nonkeratinized squamous epithelium with surface microvilli, wide intercellular borders with occasional desmosomes, multiple tonofilaments more prominent in the leading edge of the ingrowth, hemidesmosomes attached to a subepithelial connective tissue layer, and uneven sizes and shapes of epithelial cells. These findings suggested that the source of the ingrowth was from the conjunctival epithelium. We found the leading edge of the ingrowth as well as the type of damage inflicted to the underlying endothelium.

Laboratory evaluation of freeze vs nonfreeze lamellar refractive keratoplasty.

Four pairs of human eyes were operated on to correct 10 diopters of myopia. One eye underwent standard myopic keratomileusis, and the mate underwent planar lamellar refractive keratoplasty (PLRK). Cryolathing produced morphologic alterations in all layers. Planar lamellar refractive keratoplasty produced a smoother stromal surface in the optic zone. Peripheral triangular surface depressions in the lenticule, corresponding to fixation facets on the PLRK unit, were the only morphologic alterations noted. It appears that PLRK eliminates many adverse features associated with tissue freezing and lyophilization.

Refractive keratoplasty. Tissue dyes and cryoprotective solutions.

The cryoprotective dye solution KM-26 (0.25% kiton green, 8% glycerin, and 4% dimethyl sulfoxide), which is presently used for all lamellar refractive surgical procedures, was evaluated and compared to other dyes that can stain corneal tissue. With the use of canine and human eye bank tissue, we found kiton green and light green to produce the least tissue alteration and to destain readily. Glycerin with or without dimethyl sulfoxide or dye was deleterious to the endothelium in the area under the keratectomized recipient bed. On the basis of our findings, glycerin and dimethyl sulfoxide should be deleted from the cryoprotective solution and a 0.1% concentration of light green in balanced salt solution or M-K medium should be used and the frozen tissue should be thawed in a balanced salt solution or M-K medium to eliminate potential damage to the recipient corneal endothelium.

The histopathology of a case of keratophakia.

We studied a human cornea that was obtained at the time of penetrating keratoplasty four months after a keratophakia procedure and cataract extraction. We found endothelial cell loss with corneal edema, interface epithelial ingrowth, absence of keratocytes, and an abnormality in the collagen structure of the donor homograft (lenticule) and abnormal host keratocytes in the recipient lamellar (host) bed. We suspect that the cause of keratocyte and collagen injury was associated with the cryopreservation process. We recommend that if a combined cataract extraction and keratophakia procedure is contemplated, the lens extraction be performed in an intracapsular fashion if the keratophakia procedure has been completed or in an extracapsular fashion before the replacement of the donor lenticule and anterior part of the host cornea.

Combined morphologic effects of cryolathing and lyophilization on epikeratoplasty lenticules.

A correlative microscopic analysis of factory-prepared epikeratoplasty lenticules, corneas stored in McCarey-Kaufman medium for two to four days, and fresh human corneas disclosed ultrastructural abnormalities in Bowman's membrane and in the corneal stroma of the lyophilized lenticules that were not present in the control corneas. These features included mottling of Bowman's membrane, with large interfibrillar spaces; a roughness to its surface; and wide interlamellar lacunae within the corneal stroma, with significant changes in interfibrillar collagen distance and fibril diameter. The morphologic features of a clinical specimen excised three months following myopic epikeratoplasty were similar to those found with the factory-prepared lenticules. Our patient's corneal curvature steepened almost 3 diopters following lenticule removal. Our results suggest that additional studies of lyophilized epikeratoplasty lenticules should be performed.

Acute morphologic features of radial keratotomy.

We performed eight partially penetrating incisions in 19 eye-bank, 12 nonhuman primate, and 34 canine eyes. Evaluation of the posterior corneal surface by vital staining, correlative microscopy, with corneal incisions set from 80% to 110% of central pachymetric thickness, in three eyes demonstrated damage to the endothelium without anterior chamber perforation. Posterior folds in Descemet's membrane under an incision site was present in all specimens. Potential optical aberrations could be produced about the visual axis depending on the direction of the corneal incisions. Based on this study, the radial keratotomy procedure performed with up to eight deep incisions may produce optic defects. We recommend animal studies to assess the long-term effects of this procedure on the cornea and especially the endothelium.

Histopathology of a case of radial keratotomy.

A patient underwent a radial keratotomy (RK) to reduce residual astigmatism that occurred after a corneal transplant. The patient enjoyed immediate good vision, but later intense glare, photophobia, and pain forced him to quit work. Five months later the graft became cloudy, and superficial vascularization developed in the radial scars. An 8.5-mm penetrating keratoplasty was performed 5 1/2 months after RK. Analysis of the corneal button revealed diffuse epithelial edema, epithelial ingrowth into the incisions, an irregularly thickened epithelial basement membrane, immature hemidesmosomes, focal malapposition of Bowman's layer, marked cellularity of the stroma around the margins of the incisions, and posterior folds in Descemet's membrane. Our analysis of this specimen suggests RK may carry a risk of optical and visual aberrations by producing multiple defects in the anterior and posterior aspects of the cornea.

Refractive keratoplasty: microkeratome evaluation.

We performed routine microkeratome and freehand lamellar keratectomies in 65 canine eyes and 24 human eye-bank eyes. The microkeratome technique produced more predictable resections compared with the freehand technique and at the same time produced a wound that would allow for better wound coaptation. Neither technique damaged the corneal endothelium. We conclude that one of the reasons for the success of the refractive keratoplasty procedures is the refined microkeratome technique.

Refractive keratoplasty. Keratophakia in a nonhuman primate.

We performed 11 keratophakia procedures in a baboon (Papio cynocephalus) model using the same instruments and techniques that are presently clinically employed. We requested 10 diopters of correction in nine cases and 14 D in two cases. We were able to achieve a mean (+/- SD) keratometric steepening correction of 5.8 +/- 1.5 D using fresh and 9.3 +/- 5.0 D using prefrozen donor corneas. The overall change was 8.0 +/- 4.3 D. Morphologic results and corneal clarity were consistent with the excellent clinical results. The keratophakia lenticles were sparsely repopulated with keratocytes up to six months following surgery, but at 12 months, partial keratocyte repopulation of one lenticle did occur. We recommend that the baboon model be used for evaluation of all lamellar refractive surgical procedures.

An ultrastructural and histochemical study of long-term wound healing after radial keratotomy.

Using correlative microscopy and plant lectins conjugated to fluorescent dyes, we studied two human corneal specimens obtained 66 and 70 months after radial keratotomy. In one case a second radial keratotomy had been performed 11 months before we obtained the corneal specimen, which allowed us to compare wounds 11 and 66 months old in the same specimen. The 11-month-old incisions demonstrated morphologic features consistent with incomplete wound healing, whereas the incisions examined 66 and 70 months postoperatively demonstrated complete wound healing. A different lectin binding pattern of wheat germ agglutinin and concanavalin-A was observed in the 11-month-old wounds, compared with the 66-month-old wounds. Published and unpublished morphologic studies of 17 human keratotomy specimens have demonstrated incomplete wound healing up to 47 months postoperatively. The present study documents complete corneal wound healing 66 months after radial keratotomy.

Correlative microscopy and tissue culture of congenital hereditary endothelial dystrophy.

A 4 1/2-year-old boy with congenital hereditary endothelial dystrophy underwent successful bilateral penetrating keratoplasties. Visual acuity in both eyes was restored to 6/18 (20/60). Correlative microscopic analysis of the corneal button obtained from the first transplant showed an irregular epithelium, a continuously thickened Bowman's layer, fragmentation and homogenization of the anterior stromal lamellae, a mildly enlarged stromal fibril diameter, abnormal collagen layers posterior to Descemet's membrane, atrophic paracentral corneal endothelium, and absent central endothelium. The endothelial cells from the second corneal button were placed in tissue culture and failed to demonstrate any growth characteristics of differentiation into normal appearing cells after 14 days. We concluded that the endothelial cells in congenital hereditary endothelial dystrophy are functionally and morphologically abnormal. Early penetrating keratoplasty can be successful in such cases.

Clinical pathology of non-freeze lamellar refractive keratoplasty.

We studied two corneal specimens obtained following corneal transplantation for loss of best corrected vision after planar lamellar refractive keratoplasty. The epithelium appeared slightly undifferentiated in both cases. Peripheral bends and occasional breaks were found in the periphery of Bowman's layer. In one case there were areas of subepithelial fibrosis as well as ultrastructural fractures in Bowman's layer. The keratocyte population appeared to be slightly decreased in one case. In both specimens the optical interface contained active fibroblasts in the periphery. The planar lamellar refractive keratoplasty technique theoretically eliminates many of the adverse morphologic features encountered following the standard Barraquer cryolathe techniques, but clinical studies will be needed to determine if this form of lamellar keratoplasty is clinically superior to currently practiced techniques.

Epikeratophakia: clinical evaluation and histopathology of a non-human primate model.

We performed four aphakic and two myopic epikeratophakia procedures in a non-human primate model using two fresh and three prefrozen corneas and one glycerin-preserved cornea. The experiments were terminated 4 to 5 months postoperatively, and the eyes examined with correlative microscopy. The glycerin-preserved cornea sloughed and was not available for analysis. All but one prefrozen specimen demonstrated donor keratocyte repopulation. Active keratocytes were noted lining the optical interface. Focal areas of missing Bowman's layer were present in three recipient corneas. Epithelial interface ingrowth occurred in two specimens. The recipient corneas were otherwise normal.