| Treatment and prognosis of IgA nephropathy | ||
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Author Daniel C Cattran, MD Gerald B Appel, MD |
Section Editor Richard J Glassock, MD, MACP |
Deputy Editor Alice M Sheridan, MD |
INTRODUCTION — IgA nephropathy is the most common cause of primary (idiopathic) glomerulonephritis in the developed world [1-4] . Although this disorder was initially thought to follow a benign course, it is now recognized that slow progression to end-stage renal disease (ESRD) occurs in up to 50 percent of affected patients [5] . The remaining patients enter a sustained clinical remission or have persistent low grade hematuria or proteinuria. However, the prognosis is quite variable and the outcome difficult to predict with accuracy in individual patients.
The classic presentation of IgA nephropathy is that of gross hematuria, often recurrent, following shortly after an upper respiratory infection [3,6] . However, the majority of patients are diagnosed following an evaluation for asymptomatic microscopic hematuria and/or mild proteinuria. Less common presentations are nephrotic range proteinuria with or without nephrotic syndrome and rapidly progressive glomerulonephritis and, rarely, malignant hypertension. The diagnosis is usually suspected based upon the clinical history and laboratory data, but can only, at the present time, be confirmed with a kidney biopsy.
The prognosis and treatment of IgA nephropathy will be reviewed here. The causes, pathogenesis, and diagnosis of this disorder, and the outcomes in patients who undergo renal transplantation, are discussed separately. (See "Causes and diagnosis of IgA nephropathy" and see "IgA nephropathy: Recurrence after transplantation")
PROGNOSIS — Patients
with IgA nephropathy and little or no proteinuria (<500 mg/day)
have a low risk of progression in the short term. However, renal
insufficiency and proteinuria develop in a substantial
proportion of patients over the long term, and such patients may
progress to end-stage renal disease (ESRD) [5,7] . The possible
role of persistent microscopic hematuria in predicting an
adverse outcome in this group of patients is debated.
Frequency of progression — The natural history
of patients who present with isolated hematuria (ie, without
abnormal proteinuria) patients is not as benign as initially
thought. This was demonstrated in the following studies:
In a Chinese study of 72 consecutive patients
with IgA nephropathy who underwent diagnostic biopsy because of
hematuria with no or minimal proteinuria (defined as less than
0.4 g/day), patients were followed for a median of seven years
[6] . Protein excretion above 1000 mg/day, hypertension, and/or
impaired renal function (serum creatinine concentration ≥1.4 mg/dL
[120 µmol/L]) developed in 33, 26, 7 percent, respectively.
In a nationwide study of 2270 patients with
biopsy proven IgA nephropathy in Japan who were surveyed three,
five and eight years after the baseline survey, 207 patients
developed ESRD [8] . The seven year cumulative incidence of
end-stage renal disease was 8 and 15 percent for women and men,
respectively.
Among 93 patients with an initially normal
measured GFR (but usually with proteinuria), approximately
one-third had a reduced GFR within five years and one-fourth
progressed to ESRD within 20 years [9] .
Among patients who develop proteinuria and/or
elevated serum creatinine concentration, progression to ESRD is
approximately 15 to 25 percent at 10 years, and 20 to 30 percent
at 20 years [1,2,8-11] . Higher rates of progression are seen
among patients with more severely impaired kidney function.
Among the 183 patients with serum creatinine ≥1.7 mg/dL (150
µmol/L) in the previously mentioned Japanese survey, the
seven-year cumulative incidence of ESRD was ≥70 percent [8] .
However, the rate of loss of GFR was often as
low as 1 to 3 mL/min per year, a change not associated with an
elevation in the serum creatinine concentration during this time
period. Thus, a stable and normal serum creatinine does not
necessarily indicate stable disease.
These observations are generally from patients
with biopsy-confirmed IgA nephropathy in which some factor other
than hematuria prompted the biopsy (such as proteinuria or an
elevated serum creatinine concentration). Patients with only
hematuria are often not biopsied in many countries (such as the
United States).
The impact of different biopsy criteria was
shown in a retrospective study that evaluated geographic
differences in the clinical course of 711 patients with a biopsy
diagnosis of IgA nephropathy [5] . Renal survival at ten years
was 96, 87, 64, and 62 percent in Finland, Australia, Scotland,
and Canada, respectively. Better outcomes in Finland and
Australia were largely attributable to the diagnosis of milder
cases (eg, less proteinuria, higher creatinine clearance, lower
blood pressure). This raises the possibility of lead-time bias
influencing the prognosis, versus truly a better prognosis in
some geographic areas compared to others [5,12] . (See "Glomerular
hematuria: IgA; Alport; thin basement membrane nephropathy").
Repeat renal biopsy has also been used to assess
the frequency of progressive disease [13,14] . In one report,
repeat renal biopsies were performed at five years in 73
patients with persistent proteinuria but a normal or near-normal
initial serum creatinine [13] . Histologic improvement occurred
in only 4 percent, with 41 percent remaining stable, and 55
percent showing progressive glomerular and secondary vascular
and tubulointerstitial injury.
Some patients without significant proteinuria or
renal dysfunction undergo remission of abnormal laboratory
findings, with reported rates ranging between 5 and 30 percent
[10,12-15] . Remission may be more likely among children. This
was illustrated in a study of 181 Japanese children diagnosed by
renal biopsy before the age of 15 years; 30 percent had
proliferative glomerulonephritis and were treated with
immunosuppressive agents [16] . After a mean follow-up of seven
years, 50 percent had no manifestations of disease, 36 percent
had persistent hematuria with or without proteinuria, and 25 (14
percent) developed progressive disease.
Clinical predictors of progression — As in other
glomerulopathies, patients who will develop progressive disease
typically have one or more of the following clinical or
laboratory findings at diagnosis [1,2,6,7,16-20] :
Elevated serum creatinine concentration at
diagnosis — Patients who reach a serum creatinine concentration
≥2.5 mg/dL (221 µmol/L) generally continue to progress.
Hypertension — Hypertension is associated with
arteriosclerosis and tubulointerstitial changes on biopsy, and
usually significant proteinuria.
Persistent protein excretion above 500 to 1000
mg/day.
The relation between increasing proteinuria and
a worse prognosis is probably in part a reflection of
proteinuria being a marker for the severity of glomerular
disease. The rate of progression is very low among patients
excreting less than 500 mg/day, and is fastest among those
excreting more than 3.0 to 3.5 g/day of protein [9,21,22] .
The importance of the magnitude of proteinuria
on the course of IgA nephropathy was evaluated in an
observational study of 542 patients [22] . The rate of decline
in renal function was 25-fold faster in those with sustained
proteinuria of greater than 3 g/day compared to patients with
protein excretion less than 1 g/day [22] . Patients who
presented with protein excretion above 3 g/day who attained a
partial remission (less than 1 g/day) had a similar rate of
progression as patients with sustained proteinuria of less than
1 g/day. As described below,
ACE inhibitors or angiotensin II receptor
blockers are the preferred antiproteinuric drugs.
(See "Angiotensin inhibition" below).