Update on immunoglobulin a nephropathy. Part II: Clinical, diagnostic and therapeutical aspects

Table 1 Definitions of pathological variables used in the Oxford classification of immunoglobulin a nephropathy

Variable	Definition	Score
Mesangial hypercellularity	< 4 Mesangial cells/mesangial area = 0	M0 < 0.5
	4-5 Mesangial cells/mesangial area = 1	M1 > 0.5
	6-7 Mesangial cells/mesangial area = 2
	> 8 Mesangial cells/mesangial area = 3
Segmental glomerulosclerosis	Any amount of the tuft involved in sclerosis, but not involving the whole tuft or the presence of an adhesion	S0 = absent
		S1 = present
Endocapillary hypercellularity	Hypercellularity due to increased number of cells within glomerular capillary lumina causing narrowing of the lumina	E0 = absent
		E1 = present
Tubular atrophy/interstitial fibrosis	Percentage of cortical area involved by the tubular atrophy or interstitial fibrosis, whichever is greater	0%-25% - T0
		26%-50% - T1
		> 50% - T2

Table 2 Summary of studies correlating the Oxford classification for immunoglobulin a nephropathy with clinical outcomes

Study	Patients (n)	End point	Univariate analysis	Multivariate analysis
Coppo et al[19]	206 A, 59 C	Rate of eGFR decline	M, E, S T	M, E, S, T
Herzenberg et al[20]	143 A, 44 C	Rate of eGFR decline	Not done	E, S, T
Katafuchi et al[21]	702 A, C	ESRD	Not done	S, T
Zeng et al[22]	1026 A	Rate of eGFR decline	M, S, T	M, T
Shi et al[23]	410 A	ESRD	M, S, T	S, T
Edström Halling et al[24]	99 C	GFR reduction > 50%, ESRD	M, E, T	E
Shima et al[25]	161 C	eGFR < 60% mL/min per 1.73m2	M, T	M, T
Coppo et al[26]	973 A, 174 C	Rate of eGFR decline	M, E, S, T	S, T
Alamartine et al[27]	183 A	Doubling of SCr or ESRD	E, S, T	None
El Karoui et al[28]	128 A	Rate of eGFR decline	Not done	T
Lee et al[29]	69 A	GFR reduction > 50%, ESRD	E, T	E
Kang et al[30]	197 A	GFR reduction > 50%, ESRD	T	T
Le et al[31]	218 C	eGFR reduction > 50%, ESRD	T, S	T

A: Adults; C: Children; eGFR: Estimated glomerular filtration rate; E: Endothelial hypercellularity; ESRD: End-stage renal disease; GFR: Glomerular filtration rate; M: Mesangial hypercellularity; S: Segmental sclerosis; Scr: Serum creatinine; T: Tubular atrophy/interstitial fibrosis.

Table 3 Potential biomarkers for immunoglobulin a nephropathy

Biologics	Source	Rationale
Galactose deficient IgA1	Serum	Core antigen of the pathogenic IgA1 immune complex; leads to activation of mesangial cells and glomerulonephritis
Glycan-specific IgG	Serum	Form glycan-dependent complex with galactose-deficient IgA1; alanine to serine substitution in complementary-determining region 3 of IgG heavy chain; able to differentiate IgA nephropathy patients from controls with 88% specificity and 95% sensitivity
Activated complement C3	Serum	Up-regulated level in 30% of patients; correlated with deteriorating renal function
FGF 23	Serum	FGF23 serum levels are significantly associated with IgAN progression
Soluble CD89	Serum	Low levels in patients with disease progression compared with those without disease progression
Mannose-binding lectin	Urine	Significantly higher in patients than healthy controls; associated with histopathologic aggravations such as mesangial hypercellularity, tubular atrophy, interstitial fibrosis
EGF and MCP-1	Urine	An EGF/MCP-1 ratio greater than 366.66 extends renal survival to at least 84 mo in a cohort of 44 patients
Proteomic pattern	Urine	High throughput characterization of 2000 polypeptide using capillary electrophoresis on-line coupled to a mass spectrometer
microRNA profile	Urine	Sequencing identified microRNA profiling that is specific to IgA nephropathy

IgA1: Immunoglobulin A1; IgG: Immunoglobulin G; FGF23: Fibroblast growth factor 23; IgAN: Immunoglobulin a nephritis; RNA: Ribonucleic acid; EGF: Epidermal growth factor; MCP-1: Monocyte chemotactic peptide-1.

Table 4 Supportive therapy of immunoglobulin a nephropathy

Level 1	Control blood pressure (sitting systolic BP in the 120 s)
	ACE inhibitor or ARB therapy with up-titration of dosage or combination ACE inhibitor and ARB therapy
Level 2	Control protein intake
	Restrict NaCl intake/institute diuretic therapy
	Control each component of the metabolic syndrome
	Aldosterone antagonist therapy
	Beta-blocker therapy
	Smoking cessation
Other measures	Allopurinol therapy
	Empiric NaHCO3 therapy, independent of whether metabolic acidosis is present or not
	Avoid NSAIDs altogether, or no more than once or twice weekly at most
	Avoid prolonged severe hypokalemia
	Avoid phosphate cathartics
	Ergocalciferol therapy to correct vitamin D deficiency
	Control hyperphosphatemia and hyperparathyroidism

ACE: Angiotensin-converting enzyme; ARB: Angiotensin receptor blocker; NaCl: Sodium chloride; NaHCO₃: Sodium bicarbonate; NSAID: Non-steroidal anti-inflammatory drug.