Dialysis and kidney transplantation in infancy

Kidney replacement therapy for the management of acute kidney injury

AKI occurs in up to 25% of all neonatal and pediatric ICU admissions and is associated with elevated rates of morbidity and mortality. Risk factors for the development of AKI in neonates and infants include immature development of the kidneys combined with exposure to nephrotoxic medications, renal hypoperfusion related to sepsis or hypovolemia, or direct injury to the kidneys from infection, a hypoxic event, or thrombosis. Special populations including very low birth weight infants and those requiring cardiopulmonary bypass or extracorporeal membrane oxygenation have also been shown to be at higher risk for the development of AKI.

The initial treatment of AKI consists of medical management with a focus on supportive therapy and resolution of the inciting event. For sequela of AKI unresponsive to medical management, such as electrolyte disturbances (hyperkalemia, acidosis), fluid overload and the associated cardiovascular manifestations, or an inability to provide full nutrition, KRT is indicated. ^, Another indication for KRT is an infant born with an inborn error of metabolism leading to hyperammonemia. Elevated ammonia levels (>200 μmol/L) are neurotoxic and associated with poor neurocognitive outcomes, whereas rising levels (>800 μmol/L) can lead to cerebral edema and death. Acute management of hyperammonemia, for which consensus guidelines have been published, includes cessation of protein intake and introduction of intravenous glucose and lipids for neonates with ammonia levels that are elevated for age. Initiation of a nitrogen scavenger medication is indicated for ammonia levels > 150 μmol/L or rapidly rising levels or for neonates with neurologic sequela. For neonates with ammonia levels > 400 μmol/L, levels < 400 μmol/L but not responding to medical therapies, or with clinical concern for the development of neurologic involvement, rapid reduction with the use of KRT is necessary to prevent neurologic damage. Ammonia levels should be reduced to <200 μmol/L with the use of KRT prior to discontinuation of the treatment. Close monitoring for rebound hyperammonemia is essential, especially when using HD. Ammonia is a small, non-protein-bound molecule (17 Da) that is readily removed with KRT. Depending on the patient characteristics and the resources available at the treating facility, treatment may be initiated with HD followed by continuous clearance with CKRT if needed, or CKRT can be used preferentially to effectively decrease ammonia levels. In centers where extracorporeal KRT is not available, PD should be used initially to decrease ammonia levels, with consideration for transfer to a center with HD or CKRT if levels are not decreasing rapidly. ^,

Kidney replacement therapy for the management of chronic kidney disease

The main etiology resulting in ESKD in children < 1 year of age is congenital anomalies of the kidneys and urinary tract (CAKUT), which makes up approximately 55% of all infantile ESKD diagnoses. This includes infants with obstructive uropathy (e.g., posterior urethral valves), renal dysplasia or hypoplasia, and reflux nephropathy. The second most common etiology consists of cystic or genetic diseases such as congenital nephrotic syndrome and autosomal dominant or recessive polycystic kidney disease. Indications for the provision of KRT for management of CKD/ESKD are similar to those for AKI and include the inability to medically manage fluid balance and nutritional status, as well as treatment resistant electrolyte and acid-base abnormalities.

Continuous kidney replacement therapy

CKRT is a 24-hour continuous extracorporeal form of dialysis utilized in ICUs for infants and children who may be hemodynamically unstable or who may require an extracorporeal dialysis therapy for other reasons (e.g., recent abdominal surgery, omphalocele). With this modality, a CKRT machine is set up at the patient’s bedside and can be connected to an extracorporeal membrane oxygenation circuit or directly to the patient through a double-lumen HD catheter. The CKRT machine pulls blood from the patient at a slow, constant rate, which decreases the risk of hypotension that can occur secondary to abrupt or large fluid shifts with HD. The blood is then run through a filter for removal of fluid and solute (e.g., potassium, urea, phosphorus) via diffusion and/or convection, based on one of three types of CKRT prescriptions, and returned back to the patient. Continuous venovenous hemofiltration utilizes convection to clear solute without the use of dialysis fluid. Continuous venovenous hemodialysis incorporates the use of dialysis fluid to clear solute via diffusion, whereas continuous venovenous hemodiafiltration combines the two methods to use both diffusion and convection ( Fig. 12.1 ). Diffusion is the movement of small to intermediate molecular weight molecules across a semipermeable membrane from an area of higher concentration to lower concentration. Convection is the mass movement of solute that accompanies fluid across a semipermeable membrane (termed solvent drag) from an area of high pressure to low pressure. More intermediate and large molecular weight molecules can be cleared with convection compared with diffusion ( Fig. 12.2 ). In all types of CKRT, fluid removal (termed ultrafiltration) can be managed precisely by the medical team for gradual alterations in fluid balance to maintain cardiovascular stability and adequacy of nutritional support. CKRT is utilized for management of AKI until signs of kidney recovery are present or in patients with ESKD as a bridge to long-term dialysis with either HD or PD. ^,

Despite the benefits, there are several disadvantages of CKRT. Clearance is nonselective; therefore, beneficial electrolytes and nutrients accompany the waste products that are removed throughout the treatment. Although this is the case for all dialysis modalities, the impact is more significant with CKRT as a result of the continuous nature of the therapy, leading to potential difficulties with nutrition and bone and mineral management. Typically, protein, electrolyte, and vitamin (B ₁ , B ₆ , B ₉ , C) supplementation is required along with close monitoring of trace elements. When not optimally managed, the protein-energy wasting related to CKRT can lead to poor weight gain and ultimately malnutrition, which in turn has been associated with higher mortality rates than what is experienced by those with an ideal body weight. ^, Ideally, CKRT should be used for a short duration to prevent excessive removal of these products, with special care taken in the design of the nutrition plan for each patient to ensure that the appropriate replacement nutrients are provided.

Other disadvantages of CKRT include the need for central venous access and anticoagulation. An effective central venous access that facilitates the performance of dialysis can be difficult to obtain and maintain in infants due to their small vessel size. It may result in long-term vascular injury and requires close monitoring for signs of infection or thrombosis. The therapy is time intensive and requires specially trained nurses, generally in a one-to-one patient-to-nurse ratio. To prevent blood clotting in the CKRT circuit during treatment, anticoagulation is generally required (except in the case of infants with substantial alterations of their coagulation status) and can lead to hematologic complications. A commonly used anticoagulation regimen consists of regional citrate and calcium, which has the advantage of acting locally only in the CKRT circuit but cannot be used in certain circumstances (e.g., infants with liver failure). Alternatives include systemic anticoagulation with continuous heparin or bivalirudin, therapies that may be associated with an increased risk for bleeding in critically ill infants. Initiation of CKRT can also precipitate hypotension or a bradykinin release syndrome, which is associated with certain filter membranes and can lead to tachycardia, hypotension, anaphylaxis, and possible death. Strategies to decrease the risk for these potential complications have been published.

Lastly, despite the frequent off-label use of CKRT in infants and young children, the current CKRT machines in the United States are only approved by the Food and Drug Administration for pediatric patients ≥ 20 kg. The majority of the CKRT circuit volumes far exceed 10% of the total blood volume for infants and require a blood prime to be used during the initiation of each CKRT circuit to prevent hemodynamic instability. Smaller filters are now available for children 8–20 kg in weight (HF20 filter), which decreases the need for a blood prime in some, but not all, infants. Newer technology has, thankfully, resulted in the development of three small but highly effective extracorporeal volume CKRT machines made specifically for neonates and infants. The Cardiac and Renal Pediatric Dialysis Emergency Circuit (CARPEDIEM), Newcastle Infant Dialysis Ultrafiltration System (NIDUS), and the Aquadex dialysis machine all significantly decrease the need for blood product exposure in small infants. ^{, ,}