Natural History of Primary IgA Nephropathy

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Summary

Primary IgA nephropathy (IgAN) is the most frequent type of primary glomerulonephritis worldwide. The characteristic presentation is gross hematuria at the time of an infectious episode. A renal biopsy still is mandatory for the diagnosis. The natural history of the disease is characterized by clinical and pathologic progression over time, which can vary from a few years to more than 50 years. It is possible to make a broad prediction at the time of diagnosis of the long-term (20 years) risk of progressive chronic kidney disease, and then to end-stage renal disease requiring renal replacement therapy (20-year cumulative end-stage renal disease risk range, 14%-39%). The 3 major independent risk factors are arterial hypertension, proteinuria more than 1 g/d, and severe renal histopathologic lesions including hyalinosis, crescents, or defined by histopathologic scoring systems. When any clinical risk factors are present, patients should be targeted closely by appropriate treatments in the following order: (1) precise control of hypertension, (2) control of proteinuria when persisting for greater than 1 g/d, and (3) evidence-based treatment where available for severe lesions. This is a symptomatic treatment strategy because pathogenesis and etiology still remain unclear.

Section snippets

Definition of IgAN

The definition of IgAN is pathologic and still needs a renal biopsy which should be examined at least by light microscopy (LM) and by immunofluorescence microscopy. The immunofluorescence microscopy technique, necessary for identification of mesangial IgA deposits, appeared in the late 1960s, explaining why IgAN was not identified earlier. The agreed on definition is the presence of at least 1+ (on a semiquantitative scale: 0, trace, 1+, 2+, and 3+) IgA deposits in the mesangial area (also

Classification of IgAN

The spectrum of IgA nephropathies is dominated by idiopathic or primary IgAN, previously also called Berger’s disease. In our own center, an initial cohort diagnosed from 1975 to 19873 consisted of 356 patients, with 282 cases (79%) of primary IgAN, 41 cases (11.5%) secondary to Schönlein-Henoch purpura, and 33 cases (9%) secondary to cirrhosis. Similar histologic appearances may be seen in systemic lupus erythematosus, International Society of Nephrology/Renal Pathology Society (ISN/RPS) class

Epidemiology of Primary IgAN

IgAN is diagnosed worldwide, and remains the most predominant primary glomerulonephritis. It is frequent in Caucasian and Asian populations, contrasting with its apparent rarity in African populations, especially in African Americans.7

Its incidence has been estimated in France to be between 26 and 30 new cases per million population (pmp) in 2 different regions: Britanny8 and Rhône-Alpes.9 In Japanese children,10 the incidence was calculated at 45 pmp (with both sporadically identified cases

Clinical Onset of the Disease

Depending on the renal biopsy policy, extended versus restricted, the proportion of patients diagnosed at the time of an acute episode compared with those who are asymptomatic (urinary screening detection) will vary greatly, ranging from 30%3 to 80%14 both in children and adults.

The typical acute presentation is macroscopic hematuria at time of a mucosal infectious event (upper respiratory tract infection, bronchitis, or even urinary tract infection). Episodes last for 2 or 3 days, and usually

Progression of IgAN

The natural history of primary IgAN is progression both clinically and pathologically.

Clinical progression is exemplified by our prospective cohort, with collection of 332 new cases over a 10-year period from 1990 to 1999 (Table 2). With time, there is clearly a progression of the number of patients with hypertension (HT), with chronic renal failure (CRF) (defined as stage 3 or 4 CKD [GFR <60 mL/min/1.73 m2]), or reaching ESRD. The overall prevalence of CRF in other series varied from 9% to

Predictive Risk Factors of Progression in IgAN

A major step to be performed at the time of diagnosis in each individual case is to establish as accurately as possible the long-term prognosis with an appropriate management plan and follow-up procedure.

There is now a consensus about the 3 major risk factors predictive of progression toward CKD and ESRD.

The occurrence of arterial HT is the most important. By Cox regression analyses (univariate, then multivariate), HT occurring at any stage of the disease is an independent and strong risk

Conclusions

The natural history of IgAN is dominated by clinical and pathologic progression. The rate of progression to CKD and ESRD is highly variable among patients, from very fast to very slow (ie, from a few years to >50 years). It is possible to predict long-term prognosis at the time of initial diagnosis with 3 independent risk factors: occurrence of arterial HT, amount of proteinuria, and severity of some renal lesions. The natural history of the disease should be observed carefully and every effort

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