Inherited Monogenic Causes of Chronic Kidney Diseases Flashcards
What is the global prevalence of CKD?
13%
Over 800 million adults worldwide
What is polygenic?
Dual genetic diagnosis with pathogenic variants in 2 different kidney-associated genes
What is monogenic?
Commonly driven by type IV collagen genes
Can CKD be polygenic and monogenic?
Yes
What is the mode of inheritance of monogenic CKD?
AD or AR
What percentage of CKD patients do genetics affect?
30% of adult CKD
70% of pediatric CKD
How many genes have been implicated in monogenic causes of CKD?
More than 500
What is used for the diagnosis of CKD?
Genetic testing
What is the main causes or etiology of CKD?
Etiology remains elusive; they are known as kidney diseases of unknown etiology
What number of patients with KDUE account for ESRD?
1 in 10 adults
What % of the causes of KDUE can genetic testing identify?
10 to 40%
What are examples of CKDs? (7)
- Cystic kidney disease (including nephronophthisis)
- Congenital anomalies of the kidneys and urinary tract
- Chronic glomerulonephritis
- Tubulointestinal kidney disease
- Nephrolithiasis/nephrocalcinosis
- Steroid-resistant nephrotic syndrome
- Rare chronic kidney disease
What is monogenic CKD?
Mendelian or monogenic disease (single-gene disorder) resulting from a pathogenic mutation of a single causative gene.
What is nephronophtosis?
An inherited disease which usually affects children; mode of inheritance is AR
What is the mode of inheritance of monogenic CKD?
AR, both parental alleles must be mutated to cause disease
AD, where a mutation in one parental allele is sufficient to cause disease
What is age-related penetrance?
As age increases, the chances of getting affected are greater
How many distinct genetic etiologies were discovered for CKD in adults? Using what?
47 distinct genetic etiologies were identified using genome-wide investigations
What is the type of mutation of CKD during the first 10 years of life?
AR, homozygous truncating
What is the type of mutation that would lead to CKD after the age of 10 but before the age of 50?
AR, homozygous missense
What is the type of mutation that would lead to CKD after the age of 50?
AD, incomplete penetrance or “mild” allele
What is the diagnostic approach to monogenic CKD?
- Take a full history, including family history of CKD
- Detect any extrarenal manifestations of syndromic disease
- Early onset kidney disease or early onset kidney failure
Why is taking a complete history important?
It is often the first clue to both monogenic and polygenic components of CKD, especially through family history
What is the procedure in patients with unexplained kidney diseases?
Do a whole diagnostic routine, especially if there is no genetic predisposition
In which cases do you avoid completing a renal biopsy for diagnosis?
In case of bleeding