Cystic Kidney Disease: Causes

Pathogenesis (disease development)

The forms of autosomal dominant polycystic kidney disease (ADPND) are caused by genetic mutations. In most cases, the mutation is in the PKD1 gene; in approximately 15%, the mutation is in the PKD2 gene.

An essential mechanism for cyst growth in ADPND is the transport of fluid into the interior of the cysts. The chloride channel TMEM16A (anoctamine 1) has been shown to contribute significantly to cyst growth, and pharmacologic inhibition of TMEM16A significantly reduces cyst growth.

Etiology (Causes)

Biographic Causes

  • Genetic burden from parents, grandparents
    • Genetic risk depending on gene polymorphisms:
      • Genes/SNPs (single nucleotide polymorphism):
        • Genes: PKHD1
        • SNP: rs28939383 in gene PKHD1
          • Allele constellation: CT (carrier of polycystic kidney disease).
          • Allele constellation: TT (causes polycystic kidney disease).
        • SNP: rs28937907 in the PKHD1 gene.
          • Allele constellation: CT (carrier of polycystic kidney disease).
          • Allele constellation: TT (causes polycystic kidney disease).
        • SNP: rs137852946 in the PKHD1 gene.
          • Allele constellation: AG (carrier of polycystic kidney disease).
          • Allele constellation: GG (causes polycystic kidney disease).
    • Genetic diseases
      • Autosomal dominant polycystic kidney disease (ADPKD; autosomal dominant polycystic kidney disease); mutation in the PKD1 gene 85% of cases (see above), in the PKD2 gene 15% of cases; disease leads to terminal renal insufficiency (renal failure) especially in the PKD1 mutation.
      • Autosomal recessive polycystic kidney disease (ARPKD; autosomal recessive polycystic kidney disease).
      • Laurence-Moon-Biedl-Bardet syndrome (LMBBS) – rare genetic disorder with autosomal recessive inheritance; according to clinical symptoms is divided into:
        • Laurence-Moon syndrome (without polydactyly and obesity, but with paraplegia and muscle hypotonia) and
        • Bardet-Biedl syndrome (with polydactyly, obesity and peculiarities of the kidneys).
      • Medullary cystic kidney disease (MCKD); autosomal recessive inheritance.
      • Nephronophthisis (NPH) – autosomal recessive form of tubulointerstitial nephritis; consequence of the disease are cystic kidneys at the corticomedullary border of the kidneys.
      • Orofascial digital syndrome with polycystic kidneys (OFD) – X-linked inheritance.
      • Other cystic kidney disease with autosomal dominant inheritance such as Von Hippel-Lindau syndrome or tuberous sclerosis.
      • Cystic kidney disease with unknown mode of inheritance.