• A groundbreaking study in Spain has analyzed the potential genetic causes of idiopathic (i.e. of unknown origin) chronic kidney disease.
• More than 60,000 people are on dialysis or have undergone kidney transplantation in Spain, and one in five does not know the cause of their disease.
Madrid, August 22, 2024.
Chronic kidney disease (CKD) is a disorder in which kidneys experience a progressive decline in their function. It is known as idiopathic when no known or identifiable causes are present. At its most advanced stages, patients require substitutive renal therapy (dialysis or transplantation) in order to live. This is the reality for over 60,000 thousand people in Spain.
This pathology is currently considered a “silent epidemic”, as its prevalence has increased around 30% in the last decade both in our country and worldwide, but it has a high rate of underdiagnosis (about 40%). Among other factors, this is due to the fact that many of its symptoms are not easily recognizable at early stages.
In fact, in 18% of patients who need dialysis or kidney transplant to live, the origin of the disease is unknown, i.e. one in five patients with advanced CKD are started on substitutive renal therapy without having identified the cause of their pathology.
Patricia de Sequera, MD, head of the Nephrology Unit at the Infanta Leonor University Hospital, associate professor at the Medical School of the Complutense University of Madrid, and principal investigator in the GENSEN study, explained that this “embarrassing reality” originated the idea of carrying out the first study on the role of genetics in idiopathic CKD in Spain: the GENSEN study, sponsored by the Spanish Society of Nephrology. “The reality is that this lack of diagnosis without having previously ruled out a genetic disease is currently unacceptable”, stated the doctor.
A collaborative study including 53 Spanish hospitals
Fifty-three Spanish hospitals have taken part in this research, with Health in Code being in charge of genetic testing. “I honestly believe that the success of this study has been partly due to the teamwork between researchers and Health in Code, where the degree of expertise and commitment of José María García-Aznar, head of the Hereditary Kidney Diseases area, and his team, ranging from sample management to the generation of final reports, were valued from the very beginning”, said de Sequera.
This work has been published in the scientific journal American Journal of Kidney Diseases, one of the most important nephrology journals worldwide. The study analyzed 850 patients under age 45 who had advanced CKD. The results were insightful: in 28% of them (233 patients), an evident genetic cause was identified in the form of pathogenic variants that explained the disease. Moreover, an additional 180 patients (21%) showed potentially relevant genetic findings that would require additional evidence to confirm the hereditary factor as a definitive cause.
José María García-Aznar, head of Health in Code’s Hereditary Kidney Diseases area, explained the methodology applied in this study: “One of the main differentiating characteristics of this technique involves the enriched capture and analysis of more than 500 genes associated with hereditary kidney disease, and our study focused exclusively on those genes whose genetic defects are expected to be associated with diseases that potentially cause CKD. Moreover, this strategy also improves resolution for some genetic defects whose analysis is intrinsically difficult.”
Generally, the causes of hereditary kidney disease found in most cases were already known, but were not always taken into account for the purposes of suspecting a genetic origin in CKD patients. In fact, around 20 out of more than 500 studied genes were recurrently found to have genetic defects in the study population. “The results have revealed genetic defects in some poorly known genes that cause dominant, adult-onset podocytopathies that go unnoticed until the disease becomes severely evident. In other cases, novel variants not previously described have been identified, constituting a new repository of mutations for the scientific community”, José María García-Aznar pointed out.
De Sequera concluded that the results from the GENSEN study highlight the importance of genetics in kidney disease and the need for early and accurate diagnosis to implement all the available measures that can prevent the progression of a lifelong disease expected to result in the need for dialysis and kidney transplant. “Multidisciplinary work is essential: geneticists and nephrologists must maintain a constant and clear communication in order to provide patients with an accurate and timely diagnosis. Clinical genetics is increasingly recognized as an important area within nephrology care, and the expertise of geneticists is required for a correct diagnostic approach.”
Artículo científico: GENSEN Study Investigators (2024). Genetic Characterization of Kidney Failure of Unknown Etiology in Spain: Findings From the GENSEN Study. American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2024.04.021
