Our genes play a role in how the kidneys develop. As such, certain genetic mutations (changes) affect the structure and function of the kidney. Some of these genetic changes are passed on from parents to their offspring. This blog post explores 5 genetic causes of chronic kidney disease (CKD).
Autosomal dominant polycystic kidney disease (ADPKD)
ADPKD is an inherited condition resulting from mutation to the PKD 1 or PKD 2 gene. It leads to abnormalities in some organs, including the kidney, liver, heart, and brain.
In the kidneys, ADPKD results in the formation of fluid-filled sacs. These cysts can grow and multiply, causing the kidneys to enlarge. The kidneys may also progressively lose their function.
ADPKD manifests in different ways. Some people may have no symptoms at all, while others may have symptoms from disturbances in multiple organs.
People with ADPKD may notice a dragging sensation in their abdomen. This dragging sensation usually occurs from enlarging cysts in the kidneys or the liver.
There may be abdominal swelling, usually from an enlarged kidney or liver. An enlarged liver may cause predominantly right-sided abdominal swelling.
Blood in urine is another common occurrence in ADPKD. This typically happens when the cysts in the kidneys rupture. Blood in urine may also follow a urinary tract infection, another ADPKD manifestation.
Diagnosing ADPKD involves various methods, including clinical evaluation, imaging tests, and genetic analysis. Given its hereditary nature, a detailed family history of kidney disease is crucial in identifying potential risk factors. The primary methods employed in the diagnosis of ADPKD are as follows:
- Ultrasound: Ultrasound imaging is often the initial diagnostic tool for detecting kidney cysts. It is non-invasive, cost-effective, and provides a reliable visualization of kidney cysts.
- Computed Tomography (CT) Scan: CT scans offer more detailed images of the kidneys and help confirm the presence and size of cysts, aiding in the differential diagnosis of other kidney disorders.
- Magnetic Resonance Imaging (MRI): MRI may be used for patients with inconclusive ultrasound and CT scans or to assess kidney and liver complications.
- Genetic Testing: In cases where ADPKD is suspected but not confirmed by imaging, genetic testing can identify mutations in the PKD1 or PKD2 genes, establishing a definitive diagnosis.
Autosomal recessive polycystic kidney disease (ARPKD).
Although similar to autosomal polycystic kidney disease, this is rare. Here, the kidneys also develop multiple fluid-filled cysts that cause the kidneys to enlarge. Unlike ADPKD, where the cysts grow and become symptomatic in adulthood, ARPKD can cause problems even when the child is still in the womb. 30% of children die within the first week of life, and diagnosis frequently occurs in childhood.
Both parents must have the gene for a child to have the disease. But if only one parent has the gene, their child could be a carrier too.
Children with ARPKD can also develop liver disease and kidney failure.
The evaluation of ARPKD patients is similar to those done in people with ADPKD.
Alport syndrome
Alport syndrome results from abnormalities in the gene that codes for type 4 collagen. This results in kidney disease, eye abnormalities, and hearing loss. Kidney disease may manifest as blood in urine, protein in urine, hypertension, body swelling, and kidney failure. Genetic testing is used for diagnosis, although kidney biopsy is helpful in evaluating kidney disease.
There is no cure for Alport Syndrome, and treatment is mainly focused on managing symptoms and slowing the progression of kidney disease. Doctors may prescribe medications to control blood pressure and reduce proteinuria. In some cases, a kidney transplant or dialysis may be necessary.
Fabry disease
Fabry disease is a rare genetic disorder that can cause chronic kidney disease. It is caused by gene mutations that code for the enzyme alpha-galactosidase A. This enzyme breaks down certain fatty substances. In people with Fabry disease, fatty substances accumulate in the body’s cells, causing damage to various organs, including the kidneys.
Patients with Fabry disease may develop pain in the hands and feet, skin rashes, gastrointestinal problems, hearing loss, and vision problems. The disease can also cause nervous system problems, such as headaches, numbness, dizziness, and stroke. Emotional issues, such as fear and depression, are also common.
Kidney problems are a common complication of Fabry disease. A study found that 26% of adult patients with Fabry disease had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2, indicative of chronic kidney disease stages 3-5. Some patients may require dialysis or a kidney transplant.
Nephronophthisis
Abnormalities in one gene do not cause Nephronophthisis. Instead, nephronophthisis is caused by abnormalities in certain genes that code for the protein needed for cilial function. Many variants are described based on the affected gene.
Impaired cilial function in people with nephronophthisis means their kidneys cannot concentrate urine. So, these patients produce large volumes of urine and complain of excessive thirst and fatigue.
Different subtypes have been described based on when the disease manifests
Infantile nephrophthisis manifests within the first year of life. The juvenile forms manifest in childhood, while the late onset/adolescent type manifest in early adulthood.
Wrap up
Other genetic causes of CKD include medullary sponge kidney, cystinosis, and primary oxaluria.
Many of these genetic conditions affect other organs besides the kidney, so people with inherited kidney dysfunction need to take care of their overall health.
