1. Strippoli, Giovanni F. M. MD, PhD, MPH, MM


Chronic kidney disease (CKD) is a major public health challenge. Despite identification of several established cardiovascular and renal risk factors and addressing them with multiple pharmacological interventions, people with CKD continue to die, and the rate of progression of kidney disease continues to increase. In this article, we review existing evidence on the role of fluid (total fluid including fluid from water and fluid from food) and nutrient intake and the risk of kidney disease and its progression and propose a research agenda for future studies in the area. It is plausible that water and nutrient intake is an easy-to-implement strategy to reduce the risk of CKD and its progression and adverse outcomes at a population level. Cross-sectional and prospective cohort studies first and subsequently randomized trials are needed to establish the strength of association between fluid/water/nutrient intake and risk of CKD and adverse outcomes and whether a causal link exists between these exposures and the adverse outcomes.


Article Content

Chronic kidney disease (CKD) is a major public health challenge with increasing prevalence worldwide.1-3 The cardiac burden associated with renal diseases and the relevant public health expenditure mandate identification of relevant risk factors and trialing of interventions that may proficiently address them. Several risk factors, including dyslipidemia, hypertension, anemia, smoking, diabetes, and others, have been identified and addressed with pharmacological interventions.4-8


Unfortunately, the promise that such interventions for managing CKD and its associated comorbidities would impact survival and disease progression has failed. Agents such as erythropoietins for renal anemia, lipid-lowering agents, drugs for the management of bone disease in CKD, and others have not significantly halted the progression of renal diseases, nor have they reduced the cardiac burden at levels that may be considered a success. At present, we have not seen a conclusive improvement of health outcomes. Many agents were thought to be particularly interesting with the promise of reducing the progression of renal diseases toward end-stage kidney disease requiring dialysis or transplantation for renal replacement therapy, but again, the promise has failed.


In the general population, including proportions of people with some degree of renal impairment, studies have shown that intake of certain nutrient categories and antioxidants may be associated with reduced risk of cardiovascular diseases, cancer, and other degenerative diseases.9-11 In these populations, studies have been conducted to explore the benefits and harms of specific diets (the Mediterranean diet, the DASH diet, other) on health outcomes. These interventions to address novel, nonestablished, nutritional risk factors are a promising approach to be explored not only in the general population, but also in high cardiac-/renal-risk populations, such as people with CKD. In these patients, it is commonly believed and yet unproven that certain nutrients (eg, folate, fiber, and other intake) and fluid/water consumption may be a good strategy to prevent the progression of CKD. However, in the specific renal population, there had until recently been virtually no studies, except for limited animal studies, to evaluate the role of nutrients and water consumption on the risk of renal and cardiovascular diseases, not to mention the complete lack of intervention studies about the benefits and harms of nutrients and water as a potential therapeutic strategy.


Researchers have recently become interested in the topic since 2 epidemiological studies were published. The first was an epidemiological study consisting of 2 surveys based on a door-to-door census of all subjects aged 49 years living in 2 postcode areas in the Blue Mountains region, west of Sydney, Australia.9,12 In this study, participants received and completed a 145-item food frequency questionnaire, and the association between exposure to different nutrient intake (including total daily fluid intake) and the risk of several outcomes, including renal disease, was evaluated. Investigators found that fluid consumption, including fluid from water and fluid from food, could be beneficial for kidney function. There was an inverse linear relationship between intake of fluid and prevalence of CKD. The higher the fluid intake, the lower the risk, with an intake of 3.3 L/d associated with a 30% to 50% reduction in the likelihood compared with an intake of 1.7 L/d. Investigators also acknowledge the possibility of residual confounding by type of medication that people in the study were receiving (including angiotensin-converting enzyme inhibitors, [beta]-blockers, calcium-channel blockers, or diuretics individually or in combination). Although only preliminary and based on opportunistic analyses from a database designed for other purposes, these data indicate that there is potential that higher daily fluid intakes (at least 3 L) may reduce the likelihood of having CKD.12 Given the strength of these associations, confirmation was suggested as a key requirement by the investigators who advocated for analysis of longitudinal data, both from existing databases or "ad hoc designed" databases and a randomized trial, although adherence to a dietary intervention would be challenging. In the future, when appropriate evidence becomes available, these low-cost interventions may have the potential to reduce the risk of CKD.


An additional study by Lin et al13 assessed the association of dietary patterns with kidney function declines in 3121 women aged 30 to 55 years. Women whose diet was based on higher intake of red and processed meats, saturated fats, and sweets had a significant increased risk of microalbuminuria and more rapid estimated glomerular filtration rate decline.


Clark and coworkers14 evaluated the relationship between urine volume and renal decline over a 6-year period in a large community-based cohort. Their conclusion was that decline in kidney function was significantly slower in those with higher versus lower urine volume, advocating for a potential role of fluid intake in reducing the risk of renal diseases. With these data at hand, it is now mandatory to refine a specific research agenda to advance knowledge in the area of association of fluid/water intake and the risk of major patient-level outcomes, as well as whether a causal link exists between drinking/fluid uptake and the risk of developing these outcomes.



The Table shows key information about a potential prospective cohort study to be designed "ad hoc" to evaluate the association between water and different fluid intake and the risk of progression of CKD. The study may also explore the associations between intake of specific nutrients and the risk of CKD. Such a study should be an integral part of the future research agenda in the interest of identifying the role of water, fluid, and nutrients in predicting the risk of progression of renal disease and should be funded soon by either public or private stakeholders.

TABLE Prospective Co... - Click to enlarge in new windowTABLE Prospective Cohort Study of Water, Fluid, and Nutrient Intake and the Risk of Chronic Kidney Disease and Adverse Cardiovascular Outcomes
Prospective Cohort S... - Click to enlarge in new windowProspective Cohort Study of Water, Fluid, and Nutrient Intake and the Risk of Chronic Kidney Disease and Adverse Cardiovascular Outcomes, Continued
Prospective Cohort S... - Click to enlarge in new windowProspective Cohort Study of Water, Fluid, and Nutrient Intake and the Risk of Chronic Kidney Disease and Adverse Cardiovascular Outcomes, Continued

The study should then be followed by small-scale randomized trials to evaluate the benefits and harms of interventions based on the results of the preliminary prospective cohort study.



The evaluation of fluid/water and nutrient intake exposure and the risk of renal and cardiovascular outcomes is a very promising research area, which could determine identification of significant interventions that may affect the risk of adverse outcomes at a population level. Preliminary evidence on potential benefits exists and should rapidly be further explored given the major implication that such interventions may have.




1. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003; 41: 1-12. [Context Link]


2. Atkins RC. The changing patterns of chronic kidney disease: the need to develop strategies for prevention relevant to different regions and countries. Kidney Int. 2005; 68: S83-S85. [Context Link]


3. Singh NP, Ingle GK, Saini VK, et al.. Prevalence of low glomerular filtration rate, proteinuria and associated risk factors in North India using Cockcroft-Gault and Modification of Diet in Renal Disease equation: an observational, cross-sectional study. BMC Nephrol. 2009; 10: 4. [Context Link]


4. Best PJ, Reddan DN, Berger PB, Szczech LA, McCullough PA, Califf RM. Cardiovascular disease and chronic kidney disease: insights and an update. Am Heart J. 2004; 148: 230-242. [Context Link]


5. Sarnak MJ, Levey AS, Schoolwerth AC, et al.. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology and Epidemiology and Prevention. Circulation. 2003; 108: 2154-2169. [Context Link]


6. Shlipak MG, Simon JA, Grady D, Lin F, Wenger NK, Eurberg CD. Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease. J Am Coll Cardiol. 2001; 38: 705-711. [Context Link]


7. Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001; 134: 629-636. [Context Link]


8. Nass CM, Reck K. Clinical challenges: the intersection of diabetes, chronic kidney disease, and cardiovascular disease. Curr Diab Rep. 2004; 4: 1-2. [Context Link]


9. Dominguez LJ, Bes-Rastrollo M, de la Fuente-Arrillaga C, et al. Similar prediction of decreased total mortality, diabetes incidence or cardiovascular events using relative- and absolute-component Mediterranean diet score: the SUN cohort [published online ahead of print March 6, 2012]. Nutr Metab Cardiovasc Dis. 2012. [Context Link]


10. Thomazella MC, Goes MF, Andrade CR, et al.. Effects of high adherence to Mediterranean or low-fat diets in medicated secondary prevention patients [published online ahead of print September 3, 2011]. Am J Cardiol. 2011; 108: 1523-1529. [Context Link]


11. Parikh A, Lipsitz SR, Natarajan S. Association between a DASH-like diet and mortality in adults with hypertension: findings from a population-based follow-up study [published online ahead of print February 5, 2009]. Am J Hypertens 2009; 22: 409-416. [Context Link]


12. Strippoli GF, Craig JC, Rochtchina E, Flood VM, Wang JJ, Mitchell P. Fluid and nutrient intake and risk of chronic kidney disease. Nephrology (Carlton). 2011; 16: 326-334. [Context Link]


13. Lin J, Fung TT, Hu FB, Curhan GC. Association of dietary patterns with albuminuria and kidney function decline in older white women: a subgroup analysis from the Nurses' Health Study. Am J Kidney Dis. 2011; 57: 245-254. [Context Link]


14. Clark WF, Sontrop JM, Macnab JJ, et al.. Urine volume and change in estimated GFR in a community-based cohort study. Clin J Am Soc Nephrol. 2011; 6: 2634-2641. [Context Link]