IgA Np is the most commonly observed etiology of primary (idiopathic) GN in developed world. Slowly progressing to ESRD can be seen in up to 50 % of p
Treatment
and prognosis of IgA Nephropathy (IgA NP)
Abbreviations:
o
IgA Np: IgA nephropathy.
o
LM: Light
microscopy
o
E/M: Electron
microscopy
o
IF: immunofluorescence
o
HT: Hypertension
o
GN: glomerulonephritis
o
GS: Glomerulosclerosis.
o
NS: Nephrotic syndrome,
o
AKI: acute kidney
injury,
o
Im/m: immunosuppressive
therapy
o
IF/TA: Interstitial
fibrosis/Tubular
atrophy.
o
SCr: serum
creatinine concentration
o
eGFR: estimated
glomerular filtration rate,
o
MCD: minimal
change disease.
o
ATN: acute tubular
necrosis.
o
GC: glucocorticoids
o
Mp: methylprednisolone.
o
Pred: prednisolone.
IgA Np is the most commonly
observed etiology of primary (idiopathic) GN in developed world. Slowly progressing to ESRD can be seen in up to 50 % of ptns, usually
> 20-25 ys of
observation. The rest of ptns develop persistent clinical remission or have sustained
low-grade hematuria and/or proteinuria.
The clinical predictors denoting progression of IgA
Np may include:
o
Higher SCr,
o
HT, and
o
Sustained proteinuria > 1000 mg/d.
Ptns having
recurrent attacks of gross hematuria with no proteinuria considered at a lowered risk for
progressive renal disease.
Histologic
criteria on
renal biopsy in ptns with IgA Np have been correlated to a higher risk of progressive disease. These include both:
o
Markers of intense inflammatory
lesions, e.g.,
1. Crescent formation, &
2. Immune deposition in the capillary loop with mesangial deposition (found in almost all ptns) &
o
Markers of chronic fibrotic lesions e.g., GS,
IF/TA, & vascular disease.
Oxford Classification is a pathological classification identifying many variables correlating with worse renal outcome
independent from the current clinical manifestations, including mesangial proliferation, endocapillary proliferation, segmental GS, and IF/TA and
It is accepted in many cohorts.
AKI can be seen in ptns
with episodic gross hematuria that
can be related to ATN, & SCr typically
comes back to its baseline within few weeks. However, AKI may
alarm to crescentic lesion requiring urgent therapy. In IgA
Np ptn with acute decline in renal
function and not improving within a week's follow up, repeating kidney biopsy is
suggested to exclude crescentic formation.
Management
2 major approaches
have been suggested:
o
Non-im/m therapy to slow down disease progression:
1. Fish
oil.
2. BP
control,
3. ACEi/ARBs; for proteinuric ptns.
o
im/m therapy with GC, with/without other im/m medications,
to manage the underlying inflammatory lesions.
Ptns with isolated
hematuria, no or minimal proteinuria (< 500-1000 mg/d.), & normal GFR
> no ttt required & no biopsy needed and so not diagnosed as an IgA Np.
However, this group of ptns should be periodically observed at 6-12-mo durations
to detect early progress manifested by rising in proteinuria,
BP, and/or SCr.
With persistent proteinuria (> 1 g/d or > 500 mg/d), a normal or only slightly decline in GFR that’s not lowered rapidly, and only mild/moderate
histologic findings on kidney biopsy are initially ttt with non-
im/m therapies to slow down
disease progression. Approach of non- im/m therapy suggested as follows:
o
Angiotensin inhibition with ACEi or ARB. Target of urinary proteinuria < 500 mg/d or
1 g/d & BP < 130/80 mmHg.
o
Fish oil (3.3 g/d. or more), that can be tried with proteinuria
> 1 g/d
despite 3-6 mo of
therapy with ACEi/ARB. Fish
oil may have CVS benefits.
Anti-inflammatory with GC with progressively active disease including hematuria + one or more of:
o
Rising SCr
o
Persistent proteinuria > 1 g/d after maximal
anti-proteinuric non-im/m ttt
o
Morphologic evidence of active disease in
renal biopsy (e.g., proliferative or necrotizing
glomerular alterations)
o
No need to introduce GC with chronic rise in SCr
or histologic findings of prominent GS and IF/TA
Either of the following 2 protocols is
accepted for ptns selected for GC therapy:
o
IV. Mp,
1 g, for 3 successive days at
the beginning of mo 1, 3, & 5, + 0.5 mg/kg oral Pred on alternate days for 6
more mo.
o
Pred, 0.8-1 mg/kg/d,
for 2 mo followed by monthly dose decline
of 0.2 mg/kg/d. in
the next 4
mo.
Combined im/m plan can be administrated with more aggressive lesions
defined by a more aggressive clinical course and/or histological
evidence of intense active
inflammation (e.g., crescent). Many im/m combinations
have been suggested in such ptns. There’s cohort of ptns with IgA Np
presenting with acute NS, little or
no hematuria, normal kidney function,
minimal glomerular lesions on LM,
and diffusly fused of foot processes of the glomerular epithelial lining on E/M. These findings are characterizing MCD. Acute NS + diffuse
foot process fusion on kidney
biopsy are ttt as if an MCD. There’re
no particular serologic markers identifying immunologic activity in IgA Np. So, clinical parameters are typically utilized, whether or
not ptn is already on im/m. The major
clinical parameters that’re serially observed are the SCr or eGFR, & proteinuria.
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