INTRODUCTION — Kidney transplantation is the treatment of choice for end-stage kidney disease . A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients when compared with maintenance dialysis [2-4]. However, patients require close follow-up after transplantation since they are on complex immunosuppressive regimens that render them susceptible to infection, malignancy, and cardiovascular disease (CVD). In addition, patients often have multiple comorbidities due to, or as a cause of, their underlying end-stage kidney disease.
Whereas patients are generally followed by a transplant specialist for the first three to six months following transplant, thereafter they may be seen primarily by a general nephrologist or internist who is often able to address existing comorbidities. Whether a patient is followed by a transplant nephrologist, general nephrologist, or internist often depends upon the availability of services in proximity to the patient. While many believe that transplant nephrologists should be directly involved in the care of transplant recipients for the life of the graft, this is often not practical. However, communication between the internist or community-based nephrologist and the transplant center is important for optimal care of the patient.
This topic reviews the general medical care of the kidney transplant recipient including recommendations for monitoring allograft function and minimizing the risk of infections, malignancies, bone disease, CVD, and diabetes. Common medical problems encountered after transplantation are also discussed.
Maintenance immunosuppressive therapy, allograft dysfunction, and patient survival following transplantation are discussed separately:
Specific complications of transplantation are discussed in separate topic reviews.
ROUTINE FOLLOW-UP AND LABORATORY MONITORING — Patients are followed by a transplant nephrologist for at least the first three to six months following transplantation. The frequency of follow-up varies among centers and depends upon the stability of the patient. At our center, kidney transplant recipients are seen in the transplant clinic twice weekly for the first two to four weeks posttransplant, then weekly for one month, then every two weeks for one month, and then every three months for the first year after transplantation. Immunosuppressive therapy is gradually reduced during the first three to six months to avoid adverse medication effects while still preventing rejection.
Beyond 6 to 12 months, patients may be followed by an internist or general nephrologist in consultation with a transplant nephrologist since the risks of complications such as rejection are thought to have decreased beyond this time. Patients continue to require close monitoring to ensure that the graft is functioning optimally and to assess for complications due to side effects of immunosuppressive medications, such as infection, malignancy, and diabetes. In addition, patients may have complications of reduced kidney function, such as anemia and bone disease. Kidney transplant recipients are at high risk for cardiovascular complications because of their reduced kidney function and/or predisposing conditions such as diabetes mellitus.
The type and frequency of laboratory testing vary from center to center. A typical monitoring scheme, which is generally consistent with the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines , is presented in the table (table 1). At some centers, laboratory tests are checked more frequently and are in some cases independent of patient visits (as an example, weekly for 16 weeks, every other week until one year from transplantation, and then monthly for life).
The following laboratory tests should be checked regularly at each visit:
●Serum creatinine, glucose, bicarbonate, and electrolytes (sodium, potassium, calcium, magnesium, and phosphorus)
●Complete blood count and differential
●Urinalysis with, if available, a sediment examination
●Spot urine protein-to-creatinine ratio (some experts obtain a urine dipstick first and measure a spot urine protein-to-creatinine ratio if the dipstick reveals more than trace albuminuria)
In addition, we perform the following screening laboratory tests at intervals as described below:
●Fasting plasma glucose measured weekly during the first four weeks posttransplant, then at three and six months posttransplant, and then yearly. Some centers measure an afternoon capillary blood glucose level, rather than a fasting plasma glucose, in the first few weeks posttransplantation. A hemoglobin A1c can be checked starting at three months posttransplant in lieu of fasting plasma glucose if these levels are difficult to obtain.
•(See 'Diabetes mellitus' below.)
●Complete fasting lipid profile (including total cholesterol, low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides) every three months after transplant. Some centers monitor the fasting lipid profile once yearly. (See "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation", section on 'Monitoring'.)
●Parathyroid hormone (PTH) and 25-hydroxyvitamin D levels measured every 6 to 12 months.
●Urine and/or blood tests to screen for BK polyomavirus performed monthly from months 1 to 6 and then at months 9, 12, 18, and 24. Some centers do more frequent surveillance. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy", section on 'Posttransplant screening'.)
●Nucleic acid testing (ie, polymerase chain reaction [PCR] testing) for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) performed four to six weeks posttransplant in all recipients, regardless of donor risk profile (as per the 2020 United States Public Health Service [USPHS] guideline recommendations ).
●Nucleic acid testing (ie, PCR testing) for cytomegalovirus (CMV) performed weekly for the first three months posttransplant in recipients who are not receiving CMV prophylaxis therapy. (See "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients", section on 'Diagnosis'.)
MONITORING KIDNEY ALLOGRAFT FUNCTION — The routine evaluation of kidney allograft function typically involves monitoring the serum creatinine level and screening for proteinuria. Some patients with evidence of kidney allograft dysfunction and/or proteinuria may require a kidney biopsy to determine the cause of these abnormalities. A number of newer tests are now commercially available for allograft function monitoring, including donor-derived cell-free DNA (dd-cfDNA) testing as well as gene expression profiling. The exact role for how these tests should be used has yet to be determined, but registry studies are underway to better understand their utility. In addition to the individual assays of allograft function, composite scoring systems, such as the Integrative Box (iBox) Scoring System, are being developed, which may be able to predict long-term allograft function using data available at earlier time points posttransplantation. (See "Kidney transplantation in adults: Prevention and treatment of antibody-mediated rejection", section on 'Predictors of outcome'.)
Serum creatinine and GFR — Nearly all patients have a decreased glomerular filtration rate (GFR), compared with normal native kidney function, following transplantation. The baseline creatinine following transplantation tends to be higher than 1.1 mg/dL (97 micromol/L) for most patients, equivalent to an estimated GFR of less than 60 mL/min per 1.73 m2. Reasons for the modest decrease in GFR include the transplantation of a single kidney; donor-recipient size mismatch; ischemic injury (especially in the case of deceased-donor kidneys); the use of expanded-criteria donors (in which less than optimal kidneys are accepted for transplantation); and the use of calcineurin inhibitors (CNIs), which cause renal vasoconstriction.
The evaluation and diagnosis of the kidney transplant recipient with an elevated or increasing serum creatinine is discussed in more detail elsewhere. (See "Kidney transplantation in adults: Evaluation and diagnosis of acute kidney allograft dysfunction".)
Proteinuria — Mild proteinuria following transplantation predicts decreased long-term graft function  and is associated with mortality [8,9]. Proteinuria may also suggest acute allograft rejection, transplant glomerulopathy, or de novo or recurrent disease. (See "Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection", section on 'Clinical features'.)
Patients are typically screened for proteinuria at 3, 6, and 12 months, and every 12 months thereafter, or at every clinic visit. The method of screening varies among transplant centers. Some centers measure spot urine protein-to-creatinine ratios among all patients, whereas others obtain urinalyses in all patients and measure spot urine protein-to-creatinine ratios only in those who have greater than trace proteinuria on urinalysis. Among patients with a history of proteinuric kidney disease, spot urine protein-to-creatinine ratios may be checked more frequently to monitor for recurrence of the original glomerular disease. A kidney biopsy is often necessary to determine the cause of proteinuria.
Kidney biopsy — Allograft biopsies are usually performed in the setting of some evidence of allograft dysfunction, such as an elevated serum creatinine, decreased urine output, or worsening proteinuria. The ability to predict the cause of allograft dysfunction without a biopsy is notoriously low. (See 'Monitoring kidney allograft function' above and "Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection", section on 'Clinical features'.)
Some centers perform surveillance biopsies on all kidney transplant patients at regular intervals, whereas others do surveillance biopsies on all high-risk recipients, such as those with a history of BK polyomavirus, those at higher risk for recurrent disease or rejection, or highly sensitized patients.
The risks of an allograft biopsy include bleeding, damage to other organs, infection, and loss of the allograft. Studies have reported a very low major complication rate (including transfusion requirement and catheterization) of between 0.4 and 1.0 percent, with only one graft lost in approximately 2500 biopsies [10,11]. The threshold for kidney transplant biopsy should be low since the procedure is relatively safe as long as the right precautions are taken. The biopsy should be done at a transplant center and read by an experienced transplant pathologist. (See "The kidney biopsy", section on 'Patient evaluation'.)
MANAGEMENT OF IMMUNOSUPPRESSION — Recipients of a solid organ transplant receive immunosuppressive therapy in order to prevent rejection of the allograft. Immunosuppressive therapy can be divided into induction and maintenance regimens. Induction therapy is administered at or around the time of transplantation and is associated with greater immunosuppression than maintenance therapy. The goals of induction therapy are to prevent acute rejection and to permit minimization or avoidance of maintenance immunosuppressive agents that are known to cause toxicity. Induction therapy typically consists of biologic antibodies (rabbit antithymocyte globulin, basiliximab) and high-dose glucocorticoids. (See "Kidney transplantation in adults: Induction immunosuppressive therapy".)
Maintenance immunosuppression is usually initiated at the time of transplantation and continued long-term for the duration of the allograft. Maintenance regimens can include glucocorticoids, calcineurin inhibitors (CNIs; tacrolimus or cyclosporine), antimetabolic agents (mycophenolate mofetil, enteric-coated mycophenolate sodium, or azathioprine), mammalian (mechanistic) target of rapamycin (mTOR) inhibitors (sirolimus or everolimus), or costimulatory blockade agents (belatacept). These agents differ with respect to their efficacy and side effect profile (including risk of infections, malignancy, cardiovascular disease [CVD], and posttransplant diabetes [PTDM]), and these factors must be considered when choosing a regimen for a particular patient. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Some centers try to reduce glucocorticoids or use glucocorticoid-free protocols among patients who have received induction therapy . Such an approach may have a beneficial impact on blood pressure, glycemic control, bone disease, and lipid profiles. However, glucocorticoid-free protocols may increase the risk of chronic rejection, and therefore, we generally continue low-dose glucocorticoids indefinitely among most patients. This issue is discussed in depth elsewhere. (See "Kidney transplantation in adults: Withdrawal or avoidance of glucocorticoids after kidney transplantation" and "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
After 6 to 12 months, immunosuppression regimens are generally stably maintained unless there is a specific reason, such as infection, malignancy, or drug toxicity or adverse effects, to reduce immunosuppression further. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Target levels for calcineurin inhibitors — Whole-blood trough concentrations of tacrolimus or cyclosporine are routinely monitored among kidney transplant recipients to achieve proper dosing and to avoid over-immunosuppression and drug toxicity. The target levels for tacrolimus and cyclosporine are presented separately. (See 'Routine follow-up and laboratory monitoring' above and "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
With the more prevalent use of induction therapy, many centers have attempted to use even lower levels of CNIs. The use of antiproliferative agents such as mycophenolate mofetil/sodium or mTOR inhibitors such as sirolimus or everolimus may allow the safe reduction of CNIs, as does the use of belatacept [14,15]. (See "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Abnormal calcineurin inhibitor concentrations — CNI toxicity can cause kidney injury, hypertension, and neurotoxicity. The prolonged use of CNIs may cause permanent fibrosis in the kidney. As discussed above, CNI concentrations should be checked at regular intervals. (See "Cyclosporine and tacrolimus nephrotoxicity" and 'Routine follow-up and laboratory monitoring' above and "Pharmacology of cyclosporine and tacrolimus", section on 'Drug monitoring'.)
An elevated CNI concentration that is reported as a result of routine testing requires prompt evaluation. Since the CNI concentration should reflect a 12-hour trough or two-hour postdose (C2) level, it should first be confirmed that the blood was drawn at the correct time. If the blood was drawn correctly, other causes should be considered, such as the patient taking the incorrect dose or a change in preparation of the immunosuppressive agent (since generic forms of the medication may not be exactly equivalent). Another common reason for an increased CNI level is the administration of a drug or substance that interferes with CNI metabolism or transport, notably cytochrome P450 34A (CYP3A4) or P-glycoprotein (P-gp) inhibitors (table 2 and table 3). Due to the narrow therapeutic index of CNIs, even weak inhibitors of CYP3A4 (eg, amlodipine, clotrimazole) have been shown to have clinically meaningful impact on CNI serum concentrations [16-19]. As such, when altering drug therapy, use of a drug interactions database such as Lexicomp drug interactions is advised. Patients initiated on medications expected to increase CNI levels should have repeat CNI levels checked after five days. Preemptive, empiric lowering of CNI dosing may also be reasonable and should be considered in consultation with the transplant nephrologist. Additionally, inflammation of the bowel wall associated with diarrhea can lead to increased concentrations of tacrolimus, but not cyclosporine.
Low CNI concentrations may result from starting another medication that increases the elimination of the CNI, such as CYP3A4 or P-gp inducers (table 2 and table 3). Persistently low CNI concentrations may also suggest noncompliance, which should be addressed with the patient. Persistently low levels may result in rejection. In general, if levels of immunosuppressive drugs decrease below a specified target range, the drug should be increased to bring the levels back into range.
Commonly, patients will have CNI toxicity in the setting of therapeutic levels. In such cases, the CNI may be reduced or substituted, often with an increase of one of the other immunosuppressive medications. Altering the immunosuppressive regimen should only be done in consultation with the transplant nephrologist.
Toxicity associated with immunosuppressive agents — Many of the drugs used for maintenance immunosuppression have well-described side effects that vary in severity. Patients should be monitored for evidence of toxicity. Common side effects are as follows:
●CNIs – Hirsutism and gingival hyperplasia (cyclosporine), alopecia (tacrolimus), neurologic disturbances, insomnia, hypertension, acute and chronic kidney dysfunction, electrolyte abnormalities, PTDM, hyperlipidemia, malignancies, and anemia (see "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects' and "Cyclosporine and tacrolimus nephrotoxicity")
●Mycophenolate – Gastrointestinal disturbances, particularly diarrhea (see "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases", section on 'Adverse effects')
●Sirolimus/everolimus – Pulmonary edema, hypertension, poor wound healing, joint pain, anemia, edema, and hypertriglyceridemia/hypercholesterolemia (see "Pharmacology of mammalian (mechanistic) target of rapamycin (mTOR) inhibitors", section on 'Adverse effects')
●Azathioprine – Leukopenia, hepatitis, and anemia (see "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Adverse effects')
INFECTIOUS ISSUES AND COMPLICATIONS — Infections are a major cause of death following kidney transplantation [20,21]. Transplant patients are susceptible to both common and opportunistic infections. The risk of a particular infection is related to several factors including the degree of immunosuppression of the recipient. (See "Infection in the solid organ transplant recipient", section on 'Risk of infection following transplantation'.)
Infections are most likely to occur between the first and third months following transplant since immune suppression is at its maximum during this time due to induction therapy . However, the risk of infection persists as long as the patient is on immunosuppressive medication. (See "Infection in the solid organ transplant recipient".)
Common infections — As in the general adult population, common infections that occur in transplant patients who are six months or more from transplant include upper respiratory tract infections and urinary tract infections. The differential diagnosis of infections that occur in kidney transplant patients is discussed elsewhere. (See "Infection in the solid organ transplant recipient", section on 'Timing of infection post-transplantation'.)
●Upper respiratory infection – The treatment of patients who have signs or symptoms that suggest common upper respiratory infections (such as the common cold, pharyngitis, and influenza) is the same as for the general population. A chest radiograph is generally not indicated unless atypical symptoms (such as dyspnea) or signs (such as localized crackles on auscultation) are present. Patients who appear disproportionately ill, who have atypical signs and symptoms, or who have a prolonged recovery should be referred back to the transplant clinician for further evaluation.
Although over-the-counter medications are generally permitted, decongestants and nonsteroidal antiinflammatory agents should be avoided in hypertensive patients because they are vasoconstrictive.
●Urinary tract infection – Urinary tract infections are among the most common bacterial infections occurring in the kidney transplant recipient. Prolonged catheterization should be avoided if at all possible. The management of urinary tract infections is discussed elsewhere. (See "Urinary tract infection in kidney transplant recipients".)
Opportunistic infections — As a result of the growing population of immunosuppressed patients with prolonged survival, an increased incidence and spectrum of opportunistic infections are observed [21,23,24]. Opportunistic pathogens that affect kidney transplant recipients include:
●Cytomegalovirus (CMV) (see "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients")
●Polyomavirus (BK and John Cunningham [JC] virus) (see "Kidney transplantation in adults: BK polyomavirus-associated nephropathy")
●Nocardia asteroides (see "Nocardia infections: Epidemiology, clinical manifestations, and diagnosis")
●Listeria monocytogenes (see "Clinical manifestations and diagnosis of Listeria monocytogenes infection")
●Aspergillus fumigatus (see "Epidemiology and clinical manifestations of invasive aspergillosis")
●Pneumocystis jirovecii (formerly carinii) pneumonia (PCP) (see "Epidemiology, clinical manifestations, and diagnosis of Pneumocystis pneumonia in patients without HIV")
●Hepatitis B and C viruses (see "Kidney transplantation in adults: Hepatitis B virus infection in kidney transplant recipients" and "Hepatitis C infection in kidney transplant candidates and recipients")
●Herpes simplex virus (see "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection")
●Varicella-zoster virus (see "Epidemiology, clinical manifestations, and diagnosis of herpes zoster")
●Epstein-Barr virus (see "Clinical manifestations and treatment of Epstein-Barr virus infection" and "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders")
●Mycobacterium tuberculosis (see "Tuberculosis in solid organ transplant candidates and recipients")
Vaccinations — Standard age-appropriate vaccines, as well as vaccines indicated for immunocompromised patients, should be administered three to six months following transplantation (table 4). Inactivated vaccines are generally considered to be safe following kidney transplantation. However, patients should not be given any live or live attenuated vaccines after transplantation (table 5). Specific guidelines for the vaccination of transplant recipients are discussed elsewhere. (See "Immunizations in solid organ transplant candidates and recipients".)
Health care workers and close contacts (such as family members) of transplant recipients should be fully immunized. With the exception of the smallpox vaccine and oral polio virus vaccines, there is little to no risk of transmission of vaccine viruses from vaccine recipients to their close contacts. Nevertheless, health care workers and close contacts of transplant recipients should receive inactivated vaccines, when possible. (See "Immunizations in solid organ transplant candidates and recipients", section on 'Health care workers and close contacts'.)
Prophylaxis — Kidney transplant recipients are routinely given antimicrobial and antiviral prophylaxis, typically for the first six months to one year after transplantation. In addition, some transplant centers, such as those in regions or institutions with high intrinsic rates of fungal infection, administer antifungal prophylaxis. Protocols for prophylaxis differ among transplant centers and depend in part upon the type of induction therapy given and the risk of acquisition or reactivation of infections. (See "Prophylaxis of infections in solid organ transplantation" and "Prevention of cytomegalovirus disease in kidney transplant recipients".)
Screening — Kidney transplant recipients should undergo screening for the following infections:
●HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) – Nucleic acid testing (ie, polymerase chain reaction [PCR] testing) for HIV, HBV, and HCV should be performed at four to six weeks after transplantation .
●BK polyomavirus – Urine and/or blood tests to screen for BK polyomavirus are performed monthly from months 1 to 6 and then at months 9, 12, 18, and 24 after transplantation. Some centers perform more frequent surveillance. (See "Kidney transplantation in adults: BK polyomavirus-associated nephropathy", section on 'Posttransplant screening'.)
●CMV – Among patients who are not receiving prophylactic therapy for CMV, we suggest weekly monitoring of the CMV viral load using nucleic acid testing for three months following transplantation. If viremia is detected, treatment with oral valganciclovir or intravenous ganciclovir should be initiated. (See "Prevention of cytomegalovirus disease in kidney transplant recipients", section on 'Preemptive therapy (low risk)'.)
●Asymptomatic bacteriuria – We obtain a urinalysis with microscopy at 2, 4, 8, and 12 weeks posttransplant; if there is evidence suggesting urinary tract infection, we also obtain a urine culture. Some experts perform a urine culture with an accompanying urinalysis with microscopy at each of these visits. (See "Urinary tract infection in kidney transplant recipients", section on 'Monitoring for asymptomatic bacteriuria'.)
CARDIOVASCULAR DISEASE — Cardiovascular disease (CVD) is the major cause of death and graft loss in diabetic kidney transplant recipients [25-29]. Fifty to sixty percent of posttransplant deaths are directly attributable to cardiovascular disease [30,31]. Risk factors for CVD in kidney allograft recipients are presented elsewhere. (See "Risk factors for cardiovascular disease in the kidney transplant recipient".)
Hypertension — Hypertension is reported in 50 to 80 percent of the kidney transplant population [32-34]. Hypertension among kidney transplant recipients is associated with worse long-term graft outcomes, including graft loss . Calcineurin inhibitors (CNIs) and glucocorticoids contribute to hypertension by causing vasoconstriction and salt retention, weight gain, and a mineralocorticoid effect.
The optimal therapy and blood pressure goals in the transplant recipient are discussed elsewhere. (See "Hypertension after kidney transplantation".)
Dyslipidemia — Dyslipidemia is common among kidney transplant recipients  and is a major risk factor for both CVD and reduced kidney allograft survival . New-onset or worsening dyslipidemia has been associated with sirolimus, CNIs (particularly cyclosporine), and glucocorticoid use. Increases in total cholesterol and low-density lipoprotein (LDL) levels are the most common abnormalities seen in transplant recipients, with elevated triglyceride levels also frequently noted. (See "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation".)
We generally screen individuals for dyslipidemias at the time of transplant evaluation, upon presentation for transplantation, and quarterly thereafter. (See 'Routine follow-up and laboratory monitoring' above.)
The goals of treatment and choice of therapy are discussed elsewhere. (See "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation", section on 'Treatment'.)
Obesity — Fifty percent of transplant patients may be classified as obese . Weight gain after transplant is common and may be related to the use of high-dose glucocorticoids in the peritransplant period, long-term use of maintenance doses of glucocorticoids, improved appetite with reversal of uremia, and physical inactivity. (See "Risk factors for cardiovascular disease in the kidney transplant recipient", section on 'Obesity and the metabolic syndrome'.)
Diet and exercise are the mainstays in lifestyle modification for obese kidney transplant recipients. If safe, the dose of glucocorticoids can be reduced, although there is little evidence that reducing chronically administered glucocorticoid doses will result in weight loss, and late glucocorticoid withdrawal may be associated with development of subclinical rejection.
Some patients may use antidepressants (eg, paroxetine, sertraline), herbal remedies (such as St. John's wort), and oral weight loss medications (such as orlistat). These medications may interact with the cytochrome P450 pathway and reduce the efficacy of CNIs. We recommend not using such agents for transplant recipients [37,38]. (See "Obesity in adults: Overview of management".)
Bariatric surgery, including laparoscopic sleeve gastrectomy and Roux-en-Y bypass surgery, may safely and effectively reduce obesity-related morbidity in kidney transplant recipients [39-41]. However, patient selection and choice of surgical procedure are critical, and more studies are needed to quantify the risks and benefits of bariatric surgery in this population. Several nutritional deficiencies often emerge following bariatric surgery, including iron, folic acid, vitamin B12, zinc, and vitamin D deficiencies, and oxalate nephropathy in the kidney allograft has been reported as a potential complication of gastric bypass surgery, resulting from enteric hyperoxaluria [42,43]. (See "Bariatric surgery: Postoperative nutritional management", section on 'Micronutrient management'.)
DIABETES MELLITUS — Many patients develop diabetes mellitus following a kidney transplant. This was formerly called "new-onset diabetes after transplantation" (NODAT) but is now termed "posttransplant diabetes mellitus" (PTDM). (See "Kidney transplantation in adults: Posttransplantation diabetes mellitus".)
Reasons for the relatively high incidence of PTDM include the following:
●The new kidney metabolizes and excretes insulin more efficiently than the failing native kidneys.
●The transplanted kidney is gluconeogenic.
●Immunosuppression medications, such as glucocorticoids, calcineurin inhibitors (CNIs), and mammalian (mechanistic) target of rapamycin (mTOR) inhibitors, are diabetogenic.
●Preexisting risk factors (eg, increased age, obesity, being African American, family history of diabetes or gestational diabetes, and hepatitis C virus infection) predispose patients to developing diabetes.
Diabetes most commonly develops within the first few months posttransplant , although there is continued risk for the life of the patient and allograft [45,46]. Kidney transplant recipients should be routinely screened for PTDM with fasting blood glucose levels or, alternatively, hemoglobin A1c levels (beginning at three months posttransplant) if fasting plasma glucose levels are difficult to obtain. (See 'Routine follow-up and laboratory monitoring' above and "Kidney transplantation in adults: Posttransplantation diabetes mellitus", section on 'Evaluation for PTDM'.)
Most patients will require pharmacologic treatment of hyperglycemia in addition to diet modifications, exercise, and weight loss. The treatment of hyperglycemia in transplant recipients is discussed elsewhere. (See "Kidney transplantation in adults: Posttransplantation diabetes mellitus", section on 'Management of hyperglycemia in the first 6 weeks after transplantation'.)
For some patients, the immunosuppression regimen may be altered or reduced to minimize the risks of diabetic complications; in other cases, oral agents or insulin regimens will need to be implemented to properly control glucose levels . Glucocorticoids, CNIs, and mTOR inhibitors can all adversely affect blood glucose levels. Decreasing or eliminating these drugs when possible will help with abnormal blood sugar levels. (See "Kidney transplantation in adults: Posttransplantation diabetes mellitus", section on 'Adjustment of immunosuppression'.)
BONE METABOLISM AND DISEASE — Bone disease is common among patients with chronic kidney disease and often persists following kidney transplantation. Factors that contribute to posttransplant bone disease include pretransplant renal osteodystrophy, glucocorticoids, calcineurin inhibitors (CNIs), persistent hyperparathyroidism, and calcium and vitamin D deficiencies. (See "Kidney transplantation in adults: Bone disease after kidney transplantation" and "Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)
Patients should be regularly monitored for hyperparathyroidism, vitamin D deficiency, and calcium and phosphorus abnormalities (see 'Routine follow-up and laboratory monitoring' above). In addition, kidney transplant recipients should undergo bone mineral density assessment to screen for osteoporosis.
Persistent hyperparathyroidism — Persistent hyperparathyroidism occurs in up to 50 percent of kidney transplant recipients and is associated with increased mortality and lower graft survival rates. Patients commonly present with hypercalcemia and hypophosphatemia, although some patients may only have an elevated parathyroid hormone (PTH) concentration without other laboratory abnormalities. The management of persistent hyperparathyroidism depends upon the clinical presentation and is discussed in detail elsewhere. (See "Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)
Osteoporosis — Bone loss occurs rapidly following kidney transplantation. Risk factors for osteoporosis that are specific to kidney transplant recipients include the long-term use of glucocorticoids, CNIs, and persistent hyperparathyroidism.
Bone mineral density should be assessed by dual energy x-ray absorptiometry (DXA) pretransplant, with subsequent monitoring dependent upon whether the patient has evidence of osteoporosis. (See "Kidney transplantation in adults: Bone disease after kidney transplantation", section on 'Our approach to screening and monitoring kidney transplant candidates'.)
The evaluation, prevention, and treatment of osteoporosis in kidney transplant recipients are discussed in more detail elsewhere. (See "Kidney transplantation in adults: Bone disease after kidney transplantation".)
Leukopenia — Leukopenia is a common occurrence following transplantation and may be associated with lymphocytopenia, neutropenia, or both. Approximately 20 to 60 percent of patients will experience at least one episode of leukopenia or neutropenia , typically within the first year after transplantation. Leukopenia is frequently related to medications such as lymphocyte-depleting agents (rabbit antithymocyte globulin or alemtuzumab), antimetabolic agents (azathioprine or mycophenolate mofetil/sodium), antiviral agents (ganciclovir or valganciclovir), calcineurin inhibitors (CNIs), and trimethoprim-sulfamethoxazole. In addition, viral infections such as cytomegalovirus (CMV), parvovirus B19, human herpesvirus 6, and influenza can also cause leukopenia [49,50]. (See "Approach to the adult with unexplained neutropenia", section on 'Initial evaluation' and "Drug-induced neutropenia and agranulocytosis" and "Approach to the adult with lymphocytosis or lymphocytopenia", section on 'Lymphocytopenia'.)
In kidney transplant recipients with leukopenia or neutropenia, we typically reduce the dose of or discontinue the potential offending medication. A reduction in maintenance immunosuppression can be associated with increased risk of allograft rejection and should be done cautiously. In addition, we perform tests to evaluate for infection with Epstein-Barr virus, CMV, or parvovirus B19. In cases of moderate to severe leukopenia/neutropenia (absolute neutrophil count of <1500 cells/microL), patients may need to be treated with recombinant granulocyte colony-stimulating factor (G-CSF) . (See "Drug-induced neutropenia and agranulocytosis", section on 'Treatment'.)
Anemia — Posttransplant anemia occurs in approximately 30 to 40 percent of kidney transplant recipients, with 8 to 10 percent having severe anemia [51,52]. At the time of transplantation, nearly all patients have anemia due to reduced endogenous erythropoietin production and iron deficiency that is associated with chronic kidney disease. Immediately following transplantation, anemia persists primarily because of surgical blood loss and inflammation; other factors, such as delayed graft function, induction and maintenance immunosuppression therapies (causing bone marrow suppression), and the abrupt cessation of erythropoietin-stimulating agents, may also contribute to posttransplant anemia [53-55].
Anemia typically resolves within 6 to 12 months after transplantation (or earlier among patients who are not iron deficient or do not have graft dysfunction) [53,56]. However, anemia may redevelop late in the transplant period in association with decreased allograft function, immunosuppressive drugs, antiviral agents, infections, and the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.
Patients should be screened routinely for persistent anemia. In general, a complete blood count is obtained when monitoring laboratory results. (See 'Routine follow-up and laboratory monitoring' above.)
The evaluation and treatment of anemia in the kidney transplant recipient are discussed separately. (See "Anemia and the kidney transplant recipient".)
Erythrocytosis — Posttransplant erythrocytosis (PTE) is defined as persistently elevated hemoglobin (>17 g/dL) and hematocrit (>51 percent) levels that occur after kidney transplantation and persist for more than six months. PTE occurs in up to 22 percent of kidney transplant recipients and usually develops 8 to 24 months after transplantation.
A more detailed discussion of PTE is presented separately. (See "Kidney transplantation in adults: Posttransplant erythrocytosis".)
Thrombocytopenia — Thrombocytopenia is frequently seen in the first year after kidney transplantation, particularly within the first three months posttransplant. It often occurs in combination with leukopenia and anemia, as a result of bone marrow suppression. Causes for thrombocytopenia that are specific to transplant recipients include induction therapy with rabbit antithymocyte globulin (which can contain antiplatelet antibodies), the use of antimetabolites (mycophenolate mofetil/sodium and azathioprine, which can cause overall bone marrow suppression), CNIs (which can cause thrombotic microangiopathy), antiviral agents, and viral infections. (See "Diagnostic approach to thrombocytopenia in adults", section on 'Categories of causes'.)
MALIGNANCY — Kidney transplant recipients are approximately three times more likely to develop cancers than the general population [57,58]. Risk factors specific to the transplant population include the type, extent, and duration of immunosuppression; viral infections; and pretransplant dialysis. (See "Malignancy after solid organ transplantation".)
The largest increase in risk is seen for the following:
●Posttransplant lymphoproliferative disorder (PTLD) (see "Epidemiology, clinical manifestations, and diagnosis of post-transplant lymphoproliferative disorders" and "Treatment and prevention of post-transplant lymphoproliferative disorders")
●Anogenital cancers (see "Classification and epidemiology of anal cancer", section on 'Chronic immunosuppression not due to HIV' and "Malignancy after solid organ transplantation", section on 'Anogenital cancers')
Kidney transplant recipients who develop a new cancer typically require modification of their maintenance immunosuppression regimen. The decision to reduce or stop immunosuppressive therapy depends upon the type and aggressiveness of the malignancy and the ongoing need for immunosuppression to prevent graft rejection. Reduction or cessation of immunosuppression should be performed in consultation with a transplant nephrologist. (See "Malignancy after solid organ transplantation", section on 'Immunosuppression' and "Kidney transplantation in adults: Maintenance immunosuppressive therapy".)
Screening — Kidney transplant recipients should have the same routine cancer screenings as those recommended for the general population, with the exception of skin cancer screenings, which should be completed monthly by self-skin examinations, with total-body skin examinations performed every six months to yearly by expert clinicians and dermatologists (table 6) [59,60]. The individual's cancer risk, existing comorbidities, overall life expectancy, and preference for screening should also be considered .
Screening recommendations for different cancer types are presented separately:
ELECTROLYTE AND ACID-BASE DISORDERS — Electrolyte and acid-base disturbances that are commonly seen in the kidney transplant recipient include hypomagnesemia, hyperkalemia, hypercalcemia, hypophosphatemia, and metabolic acidosis.
Hypomagnesemia — Hypomagnesemia is common after transplantation . The pathogenesis of hypomagnesemia among kidney transplant recipients is thought to be due to calcineurin inhibitor (CNI)-induced downregulation of the renal Mg(2+) channel, TRPM6, which results in magnesium wasting . Hypomagnesemia may play a role in the development of posttransplant diabetes (PTDM) and CNI nephrotoxicity . (See 'Diabetes mellitus' above and "Cyclosporine and tacrolimus nephrotoxicity", section on 'Hypomagnesemia' and "Kidney transplantation in adults: Posttransplantation diabetes mellitus", section on 'Modifiable risk factors'.)
Patients with severe hypomagnesemia may be symptomatic (weakness) and are at risk of cardiac arrhythmias. The treatment of hypomagnesemia is discussed elsewhere. (See "Hypomagnesemia: Evaluation and treatment".)
Hyperkalemia — Hyperkalemia following kidney transplantation can result from impaired allograft function and the concomitant use of medications such as CNIs, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, and trimethoprim-sulfamethoxazole. In transplant recipients with hyperkalemia, we discontinue potential offending medications and correct metabolic acidosis (if present) (see 'Metabolic acidosis' below). In addition, among patients with persistent hyperkalemia, we cautiously add the use of a loop diuretic to promote urinary potassium excretion. On occasion, CNIs may need to be dose reduced or substituted, but this should be done in consultation with a transplant nephrologist. (See "Treatment and prevention of hyperkalemia in adults".)
Calcium and phosphate abnormalities — Hypercalcemia and hypophosphatemia are commonly seen following kidney transplantation, affecting approximately 30 and up to 90 percent of kidney transplant recipients, respectively, within the first year of transplantation. Hypocalcemia may also be seen in patients who have undergone parathyroidectomy. (See "Hungry bone syndrome following parathyroidectomy in end-stage kidney disease patients", section on 'Clinical features'.)
Metabolic acidosis — Kidney transplant recipients frequently have a mild metabolic acidosis from impaired allograft function, CNI nephrotoxicity, and/or defective renal acid handling as a result of reduced nephron mass (single kidney) . CNIs impair tubular acid secretion and cause a type 4 renal tubular acidosis that manifests as a normal anion gap (hyperchloremic) metabolic acidosis. The treatment of metabolic acidosis in kidney transplant recipients is similar to that of nontransplant patients with chronic kidney disease (CKD). (See "Pathogenesis, consequences, and treatment of metabolic acidosis in chronic kidney disease", section on 'Treatment of metabolic acidosis in CKD' and "Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA)".)
While bicarbonate supplementation appears to slow the progression of CKD in nontransplant patients, it has not been shown to preserve graft function in kidney transplant recipients with metabolic acidosis. In a trial in which 240 adult long-term kidney transplant recipients (mean time from transplant 8.9 years) with stable graft function (mean estimated glomerular filtration rate [eGFR] of approximately 48 mL/min/1.73 m2) and a serum bicarbonate of ≤22 mmol/L were randomly assigned to treatment with oral sodium bicarbonate or placebo, there was no significant difference in the eGFR slope over two years between the groups .
HYPERURICEMIA AND GOUT — Hyperuricemia and gout are common among kidney transplant recipients, with the highest incidence in those treated with calcineurin inhibitors (CNIs; especially cyclosporine) that reduce uric acid excretion. Additional risk factors include impaired kidney function and use of loop or thiazide diuretics. New-onset gout may occur in up to 13 percent of transplant recipients .
The prevention and treatment of gout among kidney transplant recipients are discussed in detail elsewhere. (See "Kidney transplantation in adults: Hyperuricemia and gout in kidney transplant recipients".)
PREGNANCY — Infertility is common among patients with end-stage kidney disease . Fertility is usually improved within just a few months after kidney transplantation, although some impairment may persist in men due to persistent reductions in sperm count and altered sperm morphology [69-71]. (See "Pregnancy in patients on dialysis", section on 'Epidemiology' and "Sexual and reproductive health after kidney transplantation", section on 'Sexual function after transplantation'.)
Despite the return of fertility after kidney transplantation, the rates of both pregnancy and successful pregnancy remain far lower than in the general population. Pregnancy in a transplant recipient is considered high risk given the multiple risk factors for both the mother and the developing fetus. The timing of pregnancy following transplantation is important to minimize risks to the mother and fetus. We recommend that kidney transplant recipients who are considering pregnancy be managed by a high-risk obstetrician in conjunction with a transplant nephrologist.
A more detailed discussion of pregnancy in kidney transplant recipients is discussed elsewhere. (See "Sexual and reproductive health after kidney transplantation", section on 'Pregnancy'.)
Immunosuppressive medication during pregnancy — Modification of the maintenance immunosuppression regimen is frequently necessary prior to conception. All immunosuppressive medications carry some risk in pregnancy. The use of mycophenolate mofetil/sodium and mammalian (mechanistic) target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) is contraindicated in pregnancy because of reports of severe structural malformations associated with these agents [71,72].
The modification of maintenance immunosuppression in the pregnant transplant recipient is discussed elsewhere:
Contraception — While there have been a number of pregnancies in transplant recipients, there remains an increased risk to the fetus and the mother. The most effective safe form of contraception should be used to avoid unplanned pregnancies in transplant recipients. The optimal form of contraception for transplant recipients is not known and is individualized based upon the side-effect profile.
The use of contraception in kidney transplant patients is discussed in more detail elsewhere. (See "Sexual and reproductive health after kidney transplantation", section on 'Contraception'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Kidney transplantation".)
SUMMARY AND RECOMMENDATIONS
●Routine follow-up and monitoring – Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. Patients require close follow-up after transplantation since they are on complex immunosuppressive regimens that render them susceptible to infection, malignancy, and cardiovascular disease (CVD). In addition, patients often have multiple comorbidities due to, or as a cause of, their underlying end-stage kidney disease. (See 'Introduction' above and 'Routine follow-up and laboratory monitoring' above.)
●Infectious issues – Infections such as upper respiratory or urinary tract infection are common in kidney transplant recipients. Decongestants and nonsteroidal antiinflammatory agents should be avoided. Patients are also at risk for opportunistic infections including cytomegalovirus (CMV), Pneumocystis jirovecii (formerly carinii) pneumonia (PCP), and polyomavirus (BK and John Cunningham [JC] virus). (See 'Infectious issues and complications' above and "Infection in the solid organ transplant recipient".)
●Cardiovascular disease – CVD is the major cause of death and graft loss in diabetic kidney transplant recipients. Potentially modifiable risk factors for CVD such as hypertension, hyperlipidemia, and obesity should be addressed. Some risk factors are caused or exacerbated by immunosuppressive medications. (See "Risk factors for cardiovascular disease in the kidney transplant recipient" and 'Cardiovascular disease' above.)
●Diabetes mellitus – Diabetes mellitus commonly develops within the first few months posttransplant, but there is continued risk for the life of the patient and transplant. Patients should be screened with a fasting blood glucose weekly for the first four months after transplantation, and then at three and six months and annually thereafter. A hemoglobin A1c can be checked starting at three months posttransplant in lieu of fasting plasma glucose if these levels are difficult to obtain. (See 'Diabetes mellitus' above.)
●Bone disease – Bone disease is common following kidney transplantation. Patients should be regularly monitored for hyperparathyroidism, vitamin D deficiency, hypercalcemia, and hypophosphatemia. In addition, kidney transplant recipients should undergo assessment of bone mineral density pretransplant, with subsequent monitoring dependent upon whether the patient has evidence of osteoporosis. (See 'Bone metabolism and disease' above and "Kidney transplantation in adults: Persistent hyperparathyroidism after kidney transplantation".)
●Malignancy – Cancer is more common among transplant recipients than in the general population. Kidney transplant patients should have the same routine cancer screenings as those recommended for the general population, except for skin cancer screenings, which should be performed monthly by self-skin examinations, with total-body skin examinations completed every six months to yearly by expert clinicians and dermatologists. (See 'Malignancy' above.)
●Pregnancy – Pregnancy in a transplant recipient is considered high risk. The major risks to the patient include the risk of rejection and allograft failure. The major risks to the developing fetus include the effects of immunosuppressive medications and risk of transmission of infection. All immunosuppressive medications carry some risk in pregnancy; in particular, mycophenolate mofetil/sodium and the mammalian (mechanistic) target of rapamycin (mTOR) inhibitors are contraindicated in pregnancy. The most effective safe form of contraception should be used to avoid unplanned pregnancies in transplant recipients. (See 'Pregnancy' above.)
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