IgA Nephropathy Workup
- Author: Mona Brake, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
The first step in confirming the diagnosis is a careful urinalysis of a first-void urine sample performed by an experienced urine analyst. Direct examination of the urine sediment is required to identify red blood cells (RBCs) and RBC casts, both of which indicate glomerular injury.
Proteinuria testing can be accomplished quantitatively by a 24-hour measurement of urinary protein or semiquantitatively by measuring a urine protein/creatinine ratio. A normal ratio should be less than approximately 0.1. Also, adults older than 50 years with proteinuria should have a urine protein electrophoresis performed to exclude monoclonal light chains as a cause of proteinuria.
Assess renal function in patients with proteinuria or hematuria by a 24-hour creatinine clearance test. Alternatively, the glomerular filtration rate (GFR) can be estimated using the Modification of Diet in Renal Disease (MDRD) formula.
Although the serum IgA level is elevated in up to half of patients, this finding is insensitive, nonspecific, and of no clinical utility
Diagnosis of IgA nephropathy is confirmed by renal biopsy.
In IgA nephropathy, proteinuria rarely occurs without microscopic hematuria. Mild proteinuria is common.
Nephrotic-range proteinuria is uncommon, occurring in only 5% of patients with IgA nephropathy, and is more commonly seen in children and adolescents. Nephrotic-range proteinuria can be seen early in the disease course as well as in patients with advanced disease
Patients with heavy proteinuria and nephrotic syndrome are likely to have IgA deposition with diffuse proliferative glomerular lesions or minimal-change light microscopic findings
Acute kidney injury
Acute kidney injury, with edema, hypertension, and oliguria, occurs in fewer than 5% of patients. It can develop from either of the following two distinct mechanisms:
Acute severe immune injury can manifest as necrotizing glomerulonephritis and crescent formation
Alternatively, only mild glomerular injury is observed with gross hematuria, and kidney injury is presumably due to tubular occlusion by RBCs; this is reversible, and renal function recovers with supportive measures
The most common light microscopy findings are focal or, more often, diffuse mesangial proliferation and extracellular matrix expansion (as seen in the image below). Morphology can range from normal to moderate or severe intracapillary or extracapillary proliferative lesions. While some patients have IgA deposits on immunofluorescence and little or no change by light microscopy, a few patients have segmental necrotizing lesions with crescent formation due to extensive disruption of the capillaries. Occasionally, patients have focal glomerular sclerosis indistinguishable from focal segmental glomerulosclerosis on light microscopy. A number of other findings can be observed in advanced disease, including interstitial fibrosis, tubular atrophy, and vascular sclerosis. These findings can be helpful prognostic tools in patients with IgA nephropathy.
Electron microscopy shows mesangial hypercellularity and increased mesangial matrix. The important finding is electron-dense deposits in the mesangium, such as those in the image below, but deposits in the subendothelial and subepithelial region of the glomerular capillary wall are found in a minority of patients, especially those with more severe disease.
Immunofluorescence findings are the pathologic hallmark of this disease. IgA is deposited in a diffuse granular pattern in the mesangium (as seen in the image below) and occasionally in the capillary wall. Immunoglobulin G (IgG)4 may accompany IgA, and C3 is often present.
Berger J, Hinglais N. [Intercapillary deposits of IgA-IgG]Les Depots Intercapillaires d''IgA-IgG. J Urol Nephrol (Paris). 1968 Sep. 74(9):694-5. [Medline].
IgA nephropathy. Nat Rev Dis Primers. 2016 Feb 11. 2:16002. [Medline].
Glassock RJ. IgA nephropathy: challenges and opportunities. Cleve Clin J Med. 2008 Aug. 75(8):569-76. [Medline]. [Full Text].
Cattran DC, Coppo R, Cook HT, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009 Jul 1. [Medline].
Coppo R, Troyanov S, Camilla R, et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int. 2010 Mar 3. [Medline].
Knoppova B, Reily C, Maillard N, Rizk DV, Moldoveanu Z, Mestecky J, et al. The Origin and Activities of IgA1-Containing Immune Complexes in IgA Nephropathy. Front Immunol. 2016. 7:117. [Medline].
Fabiano RC, Pinheiro SV, Simões E Silva AC. Immunoglobulin A nephropathy: a pathophysiology view. Inflamm Res. 2016 Jun 28. [Medline].
McQuarrie EP, Mackinnon B, McNeice V, Fox JG, Geddes CC. The incidence of biopsy-proven IgA nephropathy is associated with multiple socioeconomic deprivation. Kidney Int. 2014 Jan. 85(1):198-203. [Medline].
[Guideline] Yuzawa Y, Yamamoto R, Takahashi K, Katafuchi R, Tomita M, Fujigaki Y, et al. Evidence-based clinical practice guidelines for IgA nephropathy 2014. Clin Exp Nephrol. 2016 Apr 20. 70:S56-62. [Medline]. [Full Text].
Wyatt RJ, Julian BA, Baehler RW, et al. Epidemiology of IgA nephropathy in central and eastern Kentucky for the period 1975 through 1994. Central Kentucky Region of the Southeastern United States IgA Nephropathy DATABANK Project. J Am Soc Nephrol. 1998 May. 9(5):853-8. [Medline].
Rollino C, Vischini G, Coppo R. IgA nephropathy and infections. J Nephrol. 2016 Aug. 29 (4):463-8. [Medline].
Scolari F, Amoroso A, Savoldi S, et al. Familial clustering of IgA nephropathy: further evidence in an Italian population. Am J Kidney Dis. 1999 May. 33(5):857-65. [Medline].
Ai Z, Li M, Liu W, Foo JN, Mansouri O, Yin P, et al. Low α-defensin gene copy number increases the risk for IgA nephropathy and renal dysfunction. Sci Transl Med. 2016 Jun 29. 8 (345):345ra88. [Medline].
Hahn WH, Suh JS, Cho BS, Kim SD. The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy. Exp Mol Med. 2009 Nov 30. 41(11):793-801. [Medline]. [Full Text].
Appel GB, Waldman M. The IgA nephropathy treatment dilemma. Kidney Int. 2006 Jun. 69(11):1939-44. [Medline].
Gharavi AG, Yan Y, Scolari F, et al. IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23. Nat Genet. 26(3):354-7. [Medline].
Russo D, Minutolo R, Pisani A, et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis. 2001 Jul. 38(1):18-25. [Medline].
Manno C, Torres DD, Rossini M, et al. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transplant. 2009 Jul 23. [Medline].
Tang SC, Tang AW, Wong SS, et al. Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 2010 Mar. 77(6):543-9. [Medline].
Dillon JJ. Fish oil therapy for IgA nephropathy: efficacy and interstudy variability. J Am Soc Nephrol. 1997 Nov. 8(11):1739-44. [Medline].
Liu LJ, Lv JC, Shi SF, et al. Oral calcitriol for reduction of proteinuria in patients with IgA nephropathy: a randomized controlled trial. Am J Kidney Dis. 2012 Jan. 59(1):67-74. [Medline].
Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994 Mar 31. 330(13):877-84. [Medline].
Levey AS, Adler S, Caggiula AW, et al. Effects of dietary protein restriction on the progression of advanced renal disease in the Modification of Diet in Renal Disease Study. Am J Kidney Dis. 1996 May. 27(5):652-63. [Medline].
Vergano L, Loiacono E, Albera R, Coppo R, Camilla R, Peruzzi L, et al. Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy?. J Nephrol. 2014 Apr 23. [Medline].
Kovács T, Vas T, Kövesdy CP, Degrell P, Nagy G, Rékási Z, et al. Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients. Int Urol Nephrol. 2014 Sep 3. [Medline].
Maeda I, Hayashi T, Sato KK, Shibata MO, Hamada M, Kishida M, et al. Tonsillectomy has beneficial effects on remission and progression of IgA nephropathy independent of steroid therapy. Nephrol Dial Transplant. 2012 Jul. 27(7):2806-13. [Medline].
Watanabe H, Goto S, Kondo D, Takata T, Yamazaki H, Hosojima M, et al. Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients. Clin Exp Nephrol. 2016 May 23. [Medline].
Yu L, Jiang L, Zhou XJ, et al. Common genetic variants in the chromogranin a promoter are associated with renal injury in IgA nephropathy patients with malignant hypertension. Ren Fail. 2010 Jan. 32(1):41-6. [Medline].
Baek CH, Lee JG, Park JH, Kim H, Yang WS, Kim YS, et al. The clinical outcomes of second kidney transplantation in IgA nephropathy: a multicenter retrospective study. Clin Nephrol. 2016 Aug. 86 (2):87-93. [Medline].
Gutiérrez E, Zamora I, Ballarín JA, Arce Y, Jiménez S, Quereda C, et al. Long-Term Outcomes of IgA Nephropathy Presenting with Minimal or No Proteinuria. J Am Soc Nephrol. 2012 Oct. 23(10):1753-1760. [Medline]. [Full Text].
Le W, Liang S, Chen H, Wang S, Zhang W, Wang X, et al. Long-term outcome of IgA nephropathy patients with recurrent macroscopic hematuria. Am J Nephrol. 2014. 40(1):43-50. [Medline].
Walsh M, Sar A, Lee D, et al. Histopathologic features aid in predicting risk for progression of IgA nephropathy. Clin J Am Soc Nephrol. 2010 Mar. 5(3):425-30. [Medline]. [Full Text].
Shen PC, He LQ, Tang Y, et al. Clinicopathological characteristics and prognostic factors of asymptomatic IgA nephropathy. J Investig Med. 2010 Mar. 58(3):560-5. [Medline].
Pozzi C, Bolasco PG, Fogazzi GB, et al. Corticosteroids in IgA nephropathy: a randomised controlled trial. Lancet. 353(9156):883-7. [Medline].
Schena FP, Cerullo G, Rossini M, et al. Increased risk of end-stage renal disease in familial IgA nephropathy. J Am Soc Nephrol. 2002 Feb. 13(2):453-60. [Medline]. [Full Text].
Lundberg S, Qureshi AR, Olivecrona S, Gunnarsson I, Jacobson SH, Larsson TE. FGF23, Albuminuria, and Disease Progression in Patients with Chronic IgA Nephropathy. Clin J Am Soc Nephrol. 2012 May. 7(5):727-34. [Medline]. [Full Text].
Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol. 2005 Jul. 16(7):2088-97. [Medline].
Bazzi C, Rizza V, Paparella M, et al. Fractional urinary excretion of IgG is the most powerful predictor of renoprotection by ACE inhibitors in IgA nephropathy. J Nephrol. 2009 May-June. 22(3):387-396. [Medline].
Dillon JJ. Treating IgA nephropathy. J Am Soc Nephrol. 2001 Apr. 12(4):846-7. [Medline].
Donadio JV Jr, Grande JP. Immunoglobulin A nephropathy: a clinical perspective. J Am Soc Nephrol. 1997 Aug. 8(8):1324-32. [Medline].
Donadio JV Jr, Larson TS, Bergstralh EJ, Grande JP. A randomized trial of high-dose compared with low-dose omega-3 fatty acids in severe IgA nephropathy. J Am Soc Nephrol. 12(4):791-9. [Medline].
Pozzi C, Andrulli S, Del Vecchio L, et al. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol. 2004 Jan. 15(1):157-63. [Medline].
Reich HN, Troyanov S, Scholey JW, et al. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007 Dec. 18(12):3177-83. [Medline].
Russo D, Pisani A, Balletta MM, et al. Additive antiproteinuric effect of converting enzyme inhibitor and losartan in normotensive patients with IgA nephropathy. Am J Kidney Dis. 1999 May. 33(5):851-6. [Medline].
Shoji T, Nakanishi I, Suzuki A, et al. Early treatment with corticosteroids ameliorates proteinuria, proliferative lesions, and mesangial phenotypic modulation in adult diffuse proliferative IgA nephropathy. Am J Kidney Dis. 35(2):194-201. [Medline].