Kidney Transplantation: An Alternative Treatment for Chronic Kidney Disease

Kidney Transplantation: An Alternative Treatment for Chronic Kidney Disease

In this article, Dr. Karina Furaz, a nephrologist at the FRIAT Dialysis Center Los Llanos de Móstoles, makes an exhaustive review of kidney transplantation as an alternative treatment for patients with terminal CRI. Throughout the text Dr. Furaz details the protocol that is followed in Spain to be a candidate for transplantation, analyzes its advantages and disadvantages and details its contraindications, risk factors and possible complications.
KIDNEY TRANSPLANT
The first successful organ transplant was the kidney transplant performed between identical twins in Boston, USA on December 23, 1954. In the years in which the kidney transplant technique was developed between 1965 and 1980 , The patients' survival improved progressively to 90%, and the graft increased to greater than 80% after the introduction of cyclosporine. Currently, in the first transplant recipients (not sensitized), either deceased or living donors have 95% patient survival and 90% graft survival expectations.
Several groups have reported excellent results even in transplants with ABO group incompatibility, but even in hyperimmunized patients due to previous transplants, the development of better desensitization protocols and paired kidney exchange programs now offer real opportunities for successful transplantation.
RENAL TRANSPLANTATION IN THE TREATMENT OF THE ERC
Numerous studies have shown that: renal transplantation is a therapy that improves long-term survival when compared to maintenance dialysis.
The pre-dialysis transplant is an attractive option, since it improves the survival of the graft and reduces the costs. It is associated with a 25% reduction in graft failure and 16% reduction in mortality compared to recipients who are transplanted after dialysis; Although it is not possible in all cases because it will depend on the blood group of the patient and the donor offer.
Appropriately indicated renal transplantation is therefore the treatment of choice for patients with terminal CRI because it offers a better evolution of the disease and its lower costs.
Without precise rules, once the chronic nature of the renal disease process is established and renal function decreases (usually when the glomerular filtrate reaches values ​​of around 30 ml / min), it is necessary to present the different options of Renal replacement therapy (RRT) to be used when values ​​of renal function are close to being truly insufficient. At that time the patient should be evaluated by nephrologists in specific consultations of predialysis or clinical nephrology, where the different options of SRT will be presented. These include the two clearance techniques (peritoneal dialysis and hemodialysis) and the two types of kidney transplantation (living donor and deceased donor).
There are also different places where patients can access information: In Spain, this information vehicle is currently available in the National Transplant Organization (ONT) and in official pages of Foundations and Health Services of Autonomous Communities (CCAA).
PROTOCOL FOR INCLUSION IN THE RENAL TRANSPLANTATION LIST IN SPAIN
Initial assessment process:
The competence and degree of autonomy of the patient will be assessed and an informed consent will be given.
You will be informed about the possibilities of transplanting a kidney from a living donor or corpse, about the risks of surgery and rejection, complications of immunosuppression and about the overall results of the referral transplant program.
Protocol of evaluation and requirements for inclusion in transplant waiting list:
It depends on each transplant center (each one has its own protocols) but in general lines the following procedure is done:
Review of clinical and psychosocial history
Rigorous physical exploration
Analytical, radiodiagnostic and functional tests
Assessment by other specialists, according to the patient's medical history (digestive, urology, psychiatry, etc.)
The clinical history includes: personal and family history of the underlying renal disease and its extrarenal affection, data of cardiovascular disease, infections and neoplasms. Psychological characteristics of the patient, in particular degree of autonomy and compliance with prescribed treatments, are also evaluated, and documents possible risk and alcohol and / or drug addiction behaviors.
Baseline renal disease must be known and its familial or not, to assess the relevance of live donor or cadaver transplantation and the possibility of graft relapse.
The exacerbation or reactivation of infections as a consequence of immunosuppression is one of the main causes of morbidity and mortality in the transplant. That is why tests are performed for infection detection, exposure to tuberculosis, trips to areas with endemic infections, a history of infectious diseases are analyzed. It is important to know the history of vaccines, and update them if appropriate. Patients on dialysis and waiting lists must be vaccinated with influenza, pneumococcus and hepatitis B.
CONTRAINDICATIONS FOR RENAL TRANSPLANTATION
Absolute
Recent malignant neoplasm with metastatic activity
Active infection
Irreversible extrarenal disease without rehabilitation or life expectancy of less than one year
Psychiatric illness with loss of autonomy or competence
Repeated therapeutic failure
Addiction to drugs and / or alcohol without rehabilitation
IgG positive cross-match against donor T cells
Today, however, it is difficult to speak of absolute contraindications, and each patient should be evaluated individually and according to their particular situation.
Relative
Old age> 75 years old
Cardiovascular disease
Advanced chronic liver disease
Urinary tract anomalies
Previous malignant tumors
Basic disease
RISK FACTORS CONNECTED TO THE RECEIVER
Age
There is no formal age limit to exclude a patient as a candidate for transplantation.
Age is one of the criteria that has become more flexible according to the aging of the general population and dialysis. There are not many studies that provide evidence on the results in very elderly patients, over 70 years, but those obtained in recipients over 60 years are better than those that would achieve remaining on dialysis achieving, in general, an acceptable degree of Long-term renal function.
Elderly patients have higher morbidity with higher hospitalization rates for younger recipients and also greater risk of cardiovascular disease, neoplasms and infections, so the evaluation should be very rigorous. However, they also experience less rejection and require less aggressive immunosuppression.
Some groups consider very old patients as: preferential candidates to receive cadaver donor kidneys with "extended criteria" (advanced age, obtained in asystole, etc.) or to be recipients of double transplantation with this type of donors.
Transplantation of a living donor over 65 years of age raises special problems that must be resolved with strict respect for underlying ethical factors.
HLA Retractors and Hypersensitization
The restransplants (2nd, 3rd, 4th, 5th transplant) are becoming more frequent, and are associated with higher rates of graft loss especially when there is a history of previous rejections. Having received immunosuppression increases the incidence of infectious or neoplastic complications, and will reinforce measures to look for any eventuality of this type prior to reinclusion.
Patients who are hypersensitive to previous transfusions, pregnancies, or transplants should be transplanted with the highest possible HLA compatibility given their characteristics. In Spain and Portugal there is a single state list of hypersensitized recipients who are given preference for cadaver donor transplantation, but despite having a preference the waiting list time is usually lengthened.
Obesity
Patients with a body mass index greater than 30 kg / m2 have a higher incidence of surgical complications, delayed healing, which motivates longer hospital stays.
There are controversial results regarding the association of obesity with decreased survival of the grafts. However, obesity is a risk factor for the development of diabetes, cardiovascular disease and post-transplant hyperfiltration.
Therefore, significant weight loss is recommended prior to inclusion on the waiting list.
Cardiovascular disease
Ischemic heart disease is the leading cause of death in transplant patients and graft loss with adequate function.
The risk of cardiovascular disease is higher in: patients with previous cardiovascular disease, diabetics, smokers, obese (BMI greater than 30), patients with classic cardiovascular risk factors, more advanced ages, very prolonged renal failure, and Which have poorly controlled arterial hypertension and left ventricular hypertrophy.
The evaluation of ischemic heart disease is very important especially in diabetics, in whom coronary disease is often asymptomatic. Asymptomatic and low-risk patients should be treated for modifiable factors prior to inclusion in the list. At high risk (previous stroke, advanced age, diabetes), although they are asymptomatic, they will be tested for stress tolerance (ergometry, Dobutamine, thalamic gammopathy, dipyridamole, MRI or CT. Patients with noninvasive positive and symptomatic tests will be studied with coronary angiography.
Patients with severe and diffuse coronary disease not amenable to revascularization or with severe heart failure are not good candidates for kidney transplantation and, depending on the case, the double heart kidney transplant can be evaluated.
If there is a previous history or presence of cerebrovascular disease risk factors carotid dopler and surgery if necessary. The dopler is also used to evaluate peripheral circulation in diabetic patients or with intermittent claudication.
Infections
Active infections are treated before listing a patient.
Patients with HIV: can be included provided they have undetectable viral load, normal T cell count and good tolerance to antiviral treatment.
Cytomegalovirus infection is one of the main causes of morbidity in transplantation, so it is imperative to detect the presence of CMV antibodies in all patients on the waiting list and to carry out appropriate prophylaxis.
Varicella Zoster: serology should be done prior to listing, and patients who do not have specific IgG antibodies prior to transplantation will be vaccinated and given specific immunoglobulins to those exposed to the virus after transplantation to avoid development of fulminant disease.
Virus C: is not contraindication for transplantation. HCV RNA is determined and hepatic biopsy is performed. Patients with bridge fibrosis or cirrhosis are excluded as candidates or are assessed for hepato-renal transplantation.
Virus B: The results in patients with positive surface antigen are lower than those obtained in other patients. Patients with viral replication, C or D coinfection, and those with persistent elevation of transaminases have a poor prognosis.
Most of the groups propose performing a liver biopsy. Patients with no viral replication data and no active chronic hepatitis data are candidates.
Immunosuppression favors the reactivation of tuberculosis and its spread. All patients should be excluded from disease and be carriers of a chest X-ray. Patients with active infection should receive complete treatment, and those who have had a prior chemoprophylaxis infection.
Diabetes
Renal transplantation in diabetic patients can be performed whenever there is no serious vascular disease that contraindicates this therapy. The morbimortality of these patients is greater than that of the non-diabetic population. In patients with type I diabetes, double transplantation of pancreas-kidney can be indicated and in type II diabetic, kidney transplantation. In both groups of patients the pre-transplant study should be very rigorous, with special emphasis on cardiovascular status.
Malignant tumors
Recipients who have or recently had a malignant tumor should be excluded from the waiting list for kidney transplantation. If the treatment of the tumor has been effective and there have been 2 to 5 safety without relapse (depending on the type and extent of the tumor), the possibility of renal transplantation can be re-established, provided the patient knows and accepts that the probability of reactivation Tumor exists and that immunosuppression may favor it.

Lung disease
The existence of any lung disease that complicates anesthesia and surgery in the transplant due to infection and ventilatory dependence or that may compromise its evolution should be evaluated, since immunosuppression increases the frequency and severity of the infections.
There are no standardized protocols for the study and management of patients with lung disease, although spirometry is essential.
Gastrointestinal disease
Patients with a history of diverticulitis are carefully evaluated and sometimes require partial colectomy prior to transplantation.
Cholelithiasis is common in patients on the waiting list, mainly diabetics. Cholecystectomy is indicated if there were previous episodes of cholecystitis to avoid recurrence.
In patients with a history of pancreatitis, modifiable risk factors such as hypercalcemia, alcohol consumption, cholelithiasis and dyslipidemia are controlled.
Patients with active peptic ulcer disease can not be transplanted until adequately treated because of the high risk of perforation due to the use of high doses of steroids. Symptomatic patients are studied to rule out infection with Helicobacter pylori and endoscopy is performed.
Coagulation Disorders
Patients with a history of thrombosis (including recurrent fistula thrombosis) are studied to rule out hypercoagulability, which may lead to graft loss.
When treatable anomalies exist, the best therapeutic option is decided with hematology.
Basic disease
In all patients candidates for renal transplantation, it is necessary to consider the possibility of recurrence of the original disease that caused end-stage renal failure. Fortunately, less than 5% of the grafts fail because of relapse of the primary disease. The table shows the possibility of recurrence of primary and secondary kidney disease after renal transplantation. In practice, the problem arises with oxalosis, since the recurrence is 100%; The right treatment is double liver and kidney transplantation. Also with focal glomerulosclerosis of rapid evolution, fundamentally when it has already presented an early and serious relapse in the first transplant. In these cases, the second transplant should be carefully evaluated since the probability of recurrence is 80%.

POSSIBLE COMPLICATIONS AFTER TRANSPLANTATION
Surgical Complications
These usually occur in the first few days after transplant, and can be:
Of the parenchyma
Renal rupture
Kidney trauma
Urological
Fistulas
Stricture of ureter
Vesicoureteral reflux
Lithiasis
Hematuria
Urinary tract infection
Vascular
Renal artery stenosis
Arterial thrombosis
Venous Thrombosis
Arteriovenous fistula
Renal artery aneurysm
Hemorrhage
Lymphocele
Surgical wound
Seroma
Infection
Hematoma
Evisceration
Eventration
Medical Complications
Sharp
Acute tubular necrosis (NTA): NTA is the major cause of acute renal graft dysfunction in the immediate postoperative period, affecting between 15 and 40% of cadaveric donor transplants and less than 5% of donors alive.
Acute rejection: The new immunosuppressants mainly mycophenolate mofetil and tacrolimus have considerably reduced their incidence (below 20%) and severity. It usually appears from the first week, in general, during the first 3 months. However, it may appear at any time in the course of development, including late phases (often as a result of poor patient follow-up).
Hyperacute rejection (RHA): It is diagnosed in the same operative act in which the kidney does not acquire the normal consistency, appears edematous and of bluish coloration, as a result of intravascular coagulation in the graft. It is, nowadays, exceptional since the pre-transplant cross-over test is generalized; However, when it is produced it is usually intractable and irreversible.
Accelerated rejection
Kidney toxicity by tacrolimus or cyclosporine
Infections: these are the acute complications with the greatest impact in terms of morbidity and mortality in the transplanted patient. They are related to: age of the patient, nutritional and uremic situation (eg, adequacy of pre-transplantation dialysis) and presence of diabetes mellitus; Added infectious diseases (eg, hepatitis B or C virus infection); Administered immunosuppression protocol; Presence of surgical complications; Need for catheter or catheterization; Degree of renal function; Presence of leukopenia and epidemiological exposure to various agents (eg, donor and recipient CMV serology, nosocomial agents, etc.).
Cardiovascular complications: Cardiovascular diseases are the main cause of long-term mortality in the renal transplant patient, highlighting the high prevalence of hypertension and hyperlipidemia in nephrotic and renal transplant patients. No less than 75% of the transplanted patients show arterial hypertension. Steroids and anticalcineurinics, cyclosporine and tacrolimus, which are present in most immunosuppressive protocols, also contribute to the development of hypertension.
Digestive and hepatic complications. With the administration of low doses of steroids with current immunosuppression protocols and the generalization of the use of H2 antihistamines, especially in patients with a history of ulcers, in the first weeks after transplantation, peptic complications are currently rare.
Acute pancreatitis is a serious complication, with an incidence in the transplanted population ranging from 0.5% to 4%, related to steroid and cyclosporine uptake, CMV infection, hepatobiliary disease, and alcohol intake.
Among the complications of the colon is the appearance of colitis in the CMV invasive disease, as well as the risk of perforation in patients affected by acute diverticulitis.
Hepatic complications arising from hepatitis B or C virus infection appear in medium- and long-term evolutions. Nevertheless, it is possible that in the course of energetic immunosuppressive treatments they can accelerate the course of liver disease or even develop fulminant hepatitis. In addition, a higher risk of morbidity and mortality due to infectious complications has been reported in this group of patients, which has been associated with the immunomodulatory capacity of these viruses.
In the acute phase of post-transplant, the occurrence of self-limited enzymatic elevations (hepatitis) due to drug toxicity, mainly cyclosporin, or in CMV infection is more frequent.
Neoplasms in the early stage: they may be related to latent neoplasms in the recipient that become evident after the transplantation or with the transmission of the donor with the graft. Lymphoproliferative processes or Kaposi sarcomas may also develop in the first semester after transplantation, so these possibilities should be kept in mind.
Secondary hyperparathyroidism: hypercalcemia and hypophosphatemia are frequently followed, in most cases self-limited.
Haematological alterations. They are often seen in the early stages after transplantation, anemia and / or leucopenia, fundamentally. Hematologic abnormalities may also be a consequence of infections, such as CMV or lymphoma.
Relapse of originating nephropathy: Already explained above.
Chronic Complications:
Severe HTA: post-transplant hypertension (AHT) occurs between 60-80% of cases, according to the series. After renal transplantation, hypertension increases cardiovascular morbidity and mortality of the recipient and worsens long-term graft survival.
Post-transplant osteopathy: largely caused by chronic steroid use.
Hypercalcemia
Hypophosphatemia
Loss of bone mass
Occurs more markedly during the first 6 to 18 months after transplantation. Studies in transplanted patients over the longer term offer, however, more contradictory results. The key factor in the development of osteopenia is the use of glucocorticoid.
Osteonecrosis
Lymphoproliferative syndromes. Lymphoproliferative syndromes (PFS) are the most common de novo cancers in kidney transplant recipients, after skin and lip (non-melanoma) tumors. They have their highest incidence in the first year of the post-transplant period.