Patients with systemic lupus erythematosus without concurrent kidney involvement at diagnosis still face twice the risk of developing chronic kidney disease compared with the general population, a study suggests.

They also remain at increased risk of cardiovascular events and mortality despite advanced treatment, highlighting the importance of long-term monitoring and management of modifiable risk factors, the Israeli researchers say.

They identified 1,145 patients with SLE and preserved renal function (eGFR of >60 mL/min/1.73 m²) at diagnosis from a national database, who were matched with 91,681 controls by age, sex and ethnicity. Patients with lupus nephritis were excluded.

Incident CKD, was defined as at least two eGFR measurements of <60 mL/min/1.73 m², separated by more than 90 days, during follow-up.

Over a median 6 years, SLE was associated with a higher risk of:

• CKD (5.2% vs 2.7%; HR 1.96, 95% CI 1.50–2.54)
• ESKD (0.6% vs 0.1%; HR 3.13, 95% CI 1.38–7.08)
• MACE (7.2% vs 5.8%; HR 1.63, 95% CI 1.31–2.04)
• All-cause mortality (9.3% vs 3.3%; HR 4.52, 95% CI 3.71–5.50)

Unsurprisingly, smoking (HR 1.16), diabetes (HR 1.51) and hypertension (HR 2.72) were identified as the strongest risk factors associated with kidney disease.

In a sensitivity analysis restricted to patients with available urine protein measurements, the increased risks associated with SLE remained for:

• CKD (HR 1.94, 95% CI 1.06–3.53)
• ESKD (HR 2.55, 95% CI 1.03–6.34)
• All-cause mortality (HR 3.74, 95% CI 2.81–4.98)

Both lupus and control groups had similar mean eGFR at the index date and at last follow-up, with comparable mean changes over time, the researchers noted.

“Intriguingly, there are very few studies comparing the risk of CKD in patients with SLE without lupus nephritis with that of the general population, in contrast to the extensive literature comparing CKD risk between SLE patients with and without lupus nephritis,” the researchers reported in Rheumatology [link here].

They suggested mechanisms beyond immune-mediated renal injury contributed to adverse outcomes, considering patients remained at higher risk while on conventional immunosuppressive therapies and biologic agents.

“These mechanisms appear to share a common pathophysiology involving atherosclerosis and cardiometabolic disturbances. Accumulating evidence highlights accelerated atherosclerosis as a central underlying process linking renal, cardiovascular, and survival risks in this population, emphasising the pivotal role of vascular disease in the morbidity and mortality of SLE, even in the absence of clinically apparent lupus nephritis,” the researchers said.