Transporting live donor kidneys for kidney paired donation: initial national results.

Optimizing the possibilities for kidney-paired donation (KPD) requires the participation of donor-recipient pairs from wide geographic regions. Initially it was envisaged that donors would travel to the recipient center; however, to minimize barriers to participation and simplify logistics, recent trends have involved transporting the kidneys rather than the donors. The goal of this study was to review outcomes of this practice. KPD programs throughout the United States were directly queried about all transplants involving live donor kidney transport. Early graft function was assessed by urine output in the first 8 h, postoperative serum creatinine trend, and incidence of delayed graft function. Between April 27, 2007 and April 29, 2010, 56 live donor kidneys were transported among 30 transplant centers. Median CIT was 7.2 h (IQR 5.5-9.7, range 2.5-14.5). Early urine output was robust (>100 cc/h) in all but four patients. Creatinine nadir was <2.0 mg/dL in all (including the four with lower urine output) but one patient, occurring at a median of 3 days (IQR 2-5, range 1-49). No patients experienced delayed graft function as defined by the need for dialysis in the first week. Current evidence suggests that live donor kidney transport is safe and feasible.

Successful three-way kidney paired donation with cross-country live donor allograft transport.

Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.

Plasma fluorescein binding and transcapillary fluorescein escape rate in renal failure associated with diabetes.

Microvascular damage, often resulting in renal failure, is a common complication of diabetes. Transcapillary fluorescein escape rate (TCFER) as monitored by intravital microscopy has been used as an indicator of the extent of capillary damage in diabetes and to assess improvement in microvascular function after combined kidney-pancreas transplant. However, fluorescein anion binds to plasma albumin, and albumin-ligand binding may be altered in the presence of renal disease. The purpose of this study was to compare fluorescein binding by plasma from diabetics with renal failure with plasma from healthy nondiabetics. Fluorescein binding by plasma from seven type I diabetics awaiting kidney-pancreas transplant and seven healthy adults of similar age and sex was studied using ultrafiltration and dialysis. There was no significant difference in the apparent albumin binding of fluorescein at physiologically relevant fluorescein concentrations, even though the TCFER was significantly increased in the diabetics as compared with the controls. Hippurate, a ligand that accumulates in renal failure, did alter fluorescein binding in a defatted albumin solution but not sufficiently to account for the differences in TCFERs. These data indicate that impaired albumin binding of fluorescein does not contribute significantly to the TCFER in diabetics with renal failure.

Phenotypes of apolipoprotein B and apolipoprotein E after liver transplantation.

Apolipoprotein (apo) E and the two B apolipoproteins, apoB48 and apoB100, are important proteins in human lipoprotein metabolism. Commonly occurring polymorphisms in the genes for apoE and apoB result in amino acid substitutions that produce readily detectable phenotypic differences in these proteins. We studied changes in apoE and apoB phenotypes before and after liver transplantation to gain new insights into apolipoprotein physiology. In all 29 patients that we studied, the postoperative serum apoE phenotype of the recipient, as assessed by isoelectric focusing, converted virtually completely to that of the donor, providing evidence that greater than 90% of the apoE in the plasma is synthesized by the liver. In contrast, the cerebrospinal fluid apoE phenotype did not change to the donor's phenotype after liver transplantation, indicating that most of the apoE in CSF cannot be derived from the plasma pool and therefore must be synthesized locally. The apoB100 phenotype (assessed with immunoassays using monoclonal antibody MB19, an antibody that detects a two-allele polymorphism in apoB) invariably converted to the phenotype of the donor. In four normolipidemic patients, we determined the MB19 phenotype of both the apoB100 and apoB48 in the "chylomicron fraction" isolated from plasma 3 h after a fat-rich meal. Interestingly, the apoB100 in the chylomicron fraction invariably had the phenotype of the donor, indicating that the vast majority of the large, triglyceride-rich apoB100-containing lipoproteins that appear in the plasma after a fat-rich meal are actually VLDL of hepatic origin. The MB19 phenotype of the apoB48 in the plasma chylomicron fraction did not change after liver transplantation, indicating that almost all of the apoB48 in plasma chylomicrons is derived from the intestine. These results were consistent with our immunocytochemical studies on intestinal biopsy specimens of organ donors; using apoB-specific monoclonal antibodies, we found evidence for apoB48, but not apoB100, in donor intestinal biopsy specimens.

The effects of oxygen free radicals on the preserved kidney.

This study evaluated the effect of specific scavengers of oxygen derived free radicals on the results of kidney preservation. The immediate function of rabbit kidneys preserved for 24 hr by hypothermic perfusion was studied on an ex vivo shunt. A significant improvement in creatinine clearance was seen when the perfusate was treated with superoxide dismutase (SOD) and catalase (CAT), with values of 261 +/- 82 ml/hr vs control values of 203 +/- 72 ml/hr, P less than 0.05. This effect was enhanced if a long-persistent polyethylene glycol-linked form of SOD, namely PEG-SOD, was used (330 +/- 58 ml/hr, P less than 0.01). Recipient treatment and other modifications designed to protect against free radicals resulted in similar improvement in function. In contrast, no effect of free radical scavengers could be demonstrated in kidneys which were preserved by flush cooling, whether the agents were added to the flushing solution, given to the recipient, or both.

Optimal redox electrode potential for 24-hour rabbit kidney perfusion.

This study was conducted to determine whether an optimum redox electrode potential existed for 24-hr hypothermic perfusion of rabbit kidneys. The perfusate consisted of a Ringer's-albumin solution to which was added varying amounts of the reducing agents, glutathione and ascorbate, either individually or in equimolar amounts. Electrode potential was monitored with a vitreous carbon electrode in relation to a silver-silver chloride reference cell, and kidney function was measured after preservation by connection to the circulation of a perfusor animal via a shunt. The best results were obtained using equimolar amounts of the reducing agents. Under these circumstances a definite optimum range for perfusate electrode potential was identified (Es = 40-70 mV) within which renal function was indistinguishable from unpreserved controls. Higher and lower perfusate electrode potentials were associated with significantly lower creatinine clearances. However, the explanation for these results appeared to be more complex than redox control alone, since kidney function was dependent not only on the redox potential of the perfusate but also on the reducing agents with which the adjustment had been made. Ascorbate proved to be significantly better than glutathione within the optimum potential range.

Improved function of perfused rabbit kidneys by prevention of oxidative injury.

This study explored the effect of adding small amounts of the reducing agents ascorbic acid and glutathione to a Ringer's-albumin perfusate used for 24-hr hypothermic perfusion of rabbit kidneys. Maintenance of function during preservation was evaluated with a shunt perfusion model and by measuring the ability of cortical slices to restore normal K/Na ratios after incubation in a electrolyte medium. When placed in contact with the unmodified perfusate, an electrode of pyrolytic carbon registered a potential of +190 mV relative to the silver-silver chloride couple. This reading fell rapidly by 100-125 mv when kidneys were placed on the circuit. The mean creatinine clearance after 24-hr perfusion was significantly improved from 162 +/- 56 ml/hr in controls to 284 +/- 92 ml/hr when the potential indicated by this electrode was preadjusted to 43-54 mv with reducing agents, and to 237 +/- 62 ml/hr when this adjustment was made after 2 hr. These creatinine clearances were similar to those of kidneys stored on ice for only 1 hr. These findings indicate minimal injury occurred in the chemically reduced groups and emphasize the importance of preventing oxidative damage to kidneys during hypothermic organ perfusion. The time course of the changes in potential registered by this electrode was consistent with our previous finding that much of the damage to perfused kidneys occurs very early in the course of perfusion. The tissue slice studies showed no detectable damage to the renal parenchyma of the kidneys in the control group despite diminished creatinine clearance. This suggests that the site of oxidation injury is the vascular compartment.