NN&I - June 2010

Transplant Update 28 Nephrology News & Issues June 2010Subscribe to our free eNewsletter at www.nephronline.com Transplantation and autosomal recessive polycystic kidney diseaseBy Jennifer Jackson, MD, Laurence Greenbaum, MD, and Allan D. Kirk, MD, PhDRenal transplantation is a lifesaving treatment for children with kidney failure, including children with auto -somal recessive polycystic kidney dis- ease (ARPKD). The disease occurs in one of about 30,000 births. In addi-tion to renal abnormalities, extra-renal manifestations lead to severe morbid -ity and mortality in ARPKD. In the neonatal period, pulmonary disease is the most common cause of mortal-ity. Later in life, many patients develop liver disease, which varies in severity and onset. Previously thought to be a fatal condition, the prognosis for chil -dren with ARPKD has improved dra- matically. Twenty years ago, only half of the children born with the disease survived to their tenth birthday. Now it is 85%. Despite this improvement in outcome, there are unique issues that affect not only survival, but also the growth and development of children with ARPKD that must be considered to guide these children safely to renal transplantation. Background Mutations in the PKHD1 gene (MIM 606702) are responsible for the phe-notypic abnormalities in ARPKD. The severity of the disease varies depend-ing on the type of mutation and the degree of involvement of both copies of the gene. If both genes are severe-ly affected, the infant is unlikely to survive the neonatal period. Children with less severe mutations of one or both genes have a much better progno-sis. Mutations in the PKHD1 gene also cause the liver disease in ARPKD. In fact, some children with PKHD1 muta- tions may have severe liver disease, but very mild kidney disease. The immediate life-threatening issue for infants with ARPKD is the severity of lung immaturity. Lung immaturity is caused in part by insufficient amni-otic fluid, which is produced by the kidneys, due to the poor prenatal renal function. The severely enlarged kidneys also further limit pulmonary function by impairing diaphragmatic excursion and preventing adequate lung expan -sion. Mortality in the neonatal period can be as high as 30% to 50%. If an infant with ARPKD survives this critical period, kidney failure becomes the next most prominent life-threatening issue. Timing of the transplant Patients with ARPKD often develop kidney failure at a young age. However, immediate transplantation is often not possible because of the infant's small size. Most patients with ARPKD experi-ence growth retardation. The infant's weight can be misleading because of the disproportionate weight of the mas-sive kidneys, which can weigh more than 300 g each. These large dysfunc-tional kidneys are filled with thousands of microscopic cysts. For a successful renal transplant, the goal is to provide adequate nutritional support to allow the child to grow to approximately 10 kg. At this size, the child achieves the hemodynamic capacity to reliably per -fuse an adult-sized kidney, thus limit -ing the chance of graft thrombosis, and acute tubular necrosis due to hypop-erfusion or hemodynamic instability upon reperfusion. Additionally, with this growth, for the peritoneal cav -ity can accommodates the new kid- ney without undue respiratory com -promise. Reaching this goal can be challenging, as the large kidneys not only crowd the chest cavity, but also compress the stomach, which can limit caloric intake. Despite receiving transplants at a younger age, children with ARPKD enjoy similar survival as other kidney transplant recipients. Since the ability to manage the complications of kidney disease in small children has improved, children are living longer, and as a result, the liver disease associated with ARPKD is becoming more evident. Progressive scarring of the liver leads to portal vein hypertension and gastroin -testinal bleeding in approximately 80% of patients who receive a renal trans-plant for ARPKD. Infections are anoth -er serious concern for this transplant population. Children who had received a kidney transplant due to ARPKD are twice as likely to die from overwhelm- ing bacterial infection than children receiving kidney transplants for other The authors are physicians from Children's Health-care of Atlanta and the Emory Transplant Center at Emory University in Atlanta. Transplant_NNI0610_5.indd 28 5/14/10 4:47:56 PM