Smoking as risk factor for chronic kidney disease: systematic
               review

We conducted a systematic review in Medline, LILACS, SciELO, Google Scholar, Embase and Trials.gov with articles published until February/2013. Were included: cohort, clinical trials and case-control. Performed in humans, aged ≥ 18 years with smoking as a risk factor for progression of CKD. We excluded studies that reported no smoking and CKD in the title or had proposed to reduce smoking.

Results:

Among 94 citations, 12 articles were selected. Of these, six were multicenter conducted in developed countries, four were randomized. Males predominated 51-76%. There was associated with smoking progression in 11 studies. It was found that the consumption ≥ 15 packs/ year increases the risk of progression of CKD.

Conclusion:

Smoking is a risk factor for progression of CKD.

disease progression; kidney failure, chronic; renal insufficiency; review; risk factors; smoking

Authors and year	Country	Criteria adopted for CKD categorization	Study/follow-up	Randomized	Gender distribution	No. of subjects enrolled	No. of subjects with CKD	Ratio of smokers to nonsmokers with CKD	No. of controls/ comparison	No. of controls/ comparison CKD	No. of controls/ comparison nonsmokers	Mean age (years)	OR or RR (95%CI)	Cumulative effect (packs/ year) Risk (95%CI; p)	Results related to CKD progression
Orth et al. (1998)¹⁶16 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;54:926-31. PMID: 9734618 DOI: http://dx.doi.org/10.1046/j.1523-1755.1998.00067.x http://dx.doi.org/10.1046/j.1523-1755.19...	DEU ITA AUS	SCr > 3.0 mg/dL	Case-control	no	M = 144 F = 60	582	148	72/-	72	72	-	47	OR = 4.5 (1.9-10.9; p < 0.001)	00-05 p/y: 1.0 p > 0.05 5-15 p/y: 3.5 (1.3-9.6; p = 0.017) > 15 p/y: 5.8 (2.0-17; p = 0.001)	Male smokers with CKD, IgA nephropathy, and polycystic kidney disease are at a higher risk for renal function deterioration when compared to nonsmokers; disease worsens for heavy smokers
Stengel et al. (2000)¹⁵15 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;57:2519-26. PMID: 10844621	FRA	SCr > 1.96 mg/dL	Case-control 5 years	no	M = 77%	295	295	140/155	242	132	110	41	OR = 2.1 (0.9-4.9)	≥ 15 p/y: 1.9 (0.8-4.3; p > 0.05) > 15 p/y: 3.9 (1.6-4.5; p < 0.01)	No association was found between smoking and renal function deterioration in females; association between number of packs smoked a year and renal function deterioration was found for male smokers with primary glomerulonephritis
Regalado et al. (2000)²²22 Regalado M, Yang S, Wesson DE. Cigarette smoking is associated with augmented progression of renal insufficiency in severe essential hypertension. Am J Kidney Dis 2000;35:687-94. DOI: http://dx.doi.org/10.1016/S0272-6386(00)70017-5 http://dx.doi.org/10.1016/S0272-6386(00)...	USA	Hypertension SCr = 0.25 ± 0.11 mg/dL Hypertension Smoker SCr = 1.47 ± 0.13 mg/dL	Prospective cohort 2 years and 11 months	Controls only	M = 56%	192	53	30/23	139	64	75	51	na	-	Analysis of potential risk factors for renal function deterioration in hypertensive patients yielded smoking a weight of 4.3820 (p < 0.0001), even when blood pressure is controlled
Ejerblad et al. (2004)¹⁸18 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;15:2178-85. DOI: http://dx.doi.org/10.1097/01.ASN.0000135048.35659.10 http://dx.doi.org/10.1097/01.ASN.0000135...	SWE	H SCr > 3.4 mg/dL	Case-control 2 years	yes	M = 65%	998	926	567/348	994	574	420	58	OR = 1.17 (0.95-1.44)	1-15 p/y: 0.95 (0.73-1.24) 16-30 p/y: 1.32 (1.00-1.75) > 30 p/y: 1.52 (1.08-2.14)	Smoking worsens renal function of CKD patients; degree of deterioration is associated with number of packs smoked a year
	SWE	M SCr > 2.8 mg/dL	Case-control 2 years	yes	M = 65%	998	926	567/348	994	574	420	58	OR = 1.17 (0.95-1.44)
Shankar et al. (2006)²⁷27 Shankar A, Klein R, Klein BE. The association among smoking, heavy drinking, and chronic kidney disease. Am J Epidemiol 2006;164:263-71. PMID: 16775042 DOI: http://dx.doi.org/10.1093/aje/kwj173 http://dx.doi.org/10.1093/aje/kwj173...	USA	K/DOQI	Cohort 5 years	yes	M = 47,5%	4898	324	146/178	4898	967	3931	62	RR = 2.18 (1.57-3.03)	< 15 p/y: 1.11 (0.89-2.08) 15-34 p/y: 2.57 (1.79-3.70) (2.08-4.12)	Smoking worsens renal function 2.18 times more versus nonsmoking patients; renal function deterioration smoking strongly associated with the number of packs smoked a year
Kronborg et al. (2008)²⁶26 Kronborg J, Solbu M, Njølstad I, Toft I, Eriksen BO, Jenssen T. Predictors of change in estimated GFR: a population-based 7-year follow-up from the Tromso study. Nephrol Dial Transplant 2008;23:2818-26. DOI: http://dx.doi.org/10.1093/ndt/gfn148 http://dx.doi.org/10.1093/ndt/gfn148...	NOR	K/DOQI	Prospective cohort 7 years	no	M = 50.6% F = 49.4%	4441	na	na	4441	1379	3062	-	-		Alcohol intake improved renal function in males, but not in females; increased physical activity improved GFR in women; DM, CVD, systolic hypertension, and increased fibrinogen levels were correlated with GFR reductions in both genders; increase in GFR by 0.32 ml/min/1.73 m2/ year for female smokers versus nonsmokers.
Lash et al. (2009)²³23 Lash JP, Go AS, Appel LJ, He J, Ojo A, Rahman M, et al.; Chronic Renal Insufficiency Cohort (CRIC) Study Group. Chronic Renal Insufficiency Cohort (CRIC) Study: baseline characteristics and associations with kidney function. Clin J Am Soc Nephrol 2009;4:1302-11. DOI: http://dx.doi.org/10.2215/CJN.00070109 http://dx.doi.org/10.2215/CJN.00070109...	USA	K/DOQI	Prospective cohort	yes	M = 54%	-	3612	2513/ 1593	no	no	no	-	-	-	Among risk factor for progression of CKD, smoking worsens the GFR
Yacoub et al. (2010)¹⁷17 Yacoub R, Habib H, Lahdo A, Al Ali R, Varjabedian L, Atalla G, et al. Association between smoking and chronic kidney disease: a case control study. BMC Public Health 2010;10:731. DOI: http://dx.doi.org/10.1186/1471-2458-10-731 http://dx.doi.org/10.1186/1471-2458-10-7...	SIR	K/DOQI	Case-control 4 years	yes	M = 51%	-	198	86/112	351	251	251	45	OR = 1.6	1-15 p/y: 2.1 (1.12-2.29; p < 0.009) (0.96-4.57; p = 0.06) 16-30 p/y: 2.04 (1.08-3.88; p = 0.028) > 30 p/y: 2.06 (1.53-4.41; p = 0.0001)	Renal function worsens 1.6 times more in smokers than in nonsmokers; renal function deterioration is strongly associated with number of packs smoked per year
Míguez-Burbano et al. (2010)²⁴24 Míguez-Burbano MJ, Wyatt C, Lewis JE, Rodríguez A, Duncan R. Ignoring the obvious missing piece of chronic kidney disease in HIV: cigarette smoking. J Assoc Nurses AIDS Care 2010;21:16-24. DOI: http://dx.doi.org/10.1016/j.jana.2009.07.005 http://dx.doi.org/10.1016/j.jana.2009.07...	USA	K/DOQI	Case-control 1 year Patients with HIV	no	M = 306 (69%) F = 230 (31%)	536	65 (85%)	na	yes			-	OR = 1,97 p = 0,03	-	African American and Caribbean men had lower hemoglobin and albumin levels. Patients with CKD were hospitalized twice as much. 35% of the patients (HIV & CKD) had stage IV or V disease 1 to 2 packs/year increases the risk of HIV patients having CKD by 1.5 times (OR = 1.57; 95%CI 1-2.53; p = 0.05) effect not seen in former smokers (OR = 1.1; 95%CI 2-4.7; p = 0.8)
Hallan e Orth (2011)²¹21 Hallan SI, Orth SR. Smoking is a risk factor in the progression to kidney failure. Kidney Int 2011;80:516-23. PMID: 21677635 DOI: http://dx.doi.org/10.1038/ki.2011.157 http://dx.doi.org/10.1038/ki.2011.157...	NOR	K/DOQI	Cohort 10.3 years (0.1-11.3)	no	M = 78 (63%) F = 46 (37%)	65589	124	nd/nd	yes	yes	yes	50	When age < 70 years smoker RR = 4.0 (1.23-8.25) ex-smoker RR = 3.3 (1.43-11.2)	01-09 p/y: 4.21 (0.5-35.16; p = 0.18) 10-19 p/y: 8.84 (1.58-49.89; p = 0.01) 20-39	Patients aged < 70 years, smokers and former smokers versus nonsmokers had increased risk of progressing to stage-5 CKD. Smoking cessation reduced the risk of CKD, although it remained high.
Hellemons et al. (2011)²⁰20 Hellemons ME, Agarwal PK, van der Bij W, Verschuuren EA, Postmus D, Erasmus ME, et al. Former smoking is a risk factor for chronic kidney disease after lung transplantation. Am J Transplant 2011;11:2490-8. DOI: http://dx.doi.org/10.1111/j.1600-6143.2011.03701.x http://dx.doi.org/10.1111/j.1600-6143.20...	HOL	K/DOQI	Cohort 5 years Lung transplant	no	M = 166 F = 160	326	na	na	na	na	134	44	Progression to CKD III RR = 1.69 (1.27-2.24) Progression to CKD IV RR = 1.9 (1.11-3.27)	DRC III 01-10 p/y: 1.57 (1.09-2.25; p = 0.015) 11-25 p/y: 1.65 (1.15-2.36; p = 0.006) > 25 p/y: 1.92 (1.32-2.79; p = 0.001) DRC IV 01-10 p/y: 1.3 (0.63-2.7; p = 0.48) 11-25 p/y: 1.96 (1.04-3.7; p = 0.04) > 25 p/y: 2.78 (1.41-5.46; p = 0.003)	GFR decreased within the first two years after lung transplantation, and was worse during the first six months after surgery. Former smokers smoked a median 17.5 packs/year and linear association with cumulative dose was observed. Smoking was a risk factor for progression of CKD in patients with COPD
Noborisaka et al (2013)²⁸28 Noborisaka Y, Ishizaki M, Yamada Y, Honda R, Yokoyama H, Miyao M, et al. The effects of continuing and discontinuing smoking on the development of chronic kidney disease (CKD) in the healthy middle-aged working population in Japan. Environ Health Prev Med 2013;18:24-32. DOI: http://dx.doi.org/10.1007/s12199-012-0285-7 http://dx.doi.org/10.1007/s12199-012-028...	JPN	KDIGO	Retrospective cohort 6 years	no	M = 58.8% F = 41.2%	6998	na	na/na	na	na	na	M: 41 F: 42	Risk of proteinuria in smokers OR = 2.52 (1.5-4.5)	na	GFR was higher in smokers than in nonsmokers; smokers progressed more frequently to stage-1 and stage-2 CKD, but progression to stage-3 CKD was less frequent than nonsmokers and former smokers. Smoking cessation reduced protein loss by 50% and the risk of CKD progression. Male former smokers had significantly greater GRF drops than nonsmokers and smokers. In the presence of proteinuria, GFR reduction was not correlated with smoking. Moderate alcohol intake reduced the decrease in GFR

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[1] Correspondence to: Ubiracé Fernando Elihimas Júnior. Federal University of Pernambuco/UFPE - Recife/PE Brazil. Chronic Kidney Disease Conservative Care Clinic/Hospital das Clínicas, Federal University of Pernambuco. Rua Professor Mário Castro, nº 192, apto. 1201. Recife, PE, Brasil. CEP: 51031-260. E-mail: biraelihimas@yahoo.com.br, Tel: (81) 9987-2676/(81) 3341-1836.