Kidney Transplant

How to Cite This Chapter: Iqbal A, Durlik M. Kidney Transplant. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.14.94. Accessed July 17, 2024.
Last Updated: October 2, 2022
Last Reviewed: October 2, 2022
Chapter Information

Kidney transplant, first successfully performed in 1954 in monozygotic twins, improves the quantity and quality of life for suitable patients with end-stage renal disease (ESRD) by restoring normal homeostasis and endocrine functions. Because of superior health outcomes and reduced overall cost to the health-care system compared with dialysis, transplant is the therapy of choice in the treatment of ESRD.

IndicationsTop

Every patient with advanced chronic kidney disease (CKD) who is anticipated to progress to ESRD (see Chronic Kidney Disease) should be considered for kidney transplant. Kidney transplant is performed in patients receiving dialysis treatment (hemodialysis [HD] or peritoneal dialysis [PD]) or before starting dialysis treatment (preemptive transplant). Planning for renal transplant should occur when the glomerular filtration rate (GFR) is between 15 mL/min/1.73 m2 and 30 mL/min/1.73 m2 to begin preliminary testing and to allow patients to seek out potential living donors. Efforts should be made to promote and advance living donation, given its superior patient and graft survival compared with deceased donor transplant. Patients with no potential living donors should receive counseling about the deceased donor transplant process including anticipated wait time, which may vary considerably depending on blood group, status of antibodies against human leukocyte antigen (HLA), and geographic region. Patients with other organ failure should be considered for combined transplant, such as pancreas-kidney (usually in type 1 diabetes), liver-kidney, or heart-kidney.

ContraindicationsTop

1. Absolute contraindications:

1) Active malignancy, except for very low–grade, indolent malignancies.

2) Uncontrolled active infections, including osteomyelitis, AIDS, aggressive viral hepatitis.

3) Decompensated cirrhosis or severe irreversible lung disease (these patients are not candidates for multiorgan transplant).

4) Severe uncorrectable, symptomatic cardiac disease deemed by a cardiologist to preclude transplant.

5) Progressive central degenerative disease.

6) Short life expectancy due to the burden of comorbidities, advanced age, frailty (age alone is not a contraindication and is considered in the context of overall health status).

2. Relative contraindications:

1) Recurrent infections requiring active treatment.

2) Unstable psychiatric illness that significantly impairs decision making.

3) Ongoing substance use disorder that significantly impairs decision making.

4) Ongoing nonadherent behavior despite education and counseling.

5) Lesions in the distal urinary system: Mechanical obstruction in the bladder neck, urethral valve, benign prostatic hyperplasia, significant vesicoureteral reflux (transplant is possible after urologic treatment and following a decision on the route of urine outflow).

6) History of neoplastic disease (specific cancer-free waiting periods are sometimes required).

7) Advanced body-mass index (BMI) of 35 or 40 kg/m2, depending on the transplant center. Bariatric referral may be required to facilitate weight loss.

ProcedureTop

Recipient Assessment

Potential transplant recipients are typically referred by their primary nephrologists to a transplant nephrologist for initial workup. Patients are screened for absolute and relative contraindications and are referred for cardiac workup and surgical assessment. They may also be reviewed by an anesthesiologist, social worker, and transplant pharmacist. Full infectious serology and age-appropriate cancer screening (as per local guidelines) is completed. Patients receive counseling on the risks and benefits of transplant, living versus deceased donor transplant, and expected waiting time on the deceased donor list.

Donor Selection

Potential living donors undergo extensive testing to ensure they are medically, socially, and psychologically suitable for organ donation. The goal of testing is to determine if the kidney is medically suitable for the recipient and to ensure the risks to the donor are acceptable. These include the perioperative risk of nephrectomy and lifetime risk of complications of living with a solitary kidney. The potential living donor receives counseling from the donor team regarding these risks. For deceased donors, full testing including renal function testing, relevant imaging, and infectious workup is typically done in the intensive care unit (ICU) setting while the patient is on life support. Organs are retrieved once brain death is declared (neurologic determination of death [NDD], NDD donor), or once life support is withdrawn and asystole occurs (donation after circulatory death [DCD], DCD donor).

Immunologic Testing

The 2 main components of immunologic testing for donor and recipient are ABO blood group compatibility and HLA compatibility. The donor and the recipient must be compatible between the main ABO blood groups (the Rh factor is irrelevant). HLA compatibility refers to the absence of any immunologically significant antibodies (known as donor-specific antibodies [DSAs]) in the recipient’s serum against donor’s HLAs. Donors undergo tissue typing to determine which HLA they express, and recipients undergo antibody screening to determine which antibodies are present in their serum. A cross-match is also performed between the donor’s lymphocytes (which express the HLA antigen) and the recipient’s serum, which further excludes the presence of immunologically significant antibodies. The specific methods of tissue typing, antibody screening, and crossmatching are beyond the scope of this review. The degree of sensitization of the recipient awaiting transplant is assessed every 3 to 6 months by determining the calculated panel reactive antibody (cPRA). The cPRA represents the percentage of HLA antigens in the donor population against which the recipient has antibodies (results range from 0% to 100%, where 0% means no antibodies and 100% means the presence of antibodies against all tested antigens). The cPRA is useful in predicting the likelihood of finding an HLA-compatible donor for a recipient awaiting transplant.

Kidney Paired Exchange

Kidney paired exchange is a program available in many countries, which allows incompatible donor/recipient pairs to be matched with a donor and recipient who are compatible. For example, if Bob (blood group A) wants to donate to his wife Sally (blood group B), they are not compatible. Bob and Sally could be entered into a kidney paired exchange, which will match Bob with a recipient needing a blood group A kidney, and Sally with a donor with blood group B. The reasons for entering kidney paired exchange are not just immunologic incompatibility, but may also include age or size mismatch between donor and recipient. Kidney paired exchange has been instrumental in expanding opportunities for living donor transplant.

Operative Technique

The kidney is transplanted retroperitoneally into the right or left iliac fossa, the donor’s renal artery and vein are anastomosed to the recipient’s iliac vessels, and the donor’s ureter is implanted into the recipient’s bladder.

Immunosuppression

Immunosuppression for renal transplant involves induction and maintenance regimens. Typically on day 0 or day 1 of transplant, patients receive an induction regimen that includes monoclonal (basiliximab) or polyclonal (antithymocyte globulin [ATG]) antibodies along with high doses of glucocorticoids. Maintenance regimens include 2 or 3 drugs that have different mechanisms of action, which produces a synergistic effect, allowing dose reduction and decreased toxicity. After 6 to 12 months, lower maintenance doses of immunosuppressive agents can be considered. Discontinuation of calcineurin inhibitors (CNIs) is not recommended, as this poses a high risk of antibody-mediated rejection (ABMR). In selected groups of recipients at low immunologic risk, an attempt may be made to withdraw glucocorticoids early (up to day 7). The availability of a number of immunosuppressive agents allows for individualized treatment depending on the patient’s immune risk, graft function, comorbidities, and adverse effects.

Immunosuppressive agents used for induction therapy (transplant days 0-5):

1) Polyclonal ATGs, polyclonal antilymphocyte globulins (ALGs).

2) Anti–interleukin 2 (IL-2) receptor monoclonal antibody (basiliximab).

Immunosuppressive agents used for maintenance therapy (long-term use):

1) Glucocorticoids are typically tapered to a maintenance dose of 5 to 10 mg/d.

2) CNIs: Cyclosporine, tacrolimus. The dose is adjusted to target therapeutic blood levels.

3) Antiproliferative drugs: Azathioprine, mycophenolate mofetil, sodium mycophenolate.

4) mTOR inhibitors: Sirolimus (rapamycin), everolimus. Rarely used due to adverse effects, including increased cardiovascular mortality; may be considered as a CNI alternative in patients with recurrent skin cancer.

5) Costimulation inhibitor: Belatacept; can be considered as an alternative to CNI.

Most common immunosuppressive treatment regimens:

1) CNI (tacrolimus is preferred over cyclosporine) + antimetabolite (mycophenolate is preferred over azathioprine) + glucocorticoid: As of 2022 this is the most commonly used regimen in North America and is considered the standard-of-care maintenance immunosuppression regimen.

2) Belatacept + antimetabolite + glucocorticoid.

3) mTOR inhibitor (sirolimus, everolimus) + antimetabolite + glucocorticoid (usually in patients with recurrent skin cancer due to the use of CNIs).

4) CNI + antimetabolite (glucocorticoid-free regimen).

The decision regarding induction or maintenance immunosuppression regimens should be based on the balance of immunologic risk (risk of rejection) and infectious risk (risk of infection); this is usually made in a specialized setting. Currently, the CNI of choice is tacrolimus and the preferred antiproliferative agent is mycophenolate, due to reduced risk of acute rejection compared with cyclosporine and azathioprine, respectively.

Follow-upTop

Comprehensive care of a kidney transplant recipient involves:

1) Optimized and individualized immunosuppressive treatment. This includes careful consideration of immunologic risk, infectious risk, malignancy risk (particularly skin cancer and lymphoma), and adverse effects of therapy.

2) Monitoring graft function, including frequent monitoring of creatinine, estimated GFR (eGFR), assessment of proteinuria, and graft biopsy if required.

3) Early detection and treatment of complications, including diabetes, hypertension, malignancy, cardiovascular events, infection, malignancy, osteoporosis.

4) Prevention of complications: Careful malignancy screening as per local guidelines, dermatology assessment for skin cancer prevention, bone density testing, infectious prophylaxis for Pneumocystis jiroveci pneumonia (PJP) and cytomegalovirus (CMV) infection.

5) Patient education: Counseling on medication adherence, self-monitoring of blood pressure, blood sugar, etc. Education on expected graft survival, preparation for dialysis or subsequent renal transplant.

Posttransplant course:

Depending on the type of donor (eg, living donor, deceased donor) and other factors including donor anatomy, surgical complexity, and organ transport time, the early posttransplant course is variable. The kidney may start to function immediately after the transplant or with a delay, most often due to acute tubular necrosis related to ischemia/reperfusion injury. Delayed graft function (DGF) is defined by the recipient requiring dialysis within one week following the transplant. After successful transplant, it may take weeks to months for the renal function to stabilize, as the drug levels, volume status, and organ ischemia stabilize. The baseline creatinine or eGFR depends on several factors, most importantly, the type of donor (an older deceased donor transplant may end with an eGFR of 35 mL/min/1.73 m2, while a young living donor transplant, with 80 mL/min/1.73 m2). Any sustained increase in creatinine from a stable baseline or new proteinuria should be considered a deterioration in graft function and warrant further investigation.

Causes of graft dysfunction (see Complications, below):

Causes of renal dysfunction in transplant patients may be similar to those in nontransplant patients, but they also include transplant-specific entities. These causes can be categorized as prerenal, renal, or postrenal.

1) Prerenal:

a) Hypovolemia: Transplant patients are more prone to hypovolemic or prerenal acute kidney disease (AKI) due to higher risk of infection, diarrhea from medications, diuretic use, and high urine output early post transplant. Patients are encouraged to keep track of their daily intake and output to ensure adequate hydration.

b) Heart failure: Due to decreased effective circulating volume, cardiorenal syndrome may develop, as seen in nontransplant patients.

2) Renal:

a) Transplant rejection: Categorized broadly as T cell–mediated rejection or antibody-mediated rejection. The risk of acute rejection is ~10% in the first year post transplant and decreases thereafter. More information can be found below.

b) Relapse of underlying native kidney disease: Certain diseases, including focal segmental glomerulosclerosis, atypical hemolytic-uremic syndrome, or IgA nephritis, have a high rate of recurrence post transplant.

c) De novo glomerulopathy in the transplanted kidney, most commonly drug related (calcineurin inhibitors, mTOR inhibitors).

d) Interstitial graft nephritis (bacterial, nonbacterial).

e) Drug nephrotoxicity (nonsteroidal anti-inflammatory drugs [NSAIDs], angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], aminoglycosides).

f) BK nephropathy (BK polyomavirus infection), other viral infections. BK virus is a polyomavirus that can proliferate in transplant patients and cause interstitial nephritis.

3) Postrenal:

Urine outflow obstruction: Fluid collection (lymphocele, urinoma, hematoma), ureteric stenosis, nephrolithiasis, ureterolithiasis, bladder outflow obstruction.

4) Vascular:

Disorders of arterial or venous vascularization (stenosis, thrombosis). Renal vein thrombosis is an early cause of graft loss, particularly in patients at high risk for venous thromboembolism.

ComplicationsTop

1. Acute transplant rejection: The risk of acute rejection is higher in the first year post transplant (it occurs in ~10% of patients). Rejection may be precipitated by medication nonadherence or immunosuppression reduction for infection or adverse effects, or it may occur without a clear trigger. Manifestations include acute rise in serum creatinine levels by >10% to 25%, which may be accompanied by decreased urine output; pain and/or tenderness in the area of ​​the transplant; low-grade fever; increased blood pressure. Ultrasonography is nonspecific in the diagnosis of rejection. Other causes of posttransplant AKI should be excluded, including obstruction, prerenal injury, vascular anastomotic issues (renal vein thrombosis, renal artery stenosis), drug nephrotoxicity, BK nephropathy (see below), and thrombotic microangiopathy. Histologic examination of a kidney biopsy specimen is necessary for the diagnosis. The 2019 Banff classification distinguishes active ABMR, chronic active ABMR, chronic (inactive) ABMR, and acute or chronic active T cell–mediated rejection (TCMR). A mixed form can also be seen, and active changes may coexist with chronic ones. In addition to kidney biopsy, recipient serum samples should be sent to detect DSAs. A diagnosis of active or chronic active ABMR is based on the fulfillment of histopathologic criteria and identification of circulating DSAs in the patient’s serum.

Treatment of any form of acute rejection starts with IV methylprednisolone in 3 to 5 pulses of 250 to 1000 mg/d. Depending on the severity of TCMR, ATGs may also be used. In patients with ABMR, in addition to the use of glucocorticoids, attempts are made to remove DSAs by plasmapheresis and IV infusion of high-dose human immunoglobulin (IVIG). Other therapies can be considered, including rituximab, which acts on CD20 to inhibit B cells, and bortezomib, which inhibits antibody-producing plasma cells. There is some weak evidence to support the use of therapies such as eculizumab or tocilizumab for certain types of rejection, although this is not yet common practice. Once the acute rejection is treated, the maintenance immunosuppressive agents may be increased.

2. Surgical complications:

1) Wound dehiscence, wound infection.

2) Fluid collections: Lymphocele, hematoma, seroma, urinoma.

3) Incisional hernia.

3. Adverse effects of immunosuppressive treatment: Table 1. In patients who develop adverse effects, drug reduction can be considered; if ineffective, the immunosuppressive regimen may be modified.

1) Infections: Due to immunosuppressive medications, transplant patients are at higher risk for infection. These infections may be difficult to recognize due to blunted inflammatory response and may progress rapidly to severe illness. For these reasons, a rapid diagnostic workup and aggressive treatment, initially empirical, are required. Certain types of infections are more likely, depending on the stage post transplant. In the first month post transplant, surgical site infections, urinary tract infections (UTIs), nosocomial infections (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci), and aspiration pneumonia are common. At this stage, transplant recipients can also develop UTI, bacteremia, or viral infections from the donor (donor-derived infections). In the next 6 months, patients are at higher risk for opportunistic infections such as PJP or infections caused by Candida spp, Aspergillus spp, Cryptococcus spp, BK virus, Clostridioides difficile, Listeria spp, Nocardia spp, Toxoplasma gondii, Strongyloides spp, herpes simplex virus, among many others. Beyond 6 months, patients remain at high risk for opportunistic infections and are also at higher risk for usual community-acquired infections. Chronic viral infections may also develop during this period, which may lead to organ damage or malignancy (see below).

CMV infection may be asymptomatic, defined by CMV replication in blood in the absence of symptoms, or present as CMV disease, in which patients have CMV replication in blood accompanied by systemic or organ-specific manifestations. The incidence of CMV infection post transplant depends on (a) the CMV serostatus of the donor and the recipient (a seropositive donor with a seronegative recipient pose the highest risk), (b) whether CMV prophylaxis is used (typically with valganciclovir for 6 months post transplant), and (c) the intensity of the immunosuppression. Depending on these factors, the incidence of CMV infection may be as high as 69% in the first 3 months post transplant (in CMV-positive to negative transplants without prophylaxis). With valganciclovir prophylaxis, the incidence is considerably lower, but CMV infection may develop after the 6-month prophylaxis period is completed. It is important to note that although the risk is the highest during these periods, CMV can occur at any time post transplant. Approximately 10% of recipients develop CMV disease, which may present as a systemic syndrome characterized by fever and mononucleosis syndrome or as organ-specific disease (CMV colitis, pneumonitis, hepatitis, retinitis). Cases of multiorgan involvement can also occur. The recommended method for diagnosing and monitoring CMV is by quantitative polymerase chain reaction (PCR) of blood or plasma (viral load). For patients with suspected organ-specific disease (ie, CMV colitis), a tissue specimen should be obtained and examined for CMV on histopathology. Oral valganciclovir or IV ganciclovir is the drug of choice. Protocols for CMV prophylaxis are variable, depending on the transplant center. Usually patients who are considered at high risk for CMV receive 6 months of prophylaxis with oral valganciclovir dosed 900 mg daily, adjusted for renal function.

BK is a polyomavirus that establishes asymptomatic latent infection in renal tubular and uroepithelial cells in most individuals early in life. As a result of immunosuppressive treatment, BK polyomavirus reactivates and replicates in the urinary tract, which manifests as viremia (virus in urine in 25%-30% of transplant recipients and viral DNA in blood in 12% of recipients). Five to 8% of recipients develop BK nephropathy of the graft, characterized histologically by interstitial nephritis, tubulitis, viral inclusions, and positive staining for SV40 (a simian BK virus homologous to human). Although clinically asymptomatic, BK nephropathy can lead to progressive graft dysfunction and potentially graft failure. Periodic quantitative measurement of BKV DNA in blood or urine allows for early detection of BK nephropathy and risk reduction by careful decrease in immunosuppressive agents. There is no evidence-based pharmacologic therapy for BK virus (agents such as leflunomide, IVIGs, or cidofovir are sometimes tried) and reduction of immunosuppression is the only agreed management.

Vaccination: It is recommended that all kidney transplant recipients be vaccinated with inactivated (not “live”) vaccines according to the vaccination schedule for the general population 3 to 6 months after the transplant, while receiving regular maintenance immunosuppressive therapy. An exception is influenza vaccination, which is recommended as soon as 1 month after kidney transplant if it coincides with the beginning of the influenza season. Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended and can be performed 1 month post transplant.

2) Malignancies: The reported incidence rate for malignancies after kidney transplant is up to 30%, which is generally 2 to 5 times higher than in the general population. Malignancies usually occur in transplant patients due to immunosuppression itself or due to chronic infection with oncogenic viruses. In rare cases, inadvertent transmission of a malignancy from the donor’s organ has been reported (donor-derived malignancy). The development of malignancies is associated with certain viral infections. Epstein-Barr (EBV) virus infection is linked to posttransplant lymphoproliferative syndromes (in 1%-3% of kidney transplant recipients); hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, to hepatocellular carcinoma; human T-cell lymphotropic virus type I (HTLV-I) infection, to T-cell leukemia; human papillomavirus (HPV) infection, to cancer of the cervix, anus, vulva, bladder; human herpes virus 8 (HHV-8), to Kaposi sarcoma. Other more common cancers after kidney transplant include skin cancer and native kidney cancer. Patients with recurrent cancer may benefit from switching from calcineurin inhibitors to mTOR inhibitors for maintenance immunosuppression. Mycophenolate also is thought to have a lower risk of malignancy compared with azathioprine.

3) Thrombotic microangiopathy (TMA) post transplant is most commonly associated with CNIs. Rarely, infections with pathogens such as HIV, parvovirus B19, and CMV can be associated with TMA. In severe cases of ABMR, TMA may be seen on renal biopsy. If the cause is suspected to be a CNI, discontinuation of the offending agent is recommended. As of 2022, there is no consensus regarding the use of plasmapheresis in this scenario. In patients who originally developed ESRD due to a TMA, particularly due to a complement-mediated mutation, there is a significant rate of recurrence post transplant. In this situation, eculizumab should be considered for prophylaxis and treatment.

4. Chronic allograft nephropathy (CAN) presents with slowly progressive decline in graft function that is accompanied by proteinuria (usually non-nephrotic range) and hypertension. Histologically, CAN is characterized by interstitial fibrosis, tubular atrophy, and thickened, “double contour” appearance in the glomerular capillaries. There is no clear consensus regarding the pathogenesis of CAN, but it is likely driven by a slow alloimmune injury resulting in chronic ABMR. Risk factors include previous episodes of acute rejection, suboptimal immunosuppression, and history of nonadherence. Counseling patients on strict medication adherence is a key aspect to posttransplant care. Chronic ABMR is difficult to treat and may be irreversible if there is significant fibrosis on biopsy. If caught early and treatment is pursued, this may involve high-dose glucocorticoids, IVIGs, plasmapheresis, and escalation of maintenance immunosuppression.

5. Relapse of the underlying disease: Certain native kidney diseases may recur post transplant, potentially leading to allograft failure (Table 2). Diseases associated with dysregulation of the alternative complement pathway (atypical hemolytic-uremic syndrome [aHUS], complement 3 glomerulopathy [C3G]) have a high rate of recurrence. Eculizumab may be used for prophylaxis in these patients, starting before and maintained after transplant. Certain types of primary focal segmental glomerulosclerosis (FSGS) have a high rate of recurrence, and in such patients, nephrotic syndrome may develop within days after surgery. Although no strong evidence is available, possible treatment options include plasmapheresis, rituximab, and abatacept. Other diseases such as membranous nephropathy, IgA nephropathy, or lupus nephritis can also recur post transplant.

6. De novo glomerulopathies in the transplanted kidney: Membranous nephropathy (in 1.4% of recipients), glomerulonephritis associated with HBV or HCV infection, anti-GBM disease in recipients with Alport syndrome, diabetic kidney disease in recipients with diabetes and those who developed posttransplant diabetes.

7. Failure of the transplanted kidney: For living donor transplants, the expected graft survival is ~19 years, while for deceased donor transplants it is ~11 years. Once the transplant fails, most patients are started on dialysis or, if they have a suitable living donor, they may receive another transplant prior to developing ESRD (preemptive retransplant). For patients started on dialysis, the immunosuppression is typically reduced and, in some cases, discontinued completely. There are 3 main reasons to continue immunosuppression after graft failure: (a) to reduce the risk of sensitization and antibody formation to the organ, which would make subsequent transplant more difficult, (b) stopping immunosuppression completely can lead to symptomatic rejection, characterized by graft pain, refractory anemia, and low-grade fever, (c) to maintain any residual urine output the patient may still have (if >500 cc). In elderly patients who are not suitable for retransplant or in patients at high risk for infection, immunosuppression may be discontinued completely. In most cases, the failed graft is not removed unless there is a specific indication such as symptomatic rejection, malignancy, recurrent UTI, or chronic inflammation.

8. Cardiovascular complications: Coronary artery disease (CAD) develops in 15% to 40% of patients after kidney transplant. Risk factors include those for the general population (see Prevention of Cardiovascular Diseases) and those characteristic for kidney recipients: CKD and previous dialysis treatment, cardiovascular disease before kidney transplant, hyperparathyroidism, immunosuppressive treatment (glucocorticoids, cyclosporine, tacrolimus), renal transplant failure, anemia, proteinuria, calcification of the coronary arteries.

Arterial hypertension occurs in 60% to 85% of kidney transplant recipients. Risk factors include graft failure, immunosuppressive therapy (CNIs, glucocorticoids), artery stenosis in the transplanted kidney (<7%), delayed function of the transplanted kidney, kidney transplant from a deceased donor (especially with a history or family history of hypertension), chronic glomerulonephritis in the transplanted kidney, polycythemia, hypercalcemia, native kidney disease, obesity, arterial hypertension before kidney transplant. Treatment of arterial hypertension in a kidney recipient follows the general approach (see Essential Hypertension). The most commonly used agents include ACEIs/ARBs (after excluding stenosis of the artery supplying the transplanted kidney) or calcium channel blockers.

9. Metabolic disorders:

1) Posttransplant diabetes mellitus (PTDM) may develop in a person who was not diagnosed with diabetes before kidney transplant, with the incidence reported from 6% to 24%. Glucocorticoids, tacrolimus, cyclosporine, and mTOR inhibitors are diabetogenic. Treatment follows the general approach. In addition to metformin and insulin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists can be used in PTDM. Current data indicate a nephroprotective effect of SGLT-2 inhibitors also on the transplanted kidney.

2) Dyslipidemia: Increased levels of total cholesterol in 63% of kidney recipients, increased levels of low-density lipoprotein cholesterol (LDL-C) in 60%, hypertriglyceridemia in 36%. Causes are primarily immunosuppressive agents and graft failure. Treatment is usual standard of care (see Lipid Disorders).

10. Other complications:

1) Posttransplant bone disease: Persistent renal osteodystrophy, osteoporosis, osteonecrosis.

2) Gastrointestinal complications: Drug-induced transaminitis, peptic ulcer disease, pancreatitis, diarrhea.

3) Anemia (in 40%-67% of patients) may be caused by impaired erythropoietin production, erythropoietin resistance, iron deficiency, or hemolysis.

4) Polycythemia (in 10%-25% of patients): Treatment includes ACEIs, ARBs, theophylline, antithrombotic prophylaxis, and in some cases phlebotomy.

5) Leukopenia: Usually caused by immunosuppressive agents, antiviral medications (valganciclovir), or antibiotics (sulfamethoxazole with trimethoprim). It can be a sign of bone marrow suppression due to infectious complications (CMV).

ResultsTop

Based on a study of over 300,000 adult renal transplant patients in the United States, the median graft survival for deceased donor transplants was 11.7 years, and for living donor transplants, 19.2 years. In 2020, 1459 kidney transplants were performed in Canada, with over 3000 patients remaining on the waiting list and 96 patients who died while on the waiting list.

The length of time on dialysis prior to transplant is a key risk factor for patient and graft survival post transplant. Patients who receive a preemptive transplant typically have superior posttransplant graft survival and mortality. Results of living donor kidney transplants are also better than those of transplants from a deceased donor. The main causes of death after kidney transplant are cardiovascular disease (40%), infections (17%), and neoplasms (12%). Causes of graft loss include chronic rejection, interstitial fibrosis or tubular atrophy, relapse of the underlying disease, and de novo glomerulopathies (see Complications, above). In many cases, graft loss may be multifactorial.

TablesTop

Table 11.5-1. Most frequently reported adverse effects of immunosuppressive agents

Adverse effect

Glucocorticoids

Cyclosporine

Tacrolimus

Azathioprine

MMF/MPS

Rapa/Everl

Acne

2

0

0

0

0

0

Alopecia areata

0

0

2

0

0

0

Anemia

0

0

0

1

1

2

Diabetes

2

1

3

0

0

1

Diarrhea

0

1

2

0

3/2

1

Gingival hyperplasia

0

3

0

0

0

0

Hirsutism

1

3

0

0

0

0

HUS/TTP

0

2

2

0

0

1

Hyperlipidemia

2

3

1

0

0

3

Hypertension

1

2

1

0

0

0

Insomnia

2

0

0

0

0

0

Leukopenia

0

0

0

2

2

2

Malignancy

0

1

1

1

0

−1

Neurotoxicity

2

1

3

0

0

1

Obesity

3

0

0

0

0

0

Osteoporosis

3

1

1

0

0

0

Thrombocytopenia

0

0

0

1

2

3

Relationship scale: 0, no relationship with the drug; 1, weak relationship; 2, medium relationship; 3, strong relationship.

HUS, hemolytic uremic syndrome; MMF, mycophenolate mofetil; MPS, mycophenolate sodium; Rapa/Everl, sirolimus/everolimus; TTP, thrombotic thrombocytopenic purpura.

Table 11.5-2. Probability of occurrence of native kidney disease in the transplanted kidney

Disease

Occurrence (%)

Graft loss (%)

aHUSa

15-100

~50

Amyloidosis

20-40

N/A

ANCA-associated vasculitis

~17

<10

Anti-GBM disease

20-30

<10

C3 glomerulopathya

60-80

35-50

Fibrillary glomerulopathy

~50

N/A

FSGS

20-50

10-40

IgA nephropathy

30-60

15-30

IgA vasculitis (formerly Henoch-Schönlein purpura)

~50

10-20

Light chain deposition disease

~50

N/A

Lupus nephropathy

1

Rarely

Membranous nephropathy

20-30

~30

Mixed idiopathic cryoglobulinemia

~70

N/A

Systemic scleroderma

~20

N/A

Waldenström macroglobulinemia

10-25

N/A

a Depending on the mutation of genes encoding proteins regulating the activity of the alternative complement pathway and type of prophylaxis used.

aHUS, atypical hemolytic-uremic syndrome; ANCA, antineutrophil cytoplasmic antibody; FSGS, focal segmental glomerulosclerosis; GBM, glomerular basement membrane; N/A, not available.

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