IgA Nephropathy
Microscopic or episodic macroscopic hematuria is the key clinical manifestation of IgAN, which is the most common form of primary glomerulonephritis worldwide. The disease course is highly variable, ranging from a benign condition to rapidly progressive renal failure. It is estimated that 15–40% of patients will eventually reach ESKD. Consequently, research in this field has focused on identifying predictors for disease outcome in addition to evaluation of novel treatments in order to slow disease progression.
Suggested predictors for progressive disease include clinical parameters at diagnosis such as hypertension and proteinuria, in addition to decreased estimated glomerular filtration rate (eGFR), hemoglobin, and albumin levels. In addition, serum levels of IgG and IgA autoantibodies were demonstrated to be strongly associated with the progression of IgAN. A pathological classification with a predictive value, which is independent of the clinical assessment, has also been reported recently. This Oxford classification designates combinations of pathologic mesangial hypercellularity proliferation, segmental glomerulosclerosis, and tubular atrophy or interstitial fibrosis, and proposes that the presence of four lesions is predictive for renal outcome (defined by decreased eGFR). This predictive classification has also been validated for children.
The current therapeutic options for patients with IgAN range from reassurance and periodic follow-up at one extreme to tonsillectomy, glucocorticoids, and cytotoxic or immunomodulatory medications at the other extreme. Whereas many clinical studies have been reported, the benefit of steroids for IgAN patients has not been fully resolved with a high evidence level, large sample size, and randomized prospective clinical trial. Consequently, although in widespread use, the efficacy and safety of glucocorticoids remain controversial. This is compounded by differences in diagnostic and enrollment criteria. Thus, conclusions based on biopsy-proven IgAN may not reflect the larger numbers of patients whose only manifestation is persistent isolated microscopic hematuria and who do not undergo biopsy validation of the presumed diagnostic. In a recent meta-analysis, which assessed the effects of steroid therapy in IgAN, the authors concluded that glucocorticoids appear to provide renal protection in patients with IgAN, but that the benefit may be offset by an increased risk for adverse events. The need for aggressive treatment is further challenged by the observation of subsets of patients with IgAN who seem to have a favorable prognosis without intervention. In a recent study by Gutiérrez et al., 141 patients with biopsy-proven IgAN, normal renal function, and mild proteinuria (<0.5 g per day) were followed for an average period of 9 years. The primary outcome of 50% increase in serum creatinine occurred in only 3.5%, and only one patient had a doubling in serum creatinine. Although this study gives clinical reassurance that the long-term prognosis of IgAN with minimal proteinuria is favorable, the true prognosis of patients with IgAN manifesting as persistent isolated microscopic hematuria without proteinuria is not completely elucidated. Thus, in the clinical setting prognostic indicators are weak on an individualized basis, and at the time of diagnosis it remains difficult to predict the long-term clinical outcome. Importantly, because kidney biopsy is usually not performed, periodic follow-ups with assessment of blood pressure, renal function and proteinuria are highly recommended for patients presenting with persistent isolated microscopic hematuria in whom IgAN is one of the possible underlying causes.