IgA Nephropathy Treatment & Management

Updated: Oct 11, 2017
  • Author: Mona Brake, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Treatment

Medical Care

IgA nephropathy is a common cause of glomerulonephritis. Although it is a benign disease in most patients, chronic kidney disease and end-stage renal disease (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 a blood pressure of 125-130/75-80 mm Hg. [16]
  • Treat proteinuria in patients whose 24-hour urine protein level is 500 mg or more [17]

Angiotensin-converting enzyme inhibitors (ACEIs) are the preferred agents for lowering blood pressure. They are also beneficial in decreasing proteinuria and should be strongly considered even in normotensive patients with proteinuria. The decrease in proteinuria with ACEIs may be an effect of decreasing the intraglomerular pressure and of changing the glomerular size selectivity.

Reports have demonstrated that ACEIs are more effective than other antihypertensive drugs in slowing the progression of proteinuric renal disease. In a randomized, controlled trial in 44 patients with biopsy-proven IgA nephropathy who had proteinuria and normal or moderately reduced renal function, Kaplan-Meier renal survival after 7 years was 92% in patients treated with enalapril versus 55% in the control group (P <0.05). [18]

Angiotensin II receptor blockers (ARBs) should be used for patients who cannot tolerate ACEIs. ACEIs and ARBs may have an additive effect in decreasing proteinuria. Whether high-dose ACEIs better preserve renal function than combination therapy with ACEIs and ARBs is unknown.

The combination of an ACEI and the ARB losartan has shown an additive urinary protein–lowering effect compared with doubling the dose of monotherapy. [19]   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 disease.

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. [20] 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).

Results of a prospective, open-label, multicenter, centrally randomized, controlled trial in 97 patients suggested that the combination of the ACEI ramipril and prednisone was more effective than ramipril alone in discouraging progression of renal disease associated with IgA nephropathy. [21]

A randomized, controlled, long-term study by Pozzi et al found that patients with IgA nephropathy who received steroid treatment for 6 months experienced long-term benefits, with significant reduction in proteinuria and protection against deterioration in renal function. Ten-year renal survival in the steroid-treated group was 97%, compared with 53% in the control group. [22]

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. [16, 23]

Patients with crescentic rapidly progressive glomerulonephritis (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. [24, 9] 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. [25]

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Diet

A low-antigen diet, which consists of restricting dietary gluten and avoiding meats and dairy products, has been recommended to decrease mucosal antigen exposure. However, it 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. [26, 27]

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Tonsillectomy

Tonsillectomy is a controversial treatment for IgA nephropathy. Tonsillectomy may limit the production of degalactosylated IgA1 by reducing mucosal-associated lymphoid tissue (MALT). However, an Italian study found that other markers of innate immunity activation (eg, toll-like receptors) were not affected by tonsillectomy, possibly because of extra-tonsillar MALT. [28]

A study in Caucasian patients in which 98 of 264 patients underwent tonsillectomy found that tonsillectomy may slow the progression of IgA nephropathy, but mainly in patients with macroscopic hematuria. [29] A Japanese study in which 70 of 200 patients underwent tonsillectomy concluded that the procedure was associated with a favorable renal outcome of IgA nephropathy in terms of clinical remission and delayed renal deterioration, even in non-steroid-treated patients. [30]

Especially in Japan, tonsillectomy has been combined with steroid pulse administration for clinical remission. [31] Japanese guidelines from 2014 note that evidence supporting the benefit of tonsillectomy is weak, but recommend that tonsillectomy, by itself or combined with steroid pulse therapy, may be considered a treatment option. [9]

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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 in patients undergoing transplantation for common causes of end-stage renal disease (ESRD).

However, IgA nephropathy frequently recurs after transplantation (20-60%). The higher recurrence rates in transplantation from living related donors suggest genetic susceptibility to the disease. [32] 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.

Baek et al have reported reasonably good long-term results in patients receiving a second kidney transplant for IgA nephropathy. Recurrent disease was identified in only 2 of 28 patients during follow-up of 61.61 ± 47.23 months. [33]

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