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IgA_combined_treatments.htm

Pulse methylprednisolone (15 mg/kg per day for three days)
Oral prednisone (1 mg/kg per day for 60 days, followed by 0.6 mg/kg per day for 60 days, followed by 0.3 mg/kg per day for 60 days, with all patients on 10 mg/day at the time of repeat biopsy).
Monthly intravenous cyclophosphamide (0.5 g/m2) for six months
After the six month course, there was significant improvement in the serum creatinine concentration (from 2.7 to 1.5 mg/dL [240 to 133 µmol/L]) and in protein excretion (from 4 to 1.4 g/day). Repeat biopsy revealed the absence of cellular crescents and endocapillary proliferation in all patients.


Cyclosporine — Cyclosporine has been investigated in small studies, and resulted in reduced proteinuria. However, its use has been limited by the associated nephrotoxicity, leading to a rise in the serum creatinine concentration that is greater than that seen in untreated patients [97,98] . Furthermore, relapse occurs soon after the drug is discontinued.

Based upon the available data, we do not use cyclosporine for the treatment of IgA nephropathy.

Mycophenolate mofetil — There are limited data concerning the efficacy of mycophenolate mofetil in the primary treatment of progressive IgA nephropathy. Four small, prospective placebo-controlled randomized trials in which the patients were also treated with ACE inhibitors in at least three, have produced conflicting results, ranging from no benefit with mycophenolate mofetil [99,100] to a reduction in proteinuria [101,102] .
The conflicting results may be explained in part by differing severity of kidney disease, being less advanced in the studies demonstrating benefit. Additional trials are ongoing although one was recently stopped because of funding issues and futility given no differences observed between treated and control group [103] .

Intravenous immune globulin — At least part of the rationale for IVIG therapy in IgA nephropathy comes from the observation that a partial IgG deficiency, which could be corrected with IVIG, may predispose to infections that trigger flare-ups of the renal disease [112,113] .

High-dose intravenous immune globulin (IVIG) has been tried in severe IgA nephropathy, characterized by heavy proteinuria and a relatively rapid decline in GFR [113] . Eleven patients (nine with IgA nephropathy and two with the related disorder Henoch-Schönlein purpura) were treated with IVIG at a dose of 1 g/kg for two days per month for three months followed by an intramuscular preparation given every two weeks for another six months. Among the benefits that were noted were a reduction in protein excretion (5.2 to 2.3 g/day), prevention of a continued reduction in GFR (loss of 3.8 mL/min per month prior to therapy versus stable GFR after therapy), and decreased inflammatory activity and IgA deposition on repeat renal biopsy.
The benefit of IVIG needs to be confirmed prospectively in a larger number of patients.

PREGNANCY — Pregnancy is generally well tolerated in IgA nephropathy.
ACE inhibitors and/or ARBs and some immunosuppressive drugs (particularly cyclophosphamide and mycophenolate mofetil) should be discontinued at the earliest indication of pregnancy or prior to attempted conception because of risks to the fetus. (See "Angiotensin converting enzyme inhibitors and receptor blockers in pregnancy" and see "Use of immunosuppressive drugs in pregnancy and lactation").

SUMMARY AND RECOMMENDATIONS
Prognosis — Patients without significant proteinuria or renal dysfunction may undergo complete remission of abnormal clinical findings. However, most patients will have stable or slowly progressive disease.

Histologic findings associated with a worse prognosis include crescent formation, which is uncommon, and, more importantly, signs of irreversible damage such as glomerular scarring, tubular atrophy, and interstitial fibrosis. (See "Histologic predictors of progression" above).

Treatment
We suggest not treating patients with isolated hematuria, no or minimal proteinuria, and a normal GFR (Grade 2C). Such patients should be periodically monitored at 6 to 12 month intervals to assess for disease progression that might warrant therapy.

For patients with persistent proteinuria (>500 to 1000 mg/day), we recommend angiotensin inhibition with an ACE inhibitor and/or ARB (Grade 1A). We initiate monotherapy and target a minimum reduction in protein excretion of at least 60 percent from baseline values and a goal protein excretion of less than 500 to 1000 mg/day. If the proteinuria goal is not reached with monotherapy alone, we treat with combined ACE inhibitor and ARB therapy. (See "Angiotensin inhibition" above).

We suggest that all patients who meet criteria for angiotensin inhibition also receive fish oil (Grade 2B). (See "Fish oil" above).

For patients with progressive active disease (eg, hematuria with increasing proteinuria and/or increasing serum creatinine concentration) despite the use of ACE inhibitors and/or ARBs, we suggest initiating therapy with corticosteroids alone (Grade 2B). Two regimens we use are:

      – Intravenous methylprednisolone (500 to 1000 mg per dose or, in children, 7 to 15 mg/kg in children per dose to a maximum of 1000 mg) for three consecutive days at the beginning of months one, three and five, and alternate day oral prednisone (0.5 mg/kg, approximately 30 to 40 mg) for six months, then tapered to discontinuation. (See "Glucocorticoids" above).

      - An alternative regimen that avoids pulse therapy can also be used, such as 2 mg/kg of prednisone (maximum 100 to 120 mg) every other day for two months, with a rapid taper to a dose of 0.5 mg/kg (approximately 30 to 40 mg) every other day for an additional four months. Prednisone is then tapered to discontinuation.

      – Prednisone (1 mg/kg to a maximum 60 to 80 mg/day) for two to three months followed by a slow taper to a maintenance dose of 10 mg/day for one to two years.

      - Intravenous methylprednisolone for three consecutive days (500 to 1000 mg per dose or, in children, 7 to 15 mg/kg in children per dose to a maximum of 1000 mg) followed by oral prednisone (1 mg/kg per day, maximum dose 60 to 80 mg) for two to three months, then a slow taper to a maintenance dose of 10 mg/day for one to two years.

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