IgA Nephropathy Treatment & Management

IgA nephropathy is a common cause of glomerulonephritis. Although it is a benign disease in most patients, chronic renal failure and ESRD occur in about 20-40% of patients within 20 years of presentation. Currently, no cure exists for IgA nephropathy, but therapies that can delay the onset of need for dialysis and transplantation are available. Current recommendations include the following:

• Monitor patients with isolated hematuria without proteinuria or hypertension with urinalysis, renal function testing, and blood pressure measurement.
• Treat hypertension early and aggressively. A reasonable goal is to aim for BP of 125/75-130/80mmhg.^[6]
• ACE inhibitors are the preferred agents for lowering blood pressure. They are beneficial in decreasing proteinuria and should be strongly considered even in normotensive patients with proteinuria.

  • The decrease in proteinuria with ACE inhibitors may be an effect of decreasing the intraglomerular pressure and of changing the glomerular size selectivity.
  • Reports have demonstrated that ACE inhibitors are more effective than other antihypertensive drugs in slowing the progression of proteinuric renal disease.
• The goal for proteinuria control is 500mg/day or less, so ACE inhibitors or ARBs should be started in patients with 24-hour urine protein of 500 mg or more.^[7]
• One randomized, controlled trial followed patients for a mean of approximately 6 years. The group that received ACE-I had an improved renal survival rate compared to the group receiving other antihypertensive agents.
• Angiotensin II receptor blockers should be used for patients who cannot tolerate ACE inhibitors. ACE inhibitors and angiotensin II receptor blockers may have an additive effect in decreasing proteinuria. Whether high doses of ACE inhibitors better preserve renal function than combined therapy with ACE inhibitors and angiotensin II receptor blockers is unknown.
• The combination of an ACE-I and the angiotensin receptor blocker losartan has shown an additive urinary protein–lowering effect compared to doubling the dose of monotherapy. However, patients on combination therapy should be monitored closely for the development of hyperkalemia, and combination therapy should be avoided in patients with advanced kidney failure.
• Administer prednisone for 4-6 months to patients who have IgA nephropathy with preserved renal function, nephrotic syndrome, and minimal-change findings on light microscopy.
• Early treatment with prednisone in patients with proliferative IgA nephropathy has been shown to be effective in reducing proteinuria and improving histologic findings, such as proliferation and cellular crescents. Additionally, corticosteroids given for 6 months have been seen to be beneficial against deterioration in renal function in patients with moderate proteinuria (1.5-3.5 g/d).
• Manno et al, in a prospective, open-label, multicenter, centrally randomized, controlled trial, investigated whether the use of a corticosteroid in combination with an ACE inhibitor would be more effective in treating patients with IgA nephropathy than would an ACE inhibitor alone.^[8] Results of the trial, in which 49 patients with IgA nephropathy were administered the ACE inhibitor ramipril and 48 patients were given ramipril plus prednisone, suggested that the combination treatment was more effective than the ACE inhibitor alone in discouraging progression of renal disease associated with IgA nephropathy.
• A randomized, controlled, long-term study on the effectiveness of steroids in IgA nephropathy showed improved 10-year renal survival in the steroid treated group compared to the control group. Patients had a proteinuria of 1.9 g/d on average in the treatment group and 1.7 g/d in the control group. Steroids were given for 6 months.
• Mycophenolate mofetil has been used in patients with IgA nephropathy associated with proteinuria, even though some reports have shown some benefit and others have not. The studies are of small size, and longer-term studies are required for more information. At this time, the evidence for the use of mycophenolate in IgA nephropathy is inconclusive.^{[6, 9]}
• Patients with crescentic RPGN can be treated similarly to patients with idiopathic RPGN by using intravenous pulse prednisone followed by oral prednisone and cyclophosphamide.
• Fish oil (omega-3 fatty acids) at a dose of 12 g/d has been used with controversial and conflicting results, but it is frequently used in patients with declining renal function. Deficiencies of essential fatty acids have been detected in IgA nephropathy, and fish oil is rich in long-chain omega-3-polyunsaturated fatty acids. These produce altered and less biologically effective prostaglandins and leukotrienes, as well as reduced platelet aggregation.
• A study by Liu examined the effect of calcitriol on urinary protein excretion among patients with IgA nephropathy. The study found that adding calcitriol to a renin-angiotensin system inhibitor resulted in a safe decrease in proteinuria.^[10]

• Renal transplantation

  • Renal transplantation is effective in patients with IgA nephropathy. Survival of cadaveric kidney transplants in patients with IgA nephropathy is among the highest observed among common causes of ESRD.
  • IgA nephropathy frequently recurs after transplantation (20-60%). The higher recurrence rates in transplantation from living related donors suggest genetic susceptibility to the disease.^[11]
  • Some patients present with microscopic hematuria and proteinuria; others have only positive histologic findings.
  • The disease usually progresses slowly, similarly to the disease in the native kidneys, and graft loss due to recurrent disease occurs in fewer than 10% of patients.

Patients should be seen by a nephrologist.

• A low-antigen diet, which consists of restricting dietary gluten and avoiding meats and dairy products, has been recommended to decrease mucosal antigen exposure but has not been shown to preserve renal function.
• Low-protein diets have been recommended to slow the rate of progression of many nephropathies. No large trial explicitly addresses the role of low-protein diets in slowing the decline in renal function in IgA nephropathy. The MDRD Study Group trial is the largest trial of low-protein diets to date, but it included patients with a variety of renal diseases. This trial was unable to determine whether a low-protein diet was beneficial. Although the meta-analysis of studies of low-protein diets suggests some benefits, the effects are subtle and difficult to apply to a given patient.^{[12, 13]}