Sparsentan for treating primary IgA nephropathy [ID6308]

IgA nephropathy (also known as Berger’s disease) is a chronic autoimmune kidney disease. It causes a build up of IgA containing immune complexes in the glomeruli of the kidneys.

This causes inflammation and damage in the glomeruli and reduces their function eventually leading to scarring of the whole kidney. (1-4)In IgA nephropathy both kidneys are affected equally. (5) The condition is commonly classified as primary or secondary with secondary disease associated with comorbidities such as IgA vasculitis and chronic liver disease. (6)The presentation of IgA nephropathy varies considerably and in its early stages may have no symptoms.

The most common symptoms are blood or protein in the urine (haematuria or proteinuria).(5) IgA nephropathy is also associated with complications from reduced kidney function to high blood pressure high cholesterol and cardiovascular problems.

The rate of progression is variable although ongoing decline in glomerular function may eventually lead to kidney failure requiring transplant or life-long dialysis. (5)A particularly severe form of the disease known as rapidly progressive IgA nephropathy has been reported in a small proportion of people. (7)It is estimated that around 4 in 10000 people have primary IgA nephropathy in Europe. (8) An analysis of the IgA nephropathy cohort of the UK National Registry of Rare Kidney Diseases identified that between 45% to 70% of people with IgA nephropathy develop kidney failure within 10 to 20-years of diagnosis and that as the median age at diagnosis was 41-years and the median kidney survival was 11.4-years few patients are expected to avoid kidney failure in their lifetime. (9)There is no cure for IgA nephropathy.

The aim of current treatment is to prevent or delay kidney failure and associated complications. Initial treatment focuses on reducing protein levels in the urine and blood pressure.

Antihypertensives such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are given at the maximum tolerated licensed doses. (7) Supportive care also includes dietary modification and exercise with or without diuretics to remove extra fluid from the blood and reduce cholesterol levels.

Some people remain at high risk of progression despite optimised supportive care with lifestyle modifications and the maximum tolerated licensed doses of ACE inhibitors or ARBs. Second-line treatments are offered to people with more than 1 gram of proteinuria per day.

Second-line treatments may include glucocorticoids sodium-glucose cotransporter-2 (SGLT2) inhibitors or entry into a clinical trial.

Clinical experts explained that the use of glucocorticoids is rare or limited because of safety concerns associated with systemic use. SGLT2 inhibitors are being increasingly used since NICE technology appraisal guidance 775 was published.

NICE technology appraisal guidance 937 recommends targeted-release budesonide as an add on to standard care when there is a risk of rapid disease progression in adults with a urine protein-to-creatinine ratio of 1.5 g/g or more. People with severely reduced kidney function may need dialysis or a kidney transplant.References 1.

National Institute of Diabetes and Digestive and Kidney Diseases. (2015) IgA nephropathy. (Accessed February 2024) 2. Maillard N Wyatt RJ Julian BA et al. Current Understanding of the Role of Complement in IgA Nephropathy. Journal of the American Society of Nephrology : JASN. 2015; 26: 1503-12. 3. Rodrigues JC Haas M and Reich HN.

IgA Nephropathy. Clinical journal of the American Society of Nephrology: CJASN. 2017; 12: 677-86. 4. Suzuki H Kiryluk K Novak J et al. The Pathophysiology of IgA Nephropathy. Journal of the American Society of Nephrology. 2011; 22: 1795. 5. IgA Nephropathy Foundation. (2021) IgA Nephropathy – What You Need to Know. (Accessed February 2024) 6.

Wang M Lv J Zhang X Chen P Zhao M and Zhang H. Secondary IgA Nephropathy Shares the Same Immune Features With Primary IgA Nephropathy. Kidney international reports. 2020; 5: 165-72.7.

International Society of Nephrology (ISN). (2021) Kidney Disease: Improving Global Outcomes (KDIGO) (Accessed February 2024) 8.

European Medicines Agency (EMA). (2020) Orphan designation for the treatment of primary IgA nephropathy. (Accessed February 2024) 9. Pitcher D Braddon F Hendry B et al. Long-Term Outcomes in IgA Nephropathy. Clinical journal of the American Society of Nephrology: CJASN. 2023; 18(6): 727-38