Pediatrics

IgA nephropathy

OVERVIEW: What every practitioner needs to know

Are you sure your patient has IgA nephropathy? What are the typical findings for this disease?

IgA nephropathy is a primary glomerular disease that typicaly presents with gross hematuria shortly after appearance of upper respiratory infection (URI) symptoms. Diagnosis is confirmed by renal biopsy—IgA deposition in the mesangium. The clinical manifestations of IgA nephropathy are highly variable, from isolated hematuria with mild proteinuria to progressive renal failure. Although there is no cure for IgA nephropathy, antiproteinuric agents (angiotensin-converting enzyme [ACE] inhibitors and angiotensin II receptor blockers [ARBs]) are routinely used to reduce proteinuria in attempts to delay progression of renal disease.

Typical findings include one or recurrent episodes of gross hematuria shortly after the appearance of URI symptoms (synpharyngitic hematuria). Mild proteinuria may also be present (<0.5 g/day)

Severe cases (<10%)

Present as rapidly progressive glomerulonephritis or nephrotic syndrome

Rapidly progressive glomerulonephritis

Acute kidney injury (elevated blood urea nitrogen [BUN] and creatinine levels), hypertension, edema

What other disease/condition shares some of these symptoms?

Acute poststreptococcal glomerulonephritis (APSGN)

Lupus nephritis

Henoch-Schönlein purpura nephritis

Alport syndrome

Membranoproliferative glomerulonephritis

What caused this disease to develop at this time?

Deposition of IgA in the mesangium of the glomeruli may be associated with Crohn disease, ulcerative colitis, cirrhosis, celiac disease, HIV infection

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Diagnosis is by renal biopsy only; mesangial IgA deposition is seen.

Elevated IgA levels are not specific for diagnosis.

Serum chemistry panels are required to monitor renal function.

Urinalysis is needed to verify hematuria and assess for proteinuria.

Random urine protein-creatinine ratio (normal is <0.2) is necessary.

C3 and C4 determinations and an antinuclear antibody assay should be obtained to rule out APSGN and lupus nephritis.

Would imaging studies be helpful? If so, which ones?

Renal ultrasonography may be helpful to rule out other renal pathologic conditions (kidney stones, obstruction, tumor, pyelonephritis, renal vein thrombosis).

If you are able to confirm that the patient has IgA nephropathy, what treatment should be initiated?

Refer patient to a pediatric nephrologist, or if one is not available, refer to an adult nephrologist, as the disease process is similar in children and in adults.

If there is evidence of proteinuria, start ACE inhibitor or ARB.

Fish oil therapy may also be considered, but studies have produced equivocal results. In general, fish oil therapy is benign, so if the patient can tolerate the fishy aftertaste, most nephrologists will recommend it.

If there is evidence of proteinuria (urinary protein-creatinine ratio >0.2), using the combination of both an ACE inhibitor and an ARB results in greater reduction in proteinuria than is seen with either agent alone. One approach is to start with lisinopril (ACE inhibitor) at a starting dose of 0.07 mg/kg/d, then titrate by increasing the dose in increments of 2.5-5 mg to a medium dose of 20 mg daily.

If proteinuria is still present, add losartan (ARB) at a starting dose of 0.7 mg/kg/d. Increase losartan by increments of 12.5 mg. Make dose changes at weekly intervals and monitor for side effects of hyperkalemia and renal insufficiency (elevated BUN and creatinine levels) with each dose increase. The maximum dose of lisinopril is 80 mg daily and the maximum dose of losartan is 100 mg daily.

It is important to emphasize to the patient that maintaining adequate hydration is essential because volume depletion in the setting of receiving an ACE inhibitor and an ARB may result in hyperkalemia and renal insufficiency. Furthermore, both these medications are teratogenic (cause fetal renal failure), so teenaged girls must be advised accordingly.

Fish oil therapy may also be considered, but studies have produced equivocal results. In general, fish oil therapy is benign, so if the patient can tolearte the fishy aftertaste, most nephrologists will recommend it. The daily doses of fish oil therapy used to treat IgA nephropathy consist of EPA 1.8 g and DHA 1.2-1.5 g, so check each brand of fish oil capsules as doses can vary.

If there is evidence of nephrotic syndrome or mild renal impairment, consider prednisone 1-2 mg/kg/d (maximum dose 60 mg) for 3 months. If severe renal impairment is present, consider intravenous (IV) methylprednisolone 15 mg/kg/dose (maximum dose 1000 mg) for 3 consecutive days on months 1, 3, and 5. Use prednisone 0.5 mg/kg/d on the nonmethylprednisolone days for a total of 6 months.

If there is evidence of nephrotic syndrome or mild renal impairment, consider prednisone 1-2 mg/kg/d (maximum dose 60 mg) for 3 months. If there is severe renal impairment, consider IV methylprednisolone 15 mg/kg/dose (maximum dose 1000 mg) for 3 consecutive days on months 1, 3, and 5. Use prednisone 0.5 mg/kg/d on the nonmethylprednisolone days for a total of 6 months.

If hypertension is present (defined as blood pressure at the 95th percentile based on age, sex, and height percentile), start amlodipine at 2.5 mg daily. Increase dose by 2.5 mg every 48-72 hours. The maximum dose of amlodipine is 10 mg daily. Target blood pressures to less than the 95th percentile.

For severe cases, consider additional immunosuppressive agents, such as cyclophosphamide, azathioprine, cyclosporine, and/or mycophenolate mofetil. At this point, a pediatric or adult nephrologist should be consulted.

What are the adverse effects associated with each treatment option?

In the setting of acute kidney injury, an ACE inhibitor and an ARB may decrease renal perfusion and thus worsen renal dysfunction. Prednisone may cause hypertension.

What are the possible outcomes of IgA nephropathy?

Prognosis is variable and can range from mild proteinuria and/or renal insufficiency to overt proteinuria (>1 g/d) and/or end-stage renal disease. A referral to a pediatric nephrologist for further explanation of the long-term prognosis is recommended .

There is no cure for IgA nephropathy. Pharmacotherapy is given to delay progression of renal disease.

What causes this disease and how frequent is it?

IgA nephropathy is the most common idiopathic glomerulonephritis in developed countries. The prevalence rate in the United States is 2%-10%. The disease is more common in Asians and white individuals. The male-female ratio is 6:1 in the United States.

It typically develops in the second and third decades of life.

There is no evidence that environmental or infectious agents cause IgA nephropathy.

There is a possible genetic defect in the O-glycosylation of IgA1.

How do these pathogens/genes/exposures cause the disease?

Increase in proportion of poorly galactosylated IgA1 O-glycoforms results in self-aggregation and formation of IgA-immune complexes that favor deposition in the mesangium.

What complications might you expect from the disease or treatment of the disease?

Acute kidney injury

Edema

Hypertension

How can IgA nephropathy be prevented?

There is no prevention for IgA nephropathy.

What is the evidence?

The following are review articles.

The following are clinical studies of therapies.

Ongoing controversies regarding etiology, diagnosis, treatment

Studies on fish oil therapy in treating proteinuria have produced equivocal results. Tonsillectomy to remove a potential source of IgA have also produced inconsistent results in delaying progression of renal disease in IgA nephropathy. A study on eating a low-antigen (gluten-free, dairy-free, protein-free) diet did not result in reduction of proteinuria or improvement in renal function in patients with IgA nephropathy. There are limited studies on the use of immunosuppressive agents (cytoxan, cyclosporine, mycophenolate mofetil, azathioprine, rituximab) in the treatment of IgA nephropathy in children.

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