eMedicine Specialties > Pediatrics: General Medicine > Nephrology
IgA Nephropathy: Treatment & Medication
Updated: Dec 15, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Immunoglobulin A (IgA) nephropathy (IgAN) posses a therapeutic challenge to both the patient and physician. Medical treatment must address the primary disease, if a secondary form of IgA nephropathy is encountered. Because spontaneous remission may occur, aggressive therapies that may introduce additional risk are probably not indicated in children with mild disease.
Risk factors for progressive renal disease include heavy proteinuria (protein excretion >2 mg/kg/d), reduced renal clearance (estimated glomerular filtration rate [GFR] or measured creatinine clearance [CrCl] <75% of normal), hypertension, renal biopsy revealing proliferative glomerulonephritis, crescents, or advanced chronic disease. For children with progressive disease, several treatment options are available. No treatment has been shown to cure IgA nephropathy. Treatments tend to delay progression in patients with above listed risk factors.
The following treatment options are available:
- Children with the highest risk of progressive disease are most likely to benefit from therapy. The most appropriate treatment is unknown. The agents most often reported to be effective for IgA nephropathy treatment include corticosteroids (2 mg/kg), ACE inhibitors, angiotensin receptor blockers (ARB) and omega-3 polyunsaturated fatty acids (fish oil).
- The dosage and length of treatment for maximal benefit in children with IgA nephropathy are unknown for these agents. In each case, the effectiveness of these therapies should be initially assessed and periodically reassessed to determine that treatment is beneficial and that benefits outweigh the risks.
- Several investigators have reported that corticosteroids and/or fish oil have slowed the deterioration of renal function.2,3,4,5 However, a meta-analysis showed only 75% probability that fish oil was beneficial.
- Some studies have indicated that ACE inhibitors and ARB agents are useful in reducing proteinuria, controlling blood pressure, and preserving renal function in IgA nephropathy.
- High-dose pulse methylprednisolone has shown to delay the development of renal failure.
- The primary focus of treatments for IgA nephropathy is to direct therapy at reducing inflammatory mediated renal injury, controlling hypertension, decreasing proteinuria, and managing sequelae of reduced renal function, if present.
- The Japanese Pediatric IgA Study Group reported that in children with severe IgA nephropathy, treatment with the combination of azathioprine, prednisolone, heparin-warfarin, and dipyridamole might ameliorate renal immunologic injury and delays progression.4
- Hotta et al reported that complete regression of IgA nephropathy was apparent in a group of patients treated with a combination of tonsillectomy, methylprednisolone, warfarin, alternate-day prednisolone, and dipyridamole.6
- Other treatments reported to provide benefit include the following:
- Prophylactic antibiotic and tonsillectomy may reduce the episodes and frequency of gross hematuria. Beneficial effect remains questionable.
- Glucocorticoids may benefit the few patients with minimal change disease, but long-term effects do not confirm any benefit. Alternate day steroid therapy reduces long-term complications.
- Plasmapheresis combined with an immunosuppressive drug is probably of value in patients with rapidly progressive crescentic diseases, but full recovery remains unlikely.
- Phenytoin, danazol, azathioprine, dipyridamole, and heparin-warfarin have been tried but failed to influence the clinical and histological course.
- Children with reduced renal function may need treatment for growth failure, bone mineralization, and reduced RBC production.
- Patients with end-stage renal disease require dialysis or transplantation.
- After renal transplantation, recurrent IgA nephropathy may result in graft loss. Current immunosuppressive regimens do not prevent the recurrence of IgA nephropathy.
- The recurrence of IgA nephropathy in renal allograft was initially considered as benign, with a low incidence of graft failure. However, newer reports in adults show graft failure rates of 30% and 60%.7,8,9 No studies have been performed in children, but IgA nephropathy recurrence may become a concern for long-term graft survival in children.
Surgical Care
Generally, surgical care is not necessary except for dialysis access or renal transplantation.
Consultations
Because IgA nephropathy has the potential to progress to end-stage renal disease, consultation with a pediatric nephrologist is necessary.
Diet
An American Heart Association step I diet is recommended for all children older than 2 years. Patients may require consultation with a dietitian to determine a renal diet if renal insufficiency develops.
Activity
Typically, no activity restriction is necessary.
Medication
The risks and benefits of immunoglobulin A (IgA) nephropathy (IgAN) treatment with steroids, fish oil, or ACE inhibitors should be discussed with patients and parents. These agents theoretically may protect the kidney and prolong the interval between onset and renal failure.
Anti-inflammatory and immunosuppressive agents
These agents elicit anti-inflammatory and immunosuppressive properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli and reduce immune-mediated renal injury resulting from IgA deposition in the kidney.
Prednisone (Deltasone) or methylprednisolone (Solu-Medrol)
Potent anti-inflammatory and immunosuppressive therapy with corticosteroids has been reported to reduce the rate of progression of IgAN.
Adult
Methylprednisolone: 1 g IV
Prednisone: 0.5 mg/kg/d PO
Pediatric
Prednisone: 2 mg/kg (up to 80 mg/d) for 4 wk, then 1-2 mg/kg on alternate days as one of several possible reduction schedules; total treatment lasts 2 y
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin, may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Coadministration with anticoagulants or antiplatelet agents may increase risk of bleeding; may antagonize neuromuscular blockers; high-dose or long-term glucocorticoid therapy may inhibit the thyroid-stimulating hormone (TSH), thereby interfering with thyroid medication regulation
Increases blood glucose in diabetes mellitus, and higher doses of insulin may be required
Documented hypersensitivity; Cushing syndrome; fungal infection, measles, varicella
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in diabetes mellitus, abdominal pain, fever, increased intracranial pressure, pancreatitis, or infection
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Fish oil
Several investigators have suggested that fish oil delays the progression of renal disease. The precise mechanism is not fully understood.
Omega-3 polyunsaturated fatty acid (Promega, Lovaza)
May be beneficial by decreasing mediators of glomerular injury and decreasing platelet aggregation. Omega-3 fatty acids may be used as nondrug dietary supplements in early high-risk coronary disease and IgAN.
Adult
4-8 g/d PO
Pediatric
Not established; not to exceed 4 g/d PO
May increase insulin requirements; may increase effects of antiplatelet or anticoagulant drugs; concomitant use of other oils (eg, olive oil) may reduce effects
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause fishy odor, diarrhea, hyperglycemia, and bleeding due to decreased platelet aggregation; caution in bleeding disorders or diabetes mellitus
Angiotensin-converting enzyme (ACE) inhibitors
In 1980, captopril became the first ACE inhibitor approved by the US Food and Drug Administration. Subsequently, at least 40 compounds have been identified. ACE inhibitors reduce the production of angiotensin II, thereby, lowering intraglomerular filtration pressure, reducing proteinuria, and slowing the decline of glomerular function in several chronic renal diseases. All ACE inhibitors probably have similar renal protective effects.
Enalapril (Vasotec)
Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma renin and a reduction in aldosterone secretion.
Adult
2.5-5 mg/d PO qd or divided bid; not to exceed 40 mg/d
Pediatric
0.1 mg/kg/d PO qd or divided bid; not to exceed 0.5 mg/kg/d
NSAIDs may reduce hypotensive effects of enalapril; ACE inhibitors may increase digoxin, lithium, and allopurinol levels; rifampin decreases enalapril levels; probenecid may increase enalapril levels; the hypotensive effects of ACE inhibitors may be enhanced when given concurrently with diuretics; additive risk of hyperkalemia with potassium sparing diuretics or potassium supplements; may decrease insulin resistance (adjust dose of antidiabetic agents)
Documented hypersensitivity; angioedema; hyperkalemia; bilateral renal artery stenosis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal impairment, valvular stenosis, severe congestive heart failure, hypotension, hypoglycemia, angina, asthma, or neutropenia
Angiotensin Receptor Antagonist
Angiotensin II receptor antagonists may be considered if ACE inhibitors are not tolerated.
Losartan (Cozaar)
Angiotensin II receptor antagonist that blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II. May induce a more complete inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with cough and angioedema. For patients unable to tolerate ACE inhibitors.
Angiotensin II receptor blockers reduce blood pressure and proteinuria, protecting renal function, and delaying onset of end-stage renal disease.
Adult
25-100 mg PO qd or divided bid
Pediatric
Not established
May increase digoxin, lithium, and allopurinol levels; probenecid may increase losartan levels; coadministration with diuretics, increase hypotensive effects; NSAIDs may reduce hypotensive effects of losartan; may increase risk of hyperkalemia if taken concurrently with potassium supplements or other potassium-sparing diuretics
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in patients with unilateral or bilateral renal artery stenosis
More on IgA Nephropathy |
| Overview: IgA Nephropathy |
| Differential Diagnoses & Workup: IgA Nephropathy |
 Treatment & Medication: IgA Nephropathy |
| Follow-up: IgA Nephropathy |
| Multimedia: IgA Nephropathy |
| References |
| « Previous Page | Next Page » |
References
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Kobayashi Y, Sano T, Nakamura I, et al. Long-term effect of 2-year steroid therapy in progressive IgA nephropathy: A 30-year follow-up study compared with a non-steroid group. Nephrology (Carlton). Jan 2003;8 Suppl 4:A113-4. [Medline].
Oortwijn BD, Rastaldi MP, Roos A, Mattinzoli D, Daha MR, van Kooten C. Demonstration of secretory IgA in kidneys of patients with IgA nephropathy. Nephrol Dial Transplant. Jun 2007;22(11):3191-5. [Medline]. [Full Text].
IgA nephropathy. In: van Es LA, Massery SG, Glassock RJ, eds. Textbook of Nephrology. Vol 1. 2001:733-41.
Wardle EN. Is IgA nephropathy induced by hyperproduction of interferon-alpha?. Med Hypotheses. 2004;62(4):625-8. [Medline].
White RHR, Yoshikawa N, Freehally J. IgA nephropathy and Henoch-Schonlein nephritis. In: Barratt TM, Avner ED, Harmon WE, eds. Pediatric Nephrology. 4th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 1999:691-706.
Further Reading
Keywords
IgA nephropathy, IgAN, immunoglobulin A nephropathy, glomerulonephritis, focal glomerulonephritis, Berger focal glomerulonephritis, Berger's focal glomerulonephritis, Berger nephropathy, Berger's nephropathy, hypertension, proteinuria, Henoch-Schönlein purpura, HSP, Henoch-Schönlein nephropathy, HSN, end-stage renal disease, renal insufficiency, pharyngitis, poststreptococcal glomerulonephritis, PSGN, nephrotic syndrome, systemic lupus erythematosus, SLE, celiac disease, chronic ulcerative colitis, Crohn disease, dermatitis herpetiformis, psoriasis, cystic fibrosis, sarcoidosis, lung cancer, colon cancer, monoclonal IgA gammopathy, non-Hodgkin lymphoma, pancreatic cancer, human immunodeficiency virus, HIV, mycoplasma infection, toxoplasmosis, cirrhosis, pulmonary hemosiderosis, cryoglobulinemia, polycythemia, hepatitis B, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis
