Pediatric IgA Nephropathy Treatment & Management

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.

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 optimum 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.^{[6, 7, 8, 9]} 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 children with 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.^[8]

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.^[10]

Mycophenolate mofetil (MMF) has been used in patients with IgA nephropathy. The data concerning the efficacy of MMF in the primary treatment of progressive IgA nephropathy are limited. The prospective placebo-controlled randomized trials of the efficacy and safety of MMF in which the patients were also treated with ACE inhibitors have produced conflicting results, ranging from no benefit^{[11, 12]} to a reduction in proteinuria.^{[13, 14]} No strong evidence suggests that MMF safely delay the onset of end-stage renal disease (ESRD) in patients with IgA nephropathy.

A short course (< 6 months) of MMF in patients with persistent proteinuria (>1.5 g/d) and well-maintained renal function (serum creatinine < 1.5 mg/dL) despite maximum ACE inhibitor/ARB therapy may be considered in patients with mild renal histopathology on biopsy. Current evidence does not support the use of MMF in patients with advanced disease (serum creatinine >2.5-3 mg/dL).

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%.^{[15, 16, 17]} No studies have been performed in children, but IgA nephropathy recurrence may become a concern for long-term graft survival in children.

Generally, surgical care is not necessary except for dialysis access or renal transplantation.

Because IgA nephropathy has the potential to progress to end-stage renal disease, consultation with a pediatric nephrologist is necessary.

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.

Typically, no activity restriction is necessary.