Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney inter., Suppl. 2012; 2: 139–274.
Bertsias GK, Tektonidou M, Amoura Z, et al; European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. doi: 10.1136/annrheumdis-2012-201940. Epub 2012 Jul 31. PubMed PMID: 22851469; PubMed Central PMCID: PMC3465859.
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 Asians and whites.
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. Recommended blood pressure targets are at least <140/90 mm Hg, although some guidelines suggest <130/80 mm Hg in the setting of proteinuria. 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 contradictory. 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). Additional studies are ongoing.
If renin-angiotensin system blockers fail to adequately control proteinuria to <1 g/d in patients with a glomerular filtration rate (GFR) >50 mL/min/1.73 m2, one of the following glucocorticoid regimens can be considered, recognizing that the evidence is contradictory and glucocorticoids are not without significant adverse effectsEvidence 1Weak recommendation (benefits likely outweigh downsides, 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 and imprecision. Lv J, Xu D, Perkovic V, et al; TESTING Study Group. Corticosteroid therapy in IgA nephropathy. J Am Soc Nephrol. 2012 Jun;23(6):1108-16. doi: 10.1681/ASN.2011111112. Epub 2012 Apr 26. Review. PubMed PMID: 22539830; PubMed Central PMCID: PMC3358763. 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.:
1) IV methylprednisolone 0.5 to 1 g/d for 3 days followed by oral prednisone 0.5 mg/kg every other day for 6 months. Repeat methylprednisolone infusions in months 3 and 5 of treatment; or
2) Oral prednisone 0.8 to 1 mg/kg/d for 2 months, then tapered over 4 months.
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.