Kidneys are advanced filtration systems made up of thousands of fine tubules and membranes that carry filtered fluids away from the blood and collect them to make urine. They remove waste products such as acids, urea, and extra liquid from your body. They also maintain a healthy balance of water, salts, and minerals, such as sodium, calcium, phosphorus, and potassium, in your blood.
There are several types of inherited (congenital) kidney diseases that come from different genetic causes and affect different populations and age ranges. Some of the very rarest have very little known about them because so few patients have been studied. Some of these kidney diseases are described below;
- Polycystic Kidney Disease (PKD) (cysts in the kidney, seen in approx. 1 in 800 people)
- Thin Basement Membrane Disease (TBMD) (malformed kidney blood vessels, collagen gene defect, seen in less than 1 in 100 people)
- Other collagen-related kidney diseases including Alport Syndrome: (1 in 5,000-10,000)
- Gitelman Syndrome: (gene mutation, salt reabsorption (uptake back into the bloodstream of certain substances previously filtered out of it) disorder, 1 in 40,000)
- Tuberous Sclerosis: (benign tumours affect kidney function, 1 in 6,000)
- Fabry Disease: (glycolipid accumulation impairs kidney function, 1 in 40,000 males)
- Nephronophthisis: (renal ciliopathy causing reduced ability to concentrate dissolved substances, est. 1 in 80,000)
Among the most common is Polycystic Kidney Disease (PKD), a group of diseases that enlarge the kidneys and damage their function. Thin Basement Membrane Disease (TBMD) and PKD will be the main focus of this article. The links included above will take you to very good web resources for each of the rarer conditions.
Thin Basement Membrane Disease
The kidney glomeruli are tiny balls of capillaries (small blood vessels) interwoven with kidney tubules, in a structure called a nephron. The entire outer surface of the nephron is covered by a basement membrane (BM) whose function is to support the fine structure of the capillaries and tubules and to assist in regulating blood filtration. BM defects lead to leakage of blood and a protein called albumin into the kidney tubules, which then leads to blood in the urine (haematuria).
TBMD (also known as benign familial haematuria and thin basement membrane nephropathy) is usually benign and manifests itself exactly as the name suggests; the BM is thinner than normal, allowing blood components to pass across the membrane into the urine. In many respects, TBMD is a less severe form of the similar Alport Syndrome, where mutations in specific genes cause a defect in a key structural protein (collagen IV) in the BM. There is a 50% chance that children with one affected parent will be affected themselves.
There are no readily detectable signs or symptoms, and normal kidney function is usually maintained. People sometimes experience raised blood pressure, body swelling, and reduced urine output. A doctor will check your urine for blood and protein, may measure your kidney function (glomerular filtration rate (eGFR)), and may recommend a biopsy. There is no specific treatment for TBMD, and usually none is necessary, although in more severe cases treatments commonly used for chronic kidney disease (CKD) may be applied.
Polycystic Kidney Disease
PKD is a group of inherited kidney disorders that primarily cause renal cysts to develop. These are fluid-filled sacs or bumps on the kidney tubules that impair their function and enlarge and damage the kidneys. Cysts may also be present in the liver, pancreas, spleen, ovaries, large bowel, brain (where they may cause a brain aneurysm), and heart.
In the longer term, PKD causes chronic kidney disease (CKD), which can lead to kidney failure, or end-stage renal disease (ESRD). PKD is the fourth leading cause of kidney failure. Approximately 50% of people with PKD will have kidney failure by the age of 60, rising to 60% by age 70.
Certain groups have an increased risk of kidney failure:
- People assigned male at birth (AMAB)
- Patients with high blood pressure
- Patients with protein or blood in their urine
- People assigned female at birth (AFAB) with high blood pressure who have had more than three pregnancies
Types of PKD
There are two inherited types of PKD, and while they are the most common inherited kidney illnesses, they are still relatively rare:
- Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney illness, and causes cysts to form within and on the kidney, leading to major health problems from age 30. About 1 in 800 people are affected by the condition. ADPKD is caused by genetic variants (mutations) in two genes, PKD1 (85% of cases) and PKD2 (15% of cases). Symptoms are identical, but the severity of the condition tends to be worse in people with PKD1 mutations. Because it is a dominant trait, the condition can be inherited in 50% of children if only one parent is a carrier of the mutation, and in 75% of children if both parents are carriers. In around 25% of cases, the condition develops with no known family history.
- Autosomal recessive polycystic kidney disease (ARPKD) also causes cysts to form in the kidney, disrupting the normal development of the kidney tubule structure, but affects only 1 in 20,000 people. Symptoms appear in childhood and it is caused by a mutation in the PKHD1 gene. It is what is known as a recessive trait which means that both parents have to be carriers of the mutation. There is then a 1 in 4 chance their child will inherit the condition, and a 1 in 2 chance of the child being an unaffected carrier. Unlike with ADPKD, it may be that neither parent shows symptoms of ARPKD.
There is also a rarer, non-inherited, condition called Acquired Cystic Kidney Disease (ACKD). ACKD can affect kidneys with long-term damage and severe scarring, so it is often associated with kidney failure and dialysis. About 90% of people on dialysis for 5 years or more develop ACKD.
Symptoms and Complications of PKD
ADPKD symptoms can include:
- High blood pressure (hypertension)
- Chronic back or side pain
- Blood in your urine (haematuria)
- A feeling of fullness in your abdomen
- Increased size of your abdomen due to enlarged kidneys
- Kidney stones (renal calculi)
- Kidney failure
- Potentially serious upper urinary tract (UTI) or kidney infections
- Gradually deteriorating kidney function
ARPKD symptoms vary widely. ARPKD is detectable in the womb by routine ultrasound scan, which may show enlarged kidneys, underdeveloped lungs, and a lack of amniotic fluid. At birth the baby with ARPKD may exhibit:
- significant breathing difficulties
- a swollen tummy (abdomen): caused by enlargement of the kidneys
- Potter syndrome: in severe cases of ARPKD
Underdeveloped lungs are the biggest perinatal problem and breathing often needs to be assisted by a ventilator. Around a third of babies developing breathing problems will die within weeks or months. The chances for 10-year survival are 90% if the baby survives this early stage, but about a third will need treatment for kidney failure.
In older children, while less immediately life-threatening, ARPKD causes a host of clinical problems:
- High blood pressure: usually requiring medication
- Liver problems and internal bleeding: fibrosis, spleen enlargement, oesophageal varices (bleeding)
- Excessive urination (polyuria) and thirst (polydipsia): caused by disrupted water balance caused by impaired kidney function. This can lead to dehydration.
- Trouble eating: enlarged kidneys may cause stomach issues and potentially lead to vomiting and malnourishment.
- Growth problems: may require dietician support, a high-protein diet, and possibly tube feeding to overcome feeding difficulties.
- CKD and kidney failure: usually without symptoms until an advanced stage. Kidney failure is due to impaired kidney function caused by cysts. Most children with ARPKD develop kidney failure by the age of 15-20.
Treatments for PKD
There is no cure for PKD at present. Most symptoms (pain, hypertension, urinary tract infections) can be treated with medication. Cysts can be drained surgically. A low salt diet full of fruits, vegetables, and whole grains is important, as is maintaining a healthy weight and not smoking. Kidney failure is treated primarily using renal dialysis or kidney transplant. In some cases of ADPKD in adults, where CKD is advanced and progressing rapidly, a medication called tolvaptan can slow the formation of cysts.
What kidney disease can be inherited?
Two forms of Polycystic Kidney Disease (PKD) are inherited, autosomal dominant and autosomal recessive.
Which kidney disease is not to be inherited?
Many kidney diseases appear not to be inherited, e.g., ACKD.
How long can you live with polycystic kidney disease?
ADPKD patients tend to have a near-normal life span. This is different for children, however. 1 in 3 babies with ARPKD die from severe breathing difficulties during the first 4 weeks after birth, and about 8 out of 10 who survive the first month of life will live until they're at least 5 years old.
Can kidney disease run in families?
Yes, PKD generally runs in families.
Can you live with only one kidney?
Provided the kidney is healthy, yes. Life span in people with single kidneys is normal, although there is a risk of hypertension.
Can Polycystic Kidney Disease be cured?
Currently there is no cure.
How long can you live with kidney failure?
Possibly days to weeks without dialysis, depending on the amount of residual kidney function, symptom severity, and overall medical condition.
Can CKD be hereditary?
Yes, CKD may run in families, but the biggest risk factors are hypertension, diabetes, and PKD.
What age does polycystic kidney disease start?
ADPKD affects babies, children, and adults over 30.
What is the most common genetic cause of kidney disease?
Mutations in the PKD1, PKD2, or PKHD1 genes.
What are the signs that something is wrong with your kidneys?
Two or more of the following: fatigue, trouble sleeping, dry and itchy skin, the urge to urinate more often, blood in the urine, foamy urine, puffiness around the eyes, swollen feet or ankles, poor appetite, and muscle cramps (see National Kidney Foundation website).