para>Kidney function tests (blood urea nitrogen and serum creatinine), serum electrolytes, and albumin are normal in mild disease.
Variably affected depending on severity
In patients presenting with rapidly progressive glomerulonephritis, check complement levels, antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), and anti-glomerular basement membrane (GBM) antibodies to rule out other diseases.Serum IgA levels have very low sensitivity and specificity and are not recommended.
Imaging
- Kidney ultrasound findings are nonspecific and either normal or, in more severe cases, may demonstrate increased echogenicity of the renal parenchyma.
Diagnostic Procedures/Other
- Kidney biopsy is required for a definitive diagnosis.
- Hallmark of the diagnosis is the presence, on immunofluorescence staining, of IgA deposits in the mesangium, either alone or with C3 (in children), IgM and IgG, or both (in adults).
- Biopsy is generally not required in mild cases as it does not affect the management or prognosis in the absence of proteinuria.
- Biopsy findings are variable on light microscopy:
- Main finding is diffuse or focal mesangial proliferation with mesangial expansion.
- Other possible findings include segmental or global endocapillary hypercellularity with segmental crescents and segmental necrosis.
- Glomerulosclerosis in advance disease
- Tubulointerstitium is usually normal with varying degree of atrophy and fibrosis in chronic cases.
- Electron microscopy: immune complex deposits in the mesangium
- Several histologic classifications have been developed with the purpose of predicting clinical course, prognosticating, and in guiding therapy.
- The Oxford classification is one such example, based on a constellation of findings such as mesangial cellularity score, segmental glomerulosclerosis, endocapillary hypercellularity, and tubular atrophy/fibrosis.
Differential Diagnosis
- Thin basement membrane disease, Alport syndrome, or idiopathic hypercalciuria in mild cases presenting with hematuria
- Other forms of glomerulonephritis must be considered in the setting of a more acute presentation, including the following:
Postinfectious glomerulonephritis
Lupus nephritis
Membranoproliferative glomerulonephritis (MPGN)
Pauci-immune glomerulonephritis
Other vasculitides
- Henoch-Sch ¶nlein purpura nephritis has similar biopsy findings as IgA nephropathy but has additional nonrenal manifestations such as skin rash, abdominal pain, and periarthritis.
Alert
May be progressive and lead to end-stage renal disease in moderate to severe cases. Refer to a nephrologist if persistent proteinuria, abnormal creatinine, gross hematuria, or hypertension.
Treatment
- Weak evidence base and mostly derived from expert opinion
- Varies based on severity of renal impairment, amount of proteinuria, and whether or not the course is rapidly progressive with associated crescents on biopsy. Higher amounts and persistence of proteinuria are associated with greater risk of disease progression.
Medication
- Control of proteinuria and blood pressure
- Protein excretion 0.5-1 g/1.73 m2/day: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blockers (ARBs). Increase dose to effect as long as symptomatic hypotension or hyperkalemia do not develop.
- Protein excretion >1 g/1.73 m2/day despite optimum blood pressure control and the use of ACEI or ARB and when GFR is >50 mL/min/1.73 m2: Consider alternate day oral glucocorticoids for 6 months.
- Rapidly progressive glomerulonephritis and/or crescents on biopsy: intravenous (followed by oral) glucocorticoids, and consider additional immunosuppression such as cyclophosphamide or azathioprine (strength of evidence is poor for immunosuppression other than ACEI/ARB and glucocorticoids)
Additional Therapies
- Fish oil suggested when proteinuria is persistent >1 g/1.73 m2/day despite optimal supportive care.
- Mycophenolate mofetil: multiple studies with conflicting conclusions
General Measures
- Clinical presentation: Treat hypercholesterolemia associated with nephrotic syndrome. Address factors that modulate progression of chronic kidney disease-obesity, smoking, hypertension.
- Optimize blood pressure control.
Ongoing Care
Follow-up Recommendations
- IgA nephropathy may be a progressive disease. Patients should be monitored periodically for the following:
- Kidney function tests
- Level of proteinuria
- Blood pressure
- Intensity and frequency of monitoring depends on severity. Patients presenting with microscopic hematuria and minimal proteinuria should be monitored with UA every 6 months to assess for progression of proteinuria.
Prognosis
- Variable depending on severity of clinical presentation and renal histopathologic score
- 15-40% of adult patients with IgA nephropathy eventually progress to end-stage renal disease (ESRD).
- Although some reports suggest that children are more likely to have a benign course and have better prognosis than adults, other studies have reported similar outcomes for adults and children.
- In one series, renal survival rates in Japanese children were 95% at 10 years and 80% at 20 years.
- Patients who present with microscopic hematuria and minimal proteinuria have an excellent prognosis.
- Clinical predictors associated with poor outcome include severe persistent proteinuria, hypertension, and impaired renal function at presentation.
- The strongest predictive factor is the amount of proteinuria.
- Histopathologic features associated with poor outcome include mesangial hypercellularity score, endocapillary hypercellularity, tubular atrophy, and glomerular crescents.
Additional Reading
- Edstr ¶m Halling S, S ¶derberg MP, Berg UB. Predictors of outcome in pediatric IgA nephropathy with regard to clinical and histopathological variables (Oxford Classification). Nephrol Dial Transplant. 2012;27(2):715-722. [View Abstract]
- Gutierrez E, Zamora I, Ballar n JA, et al .Long-term outcomes of IgA nephropathy presenting with minimal or no proteinuria. J Am Soc Nephrol. 2012;23(10):1753-1760. [View Abstract]
- Hogg RJ, Fitzgibbons L, Atkins C, et al. Efficacy of omega-3 fatty acids in children and adults with IgA nephropathy is dosage-and size-dependent. Clin J Am Soc Nephrol. 2006;1(6):1167-1172. [View Abstract]
- Purswani MU, Chernoff MC, Mitchell CD, et al. Chronic kidney disease associated with perinatal HIV infection in children and adolescents. Pediatr Nephrol. 2012;27(6):981-989. [View Abstract]
- Radhakrishnan J, Cattran DC. The KDIGO practice guideline on glomerulonephritis: reading between the guidelines-applications to the individual patient. Kidney Int. 2012;82(8):840-856. [View Abstract]
- Ronkainen J, Ala-Houhala M, Autio-Harmainen H, et al. Long-term 19 years after childhood IgA nephritis: a retrospective cohort study. Pediatr Nephrol. 2006;21(9):1266-1273. [View Abstract]
- Shima Y, Nakanishi K, Hama T, et al. Validity of the Oxford classification of IgA nephropathy in children. Pediatr Nephrol. 2012;27(5):783-792. [View Abstract]
- Suzuki H, Kiryluk K, Novak J, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22(10):1795-1803. [View Abstract]
- Wang T, Ye F, Meng H, et al. Comparison of clinicopathological features between children and adults with IgA nephropathy. Pediatr Nephrol. 2012;27(8):1293-1300. [View Abstract]
- Welander A, Sundelin B, Fored M, et al. Increased risk of IgA nephropathy among individuals with celiac disease. J Clin Gastroenterol. 2013;47(8): 678-683. [View Abstract]
Codes
ICD09
- 583.9 Nephritis and nephropathy, not specified as acute or chronic, with unspecified pathological lesion in kidney
- 583.2 Nephritis and nephropathy, not specified as acute or chronic, with lesion of membranoproliferative glomerulonephritis
- 583.1 Nephritis and nephropathy, not specified as acute or chronic, with lesion of membranous glomerulonephritis
ICD10
- N02.8 Recurrent and persistent hematuria w oth morphologic changes
- N02.5 Recurrent and perst hematur w diffuse mesangiocap glomrlneph
- N02.2 Recurrent and perst hematur w diffuse membranous glomrlneph
SNOMED
- 236407003 IgA nephropathy (disorder)
- 68779003 Primary IgA nephropathy
FAQ
- Q: Will my child ever outgrow IgA nephropathy?
- A: No. The etiology and pathogenesis of IgA nephropathy remain uncertain. IgA nephropathy is a chronic condition, but sometimes it can go into spontaneous remission. Spontaneous remission is reported to occur in 59% of children with mild disease. More severe cases can also go into remission with medications.
- Q: My child has had a kidney transplant. Can IgA nephropathy recur in the graft?
- A: Yes. Recurrence of the condition can develop in 33% of patients. Depending on the published series, recurrence rates vary between 9 and 66%. However, even if it does come back, it can be controlled/treated with medications.
- Q: My child has microscopic hematuria and proteinuria. He has normal kidney function and blood pressure. His kidney biopsy was consistent with the diagnosis of IgA nephropathy. What is the strongest predictor for progression?
- A: The amount of proteinuria. Children with no or mild proteinuria usually have good long-term prognosis, whereas those with high amounts of protein in the urine are more likely to progress and develop long-term kidney damage.