We found an important statistically significant risk of CKD caused by smoking in hypertensive nephropathy and diabetic nephropathy patients and a weak, statistically insignificant association between smoking and CKD caused by glomerulonephritis.
Many studies indicate that the deleterious effect of smoking on renal function is not merely restricted to essential hypertension and diabetic nephropathy. Some of these studies found that smoking is an independent predictor of microalbuminuria in healthy patients with primary hypertension. It is well known that urinary albumin is a sensitive marker of glomerular injury , and the fact that there is a relationship between smoking and albuminuria indicates direct or indirect renal damage induced by smoking. Mimran et al.  studied lean subjects with essential hypertension and found that the prevalence of microalbuminuria was almost double in smokers as compared to non-smokers. Same results were found in other studies [18, 19]. Multiple Risk Factor Intervention Trial (MRFIT) found an increased risk for end-stage renal disease (ESRD) for smokers as compared to non-smokers [20, 21]. Such increased relative risk of ESRD related to smoking (up to 1.69 for heavy smokers) was independent of age, ethnicity, income, blood pressure, diabetes mellitus, prior history of myocardial infarction, or serum cholesterol.
Smoking causes kidney deterioration in diabetic patients with adverse effects on four different aspects of albumin excretion: It increases the risk of microalbuminuria, shortens the time interval between onset of diabetes and onset of albuminuria or proteinuria [6, 7], accelerates the rate of progression from microalbuminuria to persistent proteinuria [22, 23], and accelerates the rate of progression of diabetic nephropathy to ESRD [6, 8]. Chase et al.  reported that in a group of 359 young subjects with IDDM the prevalence of borderline (> 7.6 mcg/min) and abnormal (> 30 mcg/min) albumin excretion rate was 2.8 fold higher in smokers than in non-smokers. Sawicki et al.  calculated the adjusted odds ratio for the progression of diabetic nephropathy and found that the odds ratio was higher by a factor of 2.74 for each 10 pack/year smoking history. In this study all patients were administered an intensified insulin along with antihypertensive therapy so that the confounding effects of hyperglycemia and hypertension were minimized. Similar results were found by Biesenbach et al.  which concluded that the rate of loss of GFR was higher by a factor of 1.44 in smoking patients as compared to the non-smoking patients with insulin dependent diabetes mellitus (IDDM), and by a factor of 1.66 among NIDDM patients.
To determine the risk factors for noninsulin dependent diabetes in a cohort representative of middle aged British men, Perry et al.  conducted a prospective study on 7,735 males (40 to 59 years) and found that smoking was associated with a 50% increased risk of developing NIDDM. This increased risk may be related to the fact that smoking aggravates insulin resistance in healthy smokers .
Another question would be the effect of smoking cessation on kidney function. In patients with IDDM, Chase et al.  found that albuminuria improved significantly when patients stopped smoking. Sawicki et al.  studied 34 smokers, 35 nonsmokers, and 24 ex-smokers with type I diabetes, hypertension, and diabetic nephropathy for one year and found that the progression of nephropathy was less common in nonsmokers (11%) than in smokers (53%) and in patients who had quit smoking (33%). They also found that accumulated dose measured by pack/year was an independent predictive factor for the progression of diabetic nephropathy.
One of the other diseases that exacerbate with smoking is autosomal dominant polycystic kidney disease (ADPKD), Chapman et al.  found that ADPKD patients with established proteinuria had a greater pack/year smoking history than their nonproteinuric counterparts did. Smoking is also responsible for renal function deterioration in lupus nephritis, as a retrospective cohort study of 160 adults found that smoking at the time of onset of nephritis was an independent risk factor for the more rapid development of ESRD . The median time interval to terminal renal failure was 145 months in smokers, but more than 273 months in non-smokers. These effects persisted in multivariable analyses adjusting for differences among patients in age, gender, socioeconomic status, renal histology, and immunosuppressive treatment. They also found that the combination of smoking and hypertension resulted in shorter times to renal failure compared with nonsmoking hypertensive patients. This observation was not found in another study conducted on 70 lupus nephritis patients .
Appel et al.  studied 45 patients each 50 years of age or older, beginning renal replacement therapy and found that smoking aggravates renal artery stenosis. This effect was explained by increased arthrogenesis among smokers. In their study Wang et al.  stated that there is different susceptibility to arthrogenesis among smokers, and that the risk appears to be excessively high in patients who are homozygous for the endothelial nitric oxide synthase 4a (ecNOS4a) gene, which predisposes to endothelial dysfunction.
A previous, hospital-based case-control study  found a threefold increased risk for glomerulonephritis associated with CKD among heavy smokers while other studies did not find the same results. In a case-control study including 55 patients and 55 normal subjects Yaqoob et al.  reported that there was no significant correlation between tobacco and the development of primary glomerulonephritis. Merkel et al.  did not find any evidence that smoking aggravates the course of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. Our study supports the observation made by Yaqoob regarding the association between smoking and the development of primary GN. However it was found that smoking is significantly associated with pulmonary hemorrhage in anti-GBM glomerulonephritis patients .
The increment of GFR induced by smoking may play a role in the genesis of hyperfiltration as a potential mediator of accelerated progression of chronic renal disease [34, 35]. Pawlik et al.  studied renal excretory and circulatory responses to nicotine in anesthetized dogs and found that nicotine causes an increase in sodium and chloride excretion and urine flow, which is reversed after the administration of propranolol or in the group underwent adrenalectomy. This observation leads to a conclusion that nicotine action on the kidney is mediated by release of catecholamines from the adrenal medulla. Another mechanism could be the increment of vasopressin release secondary to altering cervical parasympathetic tone induced by nicotine, which increases GFR inappropriately [37, 38]. On the other hand, the increment of GFR is thought to be due to an intermittent and persistent increase in blood pressure induced by smoking nicotine products; this blood pressure alteration was absent in patient smoking nicotine-free cigarettes [39–41].
Smoking also alters the proximal tubular function leading to increased excretion of N-acetyl-f3-glucosaminidase (NAG) and impairment of organic cation transport  which correlates strongly with the amount of tobacco consumed .