1. Aspectos quirúrgicos del Transplante Renal de Donador Vivo Dr. Marco V. Benavides Sánchez Cirugía General Transplante renal Médicos Especialistas Palmore Zarco 3003. Col Guadalupe. Chihuahua, Chih., 31020. México Teléfono: 614 4185255 Urgencias: 614 215 1185 MEP
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Organ transplantation has a long history, beginning with skin autografting in India during the sixth century BCE. This procedure entered Western medicine during the early renaissance and is described in a text on the restoration of the nose, lips, and ears by Gaspare Tagliacozzi (1545-1599). The first reliable report of a transplant surgery is from 1823 when German surgeon Carl Bunger performed plastic surgery on a woman's nose, grafting skin from her thigh. In 1906, Mathieu Jaboulay carried out the first attempts at human kidney transplantation. Jaboulay used pig and goat kidneys anastomosed to blood vessels of the arm of patients with chronic renal failure, which functioned for approximately 1 hour. Alexis Carrel, Jaboulay’s student, improved the methods of vascular anastomosis and introduced cooling as a method of organ preservation in his work in Chicago. Later moving to the Rockefeller Institute in New York, Carrel found that he could successfully autograft dog kidneys; unfortunately, allografts invariably failed. This finding suggested that technical factors could not explain the failure. Carrel suggested that "the principle of immunity" might explain this observation. 1906 : Mathieu Jaboula y. Primeros intentos de transplante renal en humanos. Alexis Carrel . Mejoró los métodos de anastomosis vascular e introdujo el enfriamiento como método de preservación de órganos. Premio Nobel de Medicina en 1912. 1933 cuando se realizó el primer transplante renal en seres humanos, de un donador cadavérico, por el Dr. Voronoy en Kersov, antigua Unión Soviética. La receptora falleció 48 hrs después del transplante, sin haber producido una cantidad de orina significativa.
In 1942, Thomas Gibson and Peter Medawar published their early experience with skin allografts in the treatment of burns sustained by aviators in World War II. Gibson and Medawar noted that the second set of grafts from one donor is destroyed much faster than the first. The results of Medawar’s careful animal experiments later were developed into the immunologic concept of self and nonself. The first wholly successful human transplant took place on December 23, 1954, in Boston, Massachusetts. Surgeon Joseph Murray performed a kidney transplant between identical twin brothers. While this and subsequent twin transplants did little to solve the problem of rejection, these procedures contributed to proving the value of the procedure and to the solution of many technical problems. On December 23, 1954, a team of medical professionals at the Peter Bent Brigham Hospital in Boston, Massachusetts, led by Dr. Joseph Murray, performed the first successful human kidney transplant. Richard Herrick, diagnosed with end-stage renal disease, was successfully transplanted with a kidney donated by his identical twin brother, Ronald. In this model, in which the donor and recipient were perfectly matched, it was shown that in the absence of the body's rejection response (body's recognition of tissue as foreign), organ transplantation is possible. In 1958 French immunologist Jean Dausset discovered the histocompatibility system for tissue matching.
Michael D. Fabrizio, M.D.,Lloyd E. Ratner, M.D., Robert A. Montgomery, M.D.,PhD, and Louis R. Kavoussi, M.D. (Click here to find more About Authors...) Abstract Live donor renal transplantation has many advantages including greater graft and patient survival, shorter waiting periods, improved HLA matching, and less cold ischernia. However, until recently disincentives from the operation such as prolonged hospitalization, postoperative pain, and significant convalescence have deterred live donor renal transplantation. Herein, we describe the technique of laparoscopic live donor nephrectomy and briefly report our results. The procedure has resulted in improved postoperative recovery and shorter convalescence with no effect on recipient renal function. Click here to visit the Transplant Center... Patient selection Technique Left sided donor nephrectomy Right sided approach Postoperative management Results Summary References Renal transplantation remains the only treatment for end stage renal disease which can give patients an independent lifestyle free from dialysis. With the introduction of effective immunosuppression, graft survival has dramatically improved. Using registry data from the United Network for Organ sharing (UNOS), it is clearly evident that living donor kidney transplantation is superior to cadaver renal transplantation. The graft/patient survival rates for recipients of cadaveric donor kidneys are 88.1% - 95% at one year and 68.7% - 87.5% at three years. Comparatively, the living donor graft/patient survival rates are 93% - 98% and 83.7% - 94.3% at one and three years respectively. In addition to greater graft/patient survival, live donor kidney transplantation offers many other advantages. The waiting time for recipients of a live donor kidney is dramatically shorter than that of a cadaver renal transplant. Although the waiting period can vary within regions, recipients of live donor kidneys usually wait 2-3 months in Baltimore, Maryland (Lloyd Ratner, M.D, personal communication, July, 1998). This compares to the 3 to 5 year wait for a cadaver donor kidney significantly increasing the amount of time on dialysis. Since the live donor transplantation surgery is elective both the recipient and donor's medical status can be optimized. Living donors provide a greater chance for a zero HLA mismatch, less cold ishemic time, and reduced immunosuppression requirements. Unfortunately, living donor transplantation accounts for only 29.3% of the total renal transplants in 1997. This is related in part to the disincentives associated with donation. Such factors as prolonged hospitalization, postoperative pain, extensive postoperative recovery associated with lost wages, and even cosmetic results of major abdominal surgery share in deterring live donor renal transplantation. With the advent of minimally invasive surgical techniques more invasive procedures have been replaced using less morbid techniques such as laparoscopy. The first major laparoscopic renal procedure was performed in 1990. Clayman and associates performed a laparoscopic nephrectomy for a renal mass. Since that time laparoscopy has been used to perform not only simple nephrectornies but also radical nephrectomies, renal biopsies, pyeloplasties, partial nephrectomies, and nephroureterectomies. In 1994, Gill et al. successfully performed a laparoscopic donor nephrectomy in a porcine model. Subsequently, Ratner and associates were the first to clinically develop a technique for a laparoscopic live donor nephrectomy in February, 1995. Herein, we describe the technique of laparoscopic live donor nephrectomy and briefly report our results. Laparoscopic live donor nephrectomy has resulted in decreased hospital stay, less postoperative analgesic requirements, earlier return to the activities of daily living, and earlier return to employment with no affect on allograft function or survival. Patient selection Preoperative evaluation ensures that the donor is left with normal renal function after unilateral nephrectomy. All potential donors undergo extensive medical and psychological evaluation in accordance with guidelines published by the American Society of Transplant Physicians. The transplant team carefully evaluates the donor's motivation and emotional stability. In addition, donors have a battery of radiographic and laboratory studies including three-dimensional computed tomography and ABO histocompatibility testing. The evaluation of both donor and recipient can vary somewhat among transplantation centers. A relative contraindication to laparoscopic donor nephrectomy is in a patients with a history of multiple intrabdominal operations. Laparoscopic donor nephrectomy requires accurate preoperative radiographic imaging. When compared to its open counterpart, laparoscopic live donor nephrectomy requires a higher degree of resolution of venous anatomy on pre-operative radiologic evaluation. Preoperative radiographic images assist in planning the operative approach. We have recently employed dual phase spiral computed tomography(CT) with three dimensional angiography for preoperative evaluation of the living donor patients. In a recent study by Smith et al., CT angiography adequately depicted renal vascular anatomy when compared to standard angiography . In addition, venous anatomy which is critical during laparoscopic dissection is optimally identified. Technique In preparation for surgery, patients do not receive any specific preoperative bowel regimen. Following the induction of general endotracheal anesthesia and the administration of broad-spectrum intravenous antibiotic prophylaxis, a foley catheter is placed in the bladder. An oral-gastric tube remains in place until the completion of the procedure. The patient is placed in the modified flank position with the torso in a 45 degree lateral decubitus position and secured to the table. The hips are rolled slightly posterior to allow exposure to the lower abdominal midline. The arms are flexed and placed at chest level with appropriate axillary and lower extremity padding. A pneumoperitoneum is established using a Veress needle and three transperitoneal laparoscopic ports are placed as illustrated. The peritoneal cavity is insufflated to 15 mm Hg. The first 10/12 millimeter (mm) port is placed lateral to the rectus muscle half-way between the umbilicus and iliac crest using an optical trocar(Visiport RPF optical trocar, US Surgical Corp(USSC)., Norwalk, CT) and the zero degree lens. The second 10/12 min port is placed at the umbilicus, and a 5 mm port is placed in the midline between the umbilicus and xiphoid both under direct vision. All trocars are secured in place with a 2-0 vicryl suture to prevent inadvertent withdraw during the procedure. The umbilical port is used primarily as the camera port throughout the dissection. A 30 degree lens is used for visualization during the procedure. We employ the AESOP 1000 (Computer Motion Inc., Goleta, CA) to hold and direct the laparoscope during the procedure. This device has been shown to increase surgical efficiency and decrease assistant fatique. During the procedure, it is important keep the patient volume expanded. Pneumoperitoneum has been shown to decrease renal blood flow, however, vigorous hydration and reduced intrabdominal pressure maintains urine output. Therefore, we keep the patient volume expanded during the procedure and insufflate with the lowest pressure to safely proceed with the dissection. Patients are routinely given in excess of 5 to 7 liters of crystalloid intravenously in addition to 12.5 mg of mannitol and 40mg of lasix. Left sided donor nephrectomy Using the Debakey forceps in the 5mm port and the laparoscopic scissors in the lateral port, the ipsilateral colon is reflected medially beginning at the splenic flexure to the level of the siginoid colon by incising the lateral peritoneal reflection . Electrocautery is used as necessary, however, extreme caution must be used to avoid thermal injury to the colon. The phrenocolic ligaments at the level of the splenic flexure must be completely divided to allow the colon to be completely, reflected medially. At this point a 2 mm trochar may be placed in the flank to assist in retracting the colon medially. The lienorenal and splenocolic ligaments at the inferior border of the spleen are divided allowing the spleen to be retracted superiorly as needed. The colorenal ligaments are divided and Gerota's fascia exposed. The next step is freeing the upper pole of the kidney within Gerota's fascia. This is one of the most technically challenging parts of the procedure and care must be taken to avoid injury to the kidney, spleen, and renal hilum. Lobulations can easily be mistaken for the border of the upper pole. Once the superior extent is identified, dissection is then facilitated with gentle elevation of the upper pole with a blunt retractor such as the 5 mm irrigation/suction device in the 5mm port site(figure3) . When performing this maneuver it is important to place the retractor under direct vision and advance the tip of the retractor to the sidewall to prevent inadvertent injury to surrounding organs. Blunt and sharp dissection are needed to free the upper pole attachments. Once the upper pole is completely free, the hilar vessels are exposed. Gerota's fascia is incised on the medial aspect of the kidney,and the renal vein should be readily apparent. The renal vein is freed from its adventitial attachments, and the gonadal, adrenal, and any associated lumbar veins are identified, clipped, and divided The right angle clip applier can facilitate placement of clips on the gonadal and adrenal vein. Two clips should are placed in opposite directions to assure complete occlusion. It should be noted that the adrenal vessel can be a source of troublesome bleeding if the dissection is to aggressive along the renal vein. The lumbar vessels can be identified by gently lifting the renal vein. The renal artery which usually lies posterior to the vein is now identified and freed. Sharp dissection of the abundant lymphatic tissue is required to adequately expose the artery. Clips are helpful during the dissection to prevent lymphatic leakage. Maximal vascular should be achieved by completely dissecting the renal artery to its proximal origin at the aorta. In order to prevent vasospasm, the renal artery can be bathed with a topical solution of papaverine. At this point, the patient is given 12.5 grams of mannitol and 40 mg of lasix intravenously. The lateral, posterior, and inferior attachments to the kidney are left intact. This three point fixation limits the mobility of the kidney and prevents torsion of the kidney on its vascular pedicle. Attention is now focused on the ureteral dissection inferiorly. Just below the renal hilum, the gonadal vein is again identified and a plane is created medially toward the sidewall. This dissection proceeds inferiorly where the ureter crosses the iliac vessels. A GIA stapler is used to transect the gonadal vessels at the level of the pelvis. Once the ureter is dissected to the level of the left iliac artery and vein, it is divided using the 10 mm clip applier. The remaining inferior attachments are divided followed by the lateral attachments to the kidney. With gentle elevation of the lower pole the remaining posterior renal and ureteral attachments are divided with sharp and blunt dissection. Before dividing the vascular pedicle, a 5 cm periumbilical incision is made in the midline through the umbilicus using the umbilical port as the superior margin . Care is taken to keep the peritoneum intact in order to preserve the pneumoperitoneum. Prior to division of the vascular pedicle, the patient is given 3000 units of heparin sulfate. The camera is moved to the left lower quadrant port, and the endovascular GIA stapler(Autosuture, USSC, Norwalk, CT) is used to sequentially divide the renal artery renal vein. Once the pedicle is divided, the umbilical port is removed, and a 15mm Endocatch bag(USSC, Norwalk, CT) is placed through the umbilical port site. The kidney is placed in the bag under direct vision by grasping the perirenal adipose tissue. Once secured, the peritoneum is opened and the kidney delivered. It is imperative not to force the kidney through the incision. In fact, the incision should be lengthened in order to atraurnatically accompany the kidney. In some individuals, a pfannenstiel incision can be employed . When using this incision, the fascia is incised leaving the peritoneum intact. A purse string suture is placed in the peritoneum, and the trocar reinserted through which the Endocatch (USSC) is deployed. The pfannenstiel incision is particularly useful in small individuals allowing for greater space to manipulate the bag. Once removed, the kidney is transferred to the recipient surgical team. After injection of protamine sulfate(30 mg), the fascia is closed with interrupted number 1 Polydioxanone(PDS)suture, and a pneurnoperitoneum is reestablished. The renal bed is inspected for active bleeding as well as the trocar sites. The carbon dioxide is evacuated from the abdomen, and the lateral 12 min trocar site is closed under laparoscopic vision using a Carter Thomason closure device(Inlet Medical inc., Eden Prairie, MN) and 2-0 vicryl. The skin is closed with 4-0 vicryl(polyglactin) and Steristrips are applied. Right sided approach Left-sided donor nephrectomies are technically easier to perform. However, right-sided nephrectomies are occasionally required because of the relative renal function or vascular configuration. This side proves to be more technically difficult because the liver must be retracted cephalad to allow dissection of the upper pole. Also, the application of the endo-GIA stapler on the right renal vein results in a loss of 1.0 -1.5 cm of length. We have experienced allograft renal vein thrombosis presumably due to a short, thin right renal vein. With right sided donor nephrectomies, the following modifications are suggested. The midline port between the xiphoid and umbilicus is placed more superiorly. This trocar can be a 10/12mm port since an incision will be made through the site to deliver the kidney. The dissection of the right upper pole is difficult and requires elevation of the liver. Once again, the liver can be elevated using a blunt instrument placed directly under the liver to the right sidewall. This prevents injury to the liver and surrounding structures. A complete dissection of the lateral peritoneal reflection at the level of the liver facilitates this maneuver. Exposure of the short right renal vein at the level of the vena cava is only accomplished after the duodenum in reflected medially (Kocher maneuver). When removing the kidney, a 6 -8 cm right upper quadrant transverse incision is created as opposed to the midline or pfannenstiel incision for left-sided procedures. This incision is only created when the entire kidney has been mobilized and the ureter divided. After placement of a self-retaining retractor, the renal hilum is identified. The renal artery is divided between 0 silk ties or clips, and the renal vein is divided after placement of a Satinsky clamp across the inferior vena cava. This allows maximal length on the renal vein. The kidney is delivered to the surgical team. The Vena Cava can be closed with 4-0 prolene or the VCS clip applier(USSC). The surgical wound is closed using 1 PDS for the fascia and either a subcuticular suture or staples for the skin. The peritoneal cavity is reinsufflated and the renal bed is inspected. The port sites are closed with the modified Carter-Thomason instrument. Postoperative management At the completion of the procedure, the oral-gastric tube is removed. Patients are usually transferred to a standard urology or general surgical floor unless otherwise indicated. They may begin a clear liquid diet on the first postoperative day, and the diet is advanced as tolerated. In addition, the foley catheter is removed on post-operative day one, and a metabolic panel and complete cell count is obtained. Patients are discharged when tolerating a regular diet and are ambulating without assistance. Results Donor The first 110 laparoscopic donor nephrectomies performed at our institution were compared with the open approach. Length of hospital stay, perioperative analgesic requirements, complication, and readmission rates were significantly lower in the laparoscopic group. (16-18 ) Mean operative time was 232 minutes and estimated blood loss was 200 cc. . Patients returned to work approximately 2 weeks earlier after laparoscopic donor nephrectomy. Furthermore, live donor renal transplants increased by over 100% since the introduction of the laparoscopic operation. Live donor transplants now account for 55% of all renal transplants performed at Johns Hopkins Hospital. Complications related to the procedure were seen in 11 (10%) patients. These included one retroperitoneal bleed (0.9%), one incisional hernia (0.9%), one pneumonia (0.9%), six patients with transient thigh numbness (5.5%), and one rectus sheath hematoma (0.9%) secondary to an injury to the inferior epigastric artery requiring ligation, and one bowel injury (0.9%). Recipient Theoretical concerns that the pneumoperitoneum required for laparoscopy leads to decreased renal blood flow and transient renal ischemia with acute tubular necrosis and altered function have been unfounded. Overall recipient and graft survival rates were similar for the laparoscopic and open groups. Immediate graft function was noted in all patients. Using the Cockroft-Gault method for determining creatinine clearance, there was no clinically significant difference in the creatinine clearance in the laparoscopic and open groups at 30 months Likewise, there was no significant difference in ureteral or vascular complications. To date, there have been 10 (9.1 %) graft losses in the post-operative period. Laparoscopic live Donor Nephrectomy: The RecipientGraft LossLaparoscopic(n=10)Open(n=5)Vascular thrombosis 2 1 Rejection 1 1 HUS 1 1 Cholesterol Embolus 1 1 Recurrent disease 1 1 Non-compliance 1 1 Death 4 1 - Sepsis 3 1 - CVA 1 Two suffered vascular thrombosis. Each of these kidneys were from the right side with duplicated renal veins. As a result of these problems, we prefer to use the left kidney when using the laparoscopic approach. The right kidney should be harvested with caution. Summary Laparoscopic live donor nephrectomy offers many advantages compared to the traditional open approach. The procedure does not effect recipient outcome and can be performed safely by the experienced laparoscopic surgeon. It has resulted in less postoperative analgesic requirements, decreased hospital stay, and earlier return to activities of daily living and employment. References United Network for Organ Sharing(UNOS) and the Division of Transplantation,Bureau of Health Resources and Services Administration. Annual Report of the US Scientific Registry of Transplant Recipients and Organ Procurement and Transplantation Network-Transplant Data: 1988-1996. Rockville, MD: US Department of Health and Human Services; 1997. UNOS Scientific Registry Data, 1995. Engen, Donald. Transplantation Update. AUA Update Series. Vol. 16, 27. 1997. Clayman, RV, Kavoussi, LR, Soper, JN, et al. Laparoscopic nephrectomy: Initial case report. J. Urol. 146: 278-282. 199 1. Gill, DS, Carbone, JM, Clayman, RV, et al. Laparoscopic live donor nephrectomy. J. Endourol. 8: 143, 1994. Ratner, LE, Ciseck, LJ, Moore, RG, et al. Laparoscopic live donor nephrectomy. Transplantation. 60(9):1047, 1995 Ratner, LE, Montgomery, RA, Cohen, C. et al. Laparoscopic live donor nephrectomy: The recipient. Transplantation 65(12): 1657, 1998. Sosa, JA, Albini, TA, Powe, NR et al. Laparoscopic vs. Open live nephrectomy: Multivariate patient outcome analysis. Transplantation, 65(12): 1657, 1998. London, E, Perez, R, McVicar, J. et al. Equivalent renal allograft function with laparoscopic versus open live donor nephrectomies. American Society of Transplant Surgeons. Chicago, IL, Book of Abstracts, May, 1998. Ratner, LE, Kavoussi, LR, Sroka, M et al. Laparoscopic assisted live donor nephrectomy- a comparison with the open approach. Transplantation, 63(2): 229233,1997. Kasiske, BL, Ravenscraft, M, Ramos, EL. et al. The evaluation of living renal transplant donors: Clinical practice guidelines. Ad Hoe Clinical Practice Guidelines Subcommittee of the Patient care and Education Committee of the American Society of Transplant Physicians. J. Am. Soc. Of Nephrology 7(11): 2288,1996. Smith, PA, Ratner, LE, :Lynch, FC, et al. Role of CT angiography in the preoperative evaluation for laparoscopic nephrectomy. Radiographics. 18:589, 1998. Kavoussi, Lr, Moore, RG, Adams, JB, et al. Comparison of robotic versus human laparoscopic camera control. J. Urol. 154:2134, 1995. London, E, Neuhaus, A, Ho, H. et al. Beneficial effect of volume expansion on the altered renal hemodynamics of prolonged pneumoperitoneum. American Society of Transplant Surgeons. Book of Abstracts, Chicago, IL, May, 1998. Ratner, LE, Kavoussi, LR, Chavin, KD et al. Laparoscopic live donor nephrectomy: Technical considerations and allograft vascular length. Transplantation, Letter to the editor. 65(12): 1657, 1998. Ratner, LE, Kavoussi, LR, Schulam, PG et al. Comparison of Laparoscopic live donor nephrectomy versus the standard open approach. Transplantation Proceedings, 29: 138, 1997. Hiller, J, Sroka, M, Holochek, MJ et al. Journal of Transplantation Coord.; 7(3), 1997. Ratner, LE, Hiller, J, Sroka, R. Laparoscopic live donor nephrectomy removes disincentives to live donation. Transpl. Proceedings; 29: 3402, 1997. Cockroft, D.W., and Gault, M.W.: Prediction of creatinine from serum creatinine. Nephron, 16:31, 1976. Back to Innovative Surgical Techniques Johns Hopkins Medical Institutions - Department of Urology
Lich Gregoir
Postoperative management includes management of the operative procedure itself and immunosuppression. Managing the operative procedure itself involves management of a dynamic fluid balance with 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, which requires isotonic fluid replacement, often in the 250- to 500-cc/h range. With improving renal function, fluid balance must be maintained, hypertension management may need modification, and electrolyte abnormalities may require correction. Current immunosuppressive therapy can be divided into 2 phases: induction and maintenance. The induction phase of immunosuppression occurs during and immediately following transplantation and is divided into antibody and nonantibody regimens. The typical antibody-based induction immunosuppression uses either monoclonal or polyclonal antibody preparations directed at T lymphocytes in combination calcineurin inhibitors (eg, cyclosporine, tacrolimus), antiproliferative agents (eg, azathioprine, mycophenolate), and steroids. Both nonantibody induction therapy and most forms of maintenance therapy dispense with the antibodies but use calcineurin inhibitors, antiproliferative agents, and steroids in various combinations. The choice of induction strategy depends on several factors. Some centers employ antibody induction routinely. In those centers that do not routinely use antibody induction, most agree that antibody induction should be used in immunologically higher risk transplant cases (eg, retransplants), especially when the first kidney was lost to acute or chronic rejection, in patients of African American race, and in patients with evidence of significant prior sensitization to HLA antigens as evidenced by a high PRA titer. Calcineurin inhibitors are the mainstay of clinical immunosuppression since cyclosporine was introduced in the early 1980s. Calcineurin inhibitors were the first agents to target proliferating T lymphocytes by blocking the elaboration of cytokines (eg, interleukin-2) essential for T cell proliferation. Both cyclosporine and tacrolimus are naturally occurring products and have significant toxicities. Most notably, these 2 agents have a significant dose-related nephrotoxicity. The fact that agents that revolutionized kidney transplantation have significant nephrotoxicity is ironic. This nephrotoxicity, combined with erratic absorption and complex pharmacokinetics, necessitates ongoing monitoring of drug levels to maintain therapeutic levels while avoiding toxicities. While most centers follow drug trough levels, some have used pharmacokinetic modeling to good effect. Both cyclosporine and tacrolimus are metabolized in the liver by the cytochrome P 450 system; drugs altering cytochrome P 450 metabolism can result in higher blood levels (ie, fluconazole, verapamil) or lower drug levels (ie, rifampin, dilantin). A new strategy for immunosuppression involves the use of much lower doses of calcineurin inhibitors with sirolimus, which is a new immunosuppressive drug targeting T cells at a different site in the activation pathway. This strategy has been used successfully in kidney, liver, and pancreas transplantation, with the goal of minimizing the nephrotoxicity of the calcineurin inhibitors by reducing their levels. Mycophenolate mofetil is a prodrug that increases absorption of the active agent mycophenolic acid. Mycophenolic acid reversibly inhibits de novo synthesis of purines during S phase. Because the salvage pathway of purines synthesis is less active in lymphocytes than in other tissues, lymphocytes are more dependent on this pathway. Mycophenolate is far more selective than its predecessor, azathioprine, and it inhibits proliferation of both B and T cells. Used in conjunction with other agents, usually calcineurin inhibitors, mycophenolate significantly reduces the incidence of acute cellular rejection. This agent also reportedly reduces interstitial fibrosis associated with chronic rejection in animal models. This agent's principal toxicities occur in the gastrointestinal tract, and principally manifest as nausea and diarrhea. This toxicity may limit the use of mycophenolate, but patients who can tolerate it may experience significant reductions in allograft rejection. Steroids play an important role in all phases of immunosuppression, ie, induction, maintenance, and treatment of rejection. Unfortunately, steroids are associated with many complications of immunosuppression, including bone disease, hypertension, peptic ulcer disease, glucose intolerance, growth retardation, infection, obesity, and lipid abnormalities. Therefore, reduction in the dose of steroids used in each phase of immunosuppression is desirable. Complete steroid withdrawal is recommended when possible. Early indications suggest that this may be possible for many patients. Patients with stable graft function and no significant rejection episodes in the previous year often can be weaned off steroids and maintained on either combination therapy with a calcineurin inhibitor and an antiproliferative agent or monotherapy using a calcineurin inhibitor alone. Broader implementation of this strategy awaits the results of prospective clinical trials.
Early or late complications associated with renal transplantation may occur. Early postoperative complications include the following: Delayed graft function (DGF) varies based on donor, recipient, and transplant characteristics. Some rules are generally applicable. DGF is rare with living donor grafts, probably because of the short cold ischemia time (CIT), ie, the time between perfusion of the graft with ice-cold preservative solution and reperfusion with blood in the recipient. For cadaver kidneys, CIT remains the best predictor of DGF. While most DGF kidneys eventually function, they do have a somewhat diminished lifespan compared to kidneys that function immediately. Vascular-related and ureter-related complications are possible. Renal artery thrombosis occurs in about 1% of transplants, usually from small-caliber arteries. Nephrectomy generally is indicated, especially if the thrombosis occurs in the perioperative period. Arterial stenosis occurs in 2-10% of cases, it may occur within months or years following transplantation, and it is associated with the abrupt onset of hypertension. It can be suspected based on findings on Doppler ultrasound; confirmation generally requires angiography to confirm the presence of the stenosis and exclude proximal vascular disease. The authors have found carbon dioxide angiography useful, especially in the setting of renal insufficiency because it avoids contrast nephrotoxicity. Management of arterial stenoses has increasingly turned to percutaneous techniques, including angioplasty and stent placement. Venous thrombosis occurs in 0.5-4% of cases. Thrombosis of the main renal vein has been treated successfully in rare instances with thrombolytic agents, although typically the graft has infarcted by the time the thrombosis is detected. Graft infarction may occur with patent main arteries and veins; nephrectomy generally is required. Graft thrombosis associated with sepsis carries a significant recipient mortality rate. Prompt nephrectomy is indicated. Ureteral obstruction is the most common urinary tract problem associated with transplantation. It may occur early or late. Early obstruction may result from distal obstruction, clot, edema, or technical problems associated with the ureteroneocystostomy. When Foley catheter placement and expectant management does not resolve the problem, surgical revision of the ureteroneocystostomy over a stent may be required. Late obstruction, when not caused by external compression (eg, lymphocele, pregnancy), is associated most typically with fibrosis or nephrolithiasis. Management typically is by radiologic or cystoscopic stent placement and stricture dilatation. Urine leak can occur at any level of the urinary tract, from the renal pelvis to the urethra. Suspect urine leak when a patient with good or improving graft function develops a fluid leak from the wound or abdominal pain or perineal swelling, typically within a month of transplantation. Fluid leaking from the wound can be collected and assayed for creatinine. Nuclear renal scan probably is the most sensitive test for urine leak. Small bladder leaks often can be managed by bladder decompression with a Foley catheter. Larger and more proximal leaks typically require exploration and repair. Leakage from perivascular lymphatic vessels can lead to significant collections of lymph between the lower pole of the transplanted kidney and the bladder. Lymphocele can manifest as swelling, pain, and impaired renal function within the first year following transplantation. CT scan demonstrates the collect well and facilitates planning treatment. Aspiration occasionally resolves the problem, but prolonged catheter drainage is associated with a significant risk of infection. Sclerotherapy with 10% povidone-iodine solution may be successful in small unloculated collections, but lymphocele has a high rate of recurrence. Some early success has been observed on instilling fibrin glue containing gentamicin and iodine solution. However, the current standard of care is internal drainage of the lymphocele into the abdominal cavity. This increasingly is performed laparoscopically. Infection With improved immunosuppression, acute rejection has become less of a problem following transplantation. In the first year following transplantation, acute rejection is observed in approximately 25% of patients. Rejection usually is asymptomatic, although it sometimes presents with fever and pain at the graft site. Rejection usually presents as an unexplained rise in serum creatinine and can be confirmed with biopsy. Typical biopsy findings of acute cellular rejection include a lymphoplasmacytic infiltration of the renal interstitial areas with occasional penetration of the tubular epithelium by these cells. Most rejection episodes can be treated successfully with a short course of increased steroids. Failure to respond to steroid therapy for a particularly aggressive appearance on biopsy may prompt a change of treatment strategy (eg, antilymphocyte antibody agents). Chronic rejection appears to have both immunologic and nonimmunologic components. As a broad classification for progressive graft failure, risk factors include initial poor function of the graft and a history of acute rejection episodes.
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