Smoking as a Risk Factor for End-Stage Renal failure in men with primary renal disease
Abstract & Commentary
Synopsis: When thinking of nephrotoxic drugs, include nicotine in the list and ask your patients to reduce and, preferably, stop smoking.
Source: Orth SR, et al. Kidney Int 1998;54:926-931.
Smoking is an independent risk factor for the onset and progression of diabetic nephropathy. No information exists on the effects of smoking on the course of non-diabetic renal disease. Orth and associates undertook a retrospective multi-center matched case-control study to evaluate whether smoking increases the risk of end-stage renal disease (ESRD) in patients with primary renal disease. The renal diseases studied were IgA glomerulonephritis (IgA-GN) and autosomal dominant polycystic kidney disease (ADPKD) as models of inflammatory and noninflammatory renal disease, respectively. A pool of 582 adult patient records from nine centers in Germany, Italy, and Austria were studied. Patients with systemic diseases involving the kidney, including diabetes mellitus, were excluded. Case patients were defined as those who had progressed to ESRD, and controls were those who failed to progress to serum creatinine (> 3 mg/dL) during a minimum observation period of one year and did not require renal replacement therapy.
There were 102 matched pairs based on primary renal disease (IgA-GN—54 pairs and ADPKD—48 pairs), gender, region of residence, and age at renal death of case patients. While ADPKD had an even gender distribution (males 28, female 20 pairs), there was a male dominance in the pairs with IgA-GN (male 44, female 10). A mail questionnaire was used to assess smoking habits. Numerous other variables that are known to affect the progression of renal disease, such as blood pressure, serum cholesterol levels, antihypertensive use (including ACE inhibitors and calcium channel blockers), and lipid-lowering therapy were also evaluated.
The only form of tobacco use in the 102 matched pairs was cigarette smoking. In men with both IgA-GN and ADPKD, the risk ratios for ESRD were similar, and, hence, the data were pooled. Smoking was associated with an increased risk of ESRD in a dose-dependent manner. Compared to those with less than five pack-years (PY) of smoking, the odds ratio of ESRD risk increased to 3.5 (P = 0.017) with 5-15 PY and to 5.8 (P = 0.001) with more than 15 PY of smoking. After adjustment for systolic blood pressure and age at diagnosis, ACE inhibitor treatment was found to be protective with an odds ratio for ESRD of 1.4 (P = 0.65), while in those not receiving ACE inhibitors, the risk of ESRD in men with more than 5 PY was highly increased with an odds ratio of 10.1 (P = 0.002). In contrast, in women, smoking was not associated with an increased risk for ESRD in primary renal disease.
Comment by KAMALJIT SETHI, MD, FACP
Showing the progression of renal disease has been an important subject of study that has intrigued physiologists and clinicians alike. Millions of dollars were spent on the Modification of Diet in Renal Disease trials to assess if lower protein intake could slow chronic renal failure progression, and the answer was negative.
But what about smoking? In diabetes mellitus, smoking causes renal disease to progress faster than in non-smokers.1,2 Despite the limitations of retrospective analysis, men with primary nondiabetic renal disease develop ESRD faster if they smoke. There are more questions than answers, but it seems clear that smoking is dangerous for the kidney in those with renal disease. By a likely combination of hemodynamic effects on the endothelium as well as nonhemodynamic effects, the more a patient smokes or has smoked, the greater the risk of rapid progression to ESRD.
In managing pre-ESRD patient, therefore, the following is a useful strategy: When thinking of nephrotoxic drugs, include nicotine in the list and ask your patients to reduce and preferably stop smoking.
References
1. Orth SR, et al. Kidney Int 1997;51:1669-1677.
2. Muhlhauser I. Diabet Med 1994;11:336-343.
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