Cases
55-year-old man with back pain    

Discussion

ADPKD

Epidemiology and clinical presentation

Cystic disease of the kidney includes ADPKD, autosomal recessive polycystic kidney disease, medullary cystic disease, glomerulocystic disease, cystic renal dysplasia, and dialysis-associated acquired cystic kidney disease.

ADPKD is one of the most common potentially fatal genetic diseases. It affects 1 in 400-1,000 live births and accounts for up to 5%-7% of patients who require dialysis or transplantation. ADPKD patients develop hypertension in the fourth decade of life, pelvic pain, hematuria, renal colic, and other features of chronic kidney disease like polyuria or proteinuria. Up to 80% of patients also develop cysts in their liver. Cardiovascular disease is common. More than 40% of adult patients die of heart-related complications. Renal failure is seen in the fifth or sixth decade of life.

Pathophysiology

ADPKD is a genetic disease characterized by mutations in the genes PKD1 and PKD2. The PKD1 gene encodes polycystin 1, which is expressed in cilia. PKD2 encodes polycystin 2, which is also expressed in cilia.

Disease in patients with the PKD1 mutation is more severe, with earlier presentation, larger kidney size, more cysts, and more severe hypertension. PKD1 is more commonly mutated. Polycystin 1 and 2 localize to primary cilia and they regulate flow-sensitive calcium influx. Mutation in Polycystin 1 or 2 leads to aberrant cell signaling, leading to hyperproliferation and secretion. Cysts form when levels of functional polycystin fall below threshold. Cysts usually originate in the collecting duct part of the kidney.

Gross findings

Kidneys in patients with ADPKD are enlarged and can weigh up to 4 kg each. There are numerous cysts which are radially arranged, as opposed to autosomal recessive polycystic kidney disease. The cysts involve all levels of nephron.

Microscopic findings

In ADPKD, both kidneys are increased in size asymmetrically and contain innumerable radially arranged cysts of varying sizes with parenchymal extinction. Some cysts are filled with clear fluid while some have hemorrhagic contents.

References

  1. Gabow PA. Autosomal dominant polycystic kidney disease. N Engl J Med. 1993;329(5):332-342. doi:10.1056/NEJM199307293290508.
  2. Bergmann C, Küpper F, Schmitt CP, et al. Multi-exon deletions of the PKHD1 gene cause autosomal recessive polycystic kidney disease (ARPKD). J Med Genet. 2005;42(10):e63. doi:10.1136/jmg.2005.0323183.
  3. Fick GM, Johnson AM, Hammond WS, Gabow PA. Causes of death in autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 1995;5(12):2048-2056. doi:10.1681/ASN.V51220484.
  4. Pei Y, Obaji J, Dupuis A, et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am Soc Nephrol. 2009;20(1):205-212. doi:10.1681/ASN.20080505075.
  5. Hajj P, Ferlicot S, Massoud W, et al. Prevalence of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease and chronic renal failure. Urology. 2009;74(3):631-634. doi:10.1016/j.urology.2009.02.078.