Chronic Kidney Disease Highly Prevalent in CF, Kidney Function Poorer in Transplanted Patients, Italian Study Says

Patients with cystic fibrosis (CF) have a high prevalence of chronic kidney disease (CKD) linked to higher levels of uric acid and fats in the blood, a study has found.

These manifestations seem to be particularly severe in patients who receive a lung transplant. As such, performing early and complete screenings in these  patients is recommended to determine the risk of kidney injury, and also of cardiovascular disease.

The study, “Renal involvement and metabolic alterations in adults patients affected by cystic fibrosis” was published in the Journal of Translational Medicine.

Cystic fibrosis (CF) is a disorder caused by mutations in the CFTR gene, which causes thick mucus to build up in various organs, including the lungs, pancreas, liver, and intestine.

Although lung disease is the major cause of death in this patient population, the effects of CF are not limited to the lungs.

Thanks to early diagnosis, antibiotic therapy, and advances in CF therapies (e.g., CFTR modulators), there has been a dramatic increase in patients’ life expectancy; the median survival has improved to 45 years in two decades.

A longer lifespan has exposed patients to long-term complications that were very rarely, or not at all, reported previously, including heart and kidney disease.

Historically, CF-related kidney disease (CFKD) was considered rare. However, several studies recently have reported different types of kidney problems in CF patients, including in children.

Kidney injury can be caused by CF itself (CFTR is necessary for proper kidney function), by other disorders such as diabetes, or by taking high doses of certain medicines, such as aminoglycosides (a group of antibiotics used to treat acute CF exacerbations).

While acute kidney injury (AKI) — a sudden episode of kidney failure or kidney damage — is well-studied in CF and known to be associated with lung infections and antibiotics, the prevalence and causes of chronic kidney disease (CKD) (a gradual loss of kidney function over time) are more controversial.

To shed light on this topic, researchers at the Sapienza University of Rome, Italy, evaluated the incidence and manifestations of kidney disease in 226 CF patients, with an average age of 35 years.

The team also searched for possible links between kidney damage and laboratory markers of metabolic disease, inflammation and endothelial dysfunction — dysfunction of the blood vessels that can be associated with a greater cardiovascular risk — and respiratory impairments.

Kidney injury was evaluated using the estimated glomerular filtration rate (eGFR), a marker of kidney function, using the MDRD equation and serum creatinine values. (An eGFR below 90 mL/min/1.73 m² indicates kidney damage, and was used as a sign of CKD.)

Of a total of 226 patients, 65 were found to have CKD, which corresponded to a prevalence of 28.8%; that was considered “high” by the researchers. Most of those with kidney damage had a class II CFTR mutation (delF508), the most frequent cause of CF.

Many patients (158) also had lower-than-normal breathing function, of whom 58 had their respiratory capacity severely reduced, as measured by forced expiratory volume in one second (FEV1), a standard respiratory test.

Notably, the team found that 28 patients had received a lung transplant and this was linked with poorer kidney function (lower eGFR) compared to CF patients who had not had a transplant.

Lab tests revealed a significant association between worse kidney damage and a greater amount of lipids (fats) in the blood — including a higher level of triglycerides, total cholesterol and low-density lipoproteins (LDL). According to the researchers, this reflects “a lipid profile that favors atherosclerosis and consequent increase in cardiovascular risk.”

An increase in serum uric acid (SUA) — a circumstance associated with kidney and cardiovascular events — also was associated with worse kidney function.

No relationship was found between chronic kidney disease and blood levels of vitamin D, glucose (sugar) and hemoglobin A1C (a blood measurement of diabetes risk).

Given the association between high levels of SUA, triglycerides and LDL with worse kidney function, researchers emphasized the “need for an early and complete screening of the main metabolic indexes to reduce cardiovascular risk and progression of renal damage, in particular in patients with lung transplant.”

Also, regularly testing for eGFR could help predict and monitor kidney damage, especially in transplanted patients, they added.