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IgA Nephropathy Workup

  • Author: Mona Brake, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Jul 23, 2016
 

Approach Considerations

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.

Proteinuria

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
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Histologic Findings

Light microscopy

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.

Light microscopy of a glomerulus from a patient wi Light microscopy of a glomerulus from a patient with immunoglobulin A nephropathy showing increased mesangial matrix and cellularity.

Electron microscopy

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.

Electron microscopy showing large dark mesangial d Electron microscopy showing large dark mesangial deposits.

Immunofluorescence

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.

Immunofluorescence microscopy demonstrating large Immunofluorescence microscopy demonstrating large mesangial immunoglobulin A (IgA) deposits diagnostic of IgA nephropathy.
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Contributor Information and Disclosures
Author

Mona Brake, MD Assistant Professor, Department of Internal Medicine, Kansas University School of Medicine

Mona Brake, MD is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Departments of Pediatrics and Obstetrics and Gynecology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Royal College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Additional Contributors

James H Sondheimer, MD, FACP, FASN Associate Professor of Medicine, Wayne State University School of Medicine; Medical Director of Hemodialysis, Harper University Hospital at Detroit Medical Center; Medical Director, DaVita Greenview Dialysis (Southfield)

James H Sondheimer, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Receive dialysis unit medical director fee (as independ ent contractor) for: DaVita .

Acknowledgements

Douglas Somers, MD Assistant Professor, Department of Internal Medicine, Division of Nephrology, University of Iowa Medical Center

Douglas Somers, MD is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgments

The authors thank Dr. Tim Timmerman, pathologist, for his invaluable help with the pathology slides.

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Light microscopy of a glomerulus from a patient with immunoglobulin A nephropathy showing increased mesangial matrix and cellularity.
Electron microscopy showing large dark mesangial deposits.
Immunofluorescence microscopy demonstrating large mesangial immunoglobulin A (IgA) deposits diagnostic of IgA nephropathy.
 
 
 
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