Nephrolithiasis and the Risk of Hypertension in Women
Abstract & Commentary
Synopsis: While there is an increase in hypertension in women with nephrolithiasis, there was no increase in the risk of incident stones in those with pre-existing hypertension.
Source: Madore F, et al. Am J Kidney Dis 1998;32:802-807.
Hypertension and kidney stones are both common important public health problems. About 20% of the U.S. population has hypertension, defined as a systolic blood pressure of 140 mmHg and/or diastolic blood pressure of 90 mmHg. The prevalence of hypertension increases up to 67% in those 65 years of age or older. About 12% of adults in the United States will form a kidney stone sometime in their life. A positive association between nephrolithiasis and hypertension has been observed in cross-sectional and prospective studies of men but the association has been controversial in women. Madore and associates conducted a prospective study to further evaluate the relationship between nephrolithiasis and hypertension in a cohort of 89,376 female registered nurses aged 34-59 years in 1980, who were enrolled in the Nurses Health Study. Data on nephrolithiasis, hypertension, dietary intake, and related factors was gathered by a biennial mail questionnaire. The reliability of the reported data was confirmed by a random sample comparison of self-reported data and physician office medical records.
On cross sectional analysis, 2.86% women reported a history of nephrolithiasis before 1980 and 13.3% reported a diagnosis of hypertension before 1980. The age- adjusted prevalence odds ratio for hypertension for women with a history of nephrolithiasis was 1.49, compared to those without a history of nephrolithiasis. On prospective analysis, 12,540 women reported a new diagnosis of hypertension between 1980 and 1992, and the age-adjusted relative risk for hypertension in women with a history of nephrolithiasis was 1.36 compared to those without a history of kidney stones. After adjustment for body mass index, and dietary intake of calcium, sodium, potassium, magnesium, caffeine and alcohol, the relative risk for hypertension in those with a history of hypertension was slightly reduced to 1.24.
In contrast, there was no increase in the risk of incident stones in those with pre-existing hypertension, compared to those without hypertension.
Men with a history of nephrolithiasis are 29% more likely to develop hypertension compared to those with no history of kidney stone.1 This prospective analysis reveals a similar risk in women: female subjects with a history of nephrolithiasis are 24% more likely (all variables included) to develop hypertension, compared with those who do not historically have kidney stones. Thus, both sexes are at an equally high risk of developing hypertension if there is a history of nephrolithiasis, even though renal stones occur predominantly in males (male:female ratio, 2-4:1).
What accounts for this association between renal stone disease and hypertension? Hypercalciuria is a frequent abnormality in stone formers and hypertensives have higher urinary calcium excretion compared to normotensives. Furthermore, dietary calcium intake is inversely related to stone risk, and high dietary calcium intake has been reported to be associated with a lower blood pressure. Certainly, it would seem that perturbations in calcium metabolism may be linked to both hypertension and nephrolithiasis, even though much work needs to be done to establish cause and effect.
Given the fact that nephrolithiasis increases the risk for incident hypertension, are there any opportunities for intervention? In those with recurrent stone disease or single stone formers with a strong family history of kidney stones, the following steps should be considered to prevent kidney stones and attenuate metabolic abnormalities:
1. Metabolic evaluation to include measurement of urinary saturation for calcium, oxalate and uric acid, and urinary inhibitor concentration of citrate. Medical therapy with thiazides or citrate may be necessary.
2. Encourage increased fluid intake so that urinary output is about 2 L/d. This ensures the lowest supersaturation for calcium oxalate and uric acid. Water is the fluid of choice.
3. Continue normal dietary calcium and potassium intake, while reducing excessive salt intake. With regard to calcium and potassium, natural dietary sources are recommended rather than supplements.
These are reasonable interventions that are easy and inexpensive. It may be that the risk for future hypertension can be reduced if we can prevent kidney stones. (Dr. Sethi is Professor of Medicine, Georgetown University and Director, Georgetown Nephrology Section, DC General Hospital, Washington, DC.)
1. Madore F, et al. Am J Hypertens 1998;11:46-53.