IgA NEPHROPATHY.

IgA Np is the most commonly observed form of primary GN worldwide. IgA Np is more commonly seen among Asians & Caucasians.

 

Clinical presentation and diagnosis 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.

 

IgA Np is the most commonly observed form of primary GN worldwide. IgA Np is more commonly seen among Asians & Caucasians. There’s a 2:1 male-to-female tendency in Caucasians but not present in East Asians, where both sexes are equally involved. Pathology of IgA Np is characterized by mesangial prominent, globular deposits of IgA seen on IF testing. LM may show diffuse mesangial proliferation + matrix expansion with proliferative GN and segmental GS with IF/TA and inflammation in advanced disease. E/M usually shows mesangial dense deposits.

The Oxford classification recognizes the varieties correlated to renal outcome regardless the clinical presentation at baseline, proteinuria level, and BP control. Application of this scoring system in determining therapy requirements for further evaluation.

 

Oxford classification of IgA Np

 

The current recommendation is that each renal biopsy report should include variable scoring according to the presence/absence of these 5 variables (MEST-C). Scoring system is recognized as follows:

1)    Mesangial hypercellularity: mesangial cells counted per mesangial area, & a scoring of 0-3 is given for each glomerulus. Zero = < 4 mesangial cells per mesangial area; one = 4-5 cells; 2 = 6-7 cells; & 3 = > 8 mesangial cells are present per mesangial area. Scoring is usually in average, and hypercellularity scoring is either M0 if the mean score is < 0.5 or M1 if the mean score is > 0.5.

2)    Endocapillary hypercellularity: E1 = hypercellularity inside glomerular capillary lumen > narrowed lumen, or absent (E0) = no luminal hypercellularity.

3)    Segmental GS: S1 = any part of glomerular tuft showed sclerosis, or absent (S0) = no segmental GS.

4)    Tubular atrophy/interstitial fibrosis (IF/TA): % of cortical area with TA or IF is calculated. Scoring of T0, T1, or T2 is given if the % of affected cortical area is 0-25, 26-50, or >50 %, resp.

5)    Crescents: defined as: cellular and/or fibrocellular crescents at least one glomerulus = C1, at least 25 % of glomeruli = C2, or absent = C0.

Biopsy of < 8 glomeruli is NOT of prognostic value. A predictive tool combining clinical + histologic (MEST-C) data at Dgx can predict the risk of kidney function deterioration (= 50 % decline in eGFR or developed ESKD) within 5-7 ys.

 

IgA Np manifestations are confined to the kidney. Mesangial IgA deposits, which is usually clinically silent, may also be observed with cirrhosis, celiac disease, & HIV infection (clinically apparent disease may be also seen). Moreover, IgA Np may be rarely be seen with other forms of Glomerulopathy e.g., MCD & granulomatosis with polyangiitis.  Ptns with IgA Np are mostly presented with either gross hematuria (single or recurrent), usually with upper respiratory tract infection, or microscopic hematuria +/- mild proteinuria incidentally discovered with routine examination. Rarely, ptns may develop AKI +/- oliguria, owing to either crescentic IgA Np or to gross hematuria leading to tubular obstruction and/or RBCs damage. Dgx of IgA Np is usually established based on clinical history but can be confirmed via a kidney biopsy. Renal biopsy is usually resorted to asses suspected IgA Np only if there’re Sns suggesting more intense or progressive disease e.g., proteinuria > 500 mg/d, increased SCr, or HT.