Transplantation for the kidney has become the treatment of choice for end-stage renal failure in most age groups with perhaps the exception of the very young and the very old. That this has happened over the past 40 years represents one of the most significant developments in medicine in this century. Furthermore, advances in immunosuppression, histocompatibility, and organ preservation in the field of kidney transplantation have led to the successful transplantation of other organs, in particular the liver and heart.

The modern era of kidney transplantation began with the pioneer work of David Hume in Boston around 1950 with the transplantation of cadaver kidneys into non-immunosuppressed recipients. The kidneys were implanted in the thigh anastomosing the femoral vessels to the renal vessels with drainage of the ureter on to the skin. Some of these kidneys functioned for several weeks before being rejected. In 1954 Joseph Murray transplanted a kidney between identical twins where no immunosuppression was required, on this occasion placing the kidney retroperitoneally in the iliac fossa, essentially the technique as used today. This operation was a milestone in the field of transplantation as it confirmed that a successfully transplanted kidney in the absence of rejection was capable of essentially normal renal function.

Work continued in Boston, Paris, and the United Kingdom using total body irradiation of the recipient in an effort to prevent rejection of the transplanted kidney with some surprisingly good results in the short term, some kidneys functioning for several months. However, the discovery of the immunosuppressive properties of 6-mercaptopurine by Schwarz and Damashek in Boston in 1959 quickly led to the demonstration by Calne in England and Zukowski and Hume in Richmond, Virginia that this agent could prevent rejection of kidneys in dogs. Elion and Hitchings, who had produced 6-mercaptopurine at Burroughs Wellcome then developed azathioprine, of which 6-mercaptopurine is a metabolite. In further studies by Calne, working with Murray in Boston, azathioprine appeared to be perhaps less toxic than 6-mercaptopurine and very quickly was introduced as the standard immunosuppressive drug in clinical renal transplantation. Azathioprine, together with steroids, remained the conventional immunosuppressive therapy for 20 years until cyclosporin emerged on the clinical scene.

Today it can be truly said that there are no absolute contraindications to renal transplantation, and all patients with end-stage renal failure are potential candidates for renal transplantation (Table 1) 233. Of the metabolic disorders causing end-stage renal failure type I diabetes is by far the most common, ranging from 10 to 25 per cent of all patients coming to transplantation. Renal failure due to oxalosis has been considered an absolute contraindication to transplantation but recently successful transplantation has been reported in this condition by methods directed at prevention of the deposition of oxalate in the kidney by maintenance of a copious urine output and the administration of pyridoxine, phosphate, and magnesium solutions.

In addition the improved safety and decreased side-effects of modern immunosuppression allows the transplantation of young children and the elderly patient with very acceptable results at least in the short and medium term. In the case of infants born with renal failure due to congenital abnormalities of the urogenital tract, it is now considered preferable to maintain them on peritoneal dialysis until they are 2 or 3 years of age before giving them a renal transplant.

Recurrence of the original disease has not proved to be as big a problem as originally envisaged in the early years of renal transplantation. Although recurrence is relatively common in certain of the nephritides (e.g. mesangiocapillary–type II (dense deposit disease), IgA glomerulonephritis, and focal glomerulosclerosis), loss of the kidney due to the recurrence in these conditions is relatively uncommon (Table 2) 234.

From the point of view of graft outcome living related transplantation still provides better long-term results than cadaver transplantation. In addition the ever-increasing shortage of cadaver donors means that living related transplantation remains an important option for the patient with end-stage renal failure. The selection of a donor from within a family is based firstly on the motivation of the potential donor(s) which should be truly altruistic without coercion from the patient or other members of the family, and secondly on the basis of blood group compatibility and the optimal HLA match in the presence of a negative crossmatch between recipient and donor (see later). The ideal combination is that between HLA identical siblings and next that between one HLA haplotype disparate siblings or parent to child (see Section 10.1) 69. Having established that a family member is a suitable donor on the above psychological and immunological grounds, the donor must undergo an extensive medical evaluation, including a full investigation of renal function, and finally an angiogram to define the renal vasculature on each side.

The risks to the donor are not inconsiderable. There are first the risks associated with a major operation including a small risk of death, and second the long-term risk to a healthy donor of having one kidney. However, follow-up studies of donors for up to 20 years have revealed no excess risk of hypertension or renal failure over and above that of a normal age matched population.

There is considerable controversy in this area and there is obviously opportunity for commercial exploitation, as seen in many developing countries. However, a case can be made for the use of living unrelated donors in exceptional circumstances where there is clearly a strong emotional relationship between donor and recipient, as for example between spouses. It should be remembered that in contrast to the family donor, the use of a living unrelated donor provides no greater chance of a successful outcome than the use of a cadaver donor, although there is some recent evidence suggesting that the outcome of living unrelated transplantation is better than cadavar transplantation, and this is assumed to be due to the lack of any ischaemic damage to the kidney in the former.

Most kidney donors are cadaver donors in whom brain-stem death has been diagnosed while respiratory and cardiac function is being maintained on a ventilator. The usual cause of brain death is irreversible brain damage due to head injury or subarachnoid haemorrhage. It is important that renal function be normal and that urine output be maintained before and after the final diagnosis of brain death has been made. Most of the parameters of brain death reflect brain-stem death, for in the absence of brain-stem function respiratory and cardiac function cannot be maintained. The presence of widespread bacterial infection, cancer, or a positive test for hepatitis B, hepatitis C, or HIV would exclude a potential cadaver donor from further consideration. A history of hypertension or diabetes might be a relative contraindication to use of the kidneys but where doubt exists the kidneys can be removed and an immediate biopsy performed before a final decision is made. In general very young donors (less than 1 year) or very old donors (over the age of 70) are not considered suitable.

In living-related kidneys the selected kidney (usually the left as it provides a longer renal vein) is removed either through a flank incision with the patient in the lateral position or transperitoneally through a midline abdominal incision.

Kidneys are removed from the cadaver donor en bloc following in-situ perfusion, with subsequent dissection and perfusion of the kidneys after removal. Today the removal of kidneys is usually part of a multiorgan retrieval procedure, and then the kidneys are the last organs to be removed.

Although kidneys can be preserved by continuous perfusion with colloid solutions such as oxygenated human albumin for periods up to 72 h, machine preservation has been largely replaced by simple flushing of the kidney with one of a number of preservation solutions and storage in ice slush. This provides satisfactory preservation for up to 48 h, which is generally long enough for selection of the appropriate recipients on medical and matching grounds and transport of the kidneys within a national or even international network of organ exchange. The preservation solutions most widely used are Euro Collin's and hypertonic citrate, both solutions having in common a K⫀ content similar to that within the cell. More recently the University of Wisconsin (UW) solution, the preservation fluid of choice in liver transplantation, has become more widely used in kidney transplantation as well. The important components of the UW solution are probably lactobionate and adenosine.

Matching for HLA, the major histocompatibility complex (MHC) in man, presents major logistic problems in cadaver transplantation because of the genetic complexity of the HLA system. For this reason national or international organ exchange networks have developed, e.g. Eurotransplant, UK Transplant Support Service (UKTSS), and in the United States the United Organ Sharing scheme (UNOS), to try and ensure that as many recipients receive a beneficially matched kidney for the HLA-A, -B, and -DR antigens as possible. That this is worth trying to achieve is beyond question (Fig. 1) 691, but even so many recipients with uncommon HLA phenotypes will be excluded on this basis from ever receiving a transplant. The approach to HLA matching can be simplified by matching just for HLA-DR which still provides an improved graft outcome not much less than that obtained by matching for the whole of the MHC complex, especially in the patient who is being regrafted (Fig. 2) 692. Nevertheless the benefits of matching in terms of graft outcome are modest in the case of a first graft, and for this reason failure to find an acceptable match for a recipient should not preclude that recipient from receiving a mismatched cadaver kidney with the more potent immunosuppression available today.

Perhaps the most important aspect of the matching procedure in cadaver transplantation is the crossmatch in which donor lymphocytes are added to serum from the recipient in the presence of rabbit serum as a source of complement. If the donor lymphocytes are lysed, this is known as a positive crossmatch. For many years, following the recognition of hyperacute rejection of a transplanted kidney in the presence of a positive crossmatch between donor and recipient, a positive crossmatch was considered to be an absolute contraindication to renal transplantation.

In more recent years the complexity of antibodies found in the sera of sensitized recipients has been recognized, and indeed not all antibodies are directed against HLA antigens. Thus an apparently sensitized recipient may have antibodies, e.g. autoantibodies which react with donor lymphocytes giving a positive crossmatch but which do not damage a subsequent kidney from that donor. As most patients who are sensitized by previous pregnancies, blood transfusions, or failed transplants have a mixture of antibodies including antibodies against HLA, it is important to define the class and specificity of these antibodies before transplantation as this helps in the interpretation of a positive crossmatch. Table 3 235 summarizes the types of antibodies in a sensitized recipient which may give rise to a positive crossmatch and whether a successful transplant is possible in the presence of that positive crossmatch.

A renal transplant has been a very standard operation for many years now. The iliac vessels are exposed retroperitoneally through an oblique incision in one or other iliac fossa, the oblique muscles being divided in the line of the incision and the peritoneum reflected upwards and medially (Fig. 3) 693. The renal vein is anastomosed end-to-side to the external iliac vein and the renal artery anastomosed either end-to-end to the divided internal iliac artery or, as is more usual with a cadaver kidney where the renal artery will have a cuff of aorta, end-to-side to the external iliac artery (Fig. 4) 694.

The ureter is implanted in the bladder (ureteroneocystostomy) either through an anterior cystotomy with a submucosal tunnel to prevent reflux or as an extravesical procedure where the ureter is anastomosed to the mucosa of the dome of the bladder and then muscle is drawn over the ureter again with a view to preventing reflux. Whether the latter technique does prevent reflux is questionable. Another technique used successfully by some units (in particular at Massachusetts General Hospital) is to create a pyelo-ureterostomy in which the pelvis of the kidney is anastomosed to the recipient ureter.

Although not essential, usually a right kidney is implanted in the left iliac fossa and vice versa as this facilitates the vascular anastomoses. The wound is closed without drainage where possible, and an indwelling catheter left in the bladder for 1 to 5 days depending on the technique used.

A kidney from a living related donor would always be expected to function immediately whereas only 60 to 80 per cent of cadaver kidneys will do so. Immediate function is usually associated with an osmotic diuresis and urine output over 24 h is anywhere from 5 to 25 l. This does require meticulous attention to fluid replacement and is made easier if there is a central venous pressure line in place over the first 48 h after surgery. After 48 to 72 h the kidney will begin to concentrate and the intravenous fluid replacement can be slowed and replaced by oral fluids.

In this situation which is usually due to acute tubular necrosis, other causes of delayed or non-function must be considered (Table 4) 236. A renogram of the transplanted kidney will confirm the presence or absence of a blood supply. Ultrasound examination will demonstrate obstruction or a urine leak, while finally hyperacute rejection can be excluded by renal biopsy.

Where there is a functioning kidney with a falling or normal serum creatinine which then begins to rise, rejection is the most likely cause. This is confirmed by biopsy but an ultrasound examination will also exclude the presence of ureteric obstruction or leakage. If a renal vein or arterial thrombosis is suspected, both the ultrasound examination and a renogram will clarify the diagnosis.

1. Hyperacute rejection

This is an immediate antibody mediated rejection occurring within the first 24 h of transplantation in the presence of a positive crossmatch due to HLA class I antibody or an ABO incompatible kidney. The classical hyperacute rejection (which is evident within 60 min of revascularization of the kidney) is not seen today, unless there has been an error in the interpretation of the crossmatch or rarely an incompatible ABO kidney is transplanted in error, but less florid examples are not uncommon and present as non-function of a kidney in a sensitized patient, more usually in a patient receiving a regraft.

2. Accelerated rejection

This is also rejection in a recipient specifically sensitized against the donor and is mediated by cells. It occurs between 2 and 4 days after transplantation, presenting with a deterioration of renal function often accompanied by a fever. A biopsy will show a florid cellular infiltration within the graft, often associated with arteriolar thrombosis and interstitial haemorrhage in severe cases.

3. Acute rejection

This is the outcome of the immune response to an allograft in a non-sensitized patient. Most commonly the first rejection episode will be apparent between 7 and 21 days after transplantation, but may present at any time after transplantation. Some 60 to 70 per cent of recipients of a cadaver allograft will have at least one acute rejection episode during the first 3 months after transplantation with current immunosuppressive protocols. In a classical example of an acute rejection episode the patient would present with a modest fever, the graft would be swollen and tender, and there would be a concomitant fall in urine output and a rise in serum creatinine. This picture is relatively uncommon today with current immunosuppression, where there may be a mild fever with minimal or no graft swelling and tenderness, the main feature being a deterioration in renal function as evidenced by a rise in serum creatinine. A biopsy will confirm the diagnosis. The differential diagnosis will be firstly cyclosporin nephrotoxicity and secondly ureteric obstruction. Blood levels of cyclosporin and an ultrasound respectively can be used to exclude these possibilities.

4. Chronic rejection

This is an insidious process represented by a steady deterioration in function at any time following the first few months of transplantation. A biopsy will confirm the diagnosis, but other diagnoses to be considered are ureteric obstruction, renal artery stenosis, and recurrence of the primary disease.

If a biopsy is taken from the kidney within 1 h of revascularization (i.e. before wound closure) this may reveal a marked infiltration of the kidney with polymorphonuclear leucocytes (Fig. 5) 695. Subsequent biopsies at 24 h and later will reveal widespread glomerular capillary and arteriolar thrombosis with oedema, fibrinoid necrosis of arteriolar walls, and interstitial haemorrhage. Immunofluorescence will demonstrate deposition of IgM, IgG, and complement within the transplanted kidney.

The hallmark of these rejection reactions is the mononuclear cellular infiltrate, the density of which indicates the severity of the rejection, as does infiltration of the tubules themselves (Fig. 6) 696. Associated with the cellular infiltrate are oedema and in severe cases interstitial haemorrhage and fibrinoid necrosis of arterioles. The cellular infiltrate contains approximately 65 per cent macrophages and 30 per cent T lymphocytes with CD8+ T lymphocytes being rather more prominent than CD4+ T lymphocytes. A small percentage of the infiltrate comprises natural killer (NK) cells and eosinophils. A smaller percentage of the T lymphocytes will exhibit activation antigens such as the IL-2 receptor. In addition there will be an induction of expression of MHC class II antigens on cells such as proximal tubular cells which do not express these antigens normally.

The major features of this chronic process are interstitial fibrosis within the parenchyma of the kidney and intimal hyperplasia of arteries within the parenchyma (Fig. 7) 697.

The complications of transplantation can be considered as technical or related to the immunosuppressive therapy itself, much of which is secondary to immunosuppression induced in the recipient.

Renal artery thrombosis is very uncommon and usually presents within the first 2 weeks of transplantation as an abrupt cessation of renal function with no other clinical features. Renal vein thrombosis occurs much more commonly than hitherto, and may be related to the thrombogenic potential of cyclosporin. It usually occurs within the first few days of transplantation and is associated with an abrupt cessation of renal function associated with a painful, swollen, tender graft.

Renal artery stenosis may present at any time from several months to several years after transplantation, and although the stenosis may occur at the anastomosis it usually occurs just distal to the anastomosis. The patient presents with poorly controlled hypertension and deteriorating renal function (see later).

A urine leak, either from the bladder or the ureteric anastomosis occurs within the first 6 weeks of transplantation and is most commonly due to ischaemia of the lower end of the ureter due to a poorly removed kidney with skeletonization of the ureter or interruption of the ureteric blood supply within the hilum of the kidney. A bladder leak will heal with catheter drainage of the bladder, whereas ureteric necrosis is dealt with by excising the necrotic ureter and either reimplanting the ureter in the bladder over a ureteric stent or anastomosing the ureter to the patient's own ureter either end-to-side or end-to-end again over a stent.

Obstruction of the ureter presents at any time from weeks to years after transplantation and although the site of obstruction is usually in the lower one-third of the ureter, no doubt as a result of ischaemia, a significant number of pelviureteric obstructions are seen. Diagnosis is confirmed by ultrasound examination of the graft and an antegrade pyelogram. Immediate relief of the obstruction can be obtained by the insertion of a percutaneous ureteric stent or a percutaneous nephrostomy if this is not possible. Sometimes a stenosis can be dilated with a balloon, but otherwise corrective surgery is required, involving either reimplantation of the normal ureter if the stenosis is at the entry of the ureter into the bladder or a pelviureteric anastomosis using the patient's own ureter for a more proximal stenosis.

The incidence of urological complications after transplantation is now quite low in experienced units, being no higher than 5 per cent, which represents a marked improvement over that seen 15 to 20 years ago. This improvement is due to better techniques of kidney retrieval and implantation of the ureter, but in particular to the general use of low dose steroids after transplantation in more recent years.

This is a collection of lymph around the graft, which arises from divided host lymphatics around the iliac vessels. This complication has also become relatively uncommon since it has been recognized that lymphatics must be ligated with silk rather than occluded with with diathermy. A lymphocele is retroperitoneal and as such produces symptoms from pressure on surrounding structures. Thus, it may present with deteriorating renal function due to pressure on the transplanted ureter, a swollen leg on the side of the graft due to pressure on the iliac vein, and tenesmus or strangulation due to pressure on the rectum and bladder respectively. The diagnosis is confirmed by ultrasound examination (Fig. 8) 698. It is treated in the first instance by percutaneous drainage but if it recurs more than twice after percutaneous drainage it needs to be drained by fenestration into the peritoneal cavity. This can be done satisfactorily now by laparoscopic approach rather than an open operation.

Not only bacterial infections, but viral and protozoal infections may occur in transplant patients due in part or wholly to the immunosuppressive therapy given to prevent and treat rejection. The time at which an infection appears in relation to transplantation is important in arriving at a diagnosis, for viral (with the exception of herpes simplex) and protozoal infections are rare in the first month after transplantation. Pneumonia as a postoperative complication and urinary tract infections are common in the early weeks after transplantation. Asymptomatic urinary tract infections are relatively common due mainly to the indwelling catheter left in the bladder for several days after surgery. Wound infections are uncommon with an incidence of 1 to 2 per cent. A preventive antibiotic should be given with the induction of anaesthesia to cover contamination at the time of operation and in particular to cover the possibility of the transplanted kidney being contaminated. An appropriate broad spectrum antibiotic is used, such as cefuroxime.

Of the mycobacterial infections tuberculosis is by far the most common and generally presents as a chest infection with fever, cough, and an infiltrate on radiography. However, tuberculosis may uncommonly present as an abscess or joint infection. Any patients who are from areas where tuberculosis is common, e.g. the Indian subcontinent, or who have a history of tuberculous infection in the past should receive prophylactic therapy for 1 year after transplantation (e.g. treatment with isoniazid).

The most common and potentially the most serious of the viral infections is cytomegalovirus (CMV) infection. This may be a primary infection in a CMV-seronegative recipient who receives a kidney from a seropositive donor or reactivation of the virus in a seropositive recipient. The likelihood of a CMV infection occurring is directly related to the potency of the immunosuppression used. The primary infection is more severe, but clinically in both instances the presenting feature will be a high fever (greater than 39°C) associated with a leucopenia. This high swinging fever may last 7 to 10 days and characteristically the patient feels unwell only during the time of the fever. Diagnosis of a primary infection is confirmed by seroconversion in a seronegative patient or a rise in titre in a seropositive patient, but this does not occur till several days after the onset of fever. More overt infection such as pneumonitis or hepatitis heralds a more serious problem and is potentially fatal in a primary CMV infection. For this reason it is desirable where possible to transplant a seronegative recipient with a seronegative kidney, for primary infection does not occur in this situation provided that the recipient only receives CMV seronegative blood if transfusion is required (Table 5) 237. Vaccination of seronegative recipients before transplantation has been explored but the results of a large international multicentre trial are not yet available. Prophylactic administration of hyperimmune globulin has also been advocated but with little evidence to support its use in this way. Ganciclovir, an antiviral agent which has proved valuable in the treatment of an overt CMV infection, is now widely used prophylactically in patients at high risk of developing CMV infections, e.g. seronegative recipients given a seropositive kidney and then given ATG or OKT3 to prevent or treat rejection, where it is almost inevitable that a CMV infection will occur.

Herpes simplex infections around the mouth or less commonly the genitalia are frequent but resolve quickly with prompt treatment with systemic acyclovir. Acyclovir has been used prophylactically in patients with a history of herpes infections in the early weeks after transplantation when immunosuppression is at its highest level but is probably only justified in the case of a history of genital herpes.

Varicella zoster infections present rarely as chickenpox in recipients never previously exposed in which case the infection may be fulminating, but present commonly as shingles (Fig. 9) 699. Acyclovir is the treatment of choice.

Hepatitis B in the donor is a contraindication to transplantation, but it is not uncommon for recipients of a renal transplant to be hepatitis B positive. The outcome in those patients who are positive and immunosuppressed is uncertain in that liver failure may develop in some, but not all, patients after several years.

Hepatitis C, the cause of non-A, non-B hepatitis, in the donor is also a contraindication to transplantation, but is not uncommon amongst transplant recipients (approximately 5–10 per cent in some centres). It is unknown at this time whether this represents a longer-term risk of liver failure in the recipient when immunosuppressed following transplantation.

Pneumocystis carinii is the most important infection in this group and occurs at any time after the first month of transplantation, the patient usually presenting with a dry non-productive cough and a low grade fever. A chest radiograph may show patchy consolidation in one area of the lung at the early stages of the infection. A bronchoscopy and bronchial lavage should be carried out promptly if no alternative diagnosis is available, for cytological examination of the washings will inevitably confirm the diagnosis of pneumocystis. High dose septrin is the appropriate treatment. Pneumocystis is rare if prophylactic septrin (0.5 g/day) is used in the immunosuppressed patient and most units now use such a protocol at least for the first 6 months after transplantation.

Candida infections of the mouth are not uncommon and prophylactic amphotericin lozenges are used during the first few months after transplantation. Aspergillosis is perhaps the most common of the other fungal infections, but is still relatively uncommon, and its common presentation is as a chest infection. Again the diagnosis is established by bronchoscopy and bronchial lavage.

Although there is an increased incidence of most types of cancer in the immunosuppressed renal transplant recipient, this increased incidence is particularly dramatic in the case of tumours with a possible viral aetiology such as non-Hodgkin's lymphoma (100-fold increased incidence), squamous cell cancer of the skin (200-fold increased incidence), cervical cancer of the uterus (50-fold), and Kaposi's sarcoma (1000-fold). In countries with a high exposure to sunlight such as Australia some 50 per cent of patients will have developed at least one skin cancer within 10 years of transplantation, with a reversal of the normal basal cell to squamous cell cancer ratio of 2 : 1. Many of the squamous cell cancers are rapidly growing with an increased propensity to metastasize (Fig. 10) 700. They also occur in unusual sites, e.g. perianal sites.

The prevalence of lymphomas is greater with current immunosuppressive protocols, this undoubtedly being related to the potency of the immunosuppression. Two types of lymphoma are seen. The first is an acute lymphoproliferative disorder, usually occurring within the first year of transplantation, which may be associated with an increase in titre to Epstein-Barr virus (EBV). Its course tends to be rapidly fatal, but it may remit with reduction or cessation of immunosuppressive therapy together with a course of high dose acyclovir. Histologically that tumour is usually a polyclonal B-cell lymphoma. This acute lymphoproliferative disorder is more commonly seen in patients who have received ATG and/or OKT3 as part of their immunosuppressive protocol. The second type of lymphoma occurs at later times after transplantation and presents more typically with enlarged nodes. It may be a monoclonal B-cell lymphoma histologically and its response to conventional therapy is not dissimilar to that in a non-transplant recipient. Both types of lymphoma not uncommonly involve the base of the brain, which is an unusual site in lymphomas occurring in non-immunosuppressed patients.

As renal transplant recipients survive longer and become an increasingly more elderly population, ischaemic heart disease and cerebrovascular disease have become the major cause of death after transplantation. The major risk factors in the transplant population are hypertension and hyperlipidaemia. Hypertension requiring treatment after renal transplantation is common with current immunosuppressive protocols, and some 75 per cent of patients are on treatment at 1 year after transplantation. This incidence of hypertension has increased with the introduction of cyclosporin. Good control of hypertension is an essential part of the management of the transplant recipient, and often a combination of a diuretic, &bgr;-blocker, calcium channel inhibitor, and angiotensin converting enzyme (ACE) inhibitors is required to achieve control.

Poorly controlled hypertension, especially if associated with deteriorating renal function, should raise the question of a renal artery stenosis in the transplanted kidney (Fig. 11) 701. An angiogram will be necessary to establish the presence of a renal artery stenosis, but even if present this does not mean that the stenosis is a functional one. The cautious introduction of an ACE inhibitor can be used as a diagnostic test in this situation for if renal function deteriorates and then returns to its previous level on cessation of the drug, this would strongly suggest that a radiological stenosis is a functional one. Renal vein renins from the transplanted kidneys and the host kidneys may be measured, but usually are not helpful.

Once the diagnosis of a functional renal artery stenosis is made then correction of the stenosis is indicated. In the first instance an attempt to dilate the stenosis by balloon angioplasty should be made. If this is unsuccessful then reconstructive surgery should follow, although the dissection of the renal vessels is usually difficult and requires considerable expertise in both vascular and transplantation surgery. Many types of reconstruction are possible but the most common are reimplantation of the renal artery distal to the stenosis into the iliac artery or insertion of a saphenous vein graft between the common iliac artery and the renal artery distal to the stenosis.

Ischaemic heart disease is common in the elderly and diabetic renal transplant population, but is managed in the same way as in the non-transplant patient. There is no contraindication to major cardiac surgery in these patients if this represents the most appropriate management.

A significant increase in cholesterol levels is seen in many patients after renal transplantation, the rise being essentially in the very low density lipoprotein fraction with a concomitant decrease in the level of high density lipoprotein, a major pattern of risk for ischaemic heart disease. The hypercholesterolaemia has been attributed to cyclosporin but may be more closely related to the use of steroids. In any case these patients should be treated energetically with a low cholesterol diet and where high levels of cholesterol remain then the introduction of cholesterol lowering agents is justified, although their place in this patient population is as yet unknown.

Apart from the rare instance in which transplantation between identical twins is possible, transplantation between HLA identical siblings provides not only the best short-term and long-term outcome graft survival (Fig. 12) 702 but also as less immunosuppression is required there are fewer related problems. Living related donors and recipients sharing one HLA haplotype, i.e. parent to child or sibling transplant also have a better graft survival than cadaveric grafts. It now appears that living related and unrelated donors and recipients mismatched for both HLA haplotypes also have a better graft survival than cadaveric grafts, presumed due to the lack of ischaemic injury to the kidney in the living donor. Because of the better graft survival and also the shortage of cadaver kidneys, living related transplantation remains a justified procedure provided the donor has the appropriate motivation to be a donor without any financial or emotional coercion.

The bulk of renal transplants performed in the Western world are cadaveric (unlike in developing countries where the majority of transplants performed are still living related transplants). Graft survival has steadily improved over the last 20 years due to a variety of reasons so that around 80 to 85 per cent of grafts will be functioning at 1 year and around 65 per cent at 5 years (Fig. 13) 703. Patient survival has not altered appreciably in recent years, being around 90 to 95 per cent at 1 year and 80 per cent at 5 years, and is unlikely to improve now that more elderly patients are being transplanted.

Undoubtedly immunosuppression is the major factor in improving graft survival in recent years, with the introduction of cyclosporin resulting in a 10 to 15 per cent improvement in graft survival.

This has had a small but significant impact on cadaveric graft outcome (see earlier), while reliably predicting the outcome of living related transplantation.

The centre in which the transplant is performed remains a major determinant of graft outcome and still remains an unexplained phenomenon. It is not obviously associated with the experience of the unit, patient selection, or immunosuppressive protocols but no doubt reflects the influence of all of these and other unidentified factors.

That prior blood transfusions in the non-transfused recipient improved graft survival in the precyclosporin era is unquestioned, but today it is uncertain whether the transfusion effect exists or not, and many units are abandoning their deliberate transfusion policies in non-transfused recipients because of this and the small, but real, risk of transmitting HIV or non-A, non-B hepatitis (hepatitis C) by a blood transfusion.

The age of the recipient will influence graft outcome in that the elderly patient is more likely to have or to develop significant ischaemic heart disease and as a result the elderly recipient has a lower life expectancy than the younger recipient. However, the elderly recipient is less likely to lose a graft from irreversible rejection (Fig. 14) 704. The age of the donor also has an impact on cadaveric graft survival in that kidneys from young (less than 10 years of age) or very old (over 65 years of age) donors show a poorer graft survival.

The influence of the race of the donor or of the recipient remains uncertain. That a black patient in the United States has a poorer graft survival is undisputed, but distinguishing the possible genetic effect from the socioeconomic effect of a less privileged population has proved difficult. Nevertheless evidence has been provided that, after allowing for the socioeconomic influence, the black recipient does display a poorer graft survival than his white counterpart.

Cessation of immunosuppressive drug therapy by the patient, either because of unacceptable side-effects or for financial reasons, is now one of the more common causes of graft failure.

Although certain of the glomerulonephritides do recur (see earlier), loss of the graft as a result is relatively uncommon.

Other factors such as the sex of the donor and recipient, blood group of donor and recipient, and parity of the recipient have little if any effect on graft outcome.

The patient with a successful transplant is in general restored to a normal existence with a quality of life as perceived by the patient being little different to that of the normal population. The majority of recipients of a successful graft will return to work, study, or managing the home within 6 months of transplantation.

Pregnancy after transplantation is possible whether the father or the mother is the transplant recipient. Although there is a higher level of spontaneous abortion in the transplant recipient, the incidence of developmental abnormalities in the live births that go to term is not higher. Renal function may deteriorate during pregnancy where pre-eclampsia is more common, and rejection may occur after delivery. Provided that renal function is relatively normal there is no contraindication to pregnancy but careful monitoring of the fetus and renal function in the mother during and immediately after the pregnancy is essential.

As graft survival continues to improve with the introduction of more potent immunosuppression more attention will be paid to the side-effects of the immunosuppressive therapy and also to the prevention of cardiovascular disease. In addition, better and more specific immunosuppression may allow chronic rejection to be prevented, for this still remains a significant influence on long-term graft outcome.

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