Many kidney diseases are hereditary, and even more of them are genetic.
We’ve talked about this before; not all genetic diseases are hereditary.
According to the criteria and sources used, the number of genetic kidney diseases, most of which are also hereditary kidney diseases, ranges from over 60 to over 300. There are diseases that involve kidney damage but are not specific to that organ. The damage is part of a series of systemic alterations.
Chronic kidney disease (CKD) is the term given to the condition in which the kidneys are too damaged to properly filter the blood, whether or not it is genetically caused. In fact, three out of every four cases have diabetes and hypertension as the primary origin.
It has been suggested that there are genetic variants related to this set of diseases in 10% of adults and 20% of children.
In the United States alone, it is estimated that there are 37 million people with CKD, accounting for 15% of the adult population and making this set of diseases one of the leading causes of death.
Autosomal Dominant Polycystic Kidney Disease
The most common of all hereditary renal pathologies is Autosomal Dominant Polycystic Kidney Disease, which we will refer to as ADPKD, taking advantage of its acronym in English, as the name is too long.
This disease has a prevalence of 1:1,000, making it the third leading cause of end-stage renal disease worldwide. Less clinically, it is the third leading cause of death due to faulty kidney function.
One characteristic of dominant diseases is that if you pass the pathological gene to your child, they will also have the disease without needing anything else. In this sense, it is easy to increase the frequency compared to recessive diseases.
There is also Autosomal Recessive Polycystic Kidney Disease. It has a lower incidence, 1:20,000, and is very similar to the dominant form in phenotype, with its major difference being the causative mutation.
Although there are manifestations in other organs, the most characteristic feature of the disease is the formation of cysts in both kidneys, which gradually increase in size and number. In this early stage, symptomatic treatment is carried out.
However, with the progression of the disease, kidney efficiency decreases until renal failure occurs. Dialysis must then be performed, and the patient may need a kidney transplant.
The disease takes time to manifest, with detectable effects before adulthood being rare. But its penetrance (expression of the disease, if present, at the genetic level) is high: all patients over 80 years old show symptoms.
35-45% of patients suffer from renal failure before the age of 60. Diagnosis is simple, with ultrasound. To confirm it, we have magnetic resonance imaging and/or computed tomography.
The gene responsible in more than 80% of cases is PKD1. This gene forms calcium-permeable channels along with the PKD2 gene, although it is involved in other pathways such as the formation and development of renal tubules.
Do you know which is the second gene most involved in this pathology? The PKD2 gene. It seems that this disease runs in the family, both literally and genetically.
In the recessive pathology, the PKD1 gene is also frequently to blame, although the second gene involved in this case is usually the DZIP1L gene, which is involved in primary cilia formation.
Of the two, PKD1 is not only more common but also more serious. Using renal size as a measure of disease severity, patients with mutations in PKD1 had kidneys two-thirds larger than those affected by the PKD2 gene.
In patients with mutations in PKD1, renal cysts are more numerous and begin at younger ages.
Other Renal and Genetic Pathologies
ADPKD is the most common genetic renal disease, but it is far from being the only one that exists. Genetics has always been very versatile in finding faults.
- The Alport syndrome has the dubious honor of being the second most frequent genetic renal disease. In this disease, genes involved in the formation of type IV collagen (COL4A3, COL4A4, and COL4A5) are affected. The severity of the pathology varies among patients, although all present renal inflammation.
- Thin basement membrane disease is a nephritic syndrome characterized by significant thinning of the glomerular basement membrane. Fortunately, this pathology is usually not serious. Not all responsible mutations are known, but it is known that many are again in type IV collagen, such as the alpha-4 gene.
- Barter syndrome encompasses several renal diseases. Affected individuals eliminate a disproportionate amount of sodium, which subsequently leads to excessive potassium elimination. At least five genes causing the syndrome are known: SLC12A1, KCNJ1, CLCNKB, BSND, and CLCNKA.
- Focal segmental glomerulosclerosis is the cause of 10-15% of nephrotic syndromes in adults. More than a disease, it is a type of histological pattern. It causes the development of scar tissue in the glomeruli, with proteinuria (excess elimination of proteins from the blood through urine). In the hereditary diseases of this group, more than 60 responsible genes have been found.
- Gitelman syndrome is a tubulopathy that affects the distal tubules of the nephrons. The cause is usually inactivating mutations of the SLC12A3 or CLCNKB gene. Similar to Barter syndrome, there is loss of salts, especially sodium and magnesium. Yes, that’s very bad.
- Vesicoureteral reflux is a backward flow of urine from the bladder to the kidneys through the corresponding conduits (ureters). It may be due to problems in the junction between the ureter and the bladder or to excessively high pressure within the bladder. Aside from the absurdity, the biggest problem is the risk of urinary tract infections. It is a very complex disease in its causes, making the responsible genetic alterations very heterogeneous.
- Cystinosis is caused by a mutation in the CTNS gene. Its main characteristic is the accumulation of crystals formed by cystine, an amino acid, inside cells. In the kidneys, it causes renal failure.
Kidneys are a simple organ in their functioning compared to others, but that doesn’t save them from being vulnerable to many harmful genetic mutations. Cursed random mutations, luckily there are products like our tellmeGen Advanced kit to help you understand them.
