Congenital Kidney Abnormalities: Diagnosis, Management, and Palliative Care Jennifer N.

Cohen and Steven Alan Ringer NeoReviews 2010;11;e226-e235 DOI: 10.1542/neo.11-5-e226

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://neoreviews.aappublications.org/cgi/content/full/neoreviews;11/5/e226

NeoReviews is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 2000. NeoReviews is owned, published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2010 by the American Academy of Pediatrics. All rights reserved. Online ISSN: 1526-9906.

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

Article

renal disorders

Congenital Kidney Abnormalities:

Diagnosis, Management, and Palliative Care
Jennifer N. Cohen, MD,* Steven Alan Ringer, MD, PhD*

Abstract
This article describes major kidney disorders of genetic origin and disordered embryonic development. The most common disorders, including polycystic kidney disease and the various forms of renal dysplasia, are discussed and contrasted, including identiable abnormalities on prenatal and postnatal evaluation, management in the neonatal period, and evaluation and management in childhood. For the most severely affected fetuses and newborns, a comprehensive approach to prenatal counseling and palliative care of the newborn is described.

Author Disclosure Drs Cohen and Ringer have disclosed no nancial relationships relevant to this article. This commentary does not contain a discussion of an unapproved/ investigative use of a commercial product/ device.

Objectives

After completing this article, readers should be able to:

1. Describe the major types of kidney diseases due to genetic abnormalities or congenital malformations. 2. Delineate the basics of normal renal embryology and the potential mechanisms responsible for abnormalities. 3. Discuss the presentation, evaluation, and management of polycystic kidney disease and various types of renal dysplasia. 4. Outline the need for comprehensive prenatal counseling and palliative care for fetuses and newborns with severe forms of renal disease.

Introduction
Several kidney disorders that present during fetal life or in the newborn period are either congenital malformations or part of an inherited disorder. The malformations are usually sporadic, often with a poorly dened pathogenesis. The inherited lesions, in contrast, frequently have clear inheritance patterns such as autosomal dominant or recessive, and in many cases, the locus of the abnormal gene and the associated abnormal protein have been identied. The Table lists the major anatomic abnormalities in these categories. Although there is no curative therapy for these disorders, considerable care can be required, including monitoring and renal replacement, as well as signicant focus on the critical comorbidities and abnormalities in renal function. The most severe of these conditions are incompatible with prolonged survival, and the care needed for affected patients requires special considerations for comfort of the patient and support of the family.

Pathogenesis
Following the development and regression of the early pronephros and the intermediate mesonephros (a remnant of which forms the Wolfan or mesonephric duct), normal development of the true kidney begins with the appearance of the metanephros in the fth week of gestation (Fig. 1). The metanephric mesenchyme forms at the same time as the ureteric bud grows out of the mesonephric duct, and these two early structures reciprocally interact and promote the differentiation of each other. The mesenchymal cells proliferate and differentiate, with part of them ultimately forming the nephrons, including the glomeruli and distal tubules. The rest of the mesenchyme develops into the renal interstitium. At the same time, the ureteric bud branches and differentiates, ultimately forming the collecting ducts, renal pelvis, and ureter. Renal agenesis, complete congenital absence of the kidney, is the most extreme form of
*Divisions of Newborn Medicine, Brigham and Womens Hospital, Childrens Hospital Boston, Harvard Medical School, Boston, Mass. e226 NeoReviews Vol.11 No.5 May 2010

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

Table.

Congenital Renal Anomalies

Prenatal/Ultrasonographic Findings Genetic Associations Notes Complete absence of kidney(s) Extreme form of renal dysplasia Early, large, thin-walled cysts Often seen in syndromes Incidence: 1 in 1,000 births (visible by 20 weeks gestation), with identied gene (unilateral) 1 in 5,000 echogenic kidneys, usually mutations: eg, EYA1, SIX1 (bilateral) large kidneys, sometimes small (branchio-oto-renal), and noncystic SOX9 (camptomelic dysplasia), PAX2 (renal coloboma), 22q11 (DiGeorge) Dominant form rarely presents Large echogenic kidneys, Dominant: Mutations in in newborn; usually includes numerous cysts, not visible genes for polycystin associated hepatic cysts and until later in gestation proteins PKD1 brosis (chromosome 16) or PKD2 (chromosome 4q) Recessive: Mutations in PKHD1 (chromosome 6p21)

Disorder Renal agenesis Multicystic dysplastic kidneys

Polycystic kidney disease: Autosomal dominant Autosomal recessive

renal dysplasia, a spectrum of disorders of variable severity. Agenesis occurs when the ureteric bud fails to develop from the precursor Wolfan duct, and no kidney ever forms. If the bud is atretic or the reciprocal interaction with the mesenchyme occurs abnormally, the result is renal dysplasia, in which the renal architecture is distorted and the organ is comprised of primitive ductules, glomeruli, and metaplastic cartilage. Dysplastic kidneys may be noncystic and small (noncystic dysplastic kidney) or large and lled with numer-

Figure 1. Schematic of normal kidney development.

ous cysts (multicystic-dysplastic kidney [MCDK]). Because the aberrant developmental process often includes abnormalities in the branching and differentiation of the ureteric bud, dysplastic kidneys frequently are associated with ipsilateral dysplasia of the collecting system. Because dysplastic kidneys tend to involute over time, it is likely that some cases identied as renal agenesis evolved from an abnormally formed organ Some cases may arise from a primary defect in the ureteric bud, resulting in a completely abnormal kidney. In many cases, however, some normal nephrons are formed, but because the total number of nephrons is reduced, the mass of functioning tissue also is reduced. This leads ultimately to glomerular hypertrophy and hyperltration, with resultant systemic hypertension, and further injury and reduction in renal function. The underlying cause of the dysplasia often remains unknown. A number of genetic causes have been identied, including mutations in genes known to play a role in ureteric bud development, such as EYA1, SIX1 (associated with branchio-oto-renal syndrome), SOX9 (campomelic dysplasia), and PAX2 (renal coloboma syndrome) and deletions in 22q11 (DiGeorge syndrome) as well as several other genetic syndromes in which the phenotype includes dysplastic kidneys. It is not clear why or how some of these syndromes result in only unilateral dysplasia. Severe obstruction of the collecting system can result in cystic changes and disrupted nephrogenesis, which may mimic the ultrasonographic appearance and clinical
NeoReviews Vol.11 No.5 May 2010 e227

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

presentation of primary dysplasia. The obstructive cases differ in the mechanism of development and in presentation. The renal cysts do not grow as large as those typically seen in MCDK, making the ultrasonographic appearance somewhat different. The histology does not include the typical cartilage metaplasia, and inammatory changes are present in animal models.

Polycystic Kidney Disease

Epidemiology
Polycystic kidney disease (PKD) occurs as two distinct genetic disorders: autosomal dominant (ADPKD) and autosomal recessive (ARPKD) forms. The incidence of ADPKD is 1 in 1,000 live births, making it the most common of the inherited disorders. Most cases are caused by abnormalities in the protein polycystin1 as a result of mutations in the PKD1 gene on chromosome 16, although the role of this protein is not clear. A small percentage of cases are due to abnormalities in polycystin2, caused by mutations in the PKD2 gene on chromosome 4q. ADPKD, in which bilateral renal cysts form and progress, rarely presents in the neonate. When it does, the presentation is similar to that of the recessive form, with a broad range of severity from asymptomatic through severe renal dysfunction, along with variable degrees of hypertension. As a result, the parents of any baby who has PKD should themselves undergo ultrasonographic examinations to rule out the small possibility of the disease being the autosomal dominant form. Many patients have no renal symptoms through childhood, but in the long term, more than 50% deteriorate progressively to end-stage disease, often over decades. ARPKD occurs in about 1 in 20,000 to 40,000 live births, and it is one of the most common renal cystic diseases in childhood. This form is due to mutations in the PKHD1 locus, which maps to chromosome 6p21 and can be identied on testing. Due to the large size of the gene and the fact that any of multiple mutations may be responsible for causing the disease, current testing is successful in identifying only about 60% of mutations, but it is hoped that renements will be forthcoming. In addition, it is possible that the identication of different mutations may help explain clinical variability, as the roles of various protein products for which the gene codes are identied.

Clinical Presentation
The clinical presentation includes polycystic kidneys, congenital hepatic brosis, and some degree of biliary dysgenesis, although hepatic symptoms are uncommon
e228 NeoReviews Vol.11 No.5 May 2010

in neonates. The renal manifestations vary in severity but generally include large kidneys that appear echogenic on prenatal ultrasonography, with initially normal amniotic uid volume (Fig. 2). Characteristically, the kidney is lled with multiple small cysts that are not easily visible on early ultrasonography and only appear as gestation proceeds, although the kidneys are large and echogenic. The gross appearance of the kidney mirrors the ultrasonographic ndings, with numerous small cysts throughout the parenchyma. Ultrasonographers state that if denite cysts are noted at or before 20 weeks gestation, the disease process is much more likely to be MCDK than PKD. In more severe cases of ARPKD, the amniotic uid volume declines as gestation progresses, and in many cases, oligohydramnios is present by late in the second trimester. These most severely affected fetuses may develop the Potter phenotype (Fig. 3), with pulmonary hypoplasia and a small chest, beaked and attened nose, and deformations of the extremities and spine. This phenotype is most likely to develop when severe oligohydramnios is present by mid-gestation. In these instances, the degree of lung hypoplasia may be critical, making extrauterine survival impossible. Among a recent large cohort of patients for whom prenatal diagnosis was available, the early mortality due to ARPKD was slightly more than 25%, primarily as a result of respiratory failure and sepsis. A total of 41% of patients required mechanical ventilation after birth, and almost 12% of the survivors developed chronic lung disease. Longer term, 42% developed chronic renal insufciency, and more than 25% of patients manifested slowed or delayed growth in infancy and early childhood, related to poor renal and pulmonary function. Importantly, the median age of the patients was 5.4 years, demonstrating that survival at least through childhood is possible with this disease. Hyponatremia occurred in a large percentage of affected patients, particularly during the neonatal period. Severe hypertension, the most common comorbidity, developed in about 65% of patients, and in almost all those who had hyponatremia. This reects the likely pathogenesis of the hypertension, which is hypothesized to result from an underlying dysregulation of sodium reabsorption in the abnormally formed collecting ducts that, in turn, results in hyponatremia and an expanded intravascular volume. The ultimate result is severe hypertension but with low plasma renin concentrations. Only about 15% of patients in the modern cohort developed periportal brosis and portal hypertension,

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

Figure 2. Ultrasonographic and gross appearance of common renal anomalies. Polycystic kidney disease is identied on ultrasonography (A) as large echogenic kidneys, with multiple small cysts evident as gestation proceeds, and ndings are mirrored in the gross appearance of the kidney (B). Multicystic dysplastic kidneys also are large, but the ultrasonographic appearance (C) and gross anatomy (D) includes multiple large cysts that are evident early in gestation.

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

NeoReviews Vol.11 No.5 May 2010 e229

renal disorders

congenital kidney abnormalities

Figure 3. Fetuses that have the Potter phenotype.

although the incidence of this complication increased as patient age advanced. An association had been noted previously between increased rates and severity of hepatic disease among patients who had milder renal disease (and perhaps longer survival), but this relationship has not been noted consistently among modern cohorts.
e230 NeoReviews Vol.11 No.5 May 2010

Management
For the most severely affected fetuses and babies, survival after birth may be impossible. In these cases, specialized palliative care should be offered. For the remaining cases, acute management in the neonatal period is supportive, focusing on respiratory

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

support and evaluation and management of renal dysfunction. Hypertension often is severe and may require multiple antihypertensive medications for treatment or continuous intravenous infusions of these agents. Despite the theoretical possibility that the associated hypertension is part of a low-renin state, current therapy primarily includes angiotensin-converting enzyme inhibitors and calcium channel blockers. As the children grow, attention must turn to the special nutritional needs resulting from renal insufciency, and the progressive decrease in renal function commonly makes dialysis or kidney transplantation necessary. Monitoring for the progression of hepatic disease and therapy for the complications of portal hypertension become necessary.

signs or symptoms in the neonate, other than the presence of a large abdominal mass, which rarely can cause mechanical problems. It is, of course, diagnosed typically on prenatal ultrasonography. Data pooled from a large number of studies indicate that the disorder occurs more often on the left side (53%) and in males (59.2%). The contralateral kidney also can be affected. Between 26% and 46% of kidneys are hypertrophied, and between 20% and 43% have a urinary tract abnormality, primarily vesicoureteral reux, although more severe anomalies may occur, including obstruction leading to renal failure.

Management
Following a prenatal diagnosis, postnatal ultrasonography should be undertaken to rule out associated urinary tract anomalies and to conrm the original diagnosis. Prophylactic antibiotics (usually amoxicillin 25 mg/kg per day) are administered pending this testing. Many practitioners recommend waiting for at least 1 week after birth to perform this study to avoid false-negative results due to normal oliguria, but others have found that studies performed as early as 48 hours after birth are reliable, especially if repeated at about age 6 weeks. The recommended plan for later ultrasonographic study remains controversial, with opinions ranging from obtaining studies only if other anomalies are identied to recommending annual ultrasonography and laboratory testing. The need for voiding cystourethrography (VCUG) also is a matter of debate, unless ultrasonography yields abnormal results. Most practitioners recommend routine VCUG, although several studies have concluded that normal ultrasonography results make the likelihood of any signicant reux very low and that VCUG only be performed if a urinary tract infection occurs. Magnetic resonance imaging ultimately may replace VCUG for diagnosing structural anomalies and reux and for assessing renal function. Until this modality is fully developed, function typically is assessed by renography. A high percentage of MCDK involutes over months to 10 years. There have been anecdotal reports of an increased risk of Wilms tumor or other malignancies in MCDK, leading many practitioners to perform nephrectomies routinely. Recent analyses have demonstrated that any increase in risk is minimal, if present at all, and many centers are abandoning this practice in favor of monitoring with periodic ultrasonography. Surgical intervention for hydronephrosis due to obstruction is based on the criteria for that condition. The major risk in MCDK is the development of chronic renal failure, which develops in 12% to 50% of
NeoReviews Vol.11 No.5 May 2010 e231

Dysplastic Kidney Disease

Epidemiology and Clinical Presentation
Dysplastic kidney disease is common, occurring as unilateral disease in 1 in 1,000 births and bilaterally in 1 in 5,000. It is the most common cause of an abdominal mass in the newborn. The condition typically is diagnosed on prenatal ultrasonography (Fig. 2). The kidney is highly echogenic or bright, with multiple large, thin-walled cysts that typically are seen by 20 weeks gestation, in distinction from polycystic disease. These cysts are characteristically separate and distributed randomly throughout the renal parenchyma. Grossly, the kidneys are dysplastic, with little normal architecture evident, and the multiple large cysts are seen easily throughout the entire organ. Most often, an affected kidney is signicantly enlarged, and this large irregular mass may be easily palpated in the newborn. Both the cysts and overall enlargement may become more pronounced as gestation proceeds, but many dysplastic kidneys involute, even during the prenatal period. Unlike cases of obstruction of the lower collecting system, it can be difcult to identify the renal pelvis or ureter on ultrasonography Bilateral disease frequently is severe, and the prognosis typically is poor, with progression to severe oligohydramnios and pulmonary hypoplasia, resulting in the Potter sequence, and a low likelihood of survival after birth. This outcome usually is associated with ndings of either marked renal enlargement or involution during late pregnancy. Some cases of bilateral disease are less severe and survival is possible. Dialysis is necessary for chronic renal failure in affected children, and they require specialized care for nutrition. As the children grow, renal transplantation becomes a possibility. Unilateral disease usually presents with no specic

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

patients who have apparently normal contralateral kidneys. Serum creatinine is monitored routinely to identify developing renal failure. Hypertension is an uncommon occurrence, and blood pressure monitoring is recommended only as part of regular care.

the baby can spend with the family before dying, while causing no harm and ensuring that he or she is comfortable and free of pain. This also means that the needs, goals, and expectations of the family surrounding the birth and death of the child should be explored and outlined carefully.

Palliative Care for Fatal Renal Anomalies

In some clinical situations, antenatal evaluation provides evidence that the disease severity is so great that extrauterine survival will not be possible. These are primarily cases involving a drastic reduction in amniotic uid during the 18th to 24th weeks of gestation, the critical period of lung development. Diagnoses include bilateral renal agenesis, bilateral MCDK, severe polycystic disease, and cases in which bladder outlet obstruction occurs early in gestation. When serial ultrasonography demonstrates persistent severe oligohydramnios during this period, lung development almost universally is impaired profoundly. Even if the baby can be resuscitated successfully at birth, the absence of proper alveolar development makes it necessary to use extremely high ventilator pressures to have any chance of gas exchange. In the presence of abnormal lung architecture, it becomes impossible to achieve sufcient support without developing recurrent or persistent uncontrollable air leaks, and hypoxia and hypercarbia cannot be corrected. These attempts at support, thus, result only in pain and suffering without changing the outcome. The high risk to the patient in the absence of any benet makes it necessary to consider limiting therapeutic intervention. In some cases, families elect not to terminate pregnancies even after receiving a diagnosis that is not compatible with extrauterine survival, either because of their personal beliefs or a strong emotional need to see and hold their baby, even briey, while he or she is alive. In other cases, prenatal diagnosis is not made until late in gestation, well after the timeframe during which termination would be an option. In these situations, comfort measures should be addressed and a plan of care formulated.

Development of a Care Plan

At our institution, we begin multidisciplinary meetings with the family, starting as soon as the diagnosis and prognosis are evident. Usually, these discussions begin after 30 weeks gestation, but in some cases, they may begin as early as 25 weeks gestation. Referrals come from either our maternal-fetal medicine service or from our afliated Childrens Hospitals Advanced Fetal Care Center, both of which receive many patients from outside institutions and providers. Our palliative care team for families facing these situations includes a neonatologist, neonatal intensive care unit (NICU) or obstetric nurse, social worker, and chaplain. The parents are free to include supportive family members as they wish. During the rst meeting, the team asks the family to explain what their understanding is about the diagnosis and what their experience with this pregnancy has been so far. During that rst meeting, we clearly discuss the lethality of the diagnosis but also recognize and understand that many families have not yet given up hope for survival for their child, particularly if the diagnosis has been made only recently. Many families report to us that although they are aware of the consequences of the fetus diagnosis, they still try to hold on to the possibility that the lungs are not as poorly developed as the medical team expresses or that they believe that a miracle will take care of their baby. It is important to acknowledge and respect such hope. Rather than engaging in a fruitless discussion about the relative merits of medical evidence and the likelihood of miracles, it is better to support the family emotionally and to stress that, in fact, only a true miracle or departure from the laws of science could result in a different outcome. This does not prevent us from stressing that we strongly recommend and encourage that care be focused only on comfort measures that will not involve airway and ventilatory support. Exploring the familys belief system often allows the team to understand more clearly how we can assist them to process the diagnosis and prognosis. Engagement of the familys clergy may be helpful and should be considered. It often is true that all issues cannot be resolved at the initial meeting and that the family may not be ready to embrace the teams recommendations fully. If necessary, we leave these issues open but make a plan to readdress

Evaluation of Care Goals

Once a clearly lethal prognosis with severe pulmonary hypoplasia is determined, direction of care needs to be planned with families. In practice, accomplishing this is a complex task. The evolution of renal disorders discussed previously is such that the severity of the condition may not be apparent at the initial ultrasonography but may become clear with repeat evaluations. This means that the goals of care change dramatically from initially planning for extreme medical intervention and discussions of dialysis and transplant to focus on maximizing time that
e232 NeoReviews Vol.11 No.5 May 2010

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

them at a scheduled follow-up meeting with the family, at which we discuss specic details of the plan surrounding the birth. At our follow-up appointment, we work with the family to create a plan to infuse meaning and respect for the expected infant, attempting to meet the familys wishes about how to make the birth and death of the child the occasion they envision. Most families express their wish for as normal a birthing experience as possible. We discuss ante- and peripartum issues, including birthing classes. As in many institutions, we are developing private birthing classes designed for parents expecting a child who has a severe or lethal anomaly to allow the family to experience some of the normal joys of pregnancy that may be impossible to support in the general classes. We also discuss what type or how much fetal monitoring will occur during labor. We explain that in the context of severe oligo/anhydramnios, the risk of cord compression is high during labor and delivery, which may lead to signicant and concerning decelerations and potentially umbilical cord compromise. We make sure parents realize that this might lead to demise during labor or delivery. We help them accept this risk and point out that fetal monitoring generally is used to identify abnormalities that place a baby at risk, so an emergency cesarean section can be performed. We reiterate that this does not apply to their baby, for whom the grave outcome is certain under any circumstances. We strongly recommend against exposing the mother to the pain and potential risks of complications from a cesarean section. Many parents still might accept these risks to ensure that they have a chance to see their baby alive, even when we explain that such emergency procedures very often require general anesthesia for the mother during the time when she wishes to be awake and present for the short time that her baby may be alive. If possible, we include the mothers obstetrician in the meeting when these issues are discussed or at least make sure that he or she is aware of and agrees with all plans for the conduct of labor and the possible indications for cesarean section, including decisions about the use and extent to which fetal monitoring will be performed. Position of the fetus is another factor that must be considered when planning for delivery. If the fetus is breech, the decision must be made whether delivery will be via cesarean section or an attempted vaginal delivery. When counseling patients, it is important to discuss the risks of breech vaginal delivery and again emphasize the strong possibility of demise during labor or delivery. It is imperative to explore with the family if a live birth is a necessity to them or if they are comfortable with the

possibility of demise before delivery. If a live birth is of utmost importance, breech vaginal delivery is probably not the correct option, and cesarean section may be the chosen route of delivery.

Formulation of Ethical Decisions

It is important to recognize the complexity of the ethical decision-making surrounding these cases and to communicate it fully to all members of the care team. Considering only the ultimate prognosis for the baby may make it hard to see any benet to the mother that justies the risks of operative delivery. However, the equation rightly includes both the baby and the parents, physically and emotionally. The fully informed parents may choose a cesarean section because it maximizes their sense of doing the best possible and allows them irreplaceable time with their still living baby, which provides them with emotional benets that legitimately outweigh the physical risks of the procedure. If a cesarean section is necessary, we have the baby assessed initially by the NICU team and return the baby to the mother while she is still on the operating table. We have been able to place the baby on the mothers chest, with cooperation from the obstetrician and the obstetric anesthesiologist. In some instances, we have placed an intravenous line to facilitate the administration of analgesics and anxiolytic agents, if it appears that the baby has any discomfort or signicant respiratory distress. We discuss such actions beforehand with the family when planning the steps around delivery. An alternative to an intravenous line is sublingual or intranasal drug administration. In one case, we had a mother who was adamant about a trial of intubation for the baby, despite welldocumented severe early oligohydramnios and clearly poorly functioning kidneys. This mother also required a cesarean section. In this case, we intubated the baby at delivery, took the baby to NICU triage for 5 minutes to assess the ability to oxygenate and ventilate, and brought the baby back to the mother in her recovery room on the ventilator without a cardiorespiratory monitor. The family understood that the baby truly had no chance of survival, but the trial of ventilation rewarded them with the feeling that they had done everything that they could possibly try for their son. His two older siblings were able to meet him and have pictures taken, and his mother was able to hold him and even sleep with him on her chest on the ventilator. Throughout this process, the NICU team made sure that the baby was medicated properly and experienced no distress. This case illustrates how the usual ethical considerations need to be expanded to
NeoReviews Vol.11 No.5 May 2010 e233

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

ensure that parental and family emotional needs are met, even while risking a small chance of some discomfort for the baby.

American Board of Pediatrics Neonatal-Perinatal Medicine Content Specications

Know how to diagnose specic anatomic abnormalities of the kidneys and urinary tract in infants. Know the recommended supportive and corrective treatment of anatomic abnormalities of the kidneys and urinary tract in infants. Know how prenatal diagnosis of renal abnormalities affects postnatal management.

Additional Considerations
Other important issues that require clarication and planning before the birth include: who other than the parents will be present at the birth; which family members or friend may be given information regarding the baby; what preference of faith or religion the family has, including whether they would like any specic or hospital clergy to be present at delivery or shortly after birth; and what involvement they would like for siblings and extended family. This process is labor-intensive but no more so than the usual intensive care provided for other critically ill patients, and the absolute number of cases is low. It appears to work best when organized around a specic interdisciplinary team that acquires experience and expertise in these cases. This team not only supports the family but gives aid and counseling to other clinicians.

Suggested Reading
Al-Ahwery S, Al-Asmari A. Multicystic dysplastic kidney: conservative management and follow-up. Ren Fail. 2005;27:189 192 Capisonda R, Phan V, Traubuci J, et al. Autosomal recessive polycystic kidney disease: clinical course and outcome, a single center experience. Pediatr Nephrol. 2003;18:119 126 Chapman A, Gabow P. Hypertension in autosomal dominant polycystic kidney disaease. Kiney Int. 1997;61:S71S73 Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111:10721080 Hains DS, Bates CM, Ingraham S, Schwaderer AL. Management and etiology of the unilateral multicystic dysplastic kidney: a review. Pediatr Nephrol. 2009;24:233241 Ismaili K, Avni FE, Alexander M, et al. Routine voiding cystourethrography is of no value in neonates with unilateral multicystic dysplastic kidney. J Pediatr. 2005;146:759 763 Kaplan B, Fay J, Shah V. Autosomal recessive polycystic kidney disease. Pediatr Nephrol. 1989;3:43 49 Keneko K, Yamashiro Y, Yamataka A, Miyano T. Nephrectomy for multicystic kidneys: a new therapeutic option. Pediatr Nephrol. 2005;20:690 691 Kiyak A, Ylimaz A, Turhan P, et al. Unilateral multicystic dysplastic kidney: single center experience. Pediatr Nephrol. 2009;24: 99 104 Liapis H, Doshi RH, Watson MA, et al. Reduced renin expression and altered gene transcript proles in multicystic dysplastic kidneys. J Urol. 2002;168:1816 1820 Luque-Mialdea R, Martin Crespo R, Cebrian J, et al. Does the multicystic dysplastic kidney really involute? The role of the retroperitoneoscopic approach. J Pediatr Urol. 2007;3:48 52 Roy S, Dillon M, Trompeter R, Barratt T. Autosomal recessive polycystic kidney disease: long term outcome of neonatal survivors. Pediatr Nephrol. 1997;11:302306 Winyard P, Chitty L. Dysplastic and polycystic kidneys: diagnosis, associations and management. Prenat Diagn. 2001;21:924 935 Woolf AS. Unilateral multicystic dysplastic kidney. Kidney Int. 2006;69:190 193 Zerres K, Muecher G, Becker J, et al. Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience and fetal morphology. Am J Med Genet. 1998;76:137144

Conclusions
Abnormal renal development can result from identied genetic abnormalities or sporadic disruptions of normal embryologic mechanisms. PKD in the newborn is primarily of the autosomal recessive type and can be identied by characteristic ultrasonographic ndings during and after birth. Disease severity varies, and long-term sequelae include chronic renal insufciency and systemic hypertension. Most cases ultimately require renal replacement therapy with dialysis or transplantation. Renal dysplasia most commonly presents as MCDK. Unilateral disease is highly associated with abnormalities of the collecting system on the contralateral side, placing the patient at high risk for renal injury and insufciency on that basis. Careful monitoring and assessment of the possible need for corrective surgery is the mainstay of long-term management. Both PKD and MCDK can be bilateral and severe, and the associated lung hypoplasia may be incompatible with extrauterine survival. Institutions should consider a program of specialized antenatal counseling and palliative care for affected patients and their families.

e234 NeoReviews Vol.11 No.5 May 2010

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

renal disorders

congenital kidney abnormalities

NeoReviews Quiz
1. Renal agenesis, complete congenital absence of the kidney, is the most extreme form of renal dysplasia. Of the following, the most likely cause of renal agenesis is the failure of development of the: A. B. C. D. E. Early pronephros. Intermediate mesonephros. Interstitial mesenchyme. Late metanephros. Ureteric bud.

2. Developmental anomalies of the kidney represent either congenital malformations or inherited disorders. Whereas most congenital malformations are sporadic and have a poorly dened pathogenesis, the inherited disorders often have clearly identied abnormal genes and associated proteins. Of the following, the inherited disorder of renal coloboma syndrome is most associated with a mutation in the gene: A. B. C. D. E.

EYA1. PAX2. PKD1. SIX1. SOX9.

3. Polycystic kidney disease (PKD) occurs in two distinct forms, autosomal dominant and autosomal recessive. The autosomal recessive form of PKD is one of the most common renal cystic diseases in childhood. Of the following, the most accurate statement regarding autosomal recessive PKD is that it is: A. B. C. D. E. Accompanied by oligohydramnios and pulmonary hypoplasia in severe cases. Associated with symptoms of biliary dysgenesis in the neonatal period. Caused by a mutation in PKD2 gene on chromosome 4q. Characterized by systemic hypertension from high plasma rennin concentrations. Diagnosed by large uid-lled renal cysts on early fetal ultrasonography.

4. Dysplastic kidney disease is the most common cause of an abdominal mass in the newborn. Of the following, the most accurate statement regarding dysplastic kidney disease is that it is: A. B. C. D. E. Accompanied by an increased risk of Wilms tumor and other malignancies. Associated with progressive development of systemic hypertension. Caused by a mutation in PKHD1 gene on chromosome 6p21. Diagnosed by large uid-lled renal cysts on early fetal ultrasonography. Prevalent as bilateral disease and in females.

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010

NeoReviews Vol.11 No.5 May 2010 e235

Congenital Kidney Abnormalities: Diagnosis, Management, and Palliative Care Jennifer N. Cohen and Steven Alan Ringer NeoReviews 2010;11;e226-e235 DOI: 10.1542/neo.11-5-e226

Updated Information & Services Permissions & Licensing

including high-resolution figures, can be found at: http://neoreviews.aappublications.org/cgi/content/full/neoreview s;11/5/e226 Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://neoreviews.aappublications.org/misc/Permissions.shtml Information about ordering reprints can be found online: http://neoreviews.aappublications.org/misc/reprints.shtml

Reprints

Downloaded from http://neoreviews.aappublications.org. Provided by McMaster University on May 2, 2010