IgA nephropathy: Challenges and opportunities
ABSTRACTImmunoglobulin A (IgA) nephropathy poses many challenges to investigators and physicians in its etiology, pathogenesis, prevention, and treatment. But at the same time, opportunities abound for new tests and treatments that may eventually lead to control of this common form of chronic kidney disease.
KEY POINTS
- IgA nephropathy tends to progress slowly, and in only about half of patients does it progress to end-stage renal disease within 25 years.
- At present, the factors that predict an accelerated course and progression to end-stage renal disease are persistent proteinuria, elevated serum creatinine at diagnosis, persistent microscopic hematuria, poorly controlled hypertension, and extensive glomerulosclerosis or interstitial fibrosis, or both, on renal biopsy.
- Needed are better diagnostic and prognostic tests and therapies that address the mechanism of the disease.
- The value of treatment with an angiotensin-converting enzyme inhibitor, an angiotensin receptor blocker, or both is well established. If protein excretion does not decrease with this therapy, one can consider adding immunosuppressive therapy in selected patients, but this strategy is still empiric and unproven.
The role of more aggressive immunosuppression
At present, the evidence for using mycophenolate mofetil (CellCept) or calcineurin inhibitors (such as cyclosporin or tacrolimus) is fragmentary or contradictory.3,19,23 Similarly, the benefits of long-term azathioprine therapy are based on observational data only and so it cannot be recommended as evidence-based.24 Opportunities exist for combined therapy (eg, an ACE inhibitor or an ARB or both, combined with omega-3 fatty acids and azathioprine or mycophenolate mofetil), but at present, controlled trials are lacking. Crescentic disease and rapidly progressive glomerulonephritis should probably be treated with combined cyclophosphamide and parental and oral corticosteroids, based on observational data. Patients with IgA nephropathy and minimal change disease with nephrotic syndrome should be treated with oral steroids, but the only data available are observational. Low-protein diets could be tried in the presence of slowly progressive renal disease with estimated GFR less than 30 mL/min/1.73 m2, but there are no controlled trials demonstrating efficacy for this approach in IgA neph-ropathy.
Renal transplantation is very successful
Renal transplantation is a very suitable alternative for patients with IgA nephropathy that progresses to ESRD. Overall success rates are as good or better than those in other primary glomerular diseases. Unfortunately, the disease recurs in the majority of renal grafts and may in some cases lead to loss of the graft.25,26 We need much more information on the factors that predict such recurrences and their undesirable effects on transplantation outcomes.
MUCH WORK TO BE DONE
Much work needs to be done in the field of therapeutics in IgA nephropathy. Much of this effort will hinge on the interests of the pharmaceutical industry in IgA nephropathy as a potential therapeutic market. At present, the prospects for the development of a safe and effective novel therapy for IgA nephropathy (eg, approvable by the US Food and Drug Administration) do not appear great, but this may be overly pessimistic. The nature of the disease mandates long-term observation, agents that are very safe (with low rates of ESRD, death, and transplantation), and dependency on surrogate markers of efficacy. Therefore, designing and executing studies will not be easy.
