The clinical course of IgA nephropathy varies widely between patients. Although it is generally regarded as a benign disease, emerging data has shown that progression to ESRD and death are more common than originally believed.[1] Some patients rapidly progress into ESRD; but the majority experience a stable kidney function following diagnosis.[1]
Commonly, the progression of IgA nephropathy is slower than other notorious glomerular disease. Approximately 20-30% of patients with IgA nephropathy progress to ESRD after 10 years[1] and up to 30-50% of patients develop ESRD over 20 years.[2][3]
Complications
Complications of IgA nephropathy are generally those of renal injury.
Hypertension
Nephritic syndrome
Nephrotic syndrome
Acute kidney injury
Chronic kidney disease
End-stage renal disease
Hypercholesterolemia
Prognosis
IgA nephropathy follows an unpredictable clinical course with debatable prognostic factors. Although considered a benign disease in comparison to other forms of glomerulonephritis, new data show that up to 20-30% of patients with IgA nephropathy progress to ESRD after 10 years.[1] It is important, however, to note that experts concede that the true prognosis of IgA nephropathy is poorly established because the diagnosis by biopsy is often made late during stage 3-4 chronic kidney disease.[3] The approximately 10-year renal survival following diagnosis ranges between 67-94%, based on the findings of 5 major trials from Germany, France, UK, Japan, and Australia and 1 meta-analysis from USA.[4][5][6][7][8]
Several studies have analyzed factors associated with prognosis of IgA nephropathy. In 2011, Berthoux and colleagues established 3 main factors that have been attributed to be the core predictors of outcome when studying 332 patients with IgA nephropathy over 13 years[9]:
1- Proteinuria > 1g/24 hrs
2- Severe pathologic lesions with a global optical score ≥ 8
3- Hypertension > 140/90 mmHg
Proteinuria is the most important prognostic factor with a “dose-dependent” effect[10]
In 2011, Berthoux et al. calculated absolute renal risk (ARR) of dialysis or death.[9] The absence of all 3 risk factors was associated with a 96% prediction of survival without hemodialysis.[9] As ARR increased, survival prediction decreased, where the presence of all 3 risk factors was associated with only 36% prediction of survival without the need for dialysis.[9]
In one major meta-analysis that involved a database of 148 patients with IgA nephropathy between 1973 and 1995, Radford and colleagues[3] suggested a “glomerular score” based on previous findings from the literature that consists of the summation of 6 components:
Mesangial hypercellularity
Mesangial matrix increase
Glomerular sclerosis
Capillary narrowing or disruption
Cellular crescents
Fibrous adhesions
Observational, cross-sectional, and cohort studies to date have shown the following data to be significantly associated with progression of IgA nephropathy into ESRD and worse outcome. However, the significance of the following is variable and has not been consistent in the literature.
Genetic:
D or DD allele of insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) gene[11]
Mesangial hypercellularity and diffuse mesangial proliferation[16][17][18]
Tubular atrophy
Age remains a controversial predictor of outcome for patients with IgA nephropathy. While some studies showed that younger age is associated with worse outcomes[3], these findings were not consistent in the literature and at times, completely opposing.[16][4]
Biological Biomarkers of Progression
Change in Serum Marker
Biological Marker
Increase
Urinary ratio of Epidermal growth factor to monocyte chemotactic peptide-1[19]