*Urinary ratio of Epidermal growth factor to monocyte chemotactic peptide-1<ref name="pmid17943082">{{cite journal| author=Torres DD, Rossini M, Manno C, Mattace-Raso F, D'Altri C, Ranieri E et al.| title=The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy. | journal=Kidney Int | year= 2008 | volume= 73 | issue= 3 | pages= 327-33 | pmid=17943082 | doi=10.1038/sj.ki.5002621 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17943082 }} </ref>
Urinary ratio of Epidermal growth factor to monocyte chemotactic peptide-1<ref name="pmid17943082">{{cite journal| author=Torres DD, Rossini M, Manno C, Mattace-Raso F, D'Altri C, Ranieri E et al.| title=The ratio of epidermal growth factor to monocyte chemotactic peptide-1 in the urine predicts renal prognosis in IgA nephropathy. | journal=Kidney Int | year= 2008 | volume= 73 | issue= 3 | pages= 327-33 | pmid=17943082 | doi=10.1038/sj.ki.5002621 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17943082 }} </ref>
*Fibroblast growth factor 23 (FGF23)<ref name="pmid22383747">{{cite journal| author=Lundberg S, Qureshi AR, Olivecrona S, Gunnarsson I, Jacobson SH, Larsson TE| title=FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy. | journal=Clin J Am Soc Nephrol | year= 2012 | volume= 7 | issue= 5 | pages= 727-34 | pmid=22383747 | doi=10.2215/CJN.10331011 | pmc=PMC3338280 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22383747 }} </ref>
Fibroblast growth factor 23 (FGF23)<ref name="pmid22383747">{{cite journal| author=Lundberg S, Qureshi AR, Olivecrona S, Gunnarsson I, Jacobson SH, Larsson TE| title=FGF23, albuminuria, and disease progression in patients with chronic IgA nephropathy. | journal=Clin J Am Soc Nephrol | year= 2012 | volume= 7 | issue= 5 | pages= 727-34 | pmid=22383747 | doi=10.2215/CJN.10331011 | pmc=PMC3338280 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22383747 }} </ref>
Urinary podocalyxin and podocyturia<ref name="pmid22700887">{{cite journal| author=Asao R, Asanuma K, Kodama F, Akiba-Takagi M, Nagai-Hosoe Y, Seki T et al.| title=Relationships between levels of urinary podocalyxin, number of urinary podocytes, and histologic injury in adult patients with IgA nephropathy. | journal=Clin J Am Soc Nephrol | year= 2012 | volume= 7 | issue= 9 | pages= 1385-93 | pmid=22700887 | doi=10.2215/CJN.08110811 | pmc=PMC3430952 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22700887 }} </ref>
*Urinary podocalyxin and podocyturia<ref name="pmid22700887">{{cite journal| author=Asao R, Asanuma K, Kodama F, Akiba-Takagi M, Nagai-Hosoe Y, Seki T et al.| title=Relationships between levels of urinary podocalyxin, number of urinary podocytes, and histologic injury in adult patients with IgA nephropathy. | journal=Clin J Am Soc Nephrol | year= 2012 | volume= 7 | issue= 9 | pages= 1385-93 | pmid=22700887 | doi=10.2215/CJN.08110811 | pmc=PMC3430952 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22700887 }} </ref>
Urinary alpha-1-microglobulin and beta-2-microglobulin<ref name="pmid19299847">{{cite journal| author=Peters HP, van den Brand JA, Wetzels JF| title=Urinary excretion of low-molecular-weight proteins as prognostic markers in IgA nephropathy. | journal=Neth J Med | year= 2009 | volume= 67 | issue= 2 | pages= 54-61 | pmid=19299847 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19299847 }} </ref>
Mannose-binding lectin<ref name="pmid22774989">{{cite journal| author=Liu LL, Jiang Y, Wang LN, Liu N| title=Urinary mannose-binding lectin is a biomarker for predicting the progression of immunoglobulin (Ig)A nephropathy. | journal=Clin Exp Immunol | year= 2012 | volume= 169 | issue= 2 | pages= 148-55 | pmid=22774989 | doi=10.1111/j.1365-2249.2012.04604.x | pmc=PMC3406374 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22774989 }} </ref>
*Urinary alpha-1-microglobulin and beta-2-microglobulin<ref name="pmid19299847">{{cite journal| author=Peters HP, van den Brand JA, Wetzels JF| title=Urinary excretion of low-molecular-weight proteins as prognostic markers in IgA nephropathy. | journal=Neth J Med | year= 2009 | volume= 67 | issue= 2 | pages= 54-61 | pmid=19299847 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19299847 }} </ref>
Activated complement C3<ref name="pmid9083294">{{cite journal| author=Zwirner J, Burg M, Schulze M, Brunkhorst R, Götze O, Koch KM et al.| title=Activated complement C3: a potentially novel predictor of progressive IgA nephropathy. | journal=Kidney Int | year= 1997 | volume= 51 | issue= 4 | pages= 1257-64 | pmid=9083294 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9083294 }} </ref>
Advanced oxidative protein products<ref name="pmid21784819">{{cite journal| author=Camilla R, Suzuki H, Daprà V, Loiacono E, Peruzzi L, Amore A et al.| title=Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. | journal=Clin J Am Soc Nephrol | year= 2011 | volume= 6 | issue= 8 | pages= 1903-11 | pmid=21784819 | doi=10.2215/CJN.11571210 | pmc=PMC3156425 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21784819 }} </ref>
*Mannose-binding lectin<ref name="pmid22774989">{{cite journal| author=Liu LL, Jiang Y, Wang LN, Liu N| title=Urinary mannose-binding lectin is a biomarker for predicting the progression of immunoglobulin (Ig)A nephropathy. | journal=Clin Exp Immunol | year= 2012 | volume= 169 | issue= 2 | pages= 148-55 | pmid=22774989 | doi=10.1111/j.1365-2249.2012.04604.x | pmc=PMC3406374 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22774989 }} </ref>
Uric acid<ref name="pmid22116196">{{cite journal| author=Shi Y, Chen W, Jalal D, Li Z, Chen W, Mao H et al.| title=Clinical outcome of hyperuricemia in IgA nephropathy: a retrospective cohort study and randomized controlled trial. | journal=Kidney Blood Press Res | year= 2012 | volume= 35 | issue= 3 | pages= 153-60 | pmid=22116196 | doi=10.1159/000331453 | pmc=PMC3242707 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22116196 }} </ref><ref name="pmid23391320">{{cite journal| author=Cheng GY, Liu DW, Zhang N, Tang L, Zhao ZZ, Liu ZS| title=Clinical and prognostic implications of serum uric acid levels on IgA nephropathy: a cohort study of 348 cases with a mean 5-year follow-up. | journal=Clin Nephrol | year= 2013 | volume= 80 | issue= 1 | pages= 40-6 | pmid=23391320 | doi=10.5414/CN107813 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23391320 }} </ref>
*Activated complement C3<ref name="pmid9083294">{{cite journal| author=Zwirner J, Burg M, Schulze M, Brunkhorst R, Götze O, Koch KM et al.| title=Activated complement C3: a potentially novel predictor of progressive IgA nephropathy. | journal=Kidney Int | year= 1997 | volume= 51 | issue= 4 | pages= 1257-64 | pmid=9083294 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9083294 }} </ref>
*Advanced oxidative protein products<ref name="pmid21784819">{{cite journal| author=Camilla R, Suzuki H, Daprà V, Loiacono E, Peruzzi L, Amore A et al.| title=Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. | journal=Clin J Am Soc Nephrol | year= 2011 | volume= 6 | issue= 8 | pages= 1903-11 | pmid=21784819 | doi=10.2215/CJN.11571210 | pmc=PMC3156425 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21784819 }} </ref>
*Uric acid<ref name="pmid22116196">{{cite journal| author=Shi Y, Chen W, Jalal D, Li Z, Chen W, Mao H et al.| title=Clinical outcome of hyperuricemia in IgA nephropathy: a retrospective cohort study and randomized controlled trial. | journal=Kidney Blood Press Res | year= 2012 | volume= 35 | issue= 3 | pages= 153-60 | pmid=22116196 | doi=10.1159/000331453 | pmc=PMC3242707 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22116196 }} </ref><ref name="pmid23391320">{{cite journal| author=Cheng GY, Liu DW, Zhang N, Tang L, Zhao ZZ, Liu ZS| title=Clinical and prognostic implications of serum uric acid levels on IgA nephropathy: a cohort study of 348 cases with a mean 5-year follow-up. | journal=Clin Nephrol | year= 2013 | volume= 80 | issue= 1 | pages= 40-6 | pmid=23391320 | doi=10.5414/CN107813 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23391320 }} </ref>
|-
|-
| bgcolor="#ececec"|'''Decreased''' || *Soluble CD89 (sCD89)<ref name="pmid20811333">{{cite journal| author=Vuong MT, Hahn-Zoric M, Lundberg S, Gunnarsson I, van Kooten C, Wramner L et al.| title=Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. | journal=Kidney Int | year= 2010 | volume= 78 | issue= 12 | pages= 1281-7 | pmid=20811333 | doi=10.1038/ki.2010.314 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20811333 }} </ref>|}
| bgcolor="#ececec"|'''Decreased''' ||*Soluble CD89 (sCD89)<ref name="pmid20811333">{{cite journal| author=Vuong MT, Hahn-Zoric M, Lundberg S, Gunnarsson I, van Kooten C, Wramner L et al.| title=Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy. | journal=Kidney Int | year= 2010 | volume= 78 | issue= 12 | pages= 1281-7 | pmid=20811333 | doi=10.1038/ki.2010.314 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20811333 }} </ref>|-|}
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]
Fibroblast growth factor 23 (FGF23)[20]
Urinary podocalyxin and podocyturia[21]
Urinary alpha-1-microglobulin and beta-2-microglobulin[22]
Mannose-binding lectin[23]
Activated complement C3[24]
Advanced oxidative protein products[25]
Uric acid[26][27]