Background: – Many studies have shown adverse effects of smoking on urinary albumin excretion and creatinine clearance in diabetics, but little is known about effects of smoking on renal function in non-diabeticsObjective: – To observe renal functions alteration in healthy non-diabetic smokers. SUBJECTS AND METHODS: A total of 90 subjects, 30 non-smokers as control, 60 smokers apparently healthy subjects of either sex were randomly selected from different parts of Karachi. RESULTS: 24 hour urinary albumin excretion was significantly increased in smokers (mean s. e. m 34. 54 0. 51 mg/day) as compared to non-smokers (mean s. e. m 19. 06+ 0. 46 mg/day) having P value (<0. 001). Creatinine clearance was significantly increased in smokers (mean s. e. m 120. 16 1. 75 ml/min/1. 73m2) as compared to non-smokers (mean s. e. m 107. 25 1. 93 ml/min/1. 73m2) having P value (<0. 001). Significant positive correlation was found between number of cigarettes and 24 hour urinary albumin excretion having r value 0. 33 and P value <0. 05. Values of other correlation were insignificant. CONCLUSION: Cigarette smoking is associated with mild microalbuminuria and mild hyperfiltration in smokers as compared to nonsmokers. KEY WORDS: Smoker, urinary albumin excretion, creatinine clearance.
INTRODUCTION
In recent years smoking has emerged as a major risk factor for the progression of renal disease, the adverse effects of smoking on renal function have gained more attention through investigation in diabetic patients1. The adverse effects of smoking on renal function have not been investigated extensively in non-diabetic smokers2. A number of potentially noxious chemicals in tobacco smoke produce injury. This injury translates into a number of important diseases3. In healthy volunteers smoking causes an increases in renovascular resistance accompanied by a decrease in glomercular filtration rate (GFR) and filtration fraction in parallel with an increase in blood pressure and heart rate associated with sympathetic activation4. Some studies indicate that smoking increases the risk to develop microalbuminuria5, shortens the interval from microalbuminuria to overt nephropathy6. Cigarette smoking may affect urinary albumin excretion and glomerular filtration rate in both diabetic and non-diabetic subjects7. Endothelial dysfunction may occur in the systemic arteries of even very light smokers from adolescence onward, although the likelihood of vascular physiological abnormalities increases with total amount smoked8. Smoking may also cause injury through nonhemodynamic pathways by causing damage to the renal and particularly microvasculature as a result of its effect on platelet function, thromboxane metabolism and endothelial cell function9. Atherogenic effects of smoking in the kidney are partially mediated by its unfavorable effects on lipoprotein and glycosaminoglycans metabolism10. Oxidative stress is probably another major player in genesis of smoking induced vascular renal injury11, 12. Creatinine clearance is even slightly higher in current smokers, at least in men. The effect of current smoking on creatinine clearance was reversible upon discontinuation of smoking. These data are compatible with the notion of early hyperfiltration. A dose-dependent increase of the relative risk of end-stage renal failure (ESRF) was found in smokers as compared with nonsmokers13. Smoking is associated with risk of higher GFR and proteinuria14. Therefore this study was carried out in order to see above effects by using a series of healthy non diabetic smokers.
MATERIALS AND METHODS
This study was carried out in the Department of Physiology, Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi. A total of 90 subjects; 30 nonsmokers, 60 smokers apparently healthy subjects of either sex; age ranging between 25-40 years were randomly selected from different parts of the Karachi. On the basis of history and clinical examination, the subjects were evaluated for having cardiovascular, renal or liver disease. Subjects were further screened with the help of ultrasound and routine urine examination for having any problem in the urinary system. History of any kind of drugs was taken. A blood sample was drawn under aseptic conditions to measure plasma glucose level. The subjects fulfilling inclusion/exclusion criteria were invited for second visit to bring 24 hour urinary collection in the container provided to them. Measurement of urinary volume, albumin concentration and creatinine concentration were performed. A blood sample was drawn for serum creatinine.
INCLUSION CRITERIA
For non-smokers apparently healthy subjects of either sex; age between 25-40 years, who never smoked and avoided passive smoking; for smokers apparently healthy subjects of either sex age between 25-40 years, who were smoking cigarettes regularly for the last five years or more.
EXCLUSION CRITERIA
Subjects were excluded from the study if they had a history of cardiovascular disease, renal disease or chronic liver disease. Diabetics and drug user were also excluded.
DETERMINATION OF PARAMETERS;
Urinary albumin concentration was estimated by colorimetric test, serum creatinine by method of Brod and Sirota, urinary creatinine was determined by Jaffe’s reaction by Alkaline Picrate, creatinine clearance by the formula uv/p and was corrected for surface area. Students ‘ t’ test was performed in order to see any significance among various parameters.
CORRELATION COEFFICIENT
The computer package Microsoft Excel was used for data entry. Correlation between different variables was detected by using Pearson Coefficient of Correlation on SPSS-10. Only P values (<0. 05) are considered significant.
RESULTS
Table 1 shows comparison of Mean (SEM) of age, body mass index (BMI), body surface area (BSA), pulse rate, systolic blood pressure and diastolic blood pressure in non-smokers (control) and smokers. Non-significant differences were found in these variables. Mean values of serum creatinine, urinary creatinine, 24 hour urinary volume, creatinine clearance, and 24 hour urinary albumin excretion are depicted in table 2. It shows comparison between non-smokers (control) and smokers. Urinary creatinine and 24 hour urinary volume, were statistically insignificant when smokers were compared with non-smokers. Serum creatinine was significantly low (P <0. 01) in smokers when compared with control. The Mean (S. E. M) of Creatinine clearance, and 24 hour uninary albumin excretion were higher in smokers as compared to non-smokers All having P values <0. 001 when compared with non-smokers. Table 3. shows correlation of number of cigarettes per day and duration of smoking in years with creatinine clearance, and 24 hour urinary albumin excretion. Significant positive correlation was found between number of cigarettes and 24 hour urinary excretion having r value 0. 33 and P value <0. 05. Values of other correlations were insignificant. TABLE 1
AGE, BODY MASS INDEX, BODY SURFACE AREA, PULSE RATE,
SYSTOLIC BLOOD PRESSURE, DIASTOLIC BLOOD PRESSURE
IN NON-SMOKERS (CONTROL) AND SMOKERS
(All the values are expressed in MeanSEM)
Variables
Non-smokers (Control)
(n= 30)
Smokers
(n= 60)
Age (Years)29. 830. 7130. 530. 38Body Mass Index (Kg/m2)24. 300. 1124. 100. 07Body Surface Area (m2)1. 740. 011. 740. 008Pulse Rate (beat/min)71. 500. 2271. 930. 22Systolic Blood Pressure (mmHg)119. 000. 90118. 160. 66Diastolic Blood Pressure (mmHg)78. 330. 7378. 250. 60n = Number of subjects. All the values are not significant as compared to control. TABLE 2
24 HOUR URINARY ALBUMIN EXCRETION, SERUM CREATININE,
URINARY CREATININE, 24 HOUR URINARY VOLUME AND
CREATININE CLEARANCE IN NON-SMOKERS (CONTROLS) AND SMOKERS
(All the values are expressed in MeanSEM)
Variables
Non-smokers (Control)
(n= 30)
Smokers
(n= 60)
24 Hour Urinary Albumin Excretion (mg/day)19. 060. 46
***
34. 540. 51Serum Creatinine (mg/dl)0. 920. 02
**
0. 850. 01Urinary Creatinine (mg/dl)122. 932. 37NS123. 851. 1524 Hour Urinary Volume (ml)1157. 6628. 14NS1193. 0015. 07Creatinine Clearance (ml/min/1. 73m2)107. 251. 93
***
120. 161. 75NS = Non-significant.** = P (<0. 01) when compared to control.*** = P (<0. 001) when compared to control.
TABLE 3
CORRELATION COEFFICIENT
Creatinine clearance
(ml/min/1. 73m2)
24 Hour Urine Albumin
(mg/day)
No. of Cigarettes (per day)r = -0. 03
*
r = 0. 33Duration of Smoking (year)
r = 0. 01
r = 0. 01r = Coefficient of correlation.* = P <0. 05
DISCUSSION
The diabetic subjects are usually followed for their diabetic disease, the course of their renal function is usually well known. Non-diabetic subjects come to medical attention only after the development of renal damage, which explains why little is known about early renal functional abnormalities in these subjects15. An increased risk for end stage renal failure (ESRF) was found for smokers as compared to non-smokers. Such increased relative risk of ESRF in smokers up to 1. 69 for heavy smokers was independent of age, ethnicity, income, blood pressure, diabetes mellitus and prior history of myocardial infarction or serum cholesterol16. Our study is in agreement with this trial because in our study the subjects were healthy, non-diabetic, normotensive and non-obese having body mass index (BMI) within normal limits. In our study serum ceatinine was significantly low in smokers as compared to non- smoker creatinine clearance was significantly high in smokers as compared to non-smokers. This is in agreement with study conducted by Halimi et al17 who have shown significantly higher Creatinine clearance in current smokers as compared to non-smokers and serum ceatinine significantly low in smokers as compared to non- smoker. Our study is, in part, in agreement with study conducted by Pinto-Sietsma et al2 who have shown increased creatinine clearance ml/min/1. 73m2 in smokers. Our results do not agree with study of Ritz et al4, who have observed decreased glomerular filtration rate and Gambaro et al18, who have shown normal glomerular filtration rate. How can a smoking induced increase in glomerular filtration rate be explained in non-diabetic persons? In its acute phase smoking induces a transient decrease in renal plasma flow Ritz et al4 and Gambaro et al18 and glomerular filtration rate Ritz et al4. These small repeated episodes of transient renal hypoperfusion may damage some glomeruli and finally result in structural alterations of preglomerular vessels and glomerular obsolescence. This in turn induces hypertrophy and hyperfiltration in the remnant glomeruli19
CONCLUSION
In conclusion chronic cigarette smoking is associated with mild microalbuminuria and mild hyper filtration in smokers as compared to non-smokers. At this stage we recommend that non-diabetic chronic smokers be examined and investigated for renal function. Smoking is one of the most important preventable renal risk factor. It has negative impact on renal function even in subjects without renal disease, so cessation is advised.
