Laura Webber and Olivia Seifert
Chronic Kidney Disease (CKD) affects more than 10% of the population worldwide and is often associated with other conditions such as diabetes and hypertension. However, rare kidney diseases, although individually rare, collectively exert a notable impact on kidney health – accounting for an estimated 5–10% of CKD cases [1]. It is estimated that around 80% of these rare kidney diseases are genetic [2].
Despite their impact, rare kidney diseases often remain underdiagnosed and under-recognised within CKD care and policy frameworks. This raises critical questions: Why do so many rare kidney conditions go undiagnosed? Could rare kidney diseases account for more CKD cases than previously thought? And what would earlier diagnosis and targeted intervention mean for patients, health systems, and payers? This article aims to address these questions.
Underdiagnosis of rare kidney diseases in CKD patients
A significant proportion of CKD cases may be attributable to rare kidney diseases that are misdiagnosed or undiagnosed – with many patients being labelled as having CKD of unknown aetiology. This diagnostic gap stems from several factors: rare kidney diseases may present non-specific symptoms, which can lead to misdiagnosis with more common conditions, and genetic testing – critical for identifying rare kidney diseases with a genetic origin – has not traditionally been part of routine nephrology practice.
However, a recent study showed that 17.1% of patients with CKD of unknown aetiology could be reclassified once genetically tested, and just under 10% of adults with CKD may have a monogenic kidney condition [3]. Further, recent large-scale gene sequencing studies have suggested that pathogenic variants associated with various rare kidney diseases – including Alport syndrome [4] and autosomal dominant polycystic kidney disease (ADPKD) [5] – may be more common and more genetically complex than previously thought. These findings suggest that there may be an under-served community of rare genetic disease kidney patients that could be identified through improved CKD diagnostic practices who could benefit from rare kidney disease therapies. Applying genetic database analysis methodologies could generate data on the size of these patient populations.
Rare kidney diseases disproportionately contribute to risk of kidney failure in CKD patients
Analysis from the UK’s National Registry of Rare Kidney Diseases (RaDaR) found that the five-year risk of requiring dialysis or a transplant among rare kidney disease patients was 28 times higher than in the general CKD population, and that despite representing a minority of CKD cases, individuals with rare kidney diseases account for more than 25% of those receiving renal replacement therapy [1] and thus 25% of the cost. This trend is particularly evident in younger age groups, with rare inherited conditions accounting for the majority of paediatric CKD cases requiring kidney replacement therapies [6] – indicating that focusing diagnostic efforts within these communities could be a particularly efficient way of uncovering patients who could benefit from new or existing rare kidney disease therapies.
The importance of early CKD detection
Timely diagnosis of CKD can substantially improve clinical outcomes for patients by enabling earlier access to appropriate care pathways, which helps slow disease progression. As demonstrated by some of HealthLumen’s recent microsimulation modelling work, early detection and management of CKD is also far more cost-effective from a health system and payer perspective, than treating advanced disease, which is both resource-intensive and clinically complex [7]. Where CKD is detected at an early stage, treatment often focuses on addressing the underlying causal factors, such as by using SGLT2 inhibitors for cases linked to diabetes – and a number of targeted therapies are now available for several rare kidney conditions, such as Tolvaptan for ADPKD, and complement inhibitors for atypical haemolytic uraemic syndrome.
Policy considerations and strategic planning
Despite their significant impact, rare kidney diseases have historically received limited attention in CKD policy discussions. This is now beginning to shift. In 2023, an international panel published a roadmap recommending integrating genetic testing into routine nephrology practice [8].
Demonstrating the impact of earlier CKD diagnosis and interventions can provide valuable data for leveraging policy change. For example, as part of AstraZeneca’s Accelerate Change Together (ACT) on CKD programme, the Inside CKD online portal – informed by data generated by HealthLumen’s microsimulation-based modelling platform – compiles the results of studies which quantify the value of earlier detection and targeted intervention on CKD health and economic burden across 31 countries and regions. These insights can drive advocacy efforts pushing for earlier CKD diagnosis, support cost-effectiveness analyses and inform payer and policymaker decisions regarding new proposed therapies and interventions.
Looking ahead: Using epidemiological data to advocate for change
Rare kidney diseases represent a significant but often overlooked contributor to the global burden of CKD. As evidence of this grows, better diagnostic protocols combined with targeted therapeutic development and intervention strategies could transform care for these patients, as well as reduce the long-term health and economic burden of kidney failure on health systems, governments, and society more widely. Strengthening the epidemiological evidence base will be key to accelerating this shift – helping to prioritise rare kidney diseases within broader CKD strategies, guide resource allocation, and support policy and reimbursement decisions that enable earlier and more effective intervention.
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