CHRONIC KIDNEY DISEASE SERIES

Care of the kidney transplant recipient

Vigilant monitoring creates the best outcome

Magdalena Adeva Andany, MD; Bertram L. Kasiske, MD

VOL 112 / NO 3 / SEPTEMBER 2002 / POSTGRADUATE MEDICINE

CME learning objectives

• To review the major causes of acute and chronic renal allograft dysfunction in renal transplant recipients
• To identify the foremost risks of infection and malignancy in renal transplant recipients
• To outline the major cardiovascular disease risk factors and their optimal management in patients after kidney transplantation

The authors disclose no financial interest in this article.

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Seventh in a series of articles on chronic kidney disease, coordinated by the National Kidney Foundation and Garabed Eknoyan, MD, professor, department of medicine, Baylor College of Medicine, Houston.

Preview: Although kidney transplantation is the treatment of choice for end-stage kidney disease, recipients require careful follow-up to prevent complications. In this article, Drs Andany and Kasiske review the major causes of allograft dysfunction in kidney transplant recipients, identify recipients' foremost risks of infection and malignancy, and outline the major cardiovascular disease risk factors involved with kidney transplantation. Potential drug interactions in transplant recipients are also discussed.
Andany MA, Kasiske BL. Care of the kidney transplant recipient. Postgrad Med 2002;112(3):93-112

Transplantation is the treatment of choice for end-stage kidney disease. Removal of the dependence on thrice-weekly dialysis procedures, elimination of the need for maintenance of vascular access, and improvement in uremic symptoms provide kidney transplant recipients a better quality of life. In addition, it is now clear that transplantation yields higher patient survival rates than dialysis. However, kidney transplantation introduces new problems, most of which result from either the need to monitor and treat acute and chronic organ rejection or the need to manage complications due to immunosuppressive medications.

Recently, the American Society of Transplantation published detailed guidelines for outpatient surveillance of kidney transplant recipients (1). This review focuses on some of the more important issues involved in the care of kidney transplant recipients and is directed at family or primary care physicians involved in the follow-up care of these patients.

Monitoring graft function

Allograft function should be monitored regularly to assess dysfunction, which can be caused by a variety of factors (table 1). Acute rejection may occur at any time after transplantation, although the risk is greatest in the first 6 months. Early detection of acute rejection is crucial because delayed treatment may cause irreversible damage (2). Clinical signs and symptoms of acute rejection include oliguria, fever, hypertension, and pain or tenderness over the allograft.

Table 1. Major causes of kidney allograft dysfunction

Acute dysfunction Acute rejection (early or late) Acute pyelonephritis Viral infection, especially with BK strain of polyomavirus Volume contraction Nonsteroidal anti-inflammatory drug toxicity Calcineurin inhibitor nephrotoxicity • Reversible vasoconstriction • Endothelial dysfunction and thrombotic thrombocytopenic purpura syndrome Urologic complications • Ureteral obstruction • Urine leakage • Lymphocele Less common causes of acute dysfunction • Use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers • Graft thrombosis • Renal artery stenosis Chronic dysfunction Chronic allograft nephropathy Recurrent glomerular disease De novo glomerular disease Calcineurin inhibitor toxicity (often indistinguishable from chronic allograft nephropathy) Less common causes of chronic dysfunction • Renal artery stenosis • Ureteral obstruction

Unfortunately, most acute rejection episodes are asymptomatic. Therefore, timely diagnosis relies on detection of acute increases in serum creatinine level. However, other reasons can explain a heightened creatinine level in transplant patients, and because diagnosis of acute rejection is based on histologic findings, a kidney biopsy should be ordered when the cause of the rise in creatinine level is not immediately apparent.

Although rejection is the most common cause of an acute increase in serum creatinine value, acute pyelonephritis may occasionally mimic acute rejection by causing fever, pain, tenderness over the allograft, and pyuria. Acute pyelonephritis should also be considered when abundant polymorphonuclear cells are present in the tubules on biopsy. Kidney infection with unusual organisms, such as the BK strain of polyomavirus, also causes an acute rise in serum creatinine level. Therefore, this infection should also be considered in the differential diagnosis of reduced kidney function (3).

The calcineurin inhibitors cyclosporin A and tacrolimus (Prograf), used for prophylaxis of organ rejection in these patients, can also produce an acute rise in serum creatinine level, generally by causing reversible vasoconstriction of preglomerular arterioles. Occasionally, calcineurin inhibitors can induce thrombotic microangiopathy and acute renal failure similar to that seen in hemolytic uremic syndrome. Generally, diagnosis of acute calcineurin inhibitor toxicity is established by ruling out acute rejection with biopsy and by reducing the dose of the calcineurin inhibitor while serum creatinine levels are monitored for a decrease to baseline.

In the early posttransplant period, surgical complications also can cause acute kidney allograft dysfunction. Graft thrombosis usually occurs immediately after transplantation and is suspected when an anuric patient's renogram shows little or no radionuclide uptake. Urinary obstruction, urine leaks, or lymphocele formation can be suspected from findings seen on ultrasound.

We generally use ultrasound to guide allograft biopsies, which we obtain for any unexplained acute rise in serum creatinine level. If a severely dilated urinary collecting system is detected, biopsy can be postponed until the urinary obstruction is corrected appropriately. A large fluid collection on ultrasound may suggest a lymphocele or a urine leak.

Chronic allograft nephropathy is a major cause of allograft failure in the late posttransplant period. It generally occurs more than 6 months after transplantation and includes histologic findings of interstitial fibrosis, glomerulosclerosis, and fibrointimal proliferation of intrarenal arteries (2). Clinical features of chronic allograft nephropathy include progressive kidney dysfunction, proteinuria, and hypertension. Although there is no specific treatment for chronic allograft nephropathy, it is important to establish the diagnosis in order to exclude other, treatable causes of allograft dysfunction. In addition, nonspecific measures may help slow the rate of progression of chronic allograft nephropathy (eg, treatment of hypertension, reduction of proteinuria, correction of dyslipidemia).

Diabetes and some glomerular diseases can recur after transplantation or may appear de novo. Recurrent idiopathic focal segmental glomerulosclerosis is associated with a high rate of graft failure. Patients who lose an allograft to this disorder are at especially high risk of losing a second allograft (4).

Renal artery stenosis is an uncommon cause of chronic allograft dysfunction (<5% in most transplant centers). Although renal artery stenosis is not an incidental, infrequent radiographic finding, it is probably best to not intervene unless the stenosis is accompanied by unexplained graft dysfunction or difficult-to-control hypertension, or both. The presence of graft renal artery stenosis might first be suspected in a patient with severe hypertension and impaired kidney function or when acute graft dysfunction occurs during treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker.

Graft function should be monitored often in the first 6 months after transplantation and evaluated every 1 to 3 months thereafter. Measurement of serum creatinine is the most practical indicator of kidney function, but it is not the most accurate (5). It may be helpful to measure creatinine clearance or to estimate creatinine clearance using a standard formula, which is described earlier in this series (6). (See the article "Estimating the Glomerular Filtration Rate" in the December 2001 issue, page 55.)

Periodic screening for proteinuria is also important. Persistent proteinuria (eg, >500 mg/24 hr) is seen in acute rejection, chronic allograft nephropathy, and recurrent or de novo glomerular disease. Nonspecific measures to reduce urine protein excretion (eg, use of an ACE inhibitor or angiotensin II receptor blocker) are often warranted (7). After initiation of these agents, the serum creatinine level should be monitored.

Monitoring immunosuppressive agents

Most transplant patients are treated with a combination of prednisone, azathioprine (Imuran) or mycophenolate mofetil (CellCept), and a calcineurin inhibitor. Corticosteroids have been a mainstay of kidney transplantation since the early 1960s. Unfortunately, they are associated with a number of adverse effects, and several ongoing clinical trials are examining ways to safely replace corticosteroids in the long term (8). Steroid-related complications--including growth retardation in children, glucose intolerance, hyperlipidemia, hypertension, cataracts, and metabolic bone disease--should be monitored after transplantation (1) (table 2).

Table 2. Major (nonimmunologic) adverse effects of corticosteroids

Cardiovascular risk factors Weight gain, obesity Hypertension Hyperlipidemia Glucose intolerance Musculoskeletal Myopathy Osteoporosis Avascular necrosis Ophthalmologic Cataracts Glaucoma Neurologic Alterations in mood, psychosis Pseudotumor cerebri Other Cushingoid features Growth retardation (children) Peptic ulcer disease

Among the most frequent adverse effects of azathioprine therapy are bone marrow suppression (ie, leukopenia and thrombocytopenia), hepatotoxicity, and development of skin cancer. Allopurinol (Zyloprim) inhibits xanthine oxidase, an enzyme important in the metabolism of azathioprine. As a result, allopurinol can inhibit azathioprine metabolism and cause potentially fatal leukopenia and thrombocytopenia. If allopurinol is needed, the dose of azathioprine should be reduced by at least 50% and white blood cell count and platelet count should be monitored closely. Alternatively, azathioprine can be replaced with mycophenolate mofetil, which does not interact with allopurinol (9). Azathioprine also can cause hepatotoxicity, manifested by elevated liver enzyme levels that usually follow a cholestatic pattern. Severe gastrointestinal toxicity from azathioprine is rare (1).

Recent clinical trials have demonstrated the efficacy of mycophenolate mofetil in reducing acute rejections that occur soon after kidney transplantation. As a result, mycophenolate mofetil is currently used in place of azathioprine in many immunosuppressive protocols. The most common adverse effects of mycophenolate mofetil are leukopenia, thrombocytopenia, and gastrointestinal toxicity (eg, diarrhea, abdominal pain, nausea, vomiting, anorexia). Although the recommended dose is 1 g twice daily, many patients require dose reductions because of adverse effects.

Cyclosporin A is effective in preventing acute rejection. However, the drug has multiple adverse effects, including nephrotoxicity (acute and chronic), hepatotoxicity, neurotoxicity (especially tremor), hyperlipidemia, hypertension, hyperkalemia, hypomagnesemia, hypertrichosis, and gingival hyperplasia. For this reason, many transplant programs have recently adopted another calcineurin inhibitor, tacrolimus. The adverse effects of tacrolimus are similar to those of cyclosporin A, yet some differences are evident (10,11) (table 3). Both calcineurin inhibitors have the potential to interact with agents metabolized by the CYP3A4 enzymes of the cytochrome P-450 system (12) (table 4).

Table 3. Major adverse effects of cyclosporin A, tacrolimus, and sirolimus in kidney transplant recipients
Complication	Cyclosporin A	Tacrolimus	Sirolimus
Nephrotoxicity	++	++	-
Hyperkalemia	++	++	-
Hypokalemia	-	-	++
Hyperuricemia	++	++	-
Hypomagnesemia	++	++	-
Hypertension	++	+	-
Hyperlipidemia	+++	-	+++
Glucose intolerance	+	+++	-
Neurotoxicity	+	++	-
Gingival hyperplasia	++	-	-
Hirsutism	++	-	-
Thrombocytopenia	-	-	++
+, mild; ++, moderate; +++, severe or frequent, or both; -, no effect.

Table 4. Examples of drug interactions that can occur with calcineurin inhibitor use

Increased blood levels Amiodarone HCl (Cordarone, Pacerone) Diltiazem HCl Nicardipine HCl (Cardene) Verapamil HCl (Calan, Isoptin, Verelan) Erythromycin Grapefruit juice Itraconazole (Sporanox) Ketoconazole (Nizoral) Decreased blood levels Phenobarbital (Bellatal, Luminal Sodium, Solfoton) Clarithromycin (Biaxin) Phenytoin (Dilantin) Rifampin (Rifadin, Rimactane)

The role of sirolimus (Rapamune) in immunosuppressive protocols has yet to be established. The toxicity profile of this agent is different from that of the calcineurin inhibitors (see table 3). Although nephrotoxicity and hypertension do not appear to be major problems with sirolimus use, thrombocytopenia can occur and dyslipidemia may be severe in some patients (13,14).

Managing risk of infection

Cytomegalovirus (CMV) disease is the most common serious infection in kidney transplant recipients (1,15). The risk of CMV infection is greater when more immunosuppression is used (eg, with high doses of mycophenolate mofetil or presence of polyclonal or monoclonal antibodies, or both). The incidence of CMV infection is 50% to 75% when the recipient has no CMV antibodies (indicating no previous CMV infection) and the donor tests positive for CMV antibody (signifying previous CMV infection). It is presumed that CMV is transmitted from donor to recipient through the kidney in these cases. If serologic tests in both the donor and the recipient are negative for CMV, the incidence of CMV disease in the recipient is less than 5%. When the recipient tests positive for CMV antibody, the incidence of CMV infection, independent of the CMV-antibody status of the donor, is 25% to 40% (1).

Clinical CMV infection usually occurs in the first 3 to 4 months after transplantation, during maximal immunosuppression. It typically presents with fever, malaise, myalgias, arthralgias, and leukopenia. The infection may involve multiple organs and may cause pneumonitis, hepatitis, and gastrointestinal bleeding from ulcerations. The diagnosis of CMV infection is usually made when typical clinical findings exist along with a blood culture positive for CMV, the presence of CMV blood antigen, or high levels of viral particles in the blood, detected by polymerase chain reaction. The diagnosis can also be made by detecting CMV in biopsy specimens. Treatment of CMV disease generally requires intravenous ganciclovir (Cytovene).

Most transplant programs have adopted strategies to prevent CMV infection (1,15). Many programs use antiviral prophylaxis for high-risk patients. For instance, recipients whose donor tests positive for CMV antibody receive ganciclovir for the first 3 months after transplantation. Other programs use a preemptive therapeutic strategy, in which levels of CMV in the blood are monitored with quantitative polymerase chain reaction, and treatment with an antiviral agent (usually ganciclovir) is started as soon as levels increase. Indiscriminate use of antiviral agents is generally avoided, to combat the recent emergence of CMV strains that are resistant to these drugs.

Other infections are common among kidney transplant recipients (1,16). These include infections by viral and bacterial pathogens and opportunistic organisms. Most transplant centers have adopted prophylaxis with trimethoprim and sulfamethoxazole to reduce the incidence of pneumocystis pneumonia, toxoplasmosis, and urinary tract infection in the early posttransplant period. Oral nystatin (Mycostatin) is often used to reduce the incidence of infection from Candida species in the early period after transplantation, when doses of immunosuppressive agents are high. Vaccination against influenza (annually) and pneumococcal infection (every 2 to 5 years) is generally recommended (1).

Managing cardiovascular risk

Kidney transplant recipients are at increased risk of cardiovascular disease (CVD) (17). Several traditional risk factors contribute to the high incidence of CVD in kidney transplant recipients, including hypertension, hyperlipidemia, diabetes, and cigarette smoking.

Hypertension is present in 50% to 80% of kidney transplant recipients. Several factors contribute to hypertension in these patients, including essential hypertension (genetically determined in the recipient or transmitted with the donor kidney), use of calcineurin inhibitors or corticosteroids, chronic allograft nephropathy or other causes of impaired kidney function, the presence of a diseased native kidney, and renal artery stenosis (17).

There are no specific guidelines for the treatment of hypertension in kidney transplant recipients, but recommendations from the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure can generally be used as a framework to guide therapy (18). For patients without proteinuria, the target for blood pressure should be less than 130/85 mm Hg. When proteinuria is present, the target blood pressure should be less than 125/75 mm Hg.

Several factors unique to kidney transplant recipients need to be considered when selecting agents for managing blood pressure. For example, some of the calcium channel blockers (diltiazem hydrochloride, verapamil hydrochloride [Calan, Isoptin, Verelan], nicardipine hydrochloride [Cardene]) may increase the blood levels of calcineurin inhibitors. Anemia, hyperkalemia, and an increase in serum creatinine level may be more common with use of ACE inhibitors in kidney transplant recipients. Diuretics may be more likely to cause an increase in serum creatinine concentration in kidney transplant recipients than in the general population (1). Despite these concerns, no antihypertensive agents are contraindicated in kidney transplant recipients, and hypertension should be intensively treated.

The prevalence of lipid abnormalities after kidney transplantation is very high. About 60% of kidney transplant recipients have a total cholesterol level greater than 240 mg/dL (6.21 mmol/L); 60% have a level of low-density lipoprotein cholesterol (LDL-C) greater than 130 mg/dL (3.36 mmol/L); and 35% have hypertriglyceridemia. Low levels of high-density lipoprotein cholesterol (<35 mg/dL [0.91 mmol/L]) occur in about 15% of kidney transplant recipients--a percentage similar to that in the general population (19). It also has been reported that concentrations of lipoprotein(a) and small, dense LDL-C, which many experts believe to be particularly atherogenic, are increased in kidney transplant recipients (20).

A number of factors can contribute to posttransplant dyslipidemia, including genetic predisposition; use of prednisone, cyclosporin A, sirolimus, or a combination of these agents, or use of other medications (eg, diuretics, b-blockers); proteinuria; and impaired kidney function (19). Several studies have shown that hyperlipidemia correlates with the high incidence of CVD after kidney transplantation, and some research has also found correlations with chronic allograft nephropathy.

The National Cholesterol Education Program guidelines offer a reasonable paradigm for treatment of hyperlipidemia (21). The National Kidney Foundation Task Force on Cardiovascular Disease recommends that kidney transplant recipients are considered as being in the highest risk category when these guidelines are applied (19). Therefore, the goal for the LDL-C value for kidney transplant recipients should generally be 100 mg/dL (2.59 mmol/L).

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") are currently the most effective agents for lowering LDL-C levels. In kidney transplant recipients, consideration should be given to the possibility of drug interactions when statins are coadministered with other substrates of CYP3A4 enzymes. Generally, in patients who are also taking a calcineurin inhibitor, the statin dose should be reduced to about half the standard dose.

De novo diabetes can arise after transplantation, mostly as a consequence of certain immunosuppressive medications (22). Corticosteroids, for instance, are associated with the development of posttransplant diabetes. In randomized studies (10,11), tacrolimus appeared to be more diabetogenic than cyclosporin A. Furthermore, research comparing sirolimus and cyclosporin A (13,14) reported that the incidence of hyperglycemia and type 1 diabetes was similar between the two medications.

Studies in the general population have shown that intensive glycemic control reduces the incidence of CVD compared with standard glucose management. Whether intensive glycemic control can reduce CVD without causing a higher incidence of hypoglycemic complications in kidney transplant recipients is far from clear, however. Similarly, the role of pancreas or islet cell transplantation in reducing CVD is uncertain.

Convincing evidence from research in the general population now indicates that aspirin prophylaxis reduces both primary and secondary CVD events. Since kidney transplant recipients tend to have several abnormalities that place them in a hypercoagulable state, aspirin prophylaxis seems to be a reasonable strategy in this population.

Finally, every effort should be made to encourage kidney transplant recipients to abstain from smoking. If possible, patients should be offered a structured smoking cessation program.

Malignancies

The risk of malignancy is very high in kidney transplant recipients. Indeed, more than one in five patients experiences malignancy within 15 years after receiving a kidney transplant, and more than two in five patients experience malignancy within 20 years (23). In general, malignancies that have been linked to viruses occur more often in patients who have undergone kidney transplantation than in the general population (1,23,24).

The most common malignancies after kidney transplantation are those of the skin and lips, with squamous cell carcinomas occurring more commonly than basal cell carcinomas. The incidence of skin cancer is influenced by sun exposure, and kidney transplant recipients should be counseled to avoid exposure to sunlight, especially if they are taking azathioprine, whose metabolites can sensitize the skin to sunlight and increase the risk of skin cancer.

Lymphoproliferative disorders are also common after kidney transplantation, and the risk of these disorders seems to be associated with the total amount of immunosuppression. In most cases, non-Hodgkin's lymphoma appears to be caused by the Epstein-Barr virus. Recent evidence has linked Kaposi's sarcoma with human herpesvirus 8.

Other malignancies common in kidney transplant recipients include anogenital carcinomas, carcinomas of the uterine cervix, hepatobiliary carcinomas, and colorectal carcinomas (1,23,24). Follow-up of kidney transplant recipients should include screening for malignancies that occur most often in this patient population (table 5) (1).

Table 5. General methods of screening for malignant neoplasms after renal transplantation

Monthly self-examination of skin and lips Annual examination of skin, conjunctiva, and oropharyngeal mucosa by a physician Early referral to a dermatologist for all suspicious skin lesions Yearly examination of anogenital area, including pelvic examination Prompt referral for and treatment of venereal warts Annual cervical cytologic examination (Pap test) Mammography every 1-2 yr in women between age 50 and 70 Annual digital rectal examination of the prostate gland in men older than 50 yr Consideration of prostate-specific antigen testing in men older than 50 yr Annual fecal occult blood testing in patients older than 50 yr Flexible sigmoidoscopy or colonoscopy every 5 yr in patients older than 50 yr

Liver disease

Chronic hepatitis occurs in 5% to 15% of kidney transplant recipients. Most posttransplant liver disease is caused by viral infection. The incidence of hepatitis B virus infection in patients with end-stage kidney disease has decreased dramatically since the widespread adoption of hepatitis vaccination. In kidney transplant recipients, immunosuppressive status probably influences the likelihood for progression of hepatic injury. The incidence of hepatoma is also greater in immunosuppressed patients. The role of lamivudine (Epivir-HBV) in treatment of hepatitis B virus infection in kidney transplant recipients remains to be established (1).

Hepatitis C virus (HCV) antibodies occur in 10% to 40% of kidney transplant recipients. Biochemical evidence of liver disease is present in 40% to 50% of patients who test positive for HCV antibody. HCV infection can also induce mixed cryoglobulinemia and glomerular disease in the transplanted kidney. Treatment with interferon-a after kidney transplantation is problematic because of the risk of allograft rejection (1). The long-term prognosis of patients with HCV infection after kidney transplantation is still unclear.

Hematologic complications

The incidence of erythrocytosis after kidney transplantation is about 10% to 20%, and it may contribute to the increased risk of thromboembolic events after transplantation. ACE inhibitors and angiotensin II receptor blockers have become the treatments of choice for posttransplant erythrocytosis (1). Anemia also is a common problem after kidney transplantation. Posttransplant anemia may be attributed to numerous causes, including use of immunosuppressive drugs. ACE inhibitors and angiotensin II receptor blockers can also contribute to anemia in some cases. Other causes include gastrointestinal bleeding, malignancies, allograft dysfunction, parvovirus B19 and CMV infections, and deficiencies in iron, folate (folic acid), or vitamin B₁₂. When reduced kidney function develops, anemia may be caused by lowered production of erythropoeitin, and it may respond to use of epoetin a (Epogen, Procrit).

Metabolic complications

Hyperuricemia is common after kidney transplantation and is attributable to use of calcineurin inhibitors or diuretics or to impaired kidney function. Whereas mild asymptomatic hyperuricemia does not usually require treatment, therapy for gout may be problematic in kidney transplant recipients. Allopurinol interferes with azathioprine metabolism; nonsteroidal anti-inflammatory drugs can cause hyperkalemia and a reduction in glomerular filtration rate; and colchicine can cause neuromyopathy.

Hypomagnesemia is present, usually in a mild form, in up to 25% of kidney transplant recipients. Use of cyclosporin A or tacrolimus may cause magnesium wasting. Generally, hypomagnesemia can be effectively managed with magnesium supplement therapy. Hypophosphatemia is very common in the early posttransplant period and is usually caused by phosphate wasting. Typically, it can be managed with use of oral phosphate supplements.

Metabolic bone disease associated with chronic kidney disease often improves after successful kidney transplantation. However, hyperparathyroidism may persist. Bone loss, a significant complication in kidney transplant recipients, is attributable mostly to corticosteroid use and to persistent hyperparathyroidism. Corticosteroid-induced osteoporosis occurs soon after initiation of the therapy and contributes to both bone pain and fractures. Bone mineral density measurements of the lumbar spine and hip, taken by dual-energy x-ray absorptiometry, can be used in monitoring corticosteroid-induced demineralization. Preventive measures should be implemented early and may include weight-bearing exercise, dietary measures, smoking cessation, and use of hormone replacement therapy, a thiazide diuretic (for hypercalciuria), or antiresorptive agents (eg, calcitonin, bisphosphonates) (1,25).

Summary

Kidney transplant recipients require careful follow-up in both the early (<6 months) and late posttransplant periods. Monitoring should focus on graft function and the most common complications of immunosuppression therapy. Infections, especially CMV infection, require particular attention in the first few months after transplantation, when immunosuppression is most intense. In both the early and the late posttransplant periods, an emphasis should be placed on intensive management of CVD risk factors (eg, hypertension, hyperlipidemia, cigarette smoking). Screening for malignancies known to occur with a high incidence after transplantation is also important.

With the improved short-term survival rates brought about by new, potent immunosuppressive agents, emphasis has now shifted to the prevention and treatment of posttransplant complications in kidney transplant recipients. A heightened awareness of these complications, along with a cooperative effort between primary care physicians and transplant programs, offers the best hope for further improvement in outcomes after kidney transplantation.

References

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Dr Andany is a nephrologist in the department of internal medicine, Hospital Juan Canalejo, La Coruña, Spain. Dr Kasiske is director, division of nephrology, department of medicine, Hennepin County Medical Center, Minneapolis. Correspondence: Bertram L. Kasiske, MD, Department of Medicine, Hennepin County Medical Center, 701 Park Ave S, Minneapolis, MN 55415. E-mail: kasis001@umn.edu.

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