No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Kidney Transplantation
Objectives:
Kidney transplantation is not readily available in low-resource settings because of poor health structure, dearth of experts, and pervading poverty. Although many centers now offer kidney transplant, patients still travel outside Nigeria for this service for many reasons and many return home without a detailed medical report.
Materials and methods:
Medical records of individuals who underwent kidney transplant in Nigeria and elsewhere and who were presently receiving posttransplant care or had received such care from 2002 to 2018 at 4 Nigerian hospitals were retrospectively reviewed and analyzed.
Results:
Of 35 patients (30 males; 85.7%) analyzed (mean ages of 42 ± 16 and 47 ± 8 years for men and women, respectively; P = .54), common primary kidney diseases included hypertension (27.2%), glomerulonephritis (24.2%), and diabetes mellitus/hypertension (18.3%). Most patients received transplants in India (48.6%), with others in Nigeria (23.0%) and Pakistan (8.6%). Relationships to recipient were unrelated (28.5%), living related (22.9%), and unknown (48.6%). Less than 30% of recipients had care details in their hospital records. Almost all transplant patients were treated with prednisolone (81.8%); cyclosporine (40.0%), mycophenolate mofetil (31.4%), tacrolimus (20.0%), and azathioprine (9.1%) were also used. Complications were documented in 88.9%, with 57.0% due to bacterial infections/sepsis. Many (88.9%) had more than 2 complications. In follow-up, median first transplant duration was 24 months (interquartile range, 6-44). Of total patients, 25.7% were still alive, 17.1% had died, and 54.2% were lost to follow-up. Follow-up data for only 2 donors were available.
Conclusions:
Lapses in follow-up care of kidney transplant recipients and donors continue in lowresource settings where transplant tourism is still rife, resulting in poor graft/patient survival. Adherence to transplant guidelines is advocated. We propose a transplant stratification model according to level of development and resources of countries or regions. This model will encourage customizing strategies for improving patient outcomes.
Hyperacute rejection, the previously insurmountable obstacle to pig-to-human xenografts, has been overcome. There is reason to hope that concerted research will overcome the remaining obstacles. Pigs will be produced expressing other regulators of complement activation molecules in addition to decay accelerating factor. Modification of antigenic structure of cells could also be achieved. There is now some hope that large scale clinical xenotransplantation could become a reality.
From our point of view, the consequence of the mercury intoxication (mercury chloride) [author’s remark: in those times, mercury chloride was a common disinfectant] is imitating this condition and thereby leading to a ‘blockade of the reticulo-endothelial system’ with a simultaneous acute renal failure. Therefore, in this clinical situation with the above-mentioned constellation, the absolute indication for kidney transplantation is given because of the lack of renal function. Mercury chloride, which is known to be a salt of a heavy metal, causes localized lesions and after resorption, it causes damage to parenchymatoseous organs, particularly of the intestine and the kidneys. Obviously caused by the negative molecular charge and the binding to blood proteins, it results in a selective dysfunction of the reticulo-endothelial system. The histopathological analysis of the organs which were damaged by the mercury chloride (spleen, lymph-nodes, liver, heart, adrenal glands, etc.) showed that particularly the organs which are rich in reticulo-endothelial-system had degenerations, although they retained their ability to regenerate. Furthermore, the mercury elimination from the organism is prolonged because of a relative high blood level. So, in our case, the blood-concentration of mercury on the fourth day after the ingestion of 4.0 g of mercury chloride with suicidal intention was 1.5 mg%, and it was reduced by 10-fold on the next day, which was the first day after transplantation. Therefore, at a state of moderate intensity and in an early stage of the mercury chloride poisoning, after a complete degeneration of the parenchymatous organs did not already occur, the time window of the ‘blockade of the reticulo-endothelial system’ in a state of potential regeneration of the parenchymatous organs can be identified. In such a situation, the kidney transplantation performs the task of elimination of the poison from the organism as long as the endogenous kidneys have regenerated fairly. In summary, it can be concluded that after the question of sense and purpose of a kidney transplantation after mercury chloride poisoning was explained, we had to find an adequate organ, as we know the attempts of xenotransplantation (for example, from monkeys or domestic animals like pigs or goats) were disappointing. Particularly, in some of these experiments, a continuous anaphylaxis of the recipient animal after reperfusion of the organ which was anastomosed by vessel suture could be observed, which had a lethal result for the recipient animal. Against the background of these facts, a human cadaver seems to be the best option as a donor transplant organ because a healthy human can under no circumstances be deliberately injured by the organ removal, even if the removed organ is for transplantation. It is proven that cadaveric organs keep their sterility for some time. Furthermore, it is known from the physiology that cadaveric kidneys keep their function for some time after reperfusion with ringer-solution. Under consideration of these assessments, different groups of scientists have tried to transplant skin, joints and parathyreoideal glands from a human body to another human. The description of a kidney transplantation from a traumatic body to another human with the revascularization by vessel anastomosis is not yet known. So we report here about a kidney transplantation which was approved by Professor A. Belz.
Indefinite survival of renal allografts due to immunological enhancement has been demonstrated in eleven out of eleven inbred AS rats bearing a single (August × AS) kidney. Less striking enhancement has also been observed when kidneys from homozygous August donors were used. No immunosuppressive drugs were given to rats showing kidney-graft enhancement. It is suggested that immunological enhancement has general application in human organ transplantation.
Stored and fresh lymphocytes from 84 donors and recipients of cadaveric renal allografts have been retrospectively typed for 7 HLA-DR antigens. The match between donor and recipient was graded as 2, 1, or 0 identities. Graft function was assessed by (i) failure or success at 3 months, (ii) serum-creatinine at 3 and 6 months, and (iii) the number of rejection episodes occurring within 3 months. All 4 recipients with 2 identities had good 3-month function, and all are still functioning at 5--19 months. Recipients with 1 identity had both a higher success-rate and better quality of function than those with 0 identities. Although the differences do not reach significance, a continuing prospective study of HLA-DR matching is justified, with particular emphasis on performing transplants where two DR antigens are shared between donor and recipient.
Seven patients on dialysis with renal failure received transplants from mismatched cadaver donors and were treated with cyclosporin A (CyA), initially as the sole immunosuppressive agent. CyA was effective in inhibiting rejection but there was clear evidence of both nephrotoxicity and hepatotoxicity. A cyclophosphamide analogue was added to the CyA treatment in six of the patients. Five patients are out of hospital with functioning allografts, and two of these have received no steroids. One patient required an allograft nephrectomy because of pyelonephritis in the graft. Another died of systemic aspergillus and candida infection. Further careful study of this potentially valuable drug will by required before it can be recommended in clinical practice.
The distortions produced by personalized versions of events are well known and particularly well illustrated by a number of articles in both the older and more recent transplantation literature. Consequently, the student of history will be well advised to consult less biased accounts by younger workers such as the catalogue of landmarks in renal transplantation provided by Groth of Stockholm after his study of the written record and after discussions with most of the workers actually involved in the work done from 1950 onward.14
Nevertheless, it may be interesting to describe some of the problems of human organ transplantation as they were perceived at the time of our first clinical trials 15 years ago and subsequently. This has been done first by briefly and incompletely sketching the background that had evolved to 1961, the year before the first consistent successes began to be obtained with kidney transplantation. Second, the great advances starting in 1962 are described in the second section. Finally, unsolved or incompletely resolved problems that still exist 15 years later make up the final section.
Boston has played a significant role in the development of renal transplantation. In Boston was performed the first successful isograft between identical twins (1954) the first successful allograft between fraternal twins (1959) and the first successful allograft from a cadaveric donor (1962). An immunosuppressive drug was also described in Boston by hematologists Schwartz and Dameschek (1959) and modified for renal transplantation in dogs (1961) and used for the first time in a human recipient in March 1962. By 1965 renal transplantation had become a clinical reality. Three hundred and ninety-eight of 589 recipients (68%) since 1950 are still alive, a remarkable figure considering that it includes all the earliest experimental transplants. One hundred and ninety-five of 295 (68%) with living-related donor transplants still have functioning allografts; 104/265 (39%) with cadaveric donor transplants have functioning grafts currently. Since 1968 transplants from living-related donors have an 80% one year survival whereas cadaveric donor transplants have approximately a 50% one year survival. Seventy-nine per cent of all one year survivors have had excellent psycho-social rehabilitation.
Cell-mediated cytolysis (CMC) was assayed in a system using spleen cells from mice (C57BL/6) sensitized with allogeneic tumour cells (DBA/2 mastocytoma P-815). Anti-inflammatory drugs, immunosuppressives, inhibitors of cell division and other agents were investigated for their capacity to inhibit CMC in three different ways. First, inhibition of CMC after in vitro addition of drug was observed with corticosteroids, some immunosuppressives and inhibitors of cell division. Secondly, suppression of CMC after a single drug administration to sensitized mice shortly before being killed was found with corticosteroids, several immunosuppressives and irradiation. Thirdly, prevention of development of CMC by repeated drug treatment (immunosuppressive schedule) was achieved with most immunosuppressives and cytostatic drugs. Non-steroidal anti-inflammatory drugs were inactive in these tests. Correlation of effects between the three procedures was very poor and it is suggested that various mechanisms may be involved in the different assays.
The story of the renal transplant program of the Peter Bent Brigham Hospital (now the Brigham and Women's Hospital) in Boston weaves together three distinct threads: the study of renal disease, the phenomenon of skin grafting in twins, and the development of surgical procedures ultimately leading to the use of chemical immunosuppression. The common leitmotiv is one of a single event or report proving to be decisive. Unanticipated consequences of successful human organ transplantation include the reorganization of clinical and nonclinical disciplines, national and international cooperation in organ preservation and distribution, tissue-typing as a marker for disease, redefinition of death in terms of brain function, better understanding of disease processes, and new health care quandaries that result from the scarcity of organ donors.
Extracorporeal perfusion of canine kidneys for periods of 24 to 72 hours were consistently successful. The functional viability of the perfused kidneys was proved by reimplanting the perfused kidneys and simultaneously removing the contralateral kidneys. The essential features of successful perfusion are: (1) a pulsatile pump; (2) moderate hypothermia (8-12°C); (3) a buffered perfusate of canine plasma to which are added magnesium sulphate, dextrose, insulin, penicillin, and hydrocortisone; (4) microfiltration of the perfusate before use; (5) oxygenation by means of a membrane oxygenator to limit the air-fluid interphase; and (6) control of pH, temperature, PO2, PCO2, and flowrates during perfusion. Since a 24-hour to 72-hour period is adequate for preparing a recipient and such preliminaries as tissue-typing, the details of the technique in twelve consecutive perfusions, six for 24 hours and six for 72 hours are reported.
Biopsies of renal transplants taken within one hour after completion of vascular anastomoses revealed, in seven of 132 cases, the accumulation of large numbers of polymorphonuclear leukocytes within glomerular and peritubular capillaries, with eventual transplant failure in all cases. Serologic studies in all recipients demonstrated pre-existing antibodies reacting with human histocompatibility antigens. Heat eluates from three of four rejected kidneys also contained activity against human histocompatibility antigens. These findings suggest that serum antibody reacted with and became fixed to the histocompatibility antigens of the graft, thereby initiating an acute vascular reaction with early polymorphonuclear-leukocyte margination and progression to widespread capillary thrombosis.
PREVIOUS work in this laboratory demonstrated that administration of a purine analogue, 6-mercaptopurine, suppressed the antibody response to a soluble antigen (human serum albumin) in rabbits1. It was shown that the antimetabolite could block completely the primary immune response to the purified protein antigen; its effect on the secondary response, however, was minimal2. It is the purpose of this communication to describe the apparent induction of immunological tolerance in adult rabbits by the use of 6-mercaptopurine.
A healthy kidney of a parent or sibling was transplanted in the ; sublethally irradiated (430 to 460 rad) recipient with advanced chronic renal ; insufficiency. Three of the 6 cases showed prolonged tolerance to the grafter ; kidney, although 1 of the 3 died following further radiation therapy. In 2 of ; the unsuccessful cases, the graft was rejected within 48 hr, and a 3rd case died ; from an early infection. Renal function appeared to be normal after more than 1 ; yr in the 2 surviving successful cases, and biopsy showed normal glomerular ; structure. Radiation treatment was not accompanied by a diminution of pre-; existing circulating antibodies (blood-group isohemagglutinins), but it ; apparently reduced formation of antibodies in response to antigens in the ; transplanted kidney. In cases of early rejection of the graft, differences were ; noted in leukocyte agglutination reactions between donor and recipient, but in ; all cases the major erythrocyte blood groups were the same in the 2 individuals. ; (H.H.D.);
THIS report is a summary of our experience with kidney homografts in 13 patients treated with drugs as the sole modality for the suppression of immunity (Table 1). Five recent cases are reported in detail: 1 patient with a cadaveric kidney is still alive after one year; 1 died from cerebral hemorrhage more than five months after transplantation from an unrelated infant; 1 is alive three months after transplant from his mother; the fourth is alive six weeks after receiving a kidney from his brother; and the fifth is living four weeks after a transplant from an unrelated adult volunteer. . . .
Studies are presented in six patients receiving renal homotransplants from non-twin donors. A cadaver donor was used in one instance, a brother or sister in three instances, and a mother or father in two. No attempt was made to match the subgroups of the blood between donor and recipient. All six kidney transplants functioned well enough to maintain the patient. The function of the transplant persisted up to death in two patients who died of complications of radiation aplasia. None of the patients, however, have yet passed the one-year milestone required for assessment of long-term results. Several factors relating to the early management of patients with renal homotransplants are discussed. (P.C.H.)
An analysis of 6 patients subjected to total body irradiation followed by bone marrow, kidney, or skin homotransplantation has been made. Two patients received marrow-repressing doses of x-ray, 600 r and 700 r respectively. Four received a non-marrow-repressing dose ranging from 450 r in 2 doses to 250 r in a single dose. Bone marrow was transplanted from multiple donors, including the kidney donor in one instance, and from a single maternal donor in another. Kidney transplantation was performed on 4 occasions, twice from an unrelated neonatal donor, once from a diovular twin, and once from a father. Skin transplants were used as test grafts in 3 instances. Of all the attempts the only permanently successful homograft was of a kidney from the diovular twin to his brother following a split dose of total body x-irradiation of 450 r. Supporting laboratory studies have been used in an attempt to analyze the clinical courses.
Understanding organ procurement and the transplant bureaucracy
- Burdick
Experimentelle nierentransplantation
- von Decastello
Resultats d’une tentative de greffe rénale
- Dubost
Kidney preservation for transportation: initial perfusion and 30 hours’ ice storage
- Collins
The homotransplantation of kidneys in dogs
- Dempster
Hyperacute rejection of kidney allografts
- Kissmeyer-Nielsen
Perspectives on immunosuppression
- Schwartz
Greffe de reins au pli du coude par soudure arte
- Jaboulay