Kymora Scotland, MD, PhD
T. Ernesto Figueroa, MD, FAAP, FACS
BASICS
DESCRIPTION
• Renal dysplasia, hypoplasia, and hypodysplasia are forms of renal dysgenesis; namely, maldevelopment of kidney size, shape, or structure
• Renal dysplasia: Chiefly a histologic diagnosis based on the presence of primitive renal components (ie, ducts) and embryonic mesenchymal cells (ie, cartilage):
– Classification of renal dysplasia:
Total dysplasia: Involves both cortex and medulla; spectrum ranging from aplastic (small and solid) to multicystic (enlarged) kidneys (eg, Multicystic dysplastic kidney [MCDK])
Subtotal dysplasia: Segmental distribution in cortex and medulla
Hereditary: Zellweger and Meckel syndromes
• Renal hypoplasia: Small kidneys that have a normal nephron density with less than normal number of calyces and nephrons and are not dysplastic (1):
– Classification:
With urethral obstruction
Prune-belly syndrome
True oligonephronia
With normal ureteral orifice
With abnormal ureteral orifice
Oligomeganephronia
Segmental (Ask-Upmark kidney)
• Renal hypodysplasia: Small kidneys that have normal nephron density with less than normal number of calyces and nephrons and are dysplastic:
– Classification:
Normal ureteral orifice: With and without obstruction
Ectopic ureteral orifice with or without ureterocele: Lateral, medial, or caudal
With urethral obstruction
Prune-belly syndrome
• Renal development is dependent on the interaction between the ureteric bud and the metanephric mesenchyme
EPIDEMIOLOGY
Incidence
N/A
Prevalence
• Renal dysplasia:
– Unilateral or bilateral in 2–4 per 1,000 births
– Male > Female (1.3:1)
– Male > Female (1.9:1)
• Renal hypoplasia
– Oligomeganephronia:
Male > Female (3:1)
Increased with low birth weight, often present by age 2
– Ask-Upmark kidney:
Male < Female (1:2)
Commonly present ≤10 yr of age
RISK FACTORS
• Vesicoureteral reflux (VUR)
• Posterior urethral valves
• Ureteral abnormalities: Primary megaureter, Ureteropelvic junction obstruction (UPJO), ureterocele
• Prune-belly syndrome
Genetics
• A majority of dysplastic and hypoplastic kidney disorders are sporadic and nonheritable
• Genetic pathways can affect ureteric bud formation, branching morphogenesis within the metanephric blastema, and normal nephrogenesis
• Familial renal adysplasia: Heterogenous autosomal dominant inheritance of renal agenesis, renal dysplasia, MCDK, etc., within 1 family
PATHOPHYSIOLOGY
• Normal metanephric differentiation requires induction via the ureteric bud (1)
• The branching of the collecting system, as well as nephron formation, are determined by the ureteric bud
• Epithelial–mesenchymal interactions and peptide growth factors play a central role in nephrogenesis
• Dysplasia: Histologically manifests as distortion of renal architecture, immature or primitive glomeruli, cartilage, and tubules encircled by fibromuscular cells (primitive ducts):
– Aplastic dysplasia: Region of nonfunctioning parenchyma
Inhibition of nephron development
Increased TGF-β
S-shaped bodies and cysts
Dedifferentiation of renal cells
• Hypoplasia: Normal nephron density despite smaller size, bilateral or unilateral; can be associated with reflux:
– Oligomeganephronia:
Reduction in nephron number and hypertrophy of each nephron
Usually bilateral, but contralateral renal agenesis has been reported
No clear distinction between cortex and medulla, reduced number of renal segments, small renal artery, elongated nephrons
– Ask-Upmark kidney:
Likely secondary to reflux nephropathy
Deep groove(s) on lateral convexity with underlying tubules resembling thyroid tissue
Underdeveloped medulla
Arteriosclerosis and juxtaglomerular hyperplasia
• Hypodysplasia: Most often seen in conjunction with an ectopic ureteral orifice or obstruction; extent of dysplasia correlates with degree of ureteral ectopia:
– Normal ureteral orifice:
With obstruction: Primary obstructive megaureter and UPJO
Without obstruction: Dwarf kidney; according to bud theory is the result of deficient metanephric blastema
– Abnormal ureteral orifice:
Pan-bud anomaly; abnormal budding leads to an ectopic ureteral orifice with thin renal parenchyma and ectatic calyces
Lateral ectopia: Often associated with reflux; rounded calyces are a result of premature termination of calyceal development
Medial or caudal ectopia and ureteroceles: Dilated ureter is the norm with thin renal cortex
– Urethral obstruction:
Position of ureteral orifices correlates with degree of renal dysgenesis in posterior urethral valves (PUV): Orthotopic has normal histology; lateral orifice has hypoplasia; extremely lateral has hypodysplasia
Prune-belly syndrome: Large laterally displaced ureteral orifices with dysplastic kidneys explained by abnormal budding theory
ASSOCIATED CONDITIONS
• Branchio-oto-renal syndrome
• Ectopic ureteral orifice
• Fraser syndrome
• Jeune syndrome
• Kallmann syndrome
• Meckel–Gruber syndrome
• Oral–facial–digital syndromes
• Posterior urethral valves
• Potter syndrome
• Primary obstructing megaureter
• Prune-belly syndrome
• Pulmonary hypoplasia
• Renal coloboma syndrome
• Simpson–Golabi–Behmel syndrome
• Townes–Brocks syndrome
• Uretero pelvic junction obstruction (UPJO)
• Vesico ureteral reflux (VUR)
• Zellweger syndrome
GENERAL PREVENTION
N/A
DIAGNOSIS
HISTORY
• Systemic:
– Failure to thrive, abnormal growth, headache, fever, chills, shortness of breath, nausea, emesis, anorexia, skin pallor, vision change, mental status change
• Renal disease:
– Polyuria, polydipsia, abdominal pain or mass, flank pain, hematuria
• Bladder disease:
– Lower urinary tract symptoms (LUTS), dysuria, nocturia, incontinence
PHYSICAL EXAM
• Abnormal weight or height
• Vital signs: Hypertensive
• Mental status: Encephalopathic
• HEENT: Retinopathy, papillary edema, dehydration
• Lungs: Crackles
• Abdomen: Distention, palpable mass, guarding, CVA tenderness, ascites
• Extremities: Pallor, peripheral edema
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urinalysis: Proteinuria, hematuria, low specific gravity, bacteria
• Urine culture
• Electrolytes, BUN, Cr, K+
– Elevated Cr, hyperkalemia, uremia
Imaging
• Renal bladder ultrasound
– Kidney number and size, pelvicaliectasis, ureteral dilation, presence of cysts or mass, hyperechoic or hypoechoic parenchyma
– Bladder volume, ureterocele
• CT abdomen and pelvis
– Anomalous GU anatomy, presence of dilation, calculus disease
• Static fluid and excretory MR urography
– GU anatomy, renal function, obstruction
• Renal scan
– Split function or obstruction
• Voiding cystourethrogram
• Retrograde pyelography:
– Defines anatomy
Diagnostic Procedures/Surgery
• Cystoscopy may help define anatomic abnormalities
• Renal biopsy
Pathologic Findings
• Gross findings (2)
– Smaller renal size, mass, and contour
– Renal lobulations and cysts
– Pale and firm kidneys
– Duplicated kidney or ureter
– Dilated collecting system
– Ectopic ureteral orifice
– Ureterocele
– Thickened bladder wall
• Histologic findings
– Dysplasia
Always with decreased nephron number
Embryonic mesenchyme
Primitive renal components
Distortion of renal architecture
Primitive glomeruli
Nephron precursors: Comma and S-bodies
Primitive ducts: Cartilage and tubules encircled by collars of fibromuscular cells
– Hypoplasia
May have a normal nephron density
Oligomeganephronia: Reduction in nephron number with corresponding hypertrophy of the nephrons, nephron diverticula
Ask-Upmark kidney: Arteriosclerosis, juxtaglomerular hyperplasia, tubules resembling thyroid tissue
– Hypodysplasia
Both dysplastic and hypoplastic
DIFFERENTIAL DIAGNOSIS
• Polycystic kidney disease, autosomal dominant (ADPKD)
• Polycystic kidney disease, autosomal recessive (ARPKD)
• Juvenile nephronophthisis
• Medullary sponge kidney
• Reflux nephropathy
• Renal vein thrombosis
• Simple cysts
• Sporadic glomerulocystic kidney disease
• Tuberous sclerosis
• UPJO
• Von Hippel–Lindau disease
• VUR
• Wilms tumor
TREATMENT
GENERAL MEASURES
Consultation with nephrology and multimodality management
MEDICATION
First Line
Antibiotics for UTI or as prophylaxis for VUR
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Indications for nephrectomy: Pain, chronic infection, HTN, or increasing size (3)
• Renal transplantation for end-stage renal disease
• Ureteral reimplantation: Reflux, primary megaureter
• Pyeloplasty for UPJO
• Valve ablation for posterior urethral valves
ADDITIONAL TREATMENT
Peritoneal or hemodialysis for ESRD
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
Varies with degree of renal insufficiency and degree of comorbid conditions
COMPLICATIONS
Renal failure, anemia, UTI, failure to thrive
FOLLOW-UP
Patient Monitoring
• BP and growth chart annually
• Electrolytes, Cr, BUN annually
• Urinalysis and urine culture as indicated
• Bilateral disease: Renal US annually
• MCDK: Renal US every 2 yr to observe for involution
Patient Resources
National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC) http://kidney.niddk.nih.gov/kudiseases/pubs/kidneydysplasia/
REFERENCES
1. Glassberg KI. Renal dysgenesis and cystic disease of the kidney. In: Wein AJ, Kavoussi LR, Novick AC, et al, eds. Campbell-Walsh Urology. 9th ed. Philadelphia, PA: WB Saunders; 2007:3305–3358.
2. Grantham JJ, Winklhofer F. Cystic diseases of the kidney. In: Brenner BM, ed. The Kidney. 7th ed. Philadelphia, PA: Saunders; 2004:1743–1775.
3. La Scola C, Hewitt I, Pasini A, et al. Postnatal management of congenital bilateral renal hypodysplasia. J Matern Fet al Neonatal Med. 2010;23:97–100.
ADDITIONAL READING
• Hubert KC, Palmer JS. Current diagnosis and management of fet al genitourinary abnormalities. Urol Clin N Am. 2007;34:89–101.
• Weber S, Moriniere V, Knüppel T, et al. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: Results of the ESCAPE study. J Am Soc Nephrol. 2006;10:2864–2870.
See Also (Topic, Algorithm, Media)
• Ask-Upmark Kidney
• Chronic Kidney Disease, Pediatric (Renal Failure, Chronic)
• Prune Belly (Eagle Barrett or Triad) Syndrome
• Renal Agenesis (Bilateral and Unilateral)
• Renal Dysplasia, Hypodysplasia and Hypoplasia Image 
• Renal Malrotation
• VUR, Pediatric
CODES
ICD9
• 753.0 Renal agenesis and dysgenesis
• 753.15 Renal dysplasia
• 756.71 Prune belly syndrome
ICD10
• Q60.2 Renal agenesis, unspecified
• Q60.5 Renal hypoplasia, unspecified
• Q61.4 Renal dysplasia
CLINICAL/SURGICAL PEARLS
Prognosis varies; however, most patients have renal insufficiency and its sequelae.