Solid organ transplantation

Guidelines for DCDD

When determining which patients may be appropriate for DCDD, members of organ procurement organizations and members of transplant teams should not be a part of the decision-making process for WLST, and the decision should not be based on donor potential. Once the decision for WLST has been made, discussion regarding DCDD can occur, and arrangements for organ allocation and limits of warm and cold ischemic times must be determined. The whole process of DCDD must be explained to the patient’s family/surrogate decision makers. This includes, but is not limited to, the process of WLST and that this withdrawal may be delayed until all potential organs have been allocated; the procedures and methods of determining death; that there is a possibility that organs may not be suitable for donation; and that consent may be withdrawn at any time, even after WLST and the determination of death. No antemortem care should be provided that incurs any higher risk than the usual standard of care and should in no way be intended to hasten death.

The process of WLST can occur in the intensive care unit, near the operating room, or in the operating room, depending on the surrogate decision maker’s wishes and logistics of the institution. Family/caretakers should be allowed to be with the patient until the determination of death has been made. Predetermined limits for the time to determination of death should be made, given that organs may be hypoperfused during the time between WLST and determination of death, which could render them not suitable for donation. While the use of predictive modeling for estimating the time to death from WLST remains controversial, the requirement for high inotrope and/or vasopressor infusions, positive end-expiratory pressure >10 mm Hg, and receiving extracorporeal membrane oxygenation have been shown to be associated with a shorter time to circulatory arrest ( ). In addition to the time between WLST and the cessation of circulation, it is suggested there be a mandatory 5 minutes of hands-off time. After the cessation of circulation and the 5 minutes of hands-off time, death must be determined by two separate physicians, one of whom should be a critical care attending physician from the intensive care unit where the patient was being treated. After WLST, cessation of antegrade circulation (suggested to be determined with the use of an invasive arterial blood pressure monitor), the 5-minute hands-off period, and the confirmation of death, it is then considered suitable to begin the organ harvest process.

All actions surrounding DCDD must comply with the “dead donor rule,” stating that organs may only be procured from a dead person and that organ procurement cannot result in death ( ). Several ante- and postmortem practices remain controversial without a clear consensus in place due to the potential violation of this rule, which some believe may actually impede the care that may be in the best interest of the patient and their surrogate decision maker. For instance, the practice of heparinization to minimize thrombosis formation during periods of low and no flow is a potential violation, because it provides no direct medical benefit to the donor—that is, unless you consider their ability to more effectively donate their organs in alignment with their wishes. Also, any intervention that could potentially provide oxygenated blood to the brain must be avoided. Therefore any sort of extracorporeal membrane oxygenation must be used in a fashion that provides organ-/region-specific blood flow, excluding any cerebral circulation.

Pediatric structured donor management goals

The OPTN was created when the National Organ Transplant Act was signed into law in 1984. The OPTN managed how organs were donated and shared by creating Organ Procurement Organizations (OPOs) throughout the United States and its territories. The OPOs manage 58 donation service areas within 11 UNOS territories. In 2015 a consensus statement from the Society of Critical Care Medicine, American College of Chest Physicians, Association of Organ Procurement Organizations provided recommendations for donor management goals (DMGs) within the domains of (1) hemodynamics, (2) lung recruitment and mechanical ventilation, (3) fluids/electrolytes, (4) endocrine function, (5) blood product utilization, and (6) thermoregulation ( ). The pediatric DMGs are presented in Table 38.6 . As of 2016, 39 out of 58 (67%) OPOs followed some form of pediatric donor guidelines, and 27 out of 58 (47%) utilized DMGs for pediatric donor management ( ). Sixteen of the 39 OPOs that employed guidelines used the Updated Pediatric Donor Management and Dosing Guidelines established by the North American Transplant Coordinators Organization ( Table 38.7 ) ( ).

Hemodynamics

The goals for hemodynamic management do not differ significantly between the pediatric organ donor and the critically ill child, in that the maintenance of euvolemia, cardiac output, vascular tone, and oxygen-carrying capacity is necessary to ensure adequate organ perfusion, oxygenation and nutrient delivery, and carbon dioxide and waste removal.

Forty-three of the 58 OPOs report following guidelines for determining age-appropriate blood pressure in pediatric donors ( ). Nearly all OPOs report using an invasive arterial line for the monitoring of blood pressure, nearly 80% monitored central venous pressure (CVP), and slightly more than 30% followed serum lactate levels ( ). Hemodynamic goals for pediatric donors are presented in Table 38.6 .

Hypovolemia is common in DNDD patients due to cold diuresis from hypothermia, neuroendocrine failure and polyuria, tissue edema from inflammation, and third spacing of fluid ( ). Crystalloid solutions such as 0.9% normal saline or lactated Ringer’s solution may be used for initial volume replacement ( ). Care should be taken to avoid the hypernatremia and hyperchloremia that may result from 0.9% saline, whereas the hypoosmolar effects of lactated Ringer’s solution may not be tolerated by some donors ( ; ). Colloid solutions such as 5% albumin, or packed red blood cells in the case of unacceptable anemia, may also be used ( ; ). Hydroxyethyl starch should be avoided because it has been associated with acute kidney injury, coagulopathy, and trapping in the hepatic reticuloendothelial system ( ). In addition, hydroxyethyl starch use in donors has been associated with delayed graft function and graft failure ( ). Donor hypovolemia may be detrimental for renal graft function, whereas hypervolemia may impair pulmonary graft function. A CVP of 4 to 6 mm Hg was determined to be optimal for lung graft function, and this restrictive fluid management (CVP <6 mm Hg) has not been found to be detrimental for kidney graft survival or delayed renal graft function ( ).

Among surveyed OPOs, dopamine was the most commonly used initial vasoactive infusion (24/58, 41%), followed by phenylephrine (8/58, 14%), epinephrine (4/58, 7%), norepinephrine (2/58, 3%), vasopressin (1/58, 2%), and dobutamine (1/58, 2%) ( ). Although dopamine historically has been used as the first-line vasoactive agent for hypotension, there is insufficient evidence to preferentially recommend its use over other vasoactive agents ( ). Dopamine, epinephrine, and dobutamine may be used for cardiac dysfunction, whereas norepinephrine, phenylephrine, and vasopressin are recommended for the vasodilatory component of donor hypotension ( ; ). Recommended vasoactive medications and their doses can be found in Table 38.7 . Excessive beta-agonist use should be avoided for potential heart donors, given evidence that these may lead to myocardial cellular energy depletion and desensitization of beta receptors ( ). Furthermore, excessive vasoconstriction may have detrimental effects, especially for coronary and mesenteric vasculature (i.e., heart and intestine/multivisceral donors) ( ).

Ventilation

The overarching goals for mechanical ventilation in donors are achieving adequate oxygenation and ventilation while avoiding detrimental volutrauma, barotrauma, and atelectasis. The pediatric DMGs for mechanical ventilation are presented in Table 38.6 . Donor lungs are extremely vulnerable; any cardiopulmonary resuscitative efforts can lead to blunt force injury to the lungs during chest compressions. In addition, blood product administration—either during attempts at resuscitation or after declaration of brain death to maintain adequate hemoglobin levels and coagulation function—could result in transfusion-related acute lung injury. Furthermore, the event of brain injury and death can lead to pulmonary injury via neurogenic pulmonary edema (NPE).

The incidence of NPE can range from 2% to 42% after subarachnoid hemorrhage and 20% to 50% after traumatic brain injury ( ). The exact mechanisms underlying the development of NPE are still not clearly understood; however, the prevailing theory is that the profound catecholamine surge associated with the initial cerebral edema and neural compression, especially of the brainstem, is the inciting factor ( ; ). The sudden rise in vascular resistance forces more blood through the pulmonary vascular system and this, coupled with capillary permeability, results in pulmonary edema ( ). The ventilation management of patients with NPE is similar to those with acute respiratory distress syndrome (ARDS), which includes the use of positive end-expiratory pressure and lung-protective ventilation with lower tidal volumes (4 to 8 mL/kg) ( ).

Regardless of whether a pediatric organ donor is a candidate for lung donation, care must still be taken to manage their ventilation to preserve function of other organs to be donated. Systemic inflammation, aspiration, infection, and injury from mechanical ventilation can all result in poor ventilation and oxygenation. The routine use of beta-agonists in lung donors has been cautioned against given a lack of benefit and the side effect of tachycardia ( ).

Fluid, electrolytes, and nutrition

The absence of a functioning hypothalamic–pituitary access in addition to other systemic derangements can lead to massive diuresis and electrolyte abnormalities, necessitating fluid management aimed at maintaining intravascular volume and electrolyte management to prevent arrhythmias and organ dysfunction. Central venous catheters and pulmonary artery catheters can provide volume status information, such as central venous pressure and pulmonary artery occlusion pressure, as well as other markers of organ perfusion, such as mixed venous oxygenation, lactic acid levels, base deficit, and acid–base status ( ; ). Additional volume status measures include transthoracic echocardiography, which can also provide an assessment of cardiac function, and pulse pressure variation and systolic pressure variation obtained via an invasive arterial line can further help guide fluid management ( ). Fluid therapy guidelines aim to maintain age-appropriate blood pressure, >1 mL/kg per hour urine output, and minimize pressure utilization (i.e., dopamine <10 mcg/kg per minute) ( ). Generally, lactated Ringer’s and 0.9% saline have been used for intravenous fluids; however, hyperchloremic acidosis may limit the use of 0.9% saline ( ; ). At times sodium bicarbonate may be added to fluids to maintain a donor pH between 7.3 and 7.45 ( ). Goal-directed transfusion of blood and blood products may be indicated; however, optimal thresholds have not been determined for donor management ( ). Thirty-one of 58 (53%) OPOs reported standardized guidelines for fluid and electrolyte management of pediatric organ donors ( ).

Electrolyte abnormalities are not uncommon in DCDD organ donors, whether it be due to fluid resuscitation, the hyperosmolar agents used to try to avoid cerebral edema, or the diabetes insipidus that can occur in brain-dead patients ( ). Whereas the first two etiologies can be managed by altering intravenous fluid administration and discontinuing the use of agents like hypertonic saline and/or mannitol, diabetes insipidus may require more active management given that this can result in hypovolemia, hypernatremia, hypokalemia, hypomagnesemia, and hypophosphatemia ( ). Pediatric DMGs for electrolyte goals are presented in Table 38.6 . In particular, hypernatremia has been associated with impaired liver graft function, although these observations have been seen more so with adults, and pediatric associations are lacking ( ). Nonetheless, donor serum sodium <155 mEq/L has been recommended ( Table 38.5 ) ( ; ). Cerebral edema associated with rapid correction of hypernatremia is less of a concern in brain-dead patients; however, the rapid administration of hypotonic fluids can lead to hemolysis and hemolysis-associated kidney injury ( ). Among the 52 out of 58 (90%) OPOs reporting using serum sodium thresholds, 30 used the guideline-recommended 155 mEq/L (18 used 160 mEq/L; 4 used 150 mEq/L) ( ).

The OPTN has not provided guidelines regarding nutrition management in organ donors. Due to organ donors’ low metabolic rate, insulin resistance, and steroid-induced hyperglycemia, many centers eliminate nutrition (enteral and parenteral) altogether ( ). Fifty-three of the 58 (93%) OPOs report stopping nutrition unless otherwise instructed ( ). There is thought that since the liver is the major glycogen storage unit for the body, liver grafts may benefit from ongoing donor nutrition; however, no data is available to definitively support this theory ( ). In addition, continued enteral nutrition may preserve small bowel villi and thus potential small bowel donors may continue to receive enteral nutrition ( ; ). With regards to written guidelines for glycemic control, only 29 out of 58 (50%) OPOs utilized glucose thresholds, which ranged from lower levels of 69 ± 12 mg/dL to hyperglycemia thresholds of 171 ± 37 mg/dL ( ).

Endocrine/hormonal therapy

Brain-dead donors are susceptible to several endocrine abnormalities; most notably there can be relevant deficiencies of arginine vasopressin, thyroid hormone, and cortisol. Ischemia and infarction of the hypothalamic–pituitary axis places the donor at risk for endocrine dysregulation. Pediatric dosing guidelines for hormone replacement therapy are presented in Table 38.7 .

Arginine vasopressin is produced in the hypothalamus and released from the posterior pituitary. It has been observed that 80% of DNDD donors manifest diabetes insipidus, which makes it not surprising that 21 out of 58 (36%) OPOs empirically administer vasopressin (or another arginine vasopressin analog) ( ). Arginine vasopressin acts on the vasculature via V1 receptors to elicit vasoconstriction, the kidney via V2 receptors as an antidiuretic causing free water resorption from the collecting system, and the anterior pituitary via V3 receptors to regulate adrenocorticotropic hormone release ( ). Diabetes insipidus is the most common manifestation of arginine vasopressin insufficiency and is typically treated with either vasopressin or desmopressin ( ). Treatment should be initiated for urine output in excess of 2.5 to 3 mL/kg per hour, increased serum osmolality, inappropriately dilute urine (specific gravity <1.005 and/or urine osmolality <200 mOsm/kg H ₂ O), or serum sodium >145 mMol/L in the absence of other abnormalities ( ; ). In general, diabetes insipidus with concurrent hypotension should be treated with vasopressin, whereas diabetes insipidus in the normotensive brain-dead donor can be treated with desmopressin to avoid hypertension, given that it is more selective for the renal V2 receptor ( ). Vasopressin use in pediatric donors has led to higher organ yields, especially cardiac donors, and therefore its use is recommended ( ; ). Of note, the high concentration of V1 receptors on splanchnic vasculature results in visceral hypersensitivity to arginine vasopressin. This is particularly troubling for intestine recovery, and we suggest optimization of fluid status and utilization of only polyuria doses of arginine vasopressin to avoid splanchnic vasoconstriction and end organ ischemia.

Empiric administration of systemic steroids is even more prevalent, with all but one OPO administering corticosteroids (51 out of 58 use methylprednisolone, 5 use hydrocortisone, and 1 uses both) ( ). Despite a lack of strong evidence to support hypocortisolism, the antiinflammatory and immunomodulatory benefits outweigh the few potential risks that exist ( ). While no significant effect on hemodynamics has been observed, some benefits for liver, kidney, heart, and lung donation from pediatric donors have been shown when those donors received corticosteroids ( ; ). Hyperglycemia is common after brain death and is likely multifactorial due to massive catecholamine release or exogenous catecholamine administration, infusions of dextrose-containing fluids, corticosteroid administration, peripheral insulin resistance from catechol exposure, and altered intracellular metabolism ( ). Insulin administration to organ donors has not shown an independent benefit; however, hyperglycemia can affect pancreatic islet cells and affect renal graft function ( ; ). Pediatric DMGs recommend a serum glucose target range of 60 to 150 mg/dL ( Table 38.6 ) ( ).

It has been suggested that cellular metabolism switches from aerobic to anaerobic metabolism leading to increased lactate in DNDD donors with thyroid hormone insufficiency, and this has been implicated in graft dysfunction and failure ( ). Thyroid hormone replacement has shown benefit when used in hypotensive donors not responding to vasopressors and thus has shown a vasopressor-sparing effect ( ; ). They have also shown benefit in cardiac donors with depressed ejection fraction ( ; ; ). Empiric thyroid hormone was administered to pediatric organ donors by 37 of 58 (64%) OPOs, with 19 of 58 (33%) reserving this form of hormone replacement therapy for low cardiac output and/or potential heart donors and 2 of 58 (3%) not administering thyroid hormone at all during pediatric organ donor management ( ). The majority of OPOs (51/56, 91%) that administered thyroid hormone, either empirically or situationally, used thyroxine (T4) alone ( ). Data has not shown one (T3 or T4) to be superior to the other ( ; ).

Thermoregulation

In brain-dead patients, perfusion to the hypothalamus and pituitary ceases, resulting in thermodysregulation through the loss of shivering and vasoconstriction ( ). Adverse effects of hypothermia include arrhythmias, diuresis, coagulopathy, and insulin resistance ( ). Forty-three of 58 (74%) OPOs utilized standardized guidelines for temperature regulation in pediatric organ donors ( ). Donor management goals recommend that donors be managed to maintain a temperature of 36°C to 38°C ( Table 38.6 ). There is some evidence that mild donor hypothermia (34°C to 35°C) leads to reduced delayed graft function after kidney transplantation; however, the long-term graft outcomes are pending at this time ( ). The use of mild hypothermia must take into consideration the criteria for determining brain death, which at least for determining brain death requires normothermia (see Pediatric Brain Death).

Infection

Positive blood cultures have been observed in nearly 20% of brain dead donors, and older age and being in the intensive care unit for three or more days increases this risk ( ). Although some infections such as viral meningitis, fungal infections, and active hepatitis B preclude brain-dead patients from being organ donors, potential donors with most other bacterial infections can still be candidates and should receive a minimum of 48 hours of antibiotic therapy specific to the cultured organism(s) ( ). Bacteremia and/or sepsis and even bacterial meningitis are not absolute contraindications for organ donation as long as culture-directed antibiotics have been administered for 48 hours and the same culture-directed antibiotics are continued in the recipient for 7 to 14 days ( ). While patients with hepatitis B are typically not considered for organ donation, patients who are seropositive for hepatitis C may be candidates for donation to hepatitis C–positive recipients ( ). Although there is no specific recommendation for donor antibiotic prophylaxis, 56 out of 58 (97%) OPOs include antibiotic prophylaxis in their procurement guidelines ( ). Cefazolin was most commonly used (35/58, 60%), with piperacillin–tazobactam (8/58, 14%) being the second most commonly employed ( ).

Hypothermia

Hypothermia serves as a first-line defense against hypoxic cellular injury, and its implementation in the early stages of organ transplant allowed for longer organ ischemic times. Cooling organs to 4°C to 6°C greatly reduces but does not completely stop cellular metabolism ( ). Static cold storage of organs at this temperature range causes significant changes in cellular, energy, electrolyte, transcriptional, and gene expression homeostasis ( ). Estimating from Van ‘t Hoff’s principle (expressed as Q ₁₀ = (k ₂ /k ₁ ) ^10/(t2−t1) ), varying the temperature of preservation is expected to reduce tissue metabolism to 10% to 18% in hypothermic (0°C to 12°C), 19% to 35% in midthermic (13°C to 24°C), 36% to 85% in subnormothermic (25°C to 34°C), and more than 86% in normothermic conditions (35°C to 38°C) ( ). In addition to maintaining organs in hypothermic conditions, recent evidence has shown that maintaining the donor at 34°C to 35°C is not only safe but also reduces delayed graft function and improves 1-year graft survival ( ; ).

Preservation solutions

Collins initial preservation fluid was intended to mimic intracellular fluid with high potassium and lower sodium and chloride in an effort to reduce cellular edema by maintaining ion concentrations ( ; ). Phosphate and bicarbonate served as buffers in this initial preservation solution, and glucose was the energy source; however, glucose may have contributed to increased lactate levels via anaerobic metabolism ( ).

Since 1989, UW solution has served as a gold standard preservation solution ( ). Like Collins solution, UW solution is considered an intracellular fluid–like solution with a high potassium content. The UW solution added the adenosine triphosphate precursor, adenosine, and also removed bicarbonate and glucose ( ). Adenine breakdown products such as hypoxanthine contribute to the accumulation of reactive oxygen species ( ). The UW solution helps to combat this by containing allopurinol. There is additional antioxidant support from reduced glutathione, and the addition of raffinose and lactobionate helps minimize cellular edema ( ). Stated drawbacks to UW solution include its high potassium content, which may contribute to hyperkalemia in the recipient upon reperfusion, and its high viscosity ( ; ). Combined UW solution with blood at 4°C results in fluid 1.3 times more viscous than blood at normothermic temperatures, which may hinder organ washout upon reperfusion ( ).

Newer alternative solutions to UW include HTK solution, Celsior solution, and Institut Georges Lopez-1 (IGL-1) solution ( ). Each of these presents a lower-potassium, lower-viscosity alternative to UW solution. The HTK solution was named for its buffering constituents, membrane stabilizer, and energy substrate, respectively ( ). Celsior solution incorporates characteristics of both UW and HTK solutions including a lactobionate osmotic carrier and histidine buffer, respectively ( ; ). One main difference is Celsior’s higher sodium content compared with UW and HTK solutions. The IGL-1 solution resembles UW solution except that it replaces the hydroxyethyl starch colloid with a less viscous colloid, polyethylene glycol, and it, much like Celsior solution, has sodium and potassium concentrations that resemble that of the extracellular space as opposed to the intracellular milieu ( ; ; ). Large retrospective studies from the UNOS have failed to definitively demonstrate superiority of any of these newer preservation solutions over UW solution, aside from evidence that Celsior may provide greater benefit as the preservation solution for lung preservation ( ).

Novel additives for preservation solutions

Novel additives to preservation solutions have received increasing attention over the past decade. These include small-molecule bioregulators and mitochondria-targeted antioxidants. Of the small-molecule bioregulators, the gaseous additives for preservation solutions include carbon monoxide (CO), hydrogen sulfide (H ₂ S), and nitric oxide (NO). Each of these molecules interacts with circulating metals, enhancing cellular signaling ( ). These have also been shown to be protective for the endothelium during organ preservation ( ). In addition, microcirculatory vasodilation improves tissue perfusion. Organs preserved with CO showed reduced apoptosis, whereas the molecules H ₂ S and NO are potent vasodilators, which act to enhance tissue microperfusion ( ; ). Investigation of the use of mesenchymal stem cells has also been a recent area of interest. These multipotent stem cells can be obtained from both adult and fetal stromal tissue and act to facilitate damaged tissue repair. These stem cells are capable of secreting numerous factors that can affect the local immune system, enhance angiogenesis, prevent reactive oxygen species production and cellular apoptosis, and stimulate survival, proliferation, and differentiation of resident tissue cells ( ).

Reactive oxygen species are a major contributor to the ischemia–reperfusion injury observed in organ transplantation, with the graft mitochondria being the largest source of reactive oxygen species during static cold storage and reperfusion. Thus various additives have been studied to reduce mitochondrially derived reactive oxygen species. As previously mentioned, allopurinol present in UW solution inhibits xanthine oxidase–derived reactive oxygen species, glutathione is present in both UW and Celsior solutions to serve as a cellular redox buffer, and in HTK solution tryptophan acts as a reactive oxygen species scavenger ( ). A mild uncoupling of oxidative phosphorylation, as is observed with 2,4-dinitrophenol, has been shown to result in a lower mitochondrial respiratory rate, preservation of adenosine triphosphate, and less reactive oxygen species generation ( ). In addition, novel antioxidants combine the cation triphenylphosphonium (TPP+) with derivatives of ubiquinol (MitoQ) or plastoquinone (SkQ) to result in some of the most advanced mitochondria-targeted antioxidants ( ). These additives have been shown to increase intramitochondrial antioxidants more than 1000-fold compared with the extracellular compartment ( ).

Machine perfusion techniques

While the earliest transplants were facilitated by organ preservation via perfusion techniques, these were widely replaced by static cold storage after the success of the preservation solutions ( ). However, there has been an ever-increasing interest in machine perfusion techniques, as there is evidence that there may be less graft failure for organs from marginal donors, thus enlarging the potential donor pool to help meet transplant needs ( ). Several different temperature ranges have been studied given the balance that must be achieved between oxygen delivery and cellular metabolism that is experienced within each temperature range. The machine perfusion techniques mitigate the negative effects of cold ischemic time as well as ischemia-reperfusion injury ( ). However, the use of machine perfusion techniques can be expensive and technically more difficult. For example, the dual blood supply of the liver necessitates cannulation of both the hepatic artery and portal vein.

Hypothermic machine perfusion occurs at temperature of 0°C to 12°C, since above 12°C energy-dependent enzymatic activity increases ( ). Perfusion within this temperature range does not require significant oxygen-carrying capacity (i.e., erythrocytes and/or hemoglobin-based oxygen carriers), and preservation solutions are able to be used as the perfusate because they provide adequate substrates for continued adenosine triphosphate synthesis ( ). Midthermic machine perfusion occurs within a temperature range of 13°C to 24°C. The goal of perfusing in this range was aimed at balancing the negative effects of cold ischemia with the increased oxygen utilization at normothermic temperatures. One of the main benefits is the decreased perfusate viscosity, which allows for improved microcirculatory perfusion ( ). Subnormothermic machine perfusion utilizes temperatures between 25°C and 34°C. One of the main applications of subnormothermic perfusion is for controlled oxygenated rewarming after static cold storage of organs. This allows for gradual warming of the organ until within the subnormothermic range. Normothermic machine perfusion occurs between 35°C and 38°C, and at these temperatures perfusates based on concentrates of red blood cells, plasma, nutrients, cofactors and insulin, antibiotics, electrolytes, and buffers are required ( ). The benefits of perfusing within the normothermic range include the avoidance of hypothermia altogether and monitoring of synthetic organ function such as bile secretion by the liver, since bile synthesis is arrested during hypothermia ( ).

Pathophysiology

End-stage renal disease (ESRD) in the pediatric patient has significant effects on growth, metabolic homeostasis, cardiovascular function, and neurologic development. Chronic acidosis, hyperparathyroidism, and electrolyte imbalance (sodium, potassium, calcium, phosphorus, and magnesium) occur secondary to the kidney’s inability to excrete metabolic waste products. Anemia is common because as renal function fails, erythropoietin production decreases. The renin angiotensin system increases secondary to a decrease in renal perfusion. Hypertension, left ventricular hypertrophy, diastolic dysfunction, and hyperlipidemia are known cardiovascular consequences of ESRD. With a decreased ability to clear free water and sodium, volume overload is common. As glomerular filtration rate decreases, phosphorus levels increase. The elevated phosphorus binds to the serum calcium and magnesium, resulting in hypocalcemia, hypomagnesemia, and an increase in parathyroid hormone (PTH). Fractures in children can occur as calcium is leached from the bones secondary to the effect of PTH. Increased levels of PTH coupled with chronic metabolic acidosis and vitamin D deficiency can result in renal osteodystrophy. Developmental delay and seizures can also occur. Growth is impaired secondary to protein and calorie malnutrition, anemia, growth hormone resistance, vitamin D deficiency, chronic acidosis, and renal bone disease. Linear growth impairment may be further affected by the chronic use of corticosteroid therapy to treat an underlying disease state causing the ESRD.

Indications for transplantation

In children, the most common primary diseases causing renal failure are congenital or inherited in nature (renal dysplasia, obstructive uropathy, reflux nephropathy) and acquired glomerular diseases (focal segmental glomerulosclerosis). Educational guidelines were published in 1998 by the Pediatric Committee of the American Society of Transplantation on the indications for pediatric transplantation. It suggested that the following pediatric patients with renal disease receive a kidney transplant: patients with ESRD unresponsive to medical management, patients with growth failure in spite of optimal nutritional management, patients with developmental delay, children with progressive renal osteodystrophy in spite of optimal medical management, and patients who fail to thrive ( ). Age is no longer a contraindication in transplanting children under 2 years of age. Infants who receive kidney transplants have better growth and development than those managed on dialysis.