RENAL HYPOPLASIA
A normal kidney contains approximately 600,000 to 1,400,000 nephrons. Renal
hypoplasia occurs when a kidney possesses such a significant reduction in its
nephron endowment that it weighs less than half of the standardized mean. Renal
hypoplasia can occur in association with otherwise normal renal development; in
combination with renal dysplasia (i.e., hypodysplasia), in which case the renal
parenchyma appears undifferentiated and disorganized; or as a secondary
effect of conditions that cause renal atrophy or involution, such as chronic
reflux nephropathy secondary to vesicoureteral reflux.
The incidence of hypoplasia without
dysplasia is not known, but it is likely far rarer than hypodysplasia or
atrophic renal hypoplasia. Two major forms of pure hypoplasia have been
identified in the literature. The first, known as oligomeganephronia, is a mostly
sporadic condition in which both kidneys possess a reduced number of nephrons,
and the individual nephrons appear hypertrophic. The number of renal lobes is
also reduced, with sometimes only one or two calices seen in each kidney. The
second kind of hypoplasia, known as simple hypoplasia, is a much rarer, poorly
described condition in which there is a reduced number of nephrons in one or
both kidneys, but the individual nephrons do not appear hypertrophic.
PATHOGENESIS
Hypoplasia likely represents either a
premature arrest of nephrogenesis or partial failure of the normal interactions
between the metanephric mesenchyme and branching ureteric bud. In either case,
genetic factors appear to play a significant role, and most of the current
knowledge about the pathogenesis of renal hypoplasia comes from the study of
genetic syndromes that feature it as a component. The renal coloboma syndrome,
for example, features both optic nerve coloboma and renal hypoplasia, and it
results from mutations in the PAX2 gene, which encodes a protein that
promotes branching and survival of the ureteric bud.
In addition to genetic factors, the
intrauterine milieu and other environmental factors also appear to play a role.
Both uteroplacental insufficiency and maternal malnutrition, for example, are
known to cause intra-uterine growth restriction and a reduced nephron
endowment. Likewise, maternal vitamin A deficiency is associated with renal
hypoplasia because it prevents normal production of the RET receptor, an
essential component in normal nephrogenesis.
No matter the cause of hypoplasia, the
small nephron population is often unable to provide a normal level of filtration
function. Although the resulting renal insufficiency is initially offset by glomerular
hyperfiltration, which increases the functional output of each nephron, this
seemingly adaptive mechanism causes podocyte injury and can ultimately result
in focal segmental glomerulosclerosis (FSGS, see Plate 4-10). As FSGS becomes
more advanced, renal function continues to deteriorate, and end-stage renal
disease (ESRD) eventually occurs.
PRESENTATION AND DIAGNOSIS
Children with oligomeganephronia, the
most common kind of pure renal hypoplasia, often present in the first years of
life with evidence of renal insufficiency and dysfunction, including salt
wasting, anorexia, vomiting, polyuria, polydipsia, and failure to thrive. Urine
dipstick may reveal proteinuria if there is already a significant degree of
FSGS, while serum chemistries reveal an elevated creatinine concentration. On
ultra-sound, the size of each kidney is less than two standard deviations below
the mean size for patient age. Ultra-sound alone, however, often cannot
distinguish purely hypoplastic kidneys from those that are scarred and shrunken
secondary to chronic reflux nephropathy. A renal scan may be useful in this
setting, as purely hypo-plastic kidneys generally lack focal areas of
dysfunction, whereas kidneys with chronic reflux nephropathy exhibit areas of
renal scarring that have reduced tracer uptake. Although a definitive diagnosis
could be estab-lished with histopathologic examination of affected tissue,
renal biopsy is rarely performed.
TREATMENT
The primary goal in the treatment of
renal hypoplasia is to delay the onset of ESRD. As with any form of progressive
renal insufficiency, controlling hypertension is essential because it reduces
intraglomerular pressure and slows the progression of glomerulosclerosis.
Angiotensin-converting enzyme (ACE) inhibitors are especially useful because
they exert a selective vasodilatory effect on efferent arterioles, which
further reduces intraglomerular pressure and also decreases proteinuria. Once
ESRD occurs, however, renal transplantation becomes the only viable long-term
solution.
