Rapid Progression of CKD Can Be Detected Early Using Simple Markers in Primary Care

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Among individuals newly diagnosed with chronic kidney disease (state G3), the 3-year risk of rapid disease progression was 14.6%, according to a Danish population-based study. Of further and significant concern were findings that the 3-year risk of hospitalization was 53.5% in this population and the risk of death 18.1%¹.

The investigators, publishing in the journal Nephrology, Dialysis, Transplantation, found key risk factors for rapid progression of CKD included greater albuminuria, being male, diabetes, cardiovascular disease (CVD), and hypertension.¹

Researchers, led by Christian Fynbo Christiansen, MD, PhD, a professor in the departments of clinical medicine and epidemiology at Aarhus University in Denmark, point out that the majority of evidence available on the risk markers for rapid progression of CKD stage G3 derives from hospital settings, is often focused on kidney failure, and has limited applicability in the community primary care setting.¹ Given the rapid increase in prevalence of the disease worldwide, a result largely, they say, of escalating rates of metabolic and cardiovascular disease, type 2 diabetes, and hypertension, it is essential to better understand the risk of progression at the earliest stages of the disease and to have tools to identify affected individuals in the community setting.¹

“We chose to investigate [CKD] because some of the patients experience rapid deterioration of their condition without us knowing exactly who,” Christiansen said in a university press release.² “Our goal was to understand which patients are most at risk and whether we can intervene early to delay or even prevent this progression.”²

..."some of the patients experience rapid deterioration of their condition without us knowing exactly who. Our goal was to understand which patients are most at risk and whether we can intervene early to delay or even prevent this progression."

For the countrywide study the investigators obtained individual level data from national medical databases, including hospitals and primary care, for adults aged 18 years and older with biochemically defined incident CKD stage G3 between 2017 and 2020. Incident CKD stage G3 was identified based on estimated GFR (eGFR) values calculated from plasma creatinine measurements using the 2009 CKD Epidemiology Collaboration Creatinine equation. Rapid progression of kidney disease was defined as eGFR decline of at least 5 mL/min/1.73 m² per year and kidney failure defined as 2 or more eGFR measurements below 15 mL/min/1.73 m² separated by ≥90 days and/or kidney replacement therapy.¹

Christiansen and fellow authors also evaluated various risk markers associated with rapid progression, including sex, urine albumin–creatinine ratio (uACR), pre-existing diabetes, hypertension and CVD.

The final cohort numbered 133 433 individuals with incident CKD stage G3. The median age at inclusion was 75 years and prevalence of metabolic comorbidities was high: T2D (18%), hypertension (62%), CVD (21%). The median eGFR at inclusion was 56 mL/min/1.73 m².

FINDINGS

In addition to the overall findings above, when the researchers used a heat map to highlight risk of CKD progression based on the investigational risk markers, they found the estimated 3-year risk of rapid decline ranged from 7% (95% CI, 6 - 8) in women with no albuminuria and without either T2D or hypertension/CVD to 47% (95% CI, 41 - 52) in women and 46% (95% CI, 42 - 49) in men with severe albuminuria and both diabetes and hypertension/CVD. Further, among individuals with severe albuminuria, diabetes and hypertension/CVD, nearly half experienced rapid progression within 3 years.

In their discussion of albuminuria level as risk factor for rapid disease progression, the researchers point out that within the year preceding incident CKD stage G3, 67% of the study participants did not have uACR assessed. They conclude that their findings, based on a large national population highlight “the potential for using readily available markers in routine clinical care to identify individuals at particularly high risk of rapid progression of CKD who may benefit from regular monitoring and prophylactic interventions to slow further decline in kidney function and associated adverse events.”

References

1. Vestergaard AHS, Jensen SK, Heide-Jorgensen U, et al. Risk factor analysis for a rapid progression of chronic kidney disease. Nephrol Dial Transplant. 2024;0:1–9. doi:10.1093/ndt/gfad271

2. Study: Simple measurement can predict risk of worsening of widespread kidney disease. News release. Aarhus University. https://health.au.dk/en/display/artikel/studie-simpel-maaling-kan-forudsige-risiko-for-forvaerring-af-udbredt-nyresygdom. February 22, 2024. Accessed March 4, 2024.