Yonsei Med J.  2016 Jan;57(1):209-216. 10.3349/ymj.2016.57.1.209.

Smoking-Related Renal Histologic Injury in IgA Nephropathy Patients

• Cha YJ
• Lim BJ
• Kim BS
• Kim Y
• Yoo TH
• Han SH
• Kang SW
• Choi KH
• Jeong HJ

• KMID: 2466372
• DOI: http://doi.org/10.3349/ymj.2016.57.1.209

Abstract

PURPOSE
Smoking reportedly exerts deleterious effects on renal function; however, its effects on histology have not been clarified in patients with IgA nephropathy (IgAN).
MATERIALS AND METHODS
Renal histology was evaluated in a cohort of 397 patients diagnosed with IgAN according to smoking status and dose in relation to renal function.
RESULTS
Among the study cohort, which was predominantly male (88.5%), 52 patients (13%) were current smokers. These current smokers demonstrated more frequent hypertension and higher serum creatinine levels than non/ex-smokers at the time of diagnosis, which was apparent with increased smoking dose. The percentages of global glomerulosclerosis and arteriolar hyalinosis increased with increased smoking dose, whereas tubulointerstitial fibrosis or arterial intimal thickening did not. Glomerular mesangial alpha-smooth muscle actin expression were similar between current and non/ex-smokers matched for age, gender, hypertension, and histologic severity, although the number of glomerular CD68+ cells was significantly fewer in smokers. Initial serum creatinine level, estimated glomerular filtration rate (eGFR), and global glomerulosclerosis were found to be risk factors of serum creatinine doubling in both smokers and non/ex-smokers by univariate analysis during a mean follow-up of 3.8 years.
CONCLUSION
In addition to dose dependent renal functional decline and hypertension, smoking contributes to renal disease progression by eliciting microvascular injury in IgAN patients.

Keyword

Smoking; IgA nephropathy; arteriolar hyalinosis; macrophage infiltration; alpha-smooth muscle actin

MeSH Terms

Adult
Aged
Case-Control Studies
Cohort Studies
Creatinine/blood
Disease Progression
Female
Glomerulonephritis, IGA/blood/*diagnosis/epidemiology
Humans
Immunohistochemistry
Kidney/*pathology
Kidney Function Tests
Kidney Glomerulus/*pathology
Male
Middle Aged
Risk Factors
Smoking/*adverse effects/epidemiology
Creatinine

Reference

1. D'Amico G, Imbasciati E, Barbiano Di Belgioioso G, Bertoli S, Fogazzi G, Ferrario F, et al. Idiopathic IgA mesangial nephropathy Clinical and histological study of 374 patients. Medicine (Baltimore). 1985; 64:49–60.

2. D'Amico G. Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol. 2004; 24:179–196.

3. Working Group of the International IgA Nephropathy Network and the Renal Pathology Society. Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, et al. The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility. Kidney Int. 2009; 76:546–556.

4. Halimi JM, Giraudeau B, Vol S, Cacès E, Nivet H, Lebranchu Y, et al. Effects of current smoking and smoking discontinuation on renal function and proteinuria in the general population. Kidney Int. 2000; 58:1285–1292.

5. Stengel B, Couchoud C, Cénée S, Hémon D. Age, blood pressure and smoking effects on chronic renal failure in primary glomerular nephropathies. Kidney Int. 2000; 57:2519–2526.

6. Briganti EM, Branley P, Chadban SJ, Shaw JE, McNeil JJ, Welborn TA, et al. Smoking is associated with renal impairment and proteinuria in the normal population: the AusDiab kidney study. Australian Diabetes, Obesity and Lifestyle Study. Am J Kidney Dis. 2002; 40:704–712.

7. Ejerblad E, Fored CM, Lindblad P, Fryzek J, Dickman PW, Elinder CG, et al. Association between smoking and chronic renal failure in a nationwide population-based case-control study. J Am Soc Nephrol. 2004; 15:2178–2185.

8. Orth SR, Stöckmann A, Conradt C, Ritz E, Ferro M, Kreusser W, et al. Smoking as a risk factor for end-stage renal failure in men with primary renal disease. Kidney Int. 1998; 54:926–931.

9. Yamamoto R, Nagasawa Y, Shoji T, Iwatani H, Hamano T, Kawada N, et al. Cigarette smoking and progression of IgA nephropathy. Am J Kidney Dis. 2010; 56:313–324.

10. Lhotta K, Rumpelt HJ, König P, Mayer G, Kronenberg F. Cigarette smoking and vascular pathology in renal biopsies. Kidney Int. 2002; 61:648–654.

11. Coppo R, Camilla R, Amore A, Peruzzi L. Oxidative stress in IgA nephropathy. Nephron Clin Pract. 2010; 116:c196–c198.

12. Camilla R, Suzuki H, Daprà V, Loiacono E, Peruzzi L, Amore A, et al. Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy. Clin J Am Soc Nephrol. 2011; 6:1903–1911.

13. Raza H, John A, Nemmar A. Short-term effects of nose-only cigarette smoke exposure on glutathione redox homeostasis, cytochrome P450 1A1/2 and respiratory enzyme activities in mice tissues. Cell Physiol Biochem. 2013; 31:683–692.

14. Jaimes EA, Tian RX, Joshi MS, Raij L. Nicotine augments glomerular injury in a rat model of acute nephritis. Am J Nephrol. 2009; 29:319–326.

15. Haas M. Histologic subclassification of IgA nephropathy: a clinicopathologic study of 244 cases. Am J Kidney Dis. 1997; 29:829–842.

16. Reich HN, Troyanov S, Scholey JW, Cattran DC. Toronto Glomerulonephritis Registry. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007; 18:3177–3183.

17. Nicholls KM, Fairley KF, Dowling JP, Kincaid-Smith P. The clinical course of mesangial IgA associated nephropathy in adults. Q J Med. 1984; 53:227–250.

18. Packham DK, Yan HD, Hewitson TD, Nicholls KM, Fairley KF, Kincaid-Smith P, et al. The significance of focal and segmental hyalinosis and sclerosis (FSHS) and nephrotic range proteinuria in IgA nephropathy. Clin Nephrol. 1996; 46:225–229.

19. Elliot SJ, Karl M, Berho M, Xia X, Pereria-Simon S, Espinosa-Heidmann D, et al. Smoking induces glomerulosclerosis in aging estrogen-deficient mice through cross-talk between TGF-beta1 and IGF-I signaling pathways. J Am Soc Nephrol. 2006; 17:3315–3324.

20. Alpers CE, Hudkins KL, Gown AM, Johnson RJ. Enhanced expression of "muscle-specific" actin in glomerulonephritis. Kidney Int. 1992; 41:1134–1142.

21. Kaneko Y, Nakazawa K, Higuchi M, Hora K, Shigematsu H. Glomerular expression of alpha-smooth muscle actin reflects disease activity of IgA nephropathy. Pathol Int. 2001; 51:833–844.

22. Utsunomiya Y, Kawamura T, Abe A, Imai H, Hirano K, Maruyama N, et al. Significance of mesangial expression of alpha-smooth muscle actin in the progression of IgA nephropathy. Am J Kidney Dis. 1999; 34:902–910.

23. Nagata M, Akioka Y, Tsunoda Y, Komatsu Y, Kawaguchi H, Yamaguchi Y, et al. Macrophages in childhood IgA nephropathy. Kidney Int. 1995; 48:527–535.

24. Ikezumi Y, Suzuki T, Karasawa T, Hasegawa H, Yamada T, Imai N, et al. Identification of alternatively activated macrophages in new-onset paediatric and adult immunoglobulin A nephropathy: potential role in mesangial matrix expansion. Histopathology. 2011; 58:198–210.

25. Agarwal PK, van den Born J, van Goor H, Navis G, Gans RO, Bakker SJ. Renoprotective effects of long-term oral nicotine in a rat model of spontaneous proteinuria. Am J Physiol Renal Physiol. 2012; 302:F895–F904.

26. Gordon S. Alternative activation of macrophages. Nat Rev Immunol. 2003; 3:23–35.

27. Chalon S, Moreno H Jr, Hoffman BB, Blaschke TF. Angiotensin-converting enzyme inhibition improves venous endothelial dysfunction in chronic smokers. Clin Pharmacol Ther. 1999; 65:295–303.