Kidney Disease: Could This Be My Family's Story?

Chronic kidney disease affects more than 1 in 7 adults in the US. Most of these cases are associated with diabetes or high blood pressure, but other cases stand alone.¹

So, is kidney disease hereditary? The short answer is: it depends.

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What are the causes of kidney disease?

There are a variety of causes of chronic kidney disease. These include:

  • High blood pressure

  • Diabetes

  • Genetic disorders

  • An infection in the kidneys

  • Taking a drug that is toxic to the kidneys

  • Autoimmune disease

  • Heavy metal poisoning, most often lead

  • Smoking

  • High cholesterol that can lead to renal artery stenosis

Some of these causes are direct genetic disorders. Types of autoimmune diseases, high blood pressure, high cholesterol, and diabetes, can also be hereditary, indirectly affecting kidney health. This means that the disease itself is not inherited, but the risk factor is. Others, such as infections or heavy metal poisoning, are not.

Hereditary kidney diseases explained

Genetic causes of kidney disease include the following, some of which will be explained in more detail:

  • Polycystic kidney disease

  • Fabry disease

  • Alport syndrome (hereditary nephritis)

  • Salt-losing tubulopathies such as Bartter syndrome.² This affects the kidneys' ability to reabsorb salt, causing an electrolyte imbalance.

  • Nephronophthisis.³ This is a rare condition caused by a group of autosomal recessive cystic kidney disorders that causes inflammation and scarring of the kidneys, ultimately leading to kidney failure. 

  • Anti-GBM disease (Goodpasture disease).⁴ A rare autoimmune disease that affects the kidneys and lungs. Although the disease is not fully “hereditary,” genetic risk factors have been established.

  • Liddle syndrome. A rare disorder that causes the kidneys to have increased sodium reabsorption while having increased potassium secretion, leading to high blood pressure.

  • Tuberous sclerosis complex. A rare disorder that causes benign tumors to grow in many organs, including the brain, spinal cord, eyes, lungs, heart, skin, and kidneys. 

  • Von Hippel Lindau disease. A rare disorder that causes both benign and cancerous tumors and cysts to grow in many organs, including the kidney. 

  • Focal segmental glomerulosclerosis. A condition caused by scarring of the glomeruli or small tuff-like filters of the kidney, which can lead to loss of protein in the urine and eventually kidney failure. Although the pathogenesis of FSGS is yet to be fully established, in rare instances, it can be hereditary.

  • Congenital abnormalities of the kidney and ureteral tract, meaning you may have smaller or malpositioned kidneys, changes to the ureter, or only one kidney.

Many conditions are classified based on their main diagnostic features. Some of these conditions are linked with other issues. For instance, Nail-Patella syndrome not only causes nail abnormalities but also leads to a missing patella. Another example is HDR syndrome, an abbreviation for hypoparathyroidism, sensorineural deafness, and renal disease.

How hereditary kidney diseases are passed down

Some of these diseases are caused by single-gene inheritance, while others are polygenetic, and they may be either dominant or recessive.

If a gene is dominant, it means that one of your parents must have the condition for it to be passed down, leading to it often affecting every generation, although the expression can vary. On the other hand, recessive genes must be carried by both parents and thus may appear unexpectedly as the trait can skip generations.

Genetic disorders can also be sex-linked, meaning the abnormal gene is located on one of the sex chromosomes (X or Y). The expression of the gene is more commonly observed in one sex (usually males) because they have only one copy of the sex chromosome that carries the gene.

Polygenetic traits, which involve many different genes, typically do not have a clear inheritance pattern. In other words, a genetic disease may clearly run in the family or may show up only occasionally. Recessive diseases can remain hidden for generations before emerging and are more common in consanguineous relationships (a relationship between blood relatives).

Here are details on the most common genetic kidney disorders.

Polycystic kidney disease (PKD)

Polycystic kidney disease is one of the most common genetic disorders affecting the kidneys. It causes clusters of cysts (fluid-filled sacs) to develop in the kidneys. These physically interfere with the filtering ability of your kidneys and cause them to enlarge. Cysts may also develop in other organs, especially the liver.


There are two types of PKD:

  1. Autosomal dominant polycystic kidney disease (ADPKD). This is caused by a mutation in a dominant gene. Symptoms tend to show up in adulthood. It is divided into type 1 or type 2, depending on whether the mutation is in the PKD1 or PKD2 gene.

  2. Autosomal recessive polycystic kidney disease (ARPKD). This is caused by mutations in a single recessive gene. Symptoms show up at birth or in early infancy. ARPKD is often lethal.

Causes and who is affected

ADPKD is caused by a mutation in either the PKD1 or PKD2 gene in almost all cases. These mutations affect the production of proteins. 

PKD1 and PKD2 encode proteins called polycystin-1 and polycystin-2, which take part in cell-cell interactions as well as cell-matrix interactions. In 10–20% of cases, a family history is not immediately identifiable.⁵ Some cases may be caused by a spontaneous mutation, while others may be due to mosaicism.

A mutation in the PKHD1 gene or the DZIP1L gene causes ARPKD. In this case, both parents must carry a copy of the gene and are unaffected by the disease. Despite the parents' genetic makeup, inheriting the disease is not purely mendelian. Siblings with genes from the same parents may show variation in subtypes. 


With ADPKD, symptoms generally do not develop until the 30s or 40s, even though cysts may be present early in childhood. Symptoms do not develop until cysts have reached a certain point.

Symptoms and signs can include:

  • High blood pressure

  • Pain in the back or side

  • Increase in the size of the abdomen

  • Blood in the urine

  • Frequent bladder or kidney infections

Treatment and prognosis

PKD has no cure. Treatment aims to extend life and delay kidney failure while preventing complications. Renoprotective strategies, such as a healthy lifestyle, early detection, and rigorous control of high blood pressure, are essential. High blood pressure can worsen kidney damage. Hence, it is crucial to take prescribed medication. Otherwise, treatment is supportive and includes:

  • Monitoring for kidney or bladder infections so they can be treated promptly

  • Quitting smoking

  • Reducing salt intake

  • Physical activity, although activity that might result in kidney damage, such as contact sports or sports with a high risk of falls, should be avoided

About 50% of people with PKD will have kidney failure by age 60, and about 60% will have it by age 70.⁶ They will then need dialysis or a kidney transplant. PKD can also affect the brain or heart, causing valvular heart disease or an intracranial aneurysm. It is possible to have a successful pregnancy with PKD, but genetic counseling may be a good idea.

ARPKD is often lethal as it causes improper lung development, and most infants require breathing assistance. Mortality rates can reach up to 30%.⁷ Couples with one child with ARPKD should consult a genetic counselor and consider IVF to select healthy embryos for future children. If a sibling had ARPKD, you should get tested for the faulty gene.

Fabry disease

Fabry disease is also known as Anderson-Fabry disease and alpha-galactosidase-A deficiency. People with Fabry disease lack a functioning enzyme that breaks down certain fats. This leads to a buildup of a specific fat called globotriaosylceramide (Gb3) in various cells, such as those in the nervous system, eyes, kidneys, and heart.

Causes and who is affected

Fabry disease is inherited almost entirely by males because the faulty gene is located on the X chromosome, which males only inherit a single copy of. In females, the disease is milder unless both X chromosomes carry the faulty genes. 

Fabry disease is rare and is inherited in a sex-linked manner. However, it is possible to inherit Fabry disease from a mother who did not have symptoms.


Symptoms and signs of Fabry disease include:

  • Episodes of pain in the hands and feet

  • Angiokeratomas, which are clusters of small, dark red spots on the skin

  • Decreased ability to sweat

  • Cloudiness of the front part of the eye

  • Hearing loss

  • Gastrointestinal problems

  • Fever

Symptoms typically appear in childhood. However, milder forms can appear later in life, particularly in females with only one copy of the faulty genes. However, Fabry disease is typically found by genetic screening of newborns, allowing families to prepare for the condition.

Treatment and prognosis

Fabry disease can lead to kidney impairment and renal failure, heart enlargement (which increases the likelihood of a heart attack), and an increased risk of stroke.

There is no cure for Fabry disease. Treatment generally consists of enzyme replacement, which does not always work, but can help preserve organ function. You may also be given drugs to reduce pain and gastrointestinal distress. Antiplatelet medications can help reduce stroke, and many people with the disease need medication to lower blood pressure.

Some individuals may experience kidney failure and require dialysis or a transplant.

Alport syndrome

Alport syndrome is another rare genetic condition that causes progressive loss of kidney function.

Causes and who is affected

Alport syndrome is caused by mutations in the genes encoding different alpha chains of type IV collagen, such as COL4A3, COL4A4, or COL4A5. This causes abnormalities of a protein called type IV collagen, which is thought to enhance the ability of the glomerular basement membrane to resist protein breakdown. This membrane is responsible for selective filtration of the blood to create urine, and thus abnormalities in the structure lead to kidney issues.

There are several different inheritance patterns. The most common, like Fabry disease, is X-linked, meaning males experience severe disease, while females only have mild symptoms or no disease at all. However, it can also be inherited as both an autosomal recessive and autosomal dominant pattern.

Some patients with heterozygous COL4A3 or COL4A4 genes can also present with thin basement membrane nephropathy instead of Alport syndrome.⁸ This is a much milder condition in which most people only have blood or protein in the urine and does not typically lead to end-stage kidney failure.


The age of onset can vary from child to adult, depending on the genetic inheritance. Symptoms of Alport syndrome include:

  • Blood in the urine (often the first sign, and in some mild cases, may be the only symptom)

  • Protein in the urine

  • High blood pressure

  • Swelling in the legs, ankles, feet, and around the eye

  • Hearing loss (the same protein is important for the development of the inner ear)

  • Abnormal structure of the eye or retina, although this typically does not result in vision loss

Treatment and prognosis

There is no specific treatment for Alport syndrome. Typically, treatment consists of management of hypertension, proteinuria, and dyslipidemia.⁹

Many people with Alport syndrome will ultimately require a kidney transplant, which is typically very successful.

The lowdown

Kidney disease can sometimes be hereditary. Genetic screening may help you know if you or your partner has a gene that causes kidney disease in your children. Genetic kidney diseases may be inherited in many ways, including autosomal dominant, recessive, or X-linked patterns.

There is typically no cure for inherited kidney disease, and some families may choose to use fertility treatments to ensure the selection of healthy embryos. However, except for PKD, these conditions are extremely rare.

  1. Kidney disease statistics for the United States | NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  2. Bartter syndrome | National Organization for Rare Disorders (NORD)

  3. Nephronophthisis | MedlinePlus

  4. Anti-GBM (Goodpasture’s) disease | NIH: National Institute of Diabetes and Digestive and Kidney Diseases

  5. Next-generation sequencing for detection of somatic mosaicism in autosomal dominant polycystic kidney disease (2020)

  6. Polycystic kidney disease | National Kidney Foundation

  7. Neonatal polycystic kidney disease, a potential life-threatening condition at this age (2019)

  8. COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome (2002)

  9. Expert guidelines for the management of alport syndrome and thin basement membrane nephropathy (2013)

Other sources:

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