SCD Patient Diagnosed With Inherited Kidney Disorder: Study
PKD1, PKD2 gene mutations cause autosomal dominant polycystic kidney disease
A 16-year-old boy with sickle cell disease (SCD) was diagnosed with autosomal dominant polycystic kidney disease (ADPKD), an inherited condition that causes fluid-filled cysts to form in the kidneys, a case study reports
The report, “Dual diagnosis of autosomal dominant polycystic kidney disease and sickle cell disease in a teenage male,” was published in Pediatric Nephrology.
The authors emphasized the importance of diagnosing co-occurring conditions in SCD patients early to understand disease progression and ensure patients’ access to the best possible treatment.
SCD is caused by mutations in the beta-globin (HBB) gene that lead to the an abnormal version of hemoglobin — the protein that carries oxygen in red blood cells — being produced.
People with SCD are at an increased risk of kidney problems compared with the general population. Kidney cysts are frequently seen in people with SCD, with 58% of patients reported developing them.
Kidney cysts in SCD patients are similar to those in ADPKD, a genetic condition caused by mutations in the PKD1 or PKD2 genes. These genes encode the proteins polycystin-1 and polycystin-2 that are key regulators of kidney cells.
Given the similarity of the symptoms, it’s difficult to determine whether the presence of kidney cysts is only due to SCD or is in part driven by ADPKD, mainly in its early stages.
Excessive number of kidney cysts with SCD
A recent study reported the case of a 16-year-old boy with SCD who was initially admitted to the hospital nine years earlier due to excessive urination at night.
At that point, imaging tests showed cysts in both kidneys, which were unusually large for his age, but their function was normal. He was given medication to control urination for several years. Later imaging tests showed the cysts had increased in size and number over time.
The patient was diagnosed with sickle cell nephropathy, a serious kidney complication of SCD, that was treated with an angiotensin-converting enzyme (ACE) inhibitor — a type of medication that helps relax blood vessels and lower blood pressure.
The boy also received antibiotics to manage SCD and blood transfusions to prevent stroke.
When he was a teenager, he received blood transfusions and hydroxyurea. He also was monitored for a serious SCD complication called carotid artery stenosis, which causes the arteries supplying oxygenated blood from the heart to the brain to narrow.
Over time, he developed an increasing number of kidney cysts that were larger than normal for SCD.
Researchers analyzed the sequence of 385 kidney-related genes to look for possible genetic mutations to explain the development of such large cysts. Two mutations were found, one in the HBB gene (c.20A > T; p.Glu7Val) and the other in the PKD1 gene (c.8311G > A; p.Glu2771Lys), confirming a double diagnosis of SCD and ADPKD.
Possible reasons co-occurrence of SCD, ADPKD not researched
“Genetic testing can be an important tool in this process for patients with SCD who have ultrasonographic [imaging] evidence of cysts,” the researchers wrote, noting a lack of studies reporting the co-occurrence of both conditions. This may be due to “the attribution of cysts and kidney complications to SCD”, without the exploration of “additional causes of kidney cysts after an SCD diagnosis is made,” they said.
It also can be explained by “the shortened life expectancy historically associated with SCD, which could limit the full progression of PKD, and subsequent kidney failure,” the researchers wrote, adding the disparity “in access to quality care for people with SCD, particularly in low-income and rural communities with limited resources” could be yet another explanation.
SCD and ADPKD differ in their mechanisms and treatment regimens. As such, identifying “this patient’s ADPKD diagnosis can enable management changes that might not have otherwise been considered,” they wrote, concluding that “reporting additional cases of SCD and ADPKD occurring as dual diagnoses” will help researchers better understand the disease course and the best strategies for treatment.
The boy is currently attending high school, where he needs special education. Despite his healthy status, he had two SCD crises in the past year.
Recent imaging tests showed his kidneys were still large for his age and contained a large number of cysts. Kidney function has remained stable over time and so has his blood pressure. Further MRI scans showed brain damage with mild narrowing of his right carotid artery.
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