Decoding kidney disorders

Genetic conditions are among the common causes of kidney disease and kidney failure. Even though there is a high possibility of missing the diagnosis, it accounts for 10–15 per cent of adult patients and most paediatric patients who require dialysis or kidney transplantation. These genetic conditions may show up in different forms such as cyst formation, proteinuria (presence of excess protein in urine), affecting absorption of electrolytes and water.

Generally, genetic conditions affect multiple organs in the body, including eyes, ear, liver, skin, and brain. Looking thoroughly at family history provides a bigger hint about the diagnosis. Proper diagnosis helps in estimation of outcomes, right treatment, precautions and prevention. The diagnosis of a genetic condition can lead to significant mental stress on the family, which is why an early diagnosis and management of the health issue matters.

Cyst disorders

Cyst-forming disorders are one of the most common genetic disorders. Among them, autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent and is characterised by multiple water-filled cysts in many organs such as the liver, and particularly the kidneys. These cysts increase in size and number as age progresses and can eventually damage the kidneys. They may also cause aneurysms in the brain. The condition is called autosomal dominant because inheriting just one copy of the faulty gene from either parent is enough to cause the condition. It is most often caused by mutations in the PKD1 or PKD2 genes. There are numerous mutations and if a parent has ADPKD, each child has a 50 per cent chance of inheriting the mutation and developing the condition. This risk is the same for every pregnancy, regardless of the child’s sex.

Silent progression

While ADPKD can appear at any age, many children with the mutated gene may not show symptoms until adulthood. While generally it causes kidney failure after the age of 40 years, it may cause kidney failure in the early stages of life also. The clinical pattern has to be predicted based on how other family members were affected before. Clinical comparison has to be within the same family.  Genetic testing can confirm the presence of the mutation, but it’s often done selectively because of emotional and medical implications. Early diagnosis will help slow the disease progression and avoid complications. 

Rare variants

There are many other cyst-forming genetic conditions. When compared to ADPKD, fortunately, these are less common. Autosomal recessive polycystic kidney disease (ARPKD), tuberous sclerosis complex (TSC - marked by growth of noncancerous tumours), nephronophthisis (NPHP - impairment of kidney function), medullary sponge kidneys (MSKs - affects the innermost part of the kidney) and von Hippel-Lindau disease (VHL- rare, affecting multiple organs) are some of these conditions.

These diseases are identified based on age of onset, and assessment of whether other organs are involved, and if the kidney is enlarged or not, skin lesions, and presence (or not) of kidney stones, among others.

Filtration defects

The second set of genetic conditions affect the proteins in the glomerular basement membrane (GBM). This membrane is the main filtration site. Alport syndrome is the most common among them. It can lead to kidney disease, kidney failure, hearing loss and problems in the eyes. Blood in urine is one of the main symptoms. 

Fabry disease affects kidney, heart, skin, nerves and brain. Another disease called nail patella syndrome causes absence of patellae (bone at front of knee joint), underdeveloped nails, elbow dysplasia (abnormal development of the elbow bones) and kidney problems.

Electrolyte issues

Genetic conditions lead to abnormality of water, sodium, potassium and calcium absorption. Poor absorption can lead to hypotension, hypertension, poor growth, muscle weakness, muscle paralysis, high or low potassium, acidosis or alkalosis, among other such problems.

Closely tracking the problem, followed by a need to further investigate, a detailed family history, thorough clinical examination and evaluation will help diagnose these genetic conditions. Genetic tests need to be used appropriately. An important aspect is to create awareness and educate family members, apart from providing counselling.

(The writer is a consultant – nephrology, transplant physician at a Bengaluru hospital.)