การปลูกถ่ายไต

.

Alternative Names

References

web md

Background

Indications for renal transplantation include chronic kidney disease (CKD) and renal tumors. Studies show that renal transplantation prolongs patient lifespan compared with dialysis. Although perhaps only 25% of adult patients on dialysis are being referred for transplant evaluation (probably 95% of pediatric patients with ESRD will be referred), the number of potential candidates has resulted in burgeoning waitlists and longer waiting times for patients in need of kidney transplants.   See Tables 1 through 4, below.

Table 1. Demographics of adult patients on the waiting list for kidney transplants, United States, 2012[2] (Open Table in a new window)

คุณอาจจำเป็นต้องปลูกถ่ายไตหากคุณเป็นโรคไตระยะสุดท้าย สาเหตุที่พบบ่อยที่สุดของโรคไตระยะสุดท้ายคือโรคเบาหวาน อย่างไรก็ตาม ยังมีอีกหลายสาเหตุ

การปลูกถ่ายไตอาจไม่สามารถทำได้หากคุณมโรคหรือภาวะดังต่อไปนี้

• การติดเชื้อบางอย่าง เช่น วัณโรคหรือการติดเชื้อที่กระดูก
• ปัญหาในการรับประทานยาหลายครั้งต่อวันตลอดชีวิตของคุณ
• มีโรคหัวใจ ปอด หรือตับ
• มีโรคที่คุกคามชีวิตอื่นๆ
• เป็นโรคมะเร็ง
• การติดเชื้อ เช่น โรคตับอักเสบ
• มีพฤติกรรมไม่ดี เช่น การสูบบุหรี่ การดื่มแอลกอฮอล์ การใช้ยาเสพติด หรือพฤติกรรมเสี่ยงอื่นๆ ต่อการใช้ชีวิต

ความเสี่ยงของการปลูกถ่ายไต

ความเสี่ยง

เฉพาะที่เกี่ยวข้องกับขั้นตอนนี้ ได้แก่

• ลิ่มเลือด (deep venous thrombosis)
• หัวใจวายหรือโรคหลอดเลือดสมอง
• การติดเชื้อที่บาดแผล
• ผลข้างเคียงจากยาที่ใช้ป้องกันการต่อต้านไตที่ปลูกถ่าย
• สูญเสียไตที่ปลูกถ่าย

การเตรียมตัวก่อนทำหัตถการ

คุณจะได้รับการประเมินโดยทีมงานที่ศูนย์ปลูกถ่าย พวกเขาจะต้องการให้แน่ใจว่าคุณเป็นผู้ที่เหมาะสมสำหรับการปลูกถ่ายไต คุณจะมีการนัดตรวจหลายครั้งในช่วงหลายสัปดาห์หรือหลายเดือน คุณจะต้องเจาะเลือดและเอ็กซเรย์

การทดสอบที่ทำก่อนขั้นตอนรวมถึง:

• การพิมพ์เนื้อเยื่อและเลือดเพื่อช่วยให้แน่ใจว่าร่างกายของคุณจะไม่ปฏิเสธไตที่ได้รับบริจาค
• การตรวจเลือดหรือการทดสอบผิวหนังเพื่อตรวจหาการติดเชื้อ
• การตรวจหัวใจเช่น EKG, Echocardiogram หรือการสวนหัวใจ
• การตรวจค้นหามะเร็งในระยะแรกเริ่ม

คุณจะต้องพิจารณาศูนย์ปลูกถ่ายมากกว่าหนึ่งแห่งเพื่อพิจารณาว่าศูนย์ใดดีที่สุดสำหรับคุณ

• ถามศูนย์ว่ามีการปลูกถ่ายกี่ครั้งทุกปีและอัตราการรอดตายของพวกเขาเป็นอย่างไร เปรียบเทียบตัวเลขเหล่านี้กับตัวเลขของศูนย์ปลูกถ่ายอื่นๆ
• ถามเกี่ยวกับกลุ่มสนับสนุนที่พวกเขามี และประเภทการเดินทางและการจัดหาที่พักที่พวกเขาเสนอ

หากทีมปลูกถ่ายเชื่อว่าคุณเป็นผู้ที่เหมาะสมสำหรับการปลูกถ่ายไต คุณจะอยู่ในรายชื่อรอการปลูกถ่าย

ตำแหน่งของคุณในรายชื่อรอขึ้นอยู่กับปัจจัยหลายประการ ปัจจัยสำคัญ ได้แก่ ประเภทของปัญหาไตที่คุณมี โรคหัวใจของคุณรุนแรงเพียงใด และโอกาสที่การปลูกถ่ายจะประสบความสำเร็จ

คนส่วนใหญ่ที่รอการปลูกถ่ายไตอยู่ในการฟอกไต ในขณะที่คุณกำลังรอไตคุณจะต้องปฏิบัติตัวดังนี้:

• รับประทานอาหารที่ทีมปลูกถ่ายแนะนำ
• อย่าดื่มแอลกอฮอล์
• ห้ามสูบบุหรี่.
• ให้น้ำหนักของคุณอยู่ในช่วงที่แนะนำ ปฏิบัติตามโปรแกรมการออกกำลังกายที่แนะนำ
• ใช้ยาทั้งหมดตามที่กำหนดไว้สำหรับคุณ รายงานการเปลี่ยนแปลงใดๆและปัญหาทางการแพทย์ใหม่หรือที่แย่ลงไปยังทีมปลูกถ่าย
• ไปพบแพทย์ตามนัด ตรวจสอบให้แน่ใจว่าทีมปลูกถ่ายมีหมายเลขโทรศัพท์ที่ถูกต้อง เพื่อให้สามารถติดต่อคุณได้ทันทีหากมีไต ตรวจสอบให้แน่ใจเสมอว่าสามารถติดต่อคุณได้อย่างรวดเร็วและง่ายดาย
• เตรียมทุกอย่างให้พร้อมก่อนไปโรงพยาบาล

หลังทำหัตถการ

หากคุณได้รับบริจาคไตแล้ว คุณจะต้องพักรักษาตัวในโรงพยาบาลประมาณ 3 ถึง 7 วัน คุณจะต้องติดตามผลอย่างใกล้ชิดโดยแพทย์และตรวจเลือดเป็นประจำเป็นเวลา 1 ถึง 2 เดือน

ระยะเวลาพักฟื้นประมาณ 6 เดือน บ่อยครั้งที่ทีมปลูกถ่ายของคุณจะขอให้คุณอยู่ใกล้โรงพยาบาลในช่วง 3 เดือนแรก คุณจะต้องมีการตรวจเลือดและเอ็กซ์เรย์เป็นประจำเป็นเวลาหลายปี

ผลการรักษา

เกือบทุกคนรู้สึกว่าตนเองมีคุณภาพชีวิตที่ดีขึ้นหลังการปลูกถ่าย ผู้ที่ได้รับไตจากผู้บริจาคที่มีชีวิตทำได้ดีกว่าผู้ที่ได้รับไตจากผู้บริจาคที่เสียชีวิต หากคุณบริจาคไต คุณมักจะใช้ชีวิตได้อย่างปลอดภัยโดยไม่มีอาการแทรกซ้อนกับไตที่เหลืออยู่

ผู้ที่ได้รับไตที่ปลูกถ่ายอาจปฏิเสธอวัยวะใหม่ ซึ่งหมายความว่าระบบภูมิคุ้มกันของพวกเขาเห็นว่าไตใหม่เป็นสารแปลกปลอมและพยายามทำลายไต

เพื่อหลีกเลี่ยงการถูกปฏิเสธ ผู้รับการปลูกถ่ายไตเกือบทั้งหมด ต้องทานยาที่ระงับการตอบสนองทางภูมิคุ้มกันของตนเองไปตลอดชีวิต เรียกว่าการบำบัดด้วยภูมิคุ้มกัน แม้ว่าการรักษาจะช่วยป้องกันการปฏิเสธอวัยวะ แต่ก็ยังทำให้ผู้ป่วยมีความเสี่ยงในการติดเชื้อและมะเร็งสูงขึ้น หากคุณทานยานี้ คุณจะต้องตรวจคัดกรองมะเร็ง ยาอาจทำให้ความดันโลหิตสูงและคอเลสเตอรอลสูง และเพิ่มความเสี่ยงต่อโรคเบาหวาน

การปลูกถ่ายไตที่ประสบความสำเร็จต้องมีการติดตามผลอย่างใกล้ชิดกับแพทย์ และคุณต้องทานยาตามคำแนะนำเสมอ

ชื่ออื่น

การปลูกถ่ายไต; การปลูกถ่าย - ไต

 

Table 2. Primary causes of ESRD in adult patients on the kidney transplant waiting list: United States, 2012[2] (Open Table in a new window)

Table 3. Demographics of pediatric patients awaiting kidney transplant: United States, 2012[2] (Open Table in a new window)

Table 4. Primary causes of end-stage renal disease in pediatric patients on the kidney transplant waiting list: United States, 2012[2] (Open Table in a new window)

A resurgence of interest in living donation, possibly stimulated by the introduction of laparoscopic donor nephrectomy in 1994, has led to a substantial growth in the number of living-donor transplants, which is also associated with improved outcomes and significantly shorter waiting times.[3] In 2002, the number of living-donor transplants exceeded the number of deceased-donor transplants for the first time. Some conditions may recur in the transplanted kidney, including immunoglobulin A (IgA) nephropathy, certain glomerulonephritides, oxalosis, anddiabetes. Generally, the rate of recurrence is low enough to justify transplantation. In some patients, renal transplantation alone is not optimal treatment. Combined kidney-pancreas transplantation is the treatment of choice for patients who havetype 1 diabetes and ESRD. Candidates for this combined procedure are typically younger than 50 years and do not have significant coronary artery disease (CAD).  At present, pancreas graft survival is worse in recipients of pancreas-after-kidney transplants than in recipients of simultaneous kidney-pancreas transplants; however, this is more than offset by the reduced waiting time, better overall patient survival, and better renal allograft survival that living-donor kidney transplantation affords; thus, for diabetic patients with living donors, living-donor kidney transplantation followed by pancreas-after-kidney transplantation is a reasonable option. Combined kidney-pancreas transplantation is covered in greater detail elsewhere (see Pancreas Transplantation). The treatment of oxalosis is controversial. In some cases, renal transplantation in conjunction with pyridoxine therapy can produce good results, but combined liver-kidney transplantation is generally preferred; in some patients, staged liver-kidney transplantation may be preferable. Hemolytic-uremic syndrome (HUS), a not uncommon cause of renal failure in children, may recur after transplantation in response to cyclosporine-based or tacrolimus-based immunosuppression. Renal tumors (eg,Wilms tumor in children or renal cell carcinoma in adults) can be treated with transplantation. A 2-year disease-free interval before transplantation is strongly advised, except in adults with small asymptomatic renal cell cancers, where a waiting period after radical nephrectomy may not be needed.

A number of contraindications exist for renal transplantation. Some are contraindications for surgery, others are contraindications for immunosuppression, and still others derive from various concomitant disorders and conditions.

Contraindications for surgery

Contraindications for surgery include the following:

• Metastatic cancer
• Ongoing or recurring infections that are not effectively treated
• Serious cardiac or peripheral vascular disease
• Hepatic insufficiency (patients may be candidates for simultaneous liver-kidney transplantation)
• Serious conditions that are unlikely to improve after renal transplantation (ie, the patient’s life expectancy can be finitely measured)
• Demonstrated and repeated episodes of medical noncompliance
• Inability to perform rehabilitation adequately after transplantation

HIV seropositivity is NOT a contraindication for kidney transplantation,provided that the patient meets the following criteria[4] :

• The CD4 count has been higher than 200/µL for at least 6 months
• HIV-I RNA is undetectable
• The patient has been stable on antiretroviral therapy for at least 3 months
• The patient has no major infectious or neoplastic complications

Adverse effects of immunosuppressive drugs may exacerbateatherosclerosis, hypertension, diabetes, and lipid disordersand thus may increase cardiac risk after transplantation. Currently, patient death from cardiac disease (ie, death with a functioning kidney) is the most common cause of renal allograft failure, not direct failure of the graft.

Contraindications for immunosuppression

Infection and malignancy are the primary medical conditions to be considered. Acute infections should be fully resolved at the time of transplantation. As noted (see above), HIV infection is no longer an absolute contraindication for renal transplantation if certain conditions are met[4] ; with these conditions satisfied, outcomes are equivalent to those of patients without HIV infection.

In general, one should wait about 5 years after successful treatment of breast cancer, colorectal cancer, melanoma,diffuse bladder carcinoma, and non–in situ ovarian cancer. The risk of recurrence is about 50% if the transplant is performed within 2 years of such treatment, about 35% if it is performed between 2 and 5 years, and only about 10% if it is performed after 5 years.

Some tumors may permit shorter waiting times. For isolated nodules of prostatic carcinoma and focal bladder carcinoma, 1 year (or even less) is reasonable; for in situ uterine carcinoma, some renal tumors (eg, clear cell, Wilms, urothelioma), andbasal cell carcinoma or squamous cell skin carcinoma, no waiting time at all may be reasonable.

Poor social support, substance abuse, and intractable financial problems can compromise postoperative management and immunosuppression, contraindicating transplantation.

Other contraindications

The risk of recurrent disease is not a contraindication for renal transplantation. In about 3% of transplants, evidence of recurrence is observed by 2 years, and it is observed in about 20% of transplants by 8 years.

Glomerulonephritides (eg, mesangiocapillary glomerulonephritis type 1 and IgA nephropathy) are most likely to recur. However, loss of the kidney generally occurs late; thus, these diseases are not contraindications for transplantation. Focal segmental glomerulosclerosis is associated with a highly variable rate of recurrence in the first allograft, which approaches 30% in some series; however, if the first allograft is lost to recurrent disease, the risk of recurrence in the second allograft is approximately 85%.

Similarly, patients with diabetes mellitus have poorer outcomes after transplantation than patients without diabetes; nearly all of them demonstrate histologic evidence of diabetic nephropathy within 4 years. However, the improved quality of life for patients with diabetes after transplantation justifies its use as the treatment of choice for these patients if they have ESRD.

Increasingly, the treatment of choice for patients with type 1 diabetes and renal failure is combined kidney-pancreas transplantation or pancreas-after-kidney transplantation. The latter option is particularly attractive when the patient can receive the initial kidney transplant from a living donor.

Hereditary oxalosis is associated with a high rate of recurrence after kidney transplantation and graft failure. Optimal management remains controversial, but it may involve (1) intensive preoperative dialysis to reduce the oxalate burden and (2) combined or staged liver-kidney transplantation.

The prognosis after kidney transplantation is generally excellent, with 1-year graft survival rates ranging from 90% to 95%. Many factors influence the anticipated outcome. HLA-identical (HLA-ID) transplants from living related donors have the best overall graft survival rate, whereas transplants from complete-mismatch cadaveric donors have the worst. Complete-mismatch living-donor transplants have outcomes equivalent to those of zero-mismatch deceased-donor transplants. See Table 5, below.

Table 5. Five-year post-transplant survival with a functioning kidney graft: United States, 2012 (Open Table in a new window)

Other factors affect outcomes after kidney transplantation. One such factor is kidney preservation time. Prolonged cold ischemia can result in delayed graft function immediately after transplantation and may result in a somewhat shorter lifespan for the transplant. Another factor is donor age: older age in the donor can adversely affect both immediate graft function and long-term outcomes. In general, both delayed graft function after transplantation and early rejection episodes adversely affect the long-term outcome of the transplant.

Although advances in immunosuppression have led to significant decreases in the incidence and severity of posttransplant acute rejection, these decreases have not led to corresponding increases in long-term graft and patient survival. The most likely explanation for this discrepancy is that at present, the most common cause of kidney graft loss is death of the recipient with a functioning graft, and the nephrotoxicity of immunosuppression.

To achieve significant improvements in graft and patient survival, patients’ comorbid conditions must be addressed more effectively. Chief among these is cardiac disease, which can be exacerbated by complications of immunosuppression. Special attention should be paid to cardiac risk factors after transplantation, including hypertension, hyperlipidemia, and diabetes.

The pretransplant evaluation must address potential contraindications, should include baseline immunologic studies, and should assess the patient’s likelihood of success with transplantation.

Basic pretransplant studies

Either a need for dialysis or a creatinine clearance below 20 mL/min is generally an accepted definition of end-stage renal disease (ESRD). In the United States, a documented creatinine clearance of 20 mL/min or less is necessary to qualify for listing for transplantation. Typically, basic pretransplant studies are required, including the following:

• Echocardiography and a stress study
• Chest radiography
• Pulmonary studies
• Colonoscopy or barium enema (dependent on patient age)
• Mammography, Papanicolaou (Pap) smear, and prostate-specific antigen (PSA) test, as indicated (depending on patient age)
• Noninvasive vascular studies
• Abdominal and renal ultrasonography
• Serologic tests for HIV infection, hepatitis B and hepatitis C, cytomegalovirus (CMV) infection, and other viral infections
• Studies of bladder capacity and function (if indicated)

Immunologic studies

Immunologic studies should include human leukocyte antigen (HLA) typing and measurement of the panel-reactive antibody (PRA) titer. The panel-reactive antibody titer approximates the likelihood that a randomly chosen kidney donor has a positive cytotoxic lymphocyte crossmatch with the potential recipient, thereby ruling out that particular donor-recipient combination. Screening for donor-specific antibodies in the potential recipient by using HLA-coated beads is currently becoming routine at many transplant centers.

Evaluation of potential living donors

Evaluation of potential living donors may involve some of the studies detailed above. The choice of studies in this setting is subject to great variation among programs; however, assessment of renal function, evaluation of general health, imaging of the renal vasculature, HLA typing, and crossmatching are essential in all cases. Most centers require a donor to have a glomerular filtration rate (GFR) of at least 80 mL/min. The authors find that spiral computed tomography (CT) allows evaluation of the renal vasculature and parenchymal abnormalities.

All donors should be in good health and should not have conditions that may compromise their renal function in the future, such as hypertension or diabetes. Some centers require potential donors to undergo 24-hour ambulatory blood pressure monitoring.

Postoperative management involves two key tasks. The first task is to manage the dynamic fluid balance of a new kidney that is capable of responding to the high urea nitrogen load with an osmotic diuresis but is less capable of concentrating urine or reabsorbing sodium. With improving renal function, fluid balance must be maintained, hypertension management may need modification, and electrolyte abnormalities may require correction.

The second task is the administration of immunosuppression. Current immunosuppressive therapy can be divided into two phases: induction and maintenance. For some patients, a state of immunosuppression is induced just before the operation. This induction phase is continued during and after transplantation and is carried out by using either antibody- or nonantibody-based regimens.

Typical antibody-based induction immunosuppression uses either monoclonal or polyclonal antibody preparations directed at T cells in combination with calcineurin inhibitors (eg, cyclosporine and tacrolimus), antiproliferative agents (eg, azathioprine and mycophenolate), and corticosteroids. Maintenance therapy includes various combinations of a calcineurin inhibitor, an antiproliferative agent, and prednisone.

The choice of induction strategy depends on several factors. Some centers routinely use antibody induction. Of the centers that do not, most agree that antibody induction should still be used in immunologically higher-risk transplant cases, such as the following:

• Repeat transplants, especially when the first kidney was lost to acute or chronic rejection
• African-American patients
• Patients with evidence of significant prior sensitization to HLAs, as evidenced by a high panel-reactive antibody titer

Calcineurin inhibitors have been the mainstay of clinical immunosuppression since the introduction of cyclosporine in the early 1980s. Calcineurin inhibitors were the first agents to target proliferating T cells by blocking the elaboration of cytokines (eg, interleukin [IL]–2) essential for proliferation. Both cyclosporine and tacrolimus are naturally occurring products and have significant toxicities. In particular, they have a significant dose-related nephrotoxicity.

This nephrotoxicity, combined with erratic absorption and complex pharmacokinetics, necessitates ongoing monitoring to maintain therapeutic drug levels while avoiding toxicities. Although most centers follow drug trough levels, some have used pharmacokinetic modeling to good effect.[5] Both cyclosporine and tacrolimus are metabolized in the liver by the cytochrome P-450 (CYP-450) system. Drugs that alter CYP-450 metabolism can result in higher blood levels (eg, fluconazole or verapamil) or lower drug levels (eg, rifampin or phenytoin).

The adverse consequences of long-term cyclosporine use for solid-organ transplant rejection (eg, hypertension and renal impairment) have prompted exploration of various treatment regimens. Gallagher et al studied long-term graft survival by comparing the following three immunosuppressive regimens in 489 patients with a median follow-up of 20.6 years[6] :

• Azathioprine and prednisolone (AP)
• Long-term cyclosporine alone (Cy)
• Cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL)

Mean graft survival (with deaths censored) was longer in the WDL group (14.8 y) than in the AP group (12.4 y) or the Cy group (12.5 y). Without deaths censored, graft survival was again longer in the WDL group (9.5 y) than in the AP group (6.7 y) or the Cy group (8.5 y). Patient survival was comparable in the 3 groups. Renal function was superior in the AP group at 1, 10, and 15 years after transplantation and in the WDL group at 1, 5, 10, 15, and 20 years in comparison with the Cy group.[6]

Another strategy involves the use of sirolimus, an immunosuppressant that targets T cells at a different site in the activation pathway.[7] Sirolimus can be used in conjunction with reduced doses of calcineurin inhibitors or as a replacement for these agents in immunologically low-risk recipients. Although it lacks the nephrotoxicity of calcineurin inhibitors, it reduces wound healing and may cause myelosuppression.[8] Patients at high immunologic risk (see above) may be maintained on a combination of mycophenolate or sirolimus, tacrolimus or cyclosporine, and steroids for the first year after transplantation.

Mycophenolate reversibly inhibits de novo synthesis of purines during the S phase. Because the salvage pathway of purine synthesis is less active in lymphocytes than in other tissues, lymphocytes depend more on this pathway. Mycophenolate is far more selective than its predecessor, azathioprine, and it inhibits proliferation of both B and T cells. When used in conjunction with other agents (usually calcineurin inhibitors), mycophenolate significantly reduces the incidence of acute cellular rejection.

Mycophenolate can be administered either as a mofetil ester or as a sodium salt in enteric-coated form. It also reportedly reduces interstitial fibrosis associated with chronic rejection in animal models. Mycophenolate’s principal toxicities involve the gastrointestinal (GI) tract and principally manifest as nausea and diarrhea. These toxicities may limit its use, but patients who can tolerate them may experience significant reductions in allograft rejection.

Although steroids play a key role in induction and maintenance of immunosuppression and in treatment of rejection, they are associated with many complications of immunosuppression (eg, bone disease, hypertension, peptic ulcer disease, glucose intolerance, growth retardation, infection, obesity, and lipid abnormalities). Efforts to reduce steroid exposure have involved minimizing or completely avoiding their use. Steroids have been completely avoided in a few carefully selected cases, albeit with some increase in the rejection rate (but no long-term deterioration in graft survival).

Steroid doses have been reduced and rapidly tapered without significant increasing the risk of rejection.[9] Steroid reduction has been associated with decreases in hypertension, diabetes, and other adverse events associated with steroid therapy. Patients with stable graft function and no significant rejection episodes can often be weaned off steroids within the first 3-12 months and maintained on either combination therapy with a calcineurin inhibitor and an antiproliferative agent or, occasionally, monotherapy with a calcineurin inhibitor.[10]

Donor Procedure

Various approaches to kidney transplantation have been developed. The Gibson incision is the most common approach: it involves a curvilinear incision in a lower quadrant of the abdomen, with division of the muscles of the abdominal wall and dissection of the retroperitoneal space to expose the iliac vessels and the bladder. Occasionally, a midline incision is used; this approach is useful when a recipient has prior transplants in both lower quadrants or when a large kidney is to be placed in a small recipient.

The authors’ preferred approach involves direct end-to-side anastomosis of the renal artery to the external iliac artery (see the image below), though the common iliac may also be used. The inferior vena cava and aorta are accessible via the right-side approach. Anastomoses are typically performed with permanent vascular sutures (5-0, 6-0, or 7-0, as mandated by operating conditions). Numerous surgical options are available, including patch techniques, use of vascular autograft and allograft, and use of recipient hypogastric or epigastric arteries.