Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012; 2: 139–274.
Definition, Etiology, PathogenesisTop
IgA nephropathy is the most common primary glomerulopathy. In addition to diffuse proliferation of mesangial cells and expansion of mesangial matrix, it is characterized by deposition of IgA in the glomeruli on immunofluorescence. It represents 10% to 45% of primary glomerular diseases and is more common in Asian and white populations.
Secondary causes of IgA nephropathy are most frequently associated with IgA-related vasculitis (also referred to as Henoch-Schönlein purpura), cirrhosis and other severe liver diseases, celiac disease and other autoimmune conditions, or HIV infection. Their treatment and prognosis are related to the underlying condition.
IgA nephropathy is characterized by hematuria that can be microscopic, recurrent macroscopic, or both. Macroscopic hematuria most frequently accompanies viral or bacterial upper respiratory tract infections or gastrointestinal infections. This so-called synpharyngitic hematuria differentiates IgA nephropathy from the longer 10-to-21-day delay of postinfectious glomerulonephritis. Macroscopic hematuria may last from several hours to several days and may be accompanied by flank pain. Non–nephrotic range proteinuria is often present, although nephrotic range proteinuria and nephrotic syndrome occur in 5% to 10% of patients. The degree of proteinuria is the strongest prognostic indicator. Hypertension is present in up to 40% of patients. IgA levels are increased in approximately 50% of patients, but this is neither sensitive nor specific.
Biopsy is required for a definitive confirmation.
Diagnosis is based on pathologic findings including predominant mesangial IgA deposition on immunofluorescence.
Hypertension is associated with progression of renal disease and should be controlled (see Renal Parenchymal Hypertension). Renin-angiotensin system blockers are the first-line therapy given the usual presence of proteinuria. In patients with proteinuria >1 g/d, renin-angiotensin system blockers should be titrated to reduce proteinuria to <1 g/d, as blood pressure permits, and additional titration to <500 mg/d can be considered.
Evidence for glucocorticoids for patients who continue to have proteinuria >1 g/d despite appropriate renin-angiotensin system blockade is uncertain.Evidence 1Weak recommendation (downsides likely outweigh benefits, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias, indirectness (composite endpoint), and imprecision. Lv J, Zhang H, Wong MG, et al; TESTING Study Group. Effect of Oral Methylprednisolone on Clinical Outcomes in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial. JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362. PubMed PMID: 28763548; PubMed Central PMCID: PMC5817603. Rauen T, Eitner F, Fitzner C, et al; STOP-IgAN Investigators. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med. 2015 Dec 3;373(23):2225-36. doi: 10.1056/NEJMoa1415463. PubMed PMID: 26630142. Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007 May;2(3):445-53. Epub 2007 Apr 11. PubMed PMID: 17699450. Older studies demonstrated benefit but were criticized for multiple reasons, including lack of universal renin-angiotensin system blockade. More recently, the STOP IgAN (Supportive Versus Immunosuppressive Therapy of Progressive IgA Nephropathy) trial has not shown improvement in estimated glomerular filtration rate (eGFR) with glucocorticoid use (although the trial excluded patients with proteinuria >3.5 g/d). The TESTING (Therapeutic Evaluation of Steroids in IgA Nephropathy Global) study did show an improvement in worsening eGFR but was stopped early due to increased adverse events (serious infections) in the treatment arm. Additional studies are ongoing.
Patients presenting with rapidly progressive glomerulonephritis/crescents on biopsy can be considered for cyclophosphamide and glucocorticoids.
Between 15% and 40% of patients will develop end-stage renal disease at 25 years after diagnosis. The degree of proteinuria is the most significant indicator of poor prognosis, with hypertension and decreased GFR at presentation also associated with worse outcomes.