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Published in: BMC Nephrology 1/2017

Open Access 01-12-2017 | Research article

Significance of clinical and morphological prognostic risk factors in IgA nephropathy: follow-up study of comparison patient groups with and without renoprotection

Authors: Živile Riispere, Anne Kuudeberg, Elviira Seppet, Kristin Sepp, Madis Ilmoja, Merike Luman, Külli Kõlvald, Asta Auerbach, Mai Ots-Rosenberg

Published in: BMC Nephrology | Issue 1/2017

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Abstract

Background

IgA nephropathy (IgAN) is the most frequent glomerulonephritis in many countries including Estonia. There is no specific treatment for IgAN but renoprotection is indicated when proteinuria is >1 g/day. We aimed to assess the clinicopathological correlations of IgAN and to compare the follow-up outcome of the IgAN patients receiving renoprotection with the patients with other antihypertensive regimen treatments.

Methods

A retrospective kidney biopsy cohort study was carried out in consecutive 73 IgAN cases, using the new Oxford classification. The baseline and follow-up (FU, 4.1 years) clinical data were collected. The patients were divided into two main study groups according to their drug-treatment: the drug-treated and untreated patients’ groups. Two subgroups among patients receiving two different antihypertensive drugs were formed and statistically analysed: Renin-angiotensin system (RASb, renoprotection) - and calcium-channel blockers (CCB)-receiving patients. Also, patient’ subgroups with and without the presence of clinical and morphological risk factors were used for statistical analysis.

Results

The patients’ mean age was 33.7 years (range 16–76). Proteinuria decreased at the end of FU (0.91 g/24 h to 0.79 g/24 h). Mean arterial pressure remained at the end of FU almost at the same level. Drug treatment was prescribed to the patients who had lower eGFR, higher proteinuria and more severe histological lesions (S1, T1/2), while the patients with minimal clinical symptoms and the ones with near-normal kidney function remained without drug treatment. The kidney function remained almost at the same normal level in untreated patients irrespective of the risk factors whereas in both treated patient’ subgroups eGFR declined. The following statistically significant correlations in the IgAN cohort were found: correlations in patients with lower kidney function (eGFR <60 ml/min/1.73 m2), higher blood pressure (p = 0.00006) and proteinuria were found irrespectively of the fact whether the patients received (p = 0.006) or did not receive renoprotection (p = 0.001). The biggest significant eGFR change by Wilcoxon rank sum test was found among the patients who had clinical and morphological risk factors and received treatment. The result was confirmed by post hoc analysis and did not depend on the presence of treatment. In the investigation of the subgroups receiving RASb we found that the lowering of eGFR did depend on the presence of clinical and morphological risk factors.

Conclusions

Renoprotection is only effective in preventing the progression of IgAN when clinical and morphological risk factors are modest or missing.
Literature
1.
go back to reference D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64(245):709–27.PubMed D’Amico G. The commonest glomerulonephritis in the world: IgA nephropathy. Q J Med. 1987;64(245):709–27.PubMed
2.
go back to reference Simon P, Ramee MP, Autuly V, Laruelle E, Charasse C, Cam G, Ang KS. Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. Kidney Int. 1994;46(4):1192–8.CrossRefPubMed Simon P, Ramee MP, Autuly V, Laruelle E, Charasse C, Cam G, Ang KS. Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. Kidney Int. 1994;46(4):1192–8.CrossRefPubMed
3.
go back to reference Jegatheesan D, Nath K, Reyaldeen R, Sivasuthan G, John GT, Francis L, Rajmokan M, Ranganathan D. Epidemiology of biopsy-proven glomerulonephritis in Queensland adults. LID. Nephrology. 2015;21:28–34. doi:10.1111/nep.12559. 1440-1797 (Electronic).CrossRef Jegatheesan D, Nath K, Reyaldeen R, Sivasuthan G, John GT, Francis L, Rajmokan M, Ranganathan D. Epidemiology of biopsy-proven glomerulonephritis in Queensland adults. LID. Nephrology. 2015;21:28–34. doi:10.​1111/​nep.​12559. 1440-1797 (Electronic).CrossRef
4.
go back to reference Brazdziute E, Miglinas M, Gruodyte E, Priluckiene J, Tamosaitis A, Bumblyte IA, Kuzminskis V, Burbaickaja S, Sakalauskiene M, Jankauskiene A, et al. Nationwide renal biopsy data in Lithuania 1994-2012. Int Urol Nephrol. 2015;47(4):655–62.CrossRefPubMed Brazdziute E, Miglinas M, Gruodyte E, Priluckiene J, Tamosaitis A, Bumblyte IA, Kuzminskis V, Burbaickaja S, Sakalauskiene M, Jankauskiene A, et al. Nationwide renal biopsy data in Lithuania 1994-2012. Int Urol Nephrol. 2015;47(4):655–62.CrossRefPubMed
5.
go back to reference Maixnerova D, Jancova E, Skibova J, Rysava R, Rychlik I, Viklicky O, Merta M, Kolsky A, Reiterova J, Neprasova M, et al. Nationwide biopsy survey of renal diseases in the Czech Republic during the years 1994-2011. J Nephrol. 2015;28(1):39–49.CrossRefPubMed Maixnerova D, Jancova E, Skibova J, Rysava R, Rychlik I, Viklicky O, Merta M, Kolsky A, Reiterova J, Neprasova M, et al. Nationwide biopsy survey of renal diseases in the Czech Republic during the years 1994-2011. J Nephrol. 2015;28(1):39–49.CrossRefPubMed
6.
go back to reference Riispere Z, Ots-Rosenberg M. Occurrence of kidney diseases and patterns of glomerular disease based on a 10-year kidney biopsy material: a retrospective single-centre analysis in Estonia. Scand J Urol Nephrol. 2012;46:389–94. 1651-2065 (Electronic).CrossRefPubMed Riispere Z, Ots-Rosenberg M. Occurrence of kidney diseases and patterns of glomerular disease based on a 10-year kidney biopsy material: a retrospective single-centre analysis in Estonia. Scand J Urol Nephrol. 2012;46:389–94. 1651-2065 (Electronic).CrossRefPubMed
7.
go back to reference Mustonen J, Pasternack A, Helin H, Nikkila M. Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis. Am J Nephrol. 1985;5(3):150–7.CrossRefPubMed Mustonen J, Pasternack A, Helin H, Nikkila M. Clinicopathologic correlations in a series of 143 patients with IgA glomerulonephritis. Am J Nephrol. 1985;5(3):150–7.CrossRefPubMed
8.
go back to reference Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76(5):546–56. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, Bonsib S, Bruijn JA, Cattran DC, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009;76(5):546–56.
9.
go back to reference Berthoux F, Mariat C, Maillard N. Overweight/obesity revisited as a predictive risk factor in primary IgA nephropathy. Nephrol Dial Transplant. 2013;28(4):iv160–6.PubMed Berthoux F, Mariat C, Maillard N. Overweight/obesity revisited as a predictive risk factor in primary IgA nephropathy. Nephrol Dial Transplant. 2013;28(4):iv160–6.PubMed
10.
go back to reference Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, Feehally J, Roberts IS, Amore A, Alpers CE, et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int. 2010;77(10):921–7.CrossRefPubMed Coppo R, Troyanov S, Camilla R, Hogg RJ, Cattran DC, Cook HT, Feehally J, Roberts IS, Amore A, Alpers CE, et al. The Oxford IgA nephropathy clinicopathological classification is valid for children as well as adults. Kidney Int. 2010;77(10):921–7.CrossRefPubMed
11.
go back to reference Maixnerova D, Bauerova L, Skibova J, Rysava R, Reiterova J, Merta M, Honsova E, Tesar V. The retrospective analysis of 343 Czech patients with IgA nephropathy--one centre experience. Nephrol Dial Transplant. 2011;27(4):1492–8.CrossRefPubMed Maixnerova D, Bauerova L, Skibova J, Rysava R, Reiterova J, Merta M, Honsova E, Tesar V. The retrospective analysis of 343 Czech patients with IgA nephropathy--one centre experience. Nephrol Dial Transplant. 2011;27(4):1492–8.CrossRefPubMed
12.
go back to reference Le W, Liang S, Hu Y, Deng K, Bao H, Zeng C, Liu Z. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant. 2011;27(4):1479–85.CrossRefPubMed Le W, Liang S, Hu Y, Deng K, Bao H, Zeng C, Liu Z. Long-term renal survival and related risk factors in patients with IgA nephropathy: results from a cohort of 1155 cases in a Chinese adult population. Nephrol Dial Transplant. 2011;27(4):1479–85.CrossRefPubMed
13.
go back to reference Moriyama T, Nakayama K, Iwasaki C, Ochi A, Tsuruta Y, Itabashi M, Tsukada M, Takei T, Uchida K, Nitta K. Severity of nephrotic IgA nephropathy according to the Oxford classification. Int Urol Nephrol. 2012;44(4):1177–84.CrossRefPubMed Moriyama T, Nakayama K, Iwasaki C, Ochi A, Tsuruta Y, Itabashi M, Tsukada M, Takei T, Uchida K, Nitta K. Severity of nephrotic IgA nephropathy according to the Oxford classification. Int Urol Nephrol. 2012;44(4):1177–84.CrossRefPubMed
14.
go back to reference Tanaka S, Ninomiya T, Katafuchi R, Masutani K, Tsuchimoto A, Noguchi H, Hirakata H, Tsuruya K, Kitazono T. Development and validation of a prediction rule using the Oxford classification in IgA nephropathy. Clin J Am Soc Nephrol. 2013;8(12):2082–90.CrossRefPubMedPubMedCentral Tanaka S, Ninomiya T, Katafuchi R, Masutani K, Tsuchimoto A, Noguchi H, Hirakata H, Tsuruya K, Kitazono T. Development and validation of a prediction rule using the Oxford classification in IgA nephropathy. Clin J Am Soc Nephrol. 2013;8(12):2082–90.CrossRefPubMedPubMedCentral
15.
go back to reference Liu H, Peng Y, Liu H, Liu Y, Yuan S, Liu F, Yang D, Chen X, He L, Fu M, et al. Renal biopsy findings of patients presenting with isolated hematuria: disease associations. Am J Nephrol. 2012;36(4):377–85.CrossRefPubMed Liu H, Peng Y, Liu H, Liu Y, Yuan S, Liu F, Yang D, Chen X, He L, Fu M, et al. Renal biopsy findings of patients presenting with isolated hematuria: disease associations. Am J Nephrol. 2012;36(4):377–85.CrossRefPubMed
16.
go back to reference Haas M, Rastaldi MP, Fervenza FC. Histologic classification of glomerular diseases: clinicopathologic correlations, limitations exposed by validation studies, and suggestions for modification. Kidney Int. 2013. Haas M, Rastaldi MP, Fervenza FC. Histologic classification of glomerular diseases: clinicopathologic correlations, limitations exposed by validation studies, and suggestions for modification. Kidney Int. 2013.
17.
go back to reference Riispere Z, Laurinavicius A, Kuudeberg A, Seppet E, Sepp K, Ilmoja M, Luman M, Kõlvald K, Auerbach A, Ots-Rosenberg M. IgA Nephropathy Clinicopathologic Study based on the Oxford Classification: Progression Peculiarities and Gender-Related Differences. Medicina. 2016;52:340–8.CrossRefPubMed Riispere Z, Laurinavicius A, Kuudeberg A, Seppet E, Sepp K, Ilmoja M, Luman M, Kõlvald K, Auerbach A, Ots-Rosenberg M. IgA Nephropathy Clinicopathologic Study based on the Oxford Classification: Progression Peculiarities and Gender-Related Differences. Medicina. 2016;52:340–8.CrossRefPubMed
18.
go back to reference Mustonen J, Syrjanen J, Rantala I, Pasternack A. Clinical course and treatment of IgA nephropathy. J Nephrol. 2001;14(6):440–6.PubMed Mustonen J, Syrjanen J, Rantala I, Pasternack A. Clinical course and treatment of IgA nephropathy. J Nephrol. 2001;14(6):440–6.PubMed
19.
20.
go back to reference Eknoyan G. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(2):1–143. Eknoyan G. KDIGO Clinical Practice Guideline for Glomerulonephritis. Kidney Int. 2012;2(2):1–143.
21.
go back to reference Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76(5):534–45.CrossRefPubMed Cattran DC, Coppo R, Cook HT, Feehally J, Roberts IS, Troyanov S, Alpers CE, Amore A, Barratt J, Berthoux F, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Kidney Int. 2009;76(5):534–45.CrossRefPubMed
22.
go back to reference Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–37.CrossRefPubMedPubMedCentral Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20(3):629–37.CrossRefPubMedPubMedCentral
23.
go back to reference Barbour SJ, Espino-Hernandez G, Reich HN, Coppo R, Roberts IS, Feehally J, Herzenberg AM, Cattran DC. The MEST score provides earlier risk prediction in lgA nephropathy. Kidney Int. 2016;89(1):167–75.CrossRefPubMed Barbour SJ, Espino-Hernandez G, Reich HN, Coppo R, Roberts IS, Feehally J, Herzenberg AM, Cattran DC. The MEST score provides earlier risk prediction in lgA nephropathy. Kidney Int. 2016;89(1):167–75.CrossRefPubMed
24.
go back to reference Bellur SS, Troyanov S, Cook HT, Roberts IS. Immunostaining findings in IgA nephropathy: correlation with histology and clinical outcome in the Oxford classification patient cohort. Nephrol Dial Transplant. 2011;26(8):2533–6.CrossRefPubMed Bellur SS, Troyanov S, Cook HT, Roberts IS. Immunostaining findings in IgA nephropathy: correlation with histology and clinical outcome in the Oxford classification patient cohort. Nephrol Dial Transplant. 2011;26(8):2533–6.CrossRefPubMed
25.
go back to reference Herzenberg AM, Fogo AB, Reich HN, Troyanov S, Bavbek N, Massat AE, Hunley TE, Hladunewich MA, Julian BA, Fervenza FC, et al. Validation of the Oxford classification of IgA nephropathy. Kidney Int. 2011;80(3):310–7.CrossRefPubMed Herzenberg AM, Fogo AB, Reich HN, Troyanov S, Bavbek N, Massat AE, Hunley TE, Hladunewich MA, Julian BA, Fervenza FC, et al. Validation of the Oxford classification of IgA nephropathy. Kidney Int. 2011;80(3):310–7.CrossRefPubMed
26.
go back to reference Anderson S, Meyer TW, Rennke HG, Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest. 1985;76(2):612–9.CrossRefPubMedPubMedCentral Anderson S, Meyer TW, Rennke HG, Brenner BM. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest. 1985;76(2):612–9.CrossRefPubMedPubMedCentral
27.
go back to reference Kato S, Luyckx VA, Ots M, Lee KW, Ziai F, Troy JL, Brenner BM, MacKenzie HS. Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats. Kidney Int. 1999;56(3):1037–48.CrossRefPubMed Kato S, Luyckx VA, Ots M, Lee KW, Ziai F, Troy JL, Brenner BM, MacKenzie HS. Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats. Kidney Int. 1999;56(3):1037–48.CrossRefPubMed
28.
go back to reference Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329(20):1456–62.CrossRefPubMed Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. 1993;329(20):1456–62.CrossRefPubMed
29.
go back to reference Brenner BM, Cooper ME, De Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.CrossRefPubMed Brenner BM, Cooper ME, De Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.CrossRefPubMed
30.
go back to reference Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, Marcantoni C, De Jong PE, De Zeeuw D, Shahinfar S, Ruggenenti P, et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int. 2001;60(3):1131–40.CrossRefPubMed Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, Marcantoni C, De Jong PE, De Zeeuw D, Shahinfar S, Ruggenenti P, et al. Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease. Kidney Int. 2001;60(3):1131–40.CrossRefPubMed
31.
go back to reference Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J, Roberts IS, Morando L, Fau-Camilla R, Camilla R, Fau-Tesar V, Tesar V, Fau-Lunberg S, et al. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int. 2014;86:828–36. 1523-1755 (Electronic).CrossRefPubMedPubMedCentral Coppo R, Troyanov S, Bellur S, Cattran D, Cook HT, Feehally J, Roberts IS, Morando L, Fau-Camilla R, Camilla R, Fau-Tesar V, Tesar V, Fau-Lunberg S, et al. Validation of the Oxford classification of IgA nephropathy in cohorts with different presentations and treatments. Kidney Int. 2014;86:828–36. 1523-1755 (Electronic).CrossRefPubMedPubMedCentral
32.
go back to reference Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Ortiz A, Egido J, Praga M, Moreno JA. Pathogenesis of glomerular haematuria. World J Nephrol. 2015;4(2):185–95.CrossRefPubMedPubMedCentral Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Ortiz A, Egido J, Praga M, Moreno JA. Pathogenesis of glomerular haematuria. World J Nephrol. 2015;4(2):185–95.CrossRefPubMedPubMedCentral
33.
go back to reference Moreno JA, Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Praga M, Egido J. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review. Pediatr Nephrol. 2016;31(4):523–33.CrossRefPubMed Moreno JA, Yuste C, Gutierrez E, Sevillano AM, Rubio-Navarro A, Amaro-Villalobos JM, Praga M, Egido J. Haematuria as a risk factor for chronic kidney disease progression in glomerular diseases: A review. Pediatr Nephrol. 2016;31(4):523–33.CrossRefPubMed
Metadata
Title
Significance of clinical and morphological prognostic risk factors in IgA nephropathy: follow-up study of comparison patient groups with and without renoprotection
Authors
Živile Riispere
Anne Kuudeberg
Elviira Seppet
Kristin Sepp
Madis Ilmoja
Merike Luman
Külli Kõlvald
Asta Auerbach
Mai Ots-Rosenberg
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2017
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/s12882-017-0499-4

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