Patients with IgA Nephropathy May Not Be Receiving Optimal Supportive Care

Dana Rizk, MD

Credit: University of Alabama at Birmingham

Although optimal supportive therapy controlling blood pressure and proteinuria has proven to be pivotal in treating individuals with immunoglobulin A nephropathy (IgAN), many patients may not be receiving the right care, according to findings from a recent study.

Results highlighted the prevalence of suboptimal treatment of hypertension and proteinuria in patients with IgAN in the Cure Glomerulonephropathy Network (CureGN) study, also calling attention to patients with above-target proteinuria despite seemingly optimal blood pressure control to support the notion of more intensive conservative treatment.¹

“Our study highlights important findings about the current management of patients with IgA nephropathy and identifies opportunities for better, more holistic, management,” wrote Dana Rizk, MD, professor of medicine in the division of nephrology at the University of Alabama at Birmingham, and colleagues.¹ “In addition, a significant percentage of adult patients with IgA nephropathy remain at high risk of kidney disease progression despite optimal supportive therapy and may qualify for enrollment in clinical trials.”

In the absence of a cure for IgAN, treatment seeks to slow its progression and help manage symptoms, ultimately preventing the need for dialysis or a kidney transplant. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines outline several components thought to play an integral role in patients’ treatment plans, including monitoring blood pressure and proteinuria, using a renin-angiotensin-aldosterone system inhibitor (RAASI), and addressing cardiovascular risk. However, the real-world implementation of these recommendations and their impact on clinical outcomes merits further research to determine the best approach to disease management in this patient population.^1,2

Investigators sought to examine the prevalence of recommended robust conservative therapy among adults with IgAN enrolled in the CureGN study. In doing so, they aimed to identify patients who may benefit from more intensive conservative treatment and consideration for clinical trial enrollment.¹

Funded by the National Institutes of Health, CureGN is a longitudinal, prospective, observational study involving 2718 adult and pediatric patients with 4 glomerular diseases: minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgAN. During study visits occurring every 4-6 months, clinical parameters were measured and patient-reported outcomes, including medication adherence and clinical symptoms, were assessed.¹

The present study included patients ≥ 18 years of age with biopsy-proven IgAN. Per CureGN protocol, patients were categorized as having incident disease, defined as diagnosis < 6 months before CureGN enrollment, or prevalent disease, defined as diagnosis ≥6 months before CureGN enrollment.¹

In total, 502 adult patients with IgAN, including 165 incident cases and 337 prevalent cases, were included. Among the cohort, the mean age was 40 years and 58% of participants were male.¹

Treatment goals were based on the 2012 KDIGO guidelines for the management of patients with glomerular diseases, including long-term treatment with RAASIs for proteinuria ≥1 g/d, with up-titration of dosage as tolerated to achieve proteinuria <1 g/d. Blood pressure treatment goals were <130/80 mm Hg for patients with <1 g/d proteinuria and <125/75 mm Hg when initial proteinuria was ≥1 g/d.¹

Patients were considered to have adequate conservative therapy if they were on a maximal permissible or tolerated dose of a RAASI as monotherapy or combination therapy with alternate antihypertensive class medication(s), with blood pressure <130/80 mm Hg and urine protein-to-creatinine ratio (UPCR) <1 g/g or blood pressure <125/75 mm Hg and UPCR ≥1 g/g.¹

Investigators pointed out although 71% of patients were using a RAASI, just 41% were on a maximal tolerated dose. Despite their blood pressure allowing higher dosing, 34% of participants were not on maximal RAASI dosing.¹

At study enrollment, a median of 399 days from initial biopsy, 42% of the patients had optimal blood pressure control for their degree of proteinuria per the 2012 KDIGO guidelines. Of the remaining 58% of patients with suboptimal blood pressure and proteinuria, 7% were not on RAASIs, 27% were on submaximal tolerated RAASIs, and 24% were on maximal tolerated RAASIs but did not reach goal blood pressure.¹

At enrollment, 36% of incident patients and 46% of prevalent patients attained optimal supportive care. Immunosuppressant use was observed in 33% of the cohort, more frequently among incident (48%) than prevalent (26%) patients. Among patients not taking an immunosuppressant at enrollment, 55% had suboptimal blood pressure and proteinuria, reflecting suboptimal conservative treatment.¹

Investigators assessed in-person visits as a priority per cross-section, followed by any other type of visit within ±6 months of patients’ anniversary of the biopsy date. RAASIs, including submaximal tolerated doses, were used in 68%–78% of this cohort. Among patients who were never on an immunosuppressant throughout the study, 28%–71% had suboptimal blood pressure and proteinuria up to 6 years after biopsy.¹

Further analysis revealed 29%–38% of patients had persistence of blood pressure ≥125/75 mm Hg and UPCR ≥1.0 g/g or blood pressure ≥130/80 mm Hg and UPCR <1.0 g/g during the study period, regardless of immunosuppressant use.¹

Along with the several strengths attributable to the study design and execution, investigators also called attention to potential limitations. Of note, several pertinent subjective conservative measures for managing IgAN were not assessed, including dietary limitations and smoking cessation. Additionally, all study participants were seen at major academic centers and thus may not reflect the general US population with IgAN.¹

Still, investigators called attention to the significance of their findings: “These alarming results highlight the need to continue efforts to educate patients and care providers about the established merits of robust supportive care and demonstrate the mismatch between guideline-defined therapeutic goals and real-world achievement of those goals.”

References:

1. Rajasekaran A, Larkina M, Julian BA, et al. Optimal Conservative Therapy Use among Adult Cure Glomerulonephropathy Participants with IgA Nephropathy. Kidney360. doi:10.34067/KID.0000000000000306
2. Mayo Clinic. IgA Nephropathy (Berger Disease). Diseases & Conditions. June 9, 2023. Accessed January 23, 2024. https://www.mayoclinic.org/diseases-conditions/iga-nephropathy/diagnosis-treatment/drc-20352274