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Research shows multiple factors drive CKD risk in lupus nephritis, including nephritic flares, baseline hypertension, renal impairment, and proteinuria.

Chronic kidney disease (CKD) occurs frequently in patients with lupus nephritis, but several risk factors can be addressed before CKD occurs or worsens in this population, according to findings published in Nephrology.

“Kidney involvement (lupus nephritis [LN]) is a common and severe disease manifestation in patients with systemic lupus erythematosus, affecting 30% [to] 60% of patients in reported series,” Tak Mao Chan, MD, DSc, and colleagues wrote. “Despite the advances in LN management over the past decades, progression to end stage kidney disease (ESKD) still occurs in 10%–20% of [patients with LN].”

However, the researchers noted that there is little data on the burden of CKD in patients with LN. “In this review, we aimed to assess the prevalence and risk factors of CKD in patients with LN and discuss the management and knowledge gaps of this prevalent but under-recognized phase that predates ESKD.”

Dr. Chan and colleagues performed a scoping review of studies, screening more than 500 articles before ultimately including 15 in their review. All studies used a retrospective cohort design to examine the relationship between LN and CKD in terms of prevalence and risk factors.

Due to the heterogeneous definitions of CKD outcomes in different studies, the researchers only included studies “that defined CKD as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² as per the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, or CKD progression as a decrease in eGFR of ≥30% or doubling of serum creatinine,” Dr. Chan and colleagues wrote.

CKD Risk 3-to-6-Fold Higher in Patients With LN & SLE

The researchers reported that the prevalence rates of CKD or its progression ranged from less than 10% to nearly 50%.

In studies conducted among primarily White populations, the prevalence of CKD ranged from 14.6% to 23.7%. Studies conducted in Asian countries, among others, had slightly higher prevalence rates, ranging from 20.5% to 47.6%.

In cohorts of patients with systemic lupus erythematosus (SLE), those with LN faced a 3-to-6-fold higher risk for developing CKD. Patients with LN in these cohorts with SLE also had worse outcomes compared with those without LN:

• Worse long-term renal survival at 5, 10, and 15 years: 65.5%, 54.5%, and 43.8%, respectively, versus 87.5%, 80.3%, and 72.7%, respectively
• More rapid eGFR decline (−4.35 vs −0.66 mL/min/year; P<0.05)

Studies from Italy, India, Egypt, and the United States found rates of CKD progression ranging from 12.5% to 36.8%. CKD progression is defined as “doubling of serum creatinine or ≥30% decrease in eGFR or creatinine clearance.”

Risk Factors for CKD Onset & Progression

Traits identified as risk factors for CKD onset or progression in one or more study included:

• Occurrence of nephritic flares
• Baseline hypertension
• Worse baseline renal impairment, defined as lower eGFR, higher creatinine levels, or a proportion of patients with eGFR <60 mL/min/1.73 m²
• Higher levels of proteinuria, defined as higher time-averaged proteinuria, 24-hour urine protein of >0.9 g/day, and proteinuria levels of >0.8 g/day at 12 months
• Failure to achieve remission

Two studies, defining their thresholds as a creatinine level of >0.9 mg/dL and an eGFR ≥75 mL/min/m2, reported that renal function at 1 year was predictive of the development of CKD in patients with lupus.

Other isolated risk factors for CKD onset or progression identified included:

• Raynaud’s phenomenon
• Time-averaged cholesterol levels
• Being a man
• Low hematocrit
• Older age
• Diabetes
• Azathioprine induction
• Delayed-onset LN
• Presence of anti-histone antibodies
• Acute renal dysfunction

Addressing CKD Risk in Patients with LN

According to Dr. Chan and colleagues, findings from the scoping review indicate that CKD is an important, frequent issue for patients with LN that is under-recognized.

Further, they continued that CKD progression and ESKD represent “major determinants” of adverse patient outcomes and quality of life that incur an economic burden.

“As the above-listed risk factors and interventional strategies illustrate, the prevention of CKD should be an inherent perspective informing clinical decisions throughout the course of patient management,” the researchers wrote. “There is [a] considerable knowledge gap on the impact of various treatments on CKD progression, racial/ethnic variations, immune versus non-immune interventions, and the role of conventional or novel biomarkers for long-term renal outcome, to be addressed by future studies.”