Treatment and prognosis of IgA nephropathy page-5 |
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Controlled trials of steroid treatments
Corticosteroid therapy for 6 to 24 months or
more may be associated with a reduction in proteinuria and
perhaps improved renal survival , although this has
not been consistently noted [64] . Benefit in some of these
studies was observed only among individuals with preserved
kidney function (eg, creatinine clearance above 70 mL/min)
[75-78] . However, other studies have found improved outcomes
even among individuals with more advanced disease (eg, reduced
kidney function and more significant proteinuria)
As an example, a prospective trial from Italy
included 86 adults with proteinuria (1 to 3.5 g/day) and at most
mild renal insufficiency (median serum creatinine 1 mg/dL [88.4
µmol/L]) [77] . The patients were randomly assigned to
supportive therapy alone, or corticosteroids (1.0 gram of
intravenous methylprednisolone for three consecutive days at the
beginning of months one, three, and five, combined with 0.5
mg/kg of oral prednisolone given on alternate days for six
months).
At five and ten years, the steroid treated
patients had a markedly lower incidence of the primary end
point, which was a doubling in the serum creatinine
concentration (2 versus 21 percent at five years and 2 versus 30
percent at ten years) [78] . The effect of ACE inhibitors was
not assessed.
In contrast, the trial from the Southwest
Pediatric Nephrology Study Group described above found no
difference at three years between oral prednisone therapy for
two years and placebo in the primary outcome of reduction in GFR
to below 60 percent of the baseline value [64] . However, this
trial was underpowered for the primary end-point (See "Fish oil"
above).
There is a subset of patients with IgA
nephropathy in whom prednisone therapy appears to be more
clearly beneficial: those with an acute onset of the nephrotic
syndrome, little or no hematuria, preserved kidney function,
minimal glomerular changes on light microscopy, and diffuse
fusion of the foot processes of the glomerular epithelial cells
on electron microscopy. These histologic findings are
characteristic of minimal change disease, and these patients
behave accordingly, frequently developing a remission with
corticosteroids and occasionally requiring cyclophosphamide for
frequently relapsing proteinuria [83-85] . Mesangial IgA
deposits often disappear or are greatly reduced over time [85] .
(See "Treatment of minimal change disease in adults").
Nephrotic syndrome can also occur with severe
chronic IgA nephropathy and relatively advanced disease on renal
biopsy. These patients do not seem to benefit from steroid
therapy alone [83,84] .
The role of corticosteroids alone in the
treatment of IgA nephropathy is summarized below. (See
"Treatment" below).
Combined immunosuppressive therapy — Combined
immunosuppressive therapy should only be attempted in patients
with more severe active disease as defined by a more rapidly
progressive clinical course and/or histologic evidence of severe
active inflammation (eg, crescent formation).
Severe or progressive disease — Several trials
have suggested a possible benefit from combined
immunosuppressive therapy in patients with moderate to severe
active disease on biopsy; however, most did not include a
comparison group treated with prednisone alone [67,86-90] . In
addition, the studies were primarily performed prior to the
widespread use of aggressive antihypertensive and
antiproteinuric therapy with ACE inhibitors and/or ARBs. (See
"Treatment goals" above and see "Antihypertensive therapy and
progression of nondiabetic chronic kidney disease").
Two trials in children with moderate to severe
histologic findings on renal biopsy, but normal kidney function
(initial creatinine clearance >140 mL/min per 1.73 m2),
evaluated complicated regimens that included heparin, warfarin
and dipyridamole as well as combined immunosuppressive therapy
[89,90] . No benefit was observed with these regimens compared
with azathioprine and/or prednisone.
There are limited data concerning the
effectiveness of cytotoxic agents in adults with progressive IgA
nephropathy . Some trials evaluated cyclophosphamide
with warfarin and dipyridamole , a regimen that is not
widely used, and one evaluated cyclophosphamide with prednisone
[88] . The last trial was a single center study of 38 patients
with IgA nephropathy and initially impaired renal function (but
no crescents on biopsy) as defined by an initial serum
creatinine concentration between 1.5 and 2.8 mg/dL (130 and 250
µmol/L, respectively) that was declining at a relatively
moderate rate (by at least 15 percent over the year prior to
study entry) [88] . Mean baseline protein excretion was 4.0 to
4.5 g/day.
The patients were given antihypertensive therapy
as needed (but not specifically ACE inhibitors and/or ARBs) and
randomly assigned to no further therapy or to prednisolone (40
mg per day tapered to 10 mg/day by two years) plus low-dose
cyclophosphamide (1.5 mg/kg per day) for the initial three
months followed by low-dose azathioprine (1.5 mg/kg per day) for
a minimum of two years (some patients were given azathioprine
for up to six years). Blood pressure control was similar in both
groups, and immunosuppressive therapy was associated with a low
incidence of adverse effects.
Compared with the control group, the patients
treated with combination therapy had a significant reduction in
protein excretion during the first six months of therapy that
persisted during follow-up (eg, reached 1.8 g/day in treatment
group versus unchanged at 4.4 g/day in controls at one year).
Renal survival was significantly higher in the treatment group
at years two (82 versus 68 percent) and five (72 versus 6
percent).
Please proceed to next page for combined immunosuppressive treatments