932 SECTION VII Pediatric Critical Care Renal Sensitized Recipient The presence of preformed HLA antibodies is likely to result in severe antibody mediated rejection and early allograft loss Sev eral[.]
932 S E C T I O N V I I Pediatric Critical Care: Renal Sensitized Recipient The presence of preformed HLA antibodies is likely to result in severe antibody-mediated rejection and early allograft loss Several different assays are available to determine the sensitivity (i.e., presence of HLA antibodies) of a potential transplant recipient to donor HLA antigens These assays typically test for the presence of HLA antibodies by testing the serum from the recipient to a panel of HLA antigens or lymphocytes from different donors Patient sensitization is classically reported as the percent panel reactive antibody (PRA) and is an estimate of the likelihood of a positive crossmatch to a pool of potential donors The PRA is reported as historical (the highest value recorded on previous testing) and as current PRA Leading causes of the sensitized recipients include blood transfusion, pregnancy, and prior transplantation Surgical Procedure The transplanted kidney is usually placed in an extraperitoneal location when possible to allow for easier clinical monitoring and access to the graft In an infant or small child, it may be placed intraperitoneally Occasionally, native nephrectomy is needed at the time of transplantation Indications for nephrectomy include (1) need for space, such as in the case of polycystic kidney disease, especially in patients with massively enlarged kidneys; (2) uncontrolled renal-related hypertension; (3) persistent recurrent infections in native kidneys; (4) polyuria; and (5) nephrotic syndrome Native nephrectomy is often needed in patients with nephrotic syndrome, either congenital or acquired In this case, nephrectomies need to be done at least months before transplantation so that the nephrotic hypercoagulable physiology corrects in order to minimize the risk of vascular thrombosis The aorta and inferior vena cava are usually used for anastomosis to ensure adequate blood flow, but smaller vessels may be used These anastomoses may be difficult in children who have had previous hemodialysis accesses in the lower extremities A thorough evaluation of the vasculature is important prior to transplantation Cold ischemia time refers to the period of cold storage or machine perfusion Cold ischemia time of more than 24 hours is associated with an increased risk of delayed graft function Surgical teams make every effort to minimize cold ischemia time Warm ischemia time refers to the period between circulatory arrest and commencement of cold storage, with a goal of less than 60 minutes Serious urologic anomalies are present in many children who undergo renal transplantation, the most common being posterior urethral valves and vesicoureteral reflux Some of these children have undergone urinary diversion or bladder augmentation as a consequence of these malformations In children with significant bladder abnormalities, urology should be part of the pre- and postoperative multidisciplinary transplantation team caring for these patients in order to optimize outcomes Multiorgan Transplantation In general, genetic or anatomic disease that affects both the kidney and one other organ, such as polycystic kidney disease (may affect both liver and kidney) can serve as an indication for multiorgan transplantation Each transplantation can be performed simultaneously or at different time points In some circumstances, a liver-kidney transplantation can be performed for diseases resulting from abnormalities in liver function that affect kidney function These include primary hyperoxaluria and forms of atypical hemolytic uremic syndrome in which the disease may result from deficiency in factor H Kidney disease following heart transplantation is rare in pediatric practice, but there have been cases in which ESRD can require treatment with renal transplantation Kidney-pancreas transplantation is very rare in children; however, there are cases in which diabetic nephropathy results in ESRD in older children and young adults Immediate Arrival to the Pediatric Intensive Care Unit (Boxes 76.1, 76.2, and 76.3) Initial assessment of patients upon arrival to the pediatric intensive care unit (PICU) includes assessment of routine respiratory and hemodynamic stability The majority of children are extubated, with the occasional exception of the youngest recipients who weigh around 10 kg Sign out from the anesthesia and OR team should include details on the intraoperative blood pressures, central venous pressure (CVP), volume administered, metabolic correction, urine output, and any bleeding or need for transfusion The surgeon reports the cold and warm ischemia times and any surgical concerns It is at this time that the PICU team, along with the surgery and nephrology team, establish goals for the next 24 hours; target low and high blood pressure goals for which fluid • BOX 76.1 Immediate Pediatric Intensive Care Unit Arrival • Discuss blood pressure target parameters • Low blood pressure goal that would require fluid bolus • High blood pressure that would require PRN hypertension medications • Set target central venous pressure • Discuss urine output parameters • Urine output ,1 mL/kg/h or decrease in urine output by 50% from previous hour • Gross hematuria • Fluid management: insensible plus urine replacement • Anticoagulation plan • Immunosuppression plan; timing of induction and maintenance immunosuppression medication • Antibiotic prophylaxis • Lab monitoring plan PRN, As needed • BOX 76.2 What to Know About Kidney Transplant Recipients When They Arrive in the Pediatric Intensive Care Unit • Etiology of end-stage renal disease • Is there a risk of recurrent disease? If so, how does that change monitoring after transplantation? Example: Check daily protein/creatinine ratio for recurrent focal segmental glomerulosclerosis • Special urologic considerations, such as vesicostomy, bladder augment, or Mitrofanoff procedure • Preemptive transplantation or dialysis before transplantation • Pretransplantation blood pressures and antihypertensive medication regimen • Urine output before transplantation • Living donor or deceased donor • Cold ischemia and warm ischemia time CHAPTER 76 Pediatric Renal Transplantation • BOX 76.3 Causes of Graft Dysfunction Volume depletion Acute tubular necrosis Vascular • Renal artery stenosis • Renal vein thrombosis Urologic • Urinary obstruction • Urinary leak • Nephrotoxicity • Hyperacute rejection • Recurrence of primary disease • Thrombotic microangiopathy boluses or as needed antihypertensives should be administered Target CVP goals are established at this time in addition to goals for urine output (e.g., call for urine output less than mL/kg per hour or a decrease in 50% from the previous hour) Awareness of the child’s pretransplantation blood pressure and antihypertensive regimens and native urine output is important to help guide posttransplantation management Anticoagulation management plans are discussed, with target levels depending on the patient’s thrombosis risk The immunosuppression plan, with details on the timing of induction and maintenance medication initiation, is reviewed Renal Doppler ultrasound is performed within the first hour of arrival to the PICU to confirm graft vascular flow Posttransplantation Monitoring Hemodynamics and Tissue Perfusion It is important to avoid severe hypertension and hypotension in the immediate postoperative period Invasive blood pressure monitoring via arterial line is often necessary in the first 48 to 72 hours Blood pressure parameters, both high and low, must be established upon arrival to the PICU In general, relatively higher blood pressures in the immediate postoperative period are tolerated to avoid renal ischemia It is helpful to be aware of the patient’s pretransplantation blood pressure ranges and antihypertensive medication regimens Hypertension due to high fluid intake, steroids, and calcineurin inhibitors is problematic, adding stress on the renal arterial anastomosis and increasing the risk of hypertensive seizure However, great caution should be used in the treatment of hypertension in the initial postoperative period Blood pressures between the 90th to 95th percentile for age, gender, and height may be tolerated depending on the clinical situation The agents of choice for treatment of hypertension in the immediate postoperative period include short-acting vasodilators, b-blockers, or calcium channel blockers In general, angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists are avoided in the first few weeks after transplantation, as they may induce renal insufficiency in the setting of diminished effective arterial blood volume Diuretics may be helpful if hypervolemia is contributing to hypertension Awareness of what pretransplantation antihypertensive medications the patient took is helpful to guide posttransplant medication choices, especially if the patient’s regimen included medications such as b-blockers or clonidine, which can be associated with a risk of rebound hypertension when stopped If continuous infusion is required, PICU providers should use caution with 933 nicardipine, as it may inhibit tacrolimus metabolism by cytochrome P450, resulting in overexposure and potential toxicity.7 Hypotension and underperfusion of the adult-sized kidney in the pediatric patient is equally problematic The treatment of choice for hypotension posttransplantation is volume expansion with crystalloid and/or colloid If possible, vasopressors are avoided given the risk of renal vasoconstriction An adult kidney in a small child needs a normal to high blood pressure and good intravascular volume for adequate perfusion If the child has one or both native kidneys, be alert to hypotension and dehydration from polyuria Fluid and Electrolytes Small children may require massive volume expansion in order to maintain adequate perfusion of the adult-sized kidney It may be prudent to keep the small child intubated in the early postoperative phase if there are signs of pulmonary edema Meticulous fluid and electrolyte management is critical for pediatric patients, as they often require additional intravascular volume repletion in the perioperative period to establish diuresis and avoid delayed graft function CVP monitoring is used to help assess intravascular volume status but needs to be evaluated in the context of the child’s size Intravenous fluid management posttransplantation typically includes insensible fluids (300–400 mL/m2 per day) in addition to urine output replacement Urine output is replaced with intravenous (IV) fluid, usually ½ or 0.5% normal saline with dextrose and water In some cases, the postoperative diuresis is so large that hyperglycemia can result when 5% dextrose is used for urine replacement Urine output is usually replaced milliliter for milliliter throughout the first 24 hours with a gradual tapering off of IV urine replacement as the patient’s oral intake increases Supplemental loop diuretics or osmotic agents (mannitol) may be needed to facilitate diuresis in the oliguric patient Some centers use “renal dose dopamine” (3–5 mg/kg per minute) to enhance renal vasculature dilation, but this is controversial PICU practitioners should carefully administer medications associated with cytokine release (such as polyclonal and monoclonal T-cell antibodies) in the patient who is volume expanded Excessive volume administration may complicate blood pressure management High-volume diuresis may deplete electrolytes depending on the type of fluid replacement administered At time of transplantation, most patients have normal or elevated serum phosphorus levels In the setting of delayed graft function, phosphate binders may be necessary to control hyperphosphatemia (e.g., calcium acetate) With improved urine output, phosphaturia occurs due to hyperparathyroidism and/or the effect of calcineurin inhibitors The goal phosphate level depends on the age of the patient, with higher acceptable levels in the young growing child Oral phosphate supplements include preparations that contain potassium phosphate or a combination of sodium and potassium phosphate in either tablet or powder form The choice of supplement depends on the patient’s serum potassium and palatability Hypomagnesemia may occur due to calcineurin inhibitor– induced renal magnesium wasting A complication often seen with oral magnesium–containing preparations is diarrhea When this occurs, a dose reduction is necessary In the patient who has delayed graft function, avoid magnesium-containing antacids to prevent the development of hypermagnesemia Supplemental sodium bicarbonate may be needed in the postoperative period, especially in those with delayed graft function Patients who are undergoing substantial diuresis and receiving high-volume IV 934 S E C T I O N V I I Pediatric Critical Care: Renal fluid may also need addition of bicarbonate-containing solution to avoid metabolic acidosis Glucose management can be problematic, especially in the pediatric patient with type diabetes mellitus or in the patient on tacrolimus An insulin drip may be required to maintain glycemic control Once on a stable diet, patients can be switched to subcutaneous administration of longacting insulin with a sliding scale of a short-acting preparation Steroids complicate glycemic control and increased doses of insulin may be needed, especially when the patient is on higher doses of steroids in the first few months after transplantation After transplantation, patients who were on peritoneal dialysis prior to transplantation may have significant peritoneal fluid accumulation, presumably due to peritoneal irritation from longstanding exposure to dextrose-containing dialysate Intermittent drainage of the abdomen via the peritoneal catheter may be warranted in the setting of patient discomfort or if there is concern for increased intraabdominal pressure However, the need for peritoneal dialysis posttransplantation is rare Urine Output Close monitoring of urine output is very important in the immediate posttransplantation period In general, a Foley catheter is usually kept in the bladder for the first postoperative days to avoid stressing the ureterocystostomy and to facilitate hourly assessment of urine output It is very important to keep the Foley catheter in place and patent If the catheter is inadvertently discontinued or is not draining well, immediate evaluation is indicated In most cases, the Foley catheter will need to be replaced emergently to keep the bladder decompressed and to prevent tension in bladder-ureteral junction Urine output in the early posttransplantation period can range from oligoanuria to polyuria and can fluctuate depending on the clinical situation It is helpful to be aware of the patient’s pretransplantation urine output in order to help assess the initial urine output early after transplantation The first step in addressing low urine output is to assess the patient’s intravascular volume status (CVP, blood pressure) in addition to ensuring patency of the Foley catheter If the patient is determined to be hypovolemic, volume expansion with 10 to 20 mL/kg of isotonic saline can be administered It is not unusual for children to receive multiple fluid boluses in the first 24 hours posttransplantation In contrast, if the patient is evaluated to be hypervolemic, a dose of IV furosemide can be given If urine output does not improve with fluid resuscitation and diuretic challenge, a renal Doppler ultrasound should be performed to confirm flow to the graft and assess for obstruction Reasons for a decrease in urinary output include volume depletion, urologic complications such as urine leak or obstruction, vascular thrombosis, calcineurin inhibitor nephrotoxicity, and rejection Urine leak or lymphocele is indicated by abdominal pain, distention, elevated creatinine and blood urea nitrogen (BUN), and fever Ureteral stenosis or obstruction is indicated by decreased urine output/anuria, elevated BUN and creatinine, and pain over the graft Gross hematuria may occur after transplantation due to the use of anticoagulation However, there are some serious complications that one needs to keep in mind The differential diagnosis of gross hematuria includes renal vein thrombosis, renal artery thrombosis, infection, ureteral stent related, recurrent disease, and thrombotic microangiopathy Timely evaluation with blood work, urine analysis and microscopy, renal Doppler ultrasound, and possible biopsy is recommended Recovery of Renal Function Recovery of renal function can be divided into three broad categories: rapid recovery of graft function, slow, or delayed Delayed graft function has a specific definition and refers to the need for dialysis in the first week posttransplantation This occurs in less than 10% of pediatric kidney transplant recipients.3 Indications for dialysis posttransplantation include electrolyte abnormalities and/or significant fluid overload leading to pulmonary compromise and hypertension Caution should be used when initiating dialysis in the early posttransplantation period to avoid dramatic intravascular volume depletion that can compromise renal perfusion Immunosuppression Immunosuppression therapy can be divided into induction and maintenance phases.8 Induction immunosuppression is typically initiated in the operating room at the time of transplantation The goal of induction therapy is to prevent T-cell activation The choice of induction therapy is center and patient dependent Induction agents can be either monoclonal (binding to just one receptor) or polyclonal (binding to several different receptors) The monoclonal agents available currently include basiliximab, which binds to the interleukin-2 (IL-2) receptor (CD25) on activated T cells, and alemtuzumab, which binds to CD52, expressed on multiple immune cells The available polyclonal agent is rabbit antithymocyte globulin (Thymoglobulin) Maintenance agents include calcineurin inhibitors, cell synthesis inhibitors, mammalian target of rapamycin inhibitors, and glucocorticoids The calcineurin inhibitors cyclosporine A and tacrolimus block calcineurin-mediated activation of the IL-2 gene mTOR inhibitors (sirolimus, everolimus) block the activation process of T cells at a later stage through the mTOR pathways Cell synthesis inhibitors or antimetabolites (mycophenolates, azathioprine) block the progression of the cell synthesis cycle from G to S phase Glucocorticoids have multiple intracellular targets, including, but not limited to, IL-2 gene activation inhibition An injectable maintenance agent is belatacept, a fusion protein that blocks the CD28-B7 costimulatory pathway It is important to be aware of potential side effects of these agents that may be seen in the PICU setting Use of the induction medication Thymoglobulin can be associated with a release of cytokines by activated monocytes and lymphocytes and lead to cytokine release syndrome Serious cardiopulmonary events may result Premedication with corticosteroids, acetaminophen, and/ or an antihistamine may reduce systemic infusion-related reactions in addition to slowing down the infusion rate Other infusion reaction symptoms, including flulike symptoms (fever, chills, nausea, muscle/joint pain) may also occur Calcineurin inhibitors may be associated with hypertension and neurotoxicity Close daily monitoring of levels is important, with special caution needed for those with a history of seizure disorder to avoid supratherapeutic levels Nephrotoxicity can be seen in the early posttransplantation period wherein the initiation may be associated with a decrease in urine output and delay in renal recovery, especially with high levels In addition, it is important to be aware of the drugs that interact with immunosuppressive medications Macrolide antibiotics (erythromycin, clarithromycin, but less so azithromycin) and azole antifungal agents (ketoconazole, fluconazole) delay the metabolism of calcineurin inhibitors, such as tacrolimus, by competing for the same enzymatic degradation pathways, leading to higher drug levels that may become toxic CHAPTER 76 Pediatric Renal Transplantation Conversely, phenytoin may decrease tacrolimus levels In the early posttransplantation period, mTOR inhibitors may be associated with poor wound healing and lymphoceles Antimetabolites can lead to diarrhea and nausea, anemia, and leucopenia Infection Surveillance and Prevention The use of perioperative IV antibiotics is program specific, but many centers use a first-generation cephalosporin for the first 24 to 48 hours in the nonallergic patient.8 In a child, both elevation and depression of core body temperature may indicate infection Close daily attention to the patient’s vital signs and physical examination is critical, including evaluation of wounds, indwelling catheters, and drains Lines, drains, and urinary catheters should be discontinued as soon as medically indicated to avoid risk of infection Urine should be cultured, and the sediment examined routinely as part of posttransplantation management Workup for suspected infection in the pediatric patient should include physical examination, cultures (urine, blood, drains, and peritoneal fluid if indicated), chest radiographs, cytomegalovirus and Epstein-Barr virus polymerase chain reaction tests and consider spinal tap if signs or symptoms persist In addition, prophylaxis against Pneumocystis jirovecii using trimethoprim-sulfamethoxazole (TMP/SMZ) is indicated if the patient is not allergic Dapsone or pentamidine monthly inhalation can be used if the patient is TMP/SMZ allergic Oral antifungal prophylaxis usually is given for the first to months after transplantation, usually in the form of nystatin or clotrimazole troches Viral prophylaxis for CMV with ganciclovir or valganciclovir is routinely used in the posttransplantation period The dose for ganciclovir is adjusted according to the estimated creatinine clearance Posttransplantation Complications Acute Kidney Injury Several factors may be responsible for postischemic acute kidney injury These include the age and condition of the donor, specific recovery procedure, technique of organ preservation, adequacy of volume replacement during and after surgery, and the cold and warm ischemia times Tubular damage may be aggravated by administration of cyclosporine or tacrolimus There is evidence that the addition of sirolimus in combination with either cyclosporine or tacrolimus prolongs renal function recovery Vascular Complications Vascular thrombosis of the renal artery or vein is the third most common cause of graft failure in children receiving renal transplants The main risk for thrombosis is an extremely young donor or recipient Other risk factors include hypercoagulability (such as that due to chronic nephrotic syndrome) and venous malformation in the recipient, pretransplantation peritoneal dialysis, a hypotensive episode during or after surgery, the presence of multiple arteries, and bench surgery of graft vessels Although vascular thrombosis is usually observed within the first few days following transplantation, it can be seen as late as weeks posttransplantation Careful hemodynamic monitoring of CVP is critical to ensure adequate allograft perfusion Venous thrombosis of the transplant is indicated by decreased urine output, graft swelling and tenderness, and proteinuria 935 Screening for inherited and acquired thrombophilic risk factors, especially if there is a family history or previous episode of thrombosis, should be considered Screening is currently available for protein C, S, or antithrombin III deficiency, factor V Leiden, prothrombin gene mutations, and the presence of antiphospholipid antibodies Prophylactic therapy with heparin, low-molecularweight heparin, and/or aspirin to prevent thrombosis for those with an increased risk of thrombophilia has been successful in preventing graft loss In some centers, low-molecular-weight heparin is used prophylactically in all pediatric renal transplantation recipients Renal artery stenosis is indicated by elevated blood pressure and bruit over the transplant upon auscultation Conservative management in the setting of noncritical stenosis is observed Maximization of blood pressure control with serial imaging using renal Doppler ultrasound is used in conjunction with monitoring of renal function However, if stenosis is severe, thrombosis may occur Urologic Complications Early posttransplantation urologic complications are relatively common in pediatric kidney transplant recipients Urinary leak may occur due to ureteral necrosis, bladder injury, or obstruction Urinary tract obstruction is most often due to clots in the urinary tract, postoperative edema, or surgical complication It is detected as hydronephrosis by renal ultrasonography Many centers place ureteral stents as a measure to reduce these complications Rejection Advances in immunosuppression have led to remarkable decreases in acute rejection rates Rejection categorization is subdivided by its onset posttransplantation: hyperacute, accelerated, and acute.8 Hyperacute and accelerated acute rejection result from preformed host anti-HLA antibodies that bind to vascular endothelial cells of the graft, resulting in activation of the complement cascade and endothelial injury Neutrophils, macrophages, and platelets are attracted to the antibody binding site and cause further cellular damage Platelet aggregation on the damaged endothelium leads to fibrin deposition and vascular thrombosis There are also reports of hyperacute rejection associated with antiendothelial antibodies, which are not detected with standard crossmatch methods using donor lymphocytes Hyperacute rejection occurs within the first minutes following transplantation, while accelerated acute rejection occurs within to days posttransplantation Hyperacute and accelerated acute rejection are rare due to advances in crossmatching assessment Clinically, patients present with oligoanuria and fever and graft tenderness Diagnosis is by allograft biopsy and assessment for donor-specific antibodies Treatment is not usually successful Early acute rejection may be seen in the first week but is very rare However, it should be suspected in the setting of delayed return of renal function or an acute deterioration in allograft function, generally detected by an elevation in the serum creatinine level The two principal histologic forms of rejection are acute cellular rejection and acute antibody-mediated rejection Acute cellular rejection is characterized by infiltration of the allograft by lymphocytes and other inflammatory cells Acute antibody-mediated rejection is diagnosed by morphologic evidence of acute tissue injury, circulating donor-specific alloantibodies, and immunologic evidence of an antibody-mediated process (such as C4d deposition in the allograft) Cellular infiltrates may not be present 936 S E C T I O N V I I Pediatric Critical Care: Renal Urinary Tract Infection Urinary tract infection (UTI) is the most common bacterial infection in both adult and pediatric kidney transplant recipients.8 UTIs will develop in 20% to 40% in the first year posttransplantation and 40% to 60% by years posttransplantation UTI is not only a cause of morbidity but is also associated with higher rates of graft loss and patient death The urogenital tract is the most common entry point for systemic sepsis Numerous risk factors have been identified for UTIs posttransplantation Urologic anomalies such as neurogenic bladder, urinary tract obstruction, vesicoureteral reflux, bladder augmentation, and clean intermittent catheterization have all been associated with an increased risk of UTIs posttransplantation Foreign bodies, such as ureteral stents, have also been associated with increased UTIs posttransplantation The organisms implicated are usually the same as in immunocompetent individuals, such as Escherichia coli and Klebsiella species A higher percentage of UTIs in transplant patients is due to unusual organisms, such as Pseudomonas species Clinical symptoms may include fever, dysuria, graft tenderness, and cloudy urine In some patients, symptoms may be masked due to immunosuppression A rise in serum creatinine may occur and can mimic acute rejection UTIs can also precipitate acute rejection The diagnosis of UTI is usually made by urine culture, though patients on TMP/SMZ prophylaxis for pneumocystis may not demonstrate positive cultures Initially, the antimicrobial prescribed should cover the common gram-negative organisms Once the organism is known, the most specific and cost-effective antimicrobial can be prescribed Treatment route and total duration are determined by the severity of infection, recipient age, and other risk factors Other Infections Other bacterial infections—such as wound infections, line sepsis, and pneumonia—are seen with significant frequency in kidney transplant recipients Wound infections and line sepsis are commonly due to gram-positive staphylococcus and streptococcus Pneumonia can be due to multiple etiologies (bacterial, viral, or fungal), but bacterial pathogens are responsible for approximately 44% of cases The treatment of these infections is generally no different from standard treatment in immunocompetent hosts, though duration of therapy may be longer Kidney transplant recipients are at increased risk for oral and esophageal infections due to Candida species The use of oral clotrimazole troches or nystatin provides effective prophylaxis without systemic absorption and, hence, without concerns for side effects Although data regarding the duration of prophylaxis are not available, prophylaxis should be continued until patients are on stable maintenance immunosuppression Recurrence of Primary Renal Disease It is important to recognize the clinical presentation and natural history of diseases that recur after renal transplantation In most pediatric series, recurrence of primary disease is responsible for renal allograft failure in 5% to 15% of cases Among the glomerular diseases that may recur in the graft and can present in the early posttransplantation period, the most frequent is FSGS.9,10 Focal Segmental Glomerulosclerosis Steroid-resistant idiopathic nephrotic syndrome due to primary FSGS accounts for 10% of cases of ESRD in childhood.9,10 The overall risk of recurrence of nephrotic syndrome after transplantation is estimated to be about 30% FSGS is the most frequent cause of graft loss due to recurrent disease The risk of recurrence with FSGS is greater in children than adults In children, recurrence is more frequent when the disease begins after the age of years and there is a rapid progression to ESRD In most series, the disease recurs in one-half of patients when the duration of disease has been shorter than years The histopathologic pattern observed in the first biopsy of the original disease is also an important predictive factor of disease recurrence As an example, recurrence occurs in 50% to 80% of patients in whom the initial biopsy reveals diffuse mesangial proliferation (suggestive of more rapidly progressive disease) but in only 25% of patients with minimal-change disease Patients with FSGS due to mutations in genes encoding podocyte proteins appear to have a very low risk of recurring disease after renal transplantation Recurrence of FSGS enhances the risk of allograft loss and is associated with an increased incidence of delayed graft function and acute rejection Recurrence most often occurs within the first few days after transplantation Close daily monitoring of urine protein excretion is important for the early detection of possible disease recurrence In patients with a first graft lost to recurrent disease, the recurrence rate is approximately 80% in a subsequent graft Treatment remains controversial and may include plasmapheresis, rituximab, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers depending on the timing of recurrence The full reference list for this chapter is available atExpertConsult.com ... using donor lymphocytes Hyperacute rejection occurs within the first minutes following transplantation, while accelerated acute rejection occurs within to days posttransplantation Hyperacute and accelerated... induction and maintenance medication initiation, is reviewed Renal Doppler ultrasound is performed within the first hour of arrival to the PICU to confirm graft vascular flow Posttransplantation Monitoring... centers use “renal dose dopamine” (3–5 mg/kg per minute) to enhance renal vasculature dilation, but this is controversial PICU practitioners should carefully administer medications associated with