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Betegségjelentés · Urological

Polycystic Kidney Disease

Whole genome sequencing resolves the complete PKD1 gene (including accurate mapping through its 6 pseudogenes that confound standard sequencing) and PKD2, providing the genotype that predicts ESRD timeline and treatment response.

A betegségjelentés olyan ritka variánsokat keres, amelyekről ismert, hogy okozzák az általa lefedett betegségeket.

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A(z) condition ismertetése

A genetic disorder characterized by the growth of numerous cysts in the kidneys, impairing their function over time.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and one of the most common life-threatening genetic conditions, affecting approximately 1 in 400-1,000 people, an estimated 12.5 million individuals worldwide. ADPKD is caused by pathogenic variants in PKD1 (~78% of cases, chromosome 16p13.3) or PKD2 (~15%, chromosome 4q22.1), encoding polycystin-1 and polycystin-2 respectively. These proteins form a calcium-permeable channel complex that senses fluid flow in the primary cilium of renal epithelial cells. Progressive bilateral renal cyst development leads to massive kidney enlargement and eventual end-stage renal disease.

ADPKD causes progressive bilateral renal cyst growth over decades, producing flank pain, hematuria, hypertension, urinary tract infections, and nephrolithiasis. Hepatic cysts develop in approximately 80% of patients and are typically asymptomatic but can cause massive hepatomegaly in some women. Intracranial aneurysms occur in approximately 8% of ADPKD patients (vs 2-3% in the general population); rupture causes subarachnoid hemorrhage with high mortality. Mitral valve prolapse, colonic diverticulae, and inguinal hernias are associated features. The mean age of ESRD is approximately 54 years for PKD1 and 74 years for PKD2, a 20-year difference determined entirely by genotype.

Tolvaptan (Jynarque), a vasopressin V2 receptor antagonist, was FDA-approved in 2018 for ADPKD in adults at risk of rapid progression. Tolvaptan reduces the rate of total kidney volume growth and slows eGFR decline, delaying ESRD. The FDA label specifically targets rapidly progressing ADPKD, typically PKD1 truncating variants, which produce the fastest progression. The Mayo imaging classification (htTKV) combined with molecular genotype provides the most accurate risk stratification for tolvaptan treatment decisions. Additionally, screening for intracranial aneurysms (brain MRA) is recommended for ADPKD patients with family history of aneurysm or subarachnoid hemorrhage.

PKD1 truncating variants (frameshift, nonsense, splice disrupting) cause ESRD approximately 12 years earlier than PKD1 non-truncating (missense) variants. The specific variant type refines prognosis beyond simply PKD1 vs PKD2.

A vizsgált betegség

A usually autosomal dominant and less frequently autosomal recessive genetic disorder characterized by the presence of numerous cysts in the kidneys leading to end-stage renal failure. The autosomal dominant trait is associated with abnormalities on the short arm of chromosome 16. Symptoms in patients with the autosomal dominant trait usually appear at middle age and include abdominal pain, hematuria, and high blood pressure. Patients may develop brain aneurysms and liver cysts. Patients with the autosomal recessive trait present with progressive renal failure early in life and symptoms resulting from hepatic fibrosis. The autosomal recessive trait is associated with abnormalities of chromosome 6. Polycystic kidney disease may also result as a side effect in patients on renal dialysis.

Mit változtat a diagnózis

Tolvaptan (Jynarque, FDA 2018) for rapidly progressive ADPKD; blood pressure control (target <110/75); pain management; cyst infection treatment; brain MRA screening for intracranial aneurysms; kidney transplantation for ESRD

Vizsgált gének

Más néven

fibrocystic renal disease; PKD - polycystic kidney disease

11 kapcsolódó altípust tartalmaz ↓
  • ALG9-associated autosomal dominant polycystic kidney disease
  • autosomal dominant polycystic kidney disease
  • autosomal recessive polycystic kidney disease
  • polycystic kidney disease 1
  • polycystic kidney disease 2
  • polycystic kidney disease 3 with or without polycystic liver disease
  • polycystic kidney disease 4
  • polycystic kidney disease 5
  • polycystic kidney disease 6 with or without polycystic liver disease
  • polycystic kidney disease 7
  • polycystic kidney disease 8
MONDO:0020642MedGen 9639

Miért a teljes genom szekvenálás

PKD1 has 6 highly homologous pseudogenes on the same chromosome that confound standard sequencing. Long-read-informed whole genome sequencing maps through the pseudogene region to identify true PKD1 pathogenic variants.

PKD1 vs PKD2 determines a 20-year difference in ESRD onset: genotype is the strongest predictor of renal prognosis

Mean age of ESRD is approximately 54 years for PKD1 pathogenic variants and approximately 74 years for PKD2 pathogenic variants, making molecular genotype the single strongest predictor of renal prognosis in ADPKD, superior to baseline kidney volume, age, or eGFR slope alone. Furthermore, PKD1 truncating variants cause ESRD approximately 12 years earlier than PKD1 non-truncating variants, adding additional prognostic refinement. This information directly affects clinical decision-making: tolvaptan initiation timing, blood pressure targets, family planning discussions, and living donor kidney transplant timing all depend on the predicted ESRD timeline.

Tolvaptan eligibility requires rapid progression assessment: genotype is a key component of the risk model

The FDA label for tolvaptan (Jynarque) targets ADPKD patients at risk of rapid progression. The PROPKD score, which incorporates molecular genotype (PKD1 truncating = highest score) alongside clinical variables (sex, hypertension onset, urological events), predicts rapid progression with validated accuracy. Patients with a low PROPKD score (typically PKD2 or PKD1 non-truncating variants) may not be candidates for tolvaptan, avoiding the medication's significant side effects (polyuria, polydipsia, hepatotoxicity monitoring) in patients unlikely to benefit. Whole genome sequencing provides the molecular input for this risk-stratification model.

További urological conditions

Minden feltétel →

Egy teszt. Egy életen át tartó válaszok.

Egy csomag, házhoz szállítva. Az egész genomját a diagnosztikai döntésekhez használt klinikai színvonalon szekvenáljuk. Orvos számára is használható jelentéseit 6–8 héten belül küldjük el a Genome Manager-be. Ezek tartósan érvényesek, és a tudomány fejlődésével frissülnek.

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