Three new reviews highlight advances in diagnosis, therapeutics, and sex-specific care that could transform outcomes in chronic kidney disease.
Earlier detection, combination drug therapy, and greater recognition of sex differences could substantially improve outcomes in chronic kidney disease, according to a major new Lancet series.
The series details a rapidly evolving field in which improved diagnostics, expanding therapeutic options, and a better understanding of disease biology are challenging the traditional view of CKD as an inevitably progressive condition.
Instead, the researchers say CKD should be recognised as a treatable multisystem disorder that shares inflammatory, metabolic and fibrotic pathways with cardiovascular disease, diabetes, and obesity.
The landmark papers, authored by researchers from around the world, including Australia, and led by Dr Jennifer Lees, Senior Clinical Research Fellow at the University of Glasgow and honorary consultant nephrologist at the NHS Greater Glasgow and Clyde, detail the full extent of the healthcare burden caused by CKD, including its poor diagnosis rates and the complications and risks around delayed treatment.
“Chronic kidney disease remains one of the most concerning conditions currently impacting global health,” Dr Lees said.
“The overriding message from our series of research papers is that there remains a pressing need for attention and resource to be focused on this condition.
“There is huge potential to improve early diagnosis, treatment and healthy lifespan by testing urine for protein routinely across a range of healthcare settings. This may be particularly important in those most at risk of under diagnosis, including non-white populations and women.”
The first paper in the series, published in The Lancet this month, estimated that CKD affects up to 844 million adults worldwide and was projected to become the fifth leading cause of death by 2040. This paper included researchers from Adelaide University’s School of Public Health.
In Australia, about 2.7 million adults have markers for CKD yet only 7.4% of people are aware of their condition.
Adelaide University researcher Dr Matthew Borg said early detection was critical to improving outcomes for people living with chronic kidney disease.
“Kidney disease is often described as a silent condition because many people don’t realise they have it until it has already progressed,” Dr Borg said.
“That’s why simple, low-cost tests are so important – they can detect kidney disease early, when treatment is most effective.
“A simple combination of urine and blood tests, together with blood pressure checks, can identify kidney disease much earlier and open the door to treatments that can slow or even prevent progression to kidney failure.
“With chronic kidney disease now affecting hundreds of millions of people globally, improving access to routine screening could help save lives and reduce pressure on health systems around the world.”
Despite being recognised by both the United Nations and the World Health Organization as a major global health concern in recent years, progress in improving the diagnosis of CKD remains slow.
Many health systems rely on creatinine testing alone and fail to routinely screen for albuminuria, the researchers wrote.
“Addressing these challenges requires coordinated investment in diagnostics, workforce training, laboratory infrastructure, and health-care system strengthening alongside continued technological advancement,” they wrote.
Among the most important diagnostic advances is increasing use of cystatin C, which could improve estimation of glomerular filtration rate (eGFR), particularly in older adults, patients with low muscle mass, and those in whom creatinine-based estimates may be misleading.
The researchers highlighted evidence that combining creatinine and cystatin C improved prediction of kidney failure, acute kidney injury, cardiovascular events, and mortality.
They said that albuminuria should be viewed not merely as evidence of kidney damage but as a key marker for screening, risk stratification, and treatment decisions.
They pointed to growing roles for kidney biopsy, genetic testing and disease-specific prediction models, while advances in multiomics, imaging, and artificial intelligence are providing new insights into CKD mechanisms and progression.
Population screening using eGFR and albuminuria was increasingly cost-effective, the authors noted, particularly now that disease-modifying therapies were available.
The second paper, which included researchers from The George Institute for Global Health, University of New South Wales, and the Prince of Wales Hospital, Sydney, focused on biological sex differences, which the researchers said remained poorly incorporated into research, clinical guidelines, and prescribing decisions.
Females and males differ in kidney structure, tubular transport, immune responses, hormonal regulation, and drug metabolism, all factors that influence susceptibility to kidney injury, disease progression and treatment response.
Women with CKD faced particularly high risks during pregnancy, including pre-eclampsia, acute kidney injury, preterm delivery and maternal mortality. Pregnancy-related complications themselves are associated with increased long-term risks of CKD and kidney failure, yet routine antenatal care rarely incorporates systematic CKD screening or follow-up.
“Females remain under-represented in preclinical and clinical research, limiting understanding of sex-specific mechanisms,” the researchers noted.
“Systematic integration of sex differences into CKD education programmes across preclinical, clinical, and pharmaceutical sciences, and throughout research, diagnostics, therapeutics, and policy, is required to improve CKD outcomes.”
Menopause also brought risks and benefits, they found.
“In females, GFR declines more quickly following the onset of menopause, suggesting a protective role of endogenous oestrogens in maintaining kidney health,” they wrote.
“In the National Health and Nutrition Examination Survey (n=4945), early (<45 years) natural and surgical menopause were associated with a higher risk of CKD compared with those with menopause aged 45 years and older.”
Related
The therapeutic review, the third paper in the series, described what the researchers called a decade of progress in CKD management. Renin-angiotensin system blockade remains the foundation of treatment, but newer drug classes are delivering benefits that extend well beyond glycaemic control or blood pressure reduction.
SGLT2 inhibitors have demonstrated benefits across a broad range of CKD populations, including patients without diabetes, reducing albuminuria, slowing eGFR decline, lowering rates of acute kidney injury, decreasing hospitalisation for heart failure, and improving survival. In patients with diabetic kidney disease, non-steroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists have also shown significant reductions in kidney and cardiovascular outcomes.
“Despite these therapeutic improvements, the management of CKD continues to increase in complexity,” the researchers wrote.
“CKD only rarely occurs as an isolated health condition and is frequently seen alongside health conditions where there are shared causal pathways, including cardiovascular diseases, metabolic conditions, infections, and cancer.
“In many countries, most patients with CKD are found in the community, under general or non-nephrology specialty care, where health-care providers might be less aware of the evolving burden of CKD and the tremendous opportunities for improvements through prompt CKD detection and management.
“This growing burden requires new approaches to care and changing roles for health-care practitioners.”
The researchers said an emerging four-pillar approach to diabetic kidney disease comprised renin-angiotensin system inhibitors, SGLT2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and GLP-1 receptor agonists.
Evidence from meta-analyses and early combination studies suggests the benefits of these agents may be additive, raising the prospect of substantially greater reductions in CKD progression and cardiovascular events than achieved with single-drug strategies.
Several additional therapeutic classes were advancing through late-stage development, including endothelin receptor antagonists, aldosterone synthase inhibitors, and anti-IL-6 therapies, while APOL1-targeted treatments may offer new options for patients with genetically mediated kidney disease, the researchers noted.
However, translating these advances into routine practice will not be straightforward. The researchers noted that 96% of patients with CKD have at least one additional long-term condition and more than half have four or more comorbidities.
Polypharmacy affects more than 80% of patients, frailty is common, and most care occurs outside nephrology services.
The researchers also highlight persistent evidence gaps, with older adults, women, children, patients with advanced CKD, and populations in low- and middle-income countries frequently underrepresented in clinical trials.
First paper: The Lancet, June 2026
