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)
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.
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.