Kidney nontumor / medical renal

• Dysplasia: abnormal differentiation of renal parenchyma results from genetic abnormality or urinary tract obstruction or reflux (Arch Pathol Lab Med 2015;139:547)
  • WT1 expression stimulates ureteric bud development and early induction of renal mesenchyme
  • PAX2 and BCL2 expression induces differentiation of mesenchyme to nephron epithelium
  • In dysplastic kidneys, WT1 expression is decreased and there is persistent PAX2 and BCL2 expression, driving continued expression of immature epithelium
• Hypoplasia: inadequate branching of ureteric ducts results in a decreased number of reniculi (renal lobes) (Pediatr Res 2010;68:91)
• Agenesis: failure of the ureteric bud to develop or failure of the ureteric bud to induce metanephric mesenchyme differentiation (Am J Obstet Gynecol 2021;225:B28)

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Contributed by Robyn C. Reed, M.D., Ph.D.

 
Images hosted on other servers:

Contributed by Robyn C. Reed, M.D., Ph.D.

• At least 40 genes have been implicated in congenital abnormalities of the kidney and urinary tract, accounting for ~18% of cases (J Am Soc Nephrol 2018;29:36)
• Many genetic alterations have a phenotypic spectrum that encompasses dysplasia, hypoplasia, agenesis and other structural abnormalities
• Dysplasia is associated with numerous genetic disorders; this is a partial list (Fetal Pediatr Pathol 2014;33:293, Husain: Stocker and Dehner's Pediatric Pathology, 5th Edition, 2021)
  • Meckel-Gruber syndrome (autosomal recessive, at least 16 genes) (GeneReviews: Nephronophthisis-Related Ciliopathies [Accessed 26 July 2023])
  • Joubert syndrome (autosomal recessive or X linked, at least 34 genes) (GeneReviews: Joubert Syndrome [Accessed 26 July 2023])
  • Zellweger syndrome (autosomal recessive, at least 13 genes) (GeneReviews: Zellweger Spectrum Disorder [Accessed 26 July 2023])
  • HNF1B deficiency syndrome (autosomal dominant, HNF1B) (Cells 2023;12:307)
  • Renal - hepatic - pancreatic dysplasia (autosomal recessive, NPHP3 or NEK8) (OMIM: Renal-Hepatic-Pancreatic Dysplasia 1; RHPD1 [Accessed 26 July 2023], OMIM: Renal-Hepatic-Pancreatic Dysplasia 2; RHPD2 [Accessed 26 July 2023])
  • Short rib polydactyly syndromes, including Jeune syndrome (autosomal recessive, at least 23 genes) (Hum Mutat 2018;39:152)
  • Carnitine palmitoyltransferase II deficiency (autosomal recessive, CPT2) (GeneReviews: Carnitine Palmitoyltransferase II Deficiency [Accessed 26 July 2023])
  • Hereditary renal adysplasia (autosomal dominant, ITGA8 or FGF20) (Fetal Pediatr Pathol 2014;33:293)
  • Nail patella syndrome (autosomal dominant, LMX1B) (GeneReviews: Nail-Patella Syndrome [Accessed 26 July 2023])
  • Genitopatellar syndrome (autosomal dominant, KAT6B) (GeneReviews: KAT6B Disorders [Accessed 26 July 2023])
  • Bardet-Biedl syndrome (autosomal recessive, at least 25 genes) (GeneReviews: Bardet-Biedl Syndrome Overview [Accessed 26 July 2023])
  • Beckwith-Wiedemann syndrome (usually sporadic, CDKN1C or 11p15.5 alterations) (GeneReviews: Beckwith-Wiedemann Syndrome [Accessed 26 July 2023])
  • 22q11.2 deletion syndrome (autosomal dominant, 22q11.2 alterations) (GeneReviews: 22q11.2 Deletion Syndrome [Accessed 26 July 2023])
  • Trisomies 13, 18, 21 and numerous chromosomal deletions and duplications (sporadic) (Int J Pediatr Nephrol 1987;8:215)
• Dysplasia and other congenital abnormalities of the kidney and urinary tract have also been linked with alterations in numerous additional genes (Curr Opin Pediatr 2016;28:209, J Am Soc Nephrol 2018;29:36)
• Renal agenesis and hypoplasia are associated with numerous genetic disorders, including some of the disorders listed above for renal dysplasia as well as the following syndromes (Am J Obstet Gynecol 2021;225:B28)
  • Acro renal ocular syndrome (autosomal dominant, SALL4) (GeneReviews: SALL4-Related Disorders [Accessed 26 July 2023])
  • Branchiootorenal syndrome (autosomal dominant, EYA1, SIX1 or SIX5) (GeneReviews: Branchiootorenal Spectrum Disorder [Accessed 26 July 2023])
  • Pallister-Hall syndrome (autosomal dominant, GLI3) (GeneReviews: GLI3-Related Pallister-Hall Syndrome [Accessed 26 July 2023])
  • Fraser syndrome (autosomal recessive, FRAS1, FREM2 and GRIP1) (OMIM: Fraser Syndrome 1; FRASRS1 [Accessed 26 July 2023])
• Renal agenesis has also been linked with alterations in GREB1L, GFRA1, ITA8 and FGF20 (Am J Obstet Gynecol 2021;225:B28)

An infant died of respiratory insufficiency shortly after birth. At autopsy, both kidneys had the appearance shown in the image above. Which of the following is most suggestive of bilateral renal dysplasia as the correct diagnosis?

1. Ectatic and cystic collecting ducts in the medulla
2. Family history of congenital renal cysts in 2 of 5 siblings
3. Foci of primitive tubules with collarettes of mesenchyme
4. Known homozygous mutation in PKHD1
5. Markedly small bilateral kidneys with normal histology

C. Foci of primitive tubules with collarettes of mesenchyme. The differential diagnosis in the case of a neonate with bilateral cystic kidneys includes bilateral cystic renal dysplasia, autosomal recessive polycystic kidney disease, autosomal dominant polycystic kidney disease and nephronophthisis. (Medullary sponge kidney and other causes of renal cysts are less likely, as onset is almost always postnatal.) The presence of primitive tubules with collarettes of mesenchyme is highly suggestive of renal dysplasia and is not seen in the other entities listed.

Answer A is incorrect because medullary collecting ducts are dilated in autosomal recessive polycystic kidney disease and nephronophthisis but are not specifically affected in renal dysplasia. Answer B is incorrect because this strong family history is more suggestive of autosomal recessive polycystic kidney disease or autosomal dominant polycystic kidney disease. Although renal dysplasia can recur within families, inheritance is rarely Mendelian. Answer D is incorrect because mutations in PKHD1 are associated with autosomal recessive polycystic kidney disease, not renal dysplasia. Answer E is incorrect because small bilateral kidneys with normal histology is the definition of renal hypoplasia, not renal dysplasia.

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Reference: Dysplasia / hypoplasia / agenesis

Which of the following conditions, when identified prenatally, is most likely to result in severe renal insufficiency and oligohydramnios sequence?

1. Agenesis of the left kidney, dysplastic right kidney
2. Agenesis of the left kidney, normal appearing right kidney
3. Horseshoe kidney with fused lower poles
4. Normal appearing left kidney, hypoplastic right kidney

A. Agenesis of the left kidney, dysplastic right kidney. Clinical consequences of congenital abnormalities of the kidneys and urinary tract encompass the entire spectrum from asymptomatic to incompatible with life. Severity of renal abnormalities in utero depends on whether there is sufficient remaining renal parenchyma to support the ongoing production of fetal urine, contributing to amniotic fluid volume. If there is insufficient amniotic fluid (oligohydramnios), lung development and maturation is impaired, leading to respiratory insufficiency at birth. In the setting of contralateral renal agenesis, a dysplastic kidney is unlikely to contribute sufficiently to the amniotic fluid volume (and in fact it may be dysplastic due to an obstructive lesion within the urinary tract).

Answer B is incorrect because a single, normally functioning kidney is sufficient to support renal function and amniotic fluid production. Answer C is incorrect because, despite its aberrant shape and location, a horseshoe kidney maintains normal renal function in utero. Answer D is incorrect because a normal kidney and a hypoplastic kidney together are sufficient to support renal function and amniotic fluid production.

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Reference: Dysplasia / hypoplasia / agenesis