Smoking has been pinpointed as a factor causing progression of chronic nephropathies. It is worth noting that smoking increases urinary albumin concentration, even at albumin concentrations below that of microalbuminuria (1). There is growing evidence that smoking not only increases the risk of albuminuria but also the risk of renal functional deterioration. The frequency of nephropathy is progressively higher with increasing cigarette consumption. The available literature documents that smoking increases the risk of developing microalbuminuria, accelerates the rate of progression from microalbumunuria to manifest proteinuria, and accelerates the progression of renal failure (1). Chase et al. (2) reported that in a group of 359 young patients with type 1 diabetes, the prevalence of borderline and frankly elevated urinary albumin excretion rates was 2.8-fold higher in smokers than in nonsmokers. Concerning the risk of microalbumunuria progressing to overt proteinuria, a 4-year prospective study on 794 patients with type 2 diabetes reported a 2- to 2.5-fold higher relative risk in heavy smokers than in nonsmokers (3). Cigarette smoking in patients with kidney disease, including diabetic nephropathy, is associated with myointimal hyperplasia of intrarenal arteries, and there is a trend toward arteriolar hyalinosis in smokers. The renal vessels are the main targets of cigarette smoke in the kidney (4). In addition, smoke damages endothelial cells, and nicotine induces smooth muscle cell proliferation (5). However, the effects of smoking on podocyte injuries in patients with diabetic nephropathy are still unclear.

The podocyte is a highly differentiated cell that is strategically located on the outside of the glomerular capillary wall. Podocytes play an important role in glomerular filtration. Injuries to the podocytes are accompanied by marked morphological changes. The most severe podocyte lesion occurs as podocytes detach from the glomerular basement membrane, and these cells subsequently appear in the urine (6). By measuring urinary podocytes, we previously reported that podocyte injury may occur in patients with early diabetic nephropathy (7). Meyer et al. (8) reported that among the glomerular morphological characteristics used to diagnose nephropathy, urinary podocyte number was the best predictor in diabetic patients. The aim of the present study was to determine whether smoking affects podocyte injuries in patients with type 2 diabetes with microalbuminuria.

Eighty type 2 diabetic patients with microalbuminuria (50 men and 30 women, mean age 50.8 years, 50 smokers and 30 nonsmokers) and 30 healthy subjects (18 men and 12 women, mean age 49.5 years) were included in the present study. No patients had serum creatinine levels in excess of 2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy as previously reported (6,7). Urinary podocytes were detected in 35 diabetic patients with microalbuminuria (27 smokers and 8 nonsmokers, 1.4 ± 0.7 cells/ml) but were not detected in the remaining 45 patients (23 smokers and 22 nonsmokers) or the 30 healthy subjects. More podocytes are excreted in the urine in smokers (27 of 50 patients) with microalbuminuria than in nonsmokers (8 of 30 patients) with microalbuminuria (P = 0.017, χ2 test). The 27 diabetic patients (smokers) who had urinary podocytes were divided into two groups: 13 patients who stopped smoking and 14 patients who continued smoking. Urinary podocytes disappeared after 3 years in 10 of the 13 patients who had stopped smoking, whereas urinary podocytes increased in all patients who continued to smoke (from 1.1 ± 0.8 to 1.7 ± 0.4 cells/ml, P < 0.01). These data suggest that smoking may be associated with podocyte injuries in patients with early diabetic nephropathy.

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J Am Soc Nephrol
Chase HP, Garg SK, Marshall G, Berg CL, Harris S, Jackson WE, Hamman RE: Cigarette smoking increases the risk of albuminuria among subjects with type 1 diabetes.
Klein R, Klein BE, Moss SE: Incidence of gross proteinuria in older-onset diabetes: a population-based perspective.
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Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, Ebihara I, Koide H: Urinary podocytes for the assessment of disease activity in lupus nephritis.
Am J Med Sci
Nakamura T, Ushiyama C, Shimada N, Sekizuka K, Ebihara I, Hara M, Koide H: Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy.
Diabetes Care
Meyer TW, Bennett PH, Nelson RG: Podocyte number predicts long-term urinary albumin excretion in Pima Indians with type 2 diabetes and microalbuminuria.

Address correspondence to Hikaru Koide, MD, Department of Medicine, Koto Hospital, 6-8-5 Ojima, Koto-ku, Tokyo 136-0072, Japan. E-mail: