Introduction
Hypothesis
Literature review and search strategy
Author (year) Study type, cohort name, follow-up period Population | Fluid intake or urinary hydration marker associated with health outcome | Health Outcome (Risk or Benefit) | |
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Total fluid intake volume (TFI, L·day−1) | 24-h urine volume (UVol, L·day−1) or Urine osmolality (UOsm, mOsm·kg−1) | ||
Borghi et al. (1996) [23] Case–control Recurrent stone formers vs. healthy controls | UVol, Mean [sd] Stone formers: 1.04 [0.24] Controls: 1.35 [0.53] | Risk: Stone formers had lower spontaneous 24 h urine volume than age, sex, body weight, and socioeconomic-matched controls | |
Borghi et al. (1996) [23] RCT, 5-year follow-up Recurrent stone formers | UVol, Mean [sd] Intervention: Pre: 1.1 [0.2] Post: 2.6 [0.4] Control: Pre: 1.0 [0.2] Post: 1.0 [0.2] | Benefit: Increasing urine volume reduced kidney stone recurrence (12% vs. 27% in control group), time between episodes, and urine supersaturation in stone formers | |
Curhan et al. (2004) [117] Prospective, NHS II cohort, 8-year follow-up General population (women) | TFI, quintiles Q1: ≤ 1.43 Q2: 1.43–1.85 Q3: 1.85–2.25 Q4: 2.25–2.77 Q5: ≥ 2.77 | Benefit: Reduction in multivariate-adjusted RR for incident kidney stones in women in Q3, Q4, and Q5 (RR 0.79, 0.72, and 0.68, respectively), compared to reference (women with FI ≤ 1.43 L·day−1) | |
Curhan & Taylor (2008) [24] Pooled retrospective study of 3 cohorts (NHS I, NHS II, HPFS) General population | UVol, Cutoff value From 1.5 to ≥ 2.5 | Benefit: Across three cohorts including 2,237 stone formers, individuals with a urine volume ranging from 1.5L to more than 2.5L·day−1 were shown to be at lower risk of developing kidney stones with corresponding RR ranging from 0.46 (urine volume 1.5 to 1.74L·day−1) to 0.22 (urine volume ≥ 2,5 L·day−1), compared to reference (urine volume ≤ 1.0L·day−1) | |
Curhan et al. (1993) [22] Prospective cohort (HPFS), 4-year follow up General population (men) | TFI, quintiles Q1: < 1.28 Q2: 1.28–1.67 Q3: 1.67–2.05 Q4: 2.05–2.54 Q5: ≥ 2.54 | Benefit: Reduction in multivariate-adjusted RR for incident kidney stones in men in Q5 (RR = 0.71), compared to reference (men with FI < 1.28 L·day−1) | |
Hooton et al. (2018) [42] RCT, 12-month follow-up Recurrent UTI (women) | TFI (intervention group), Mean [sd] Pre: 1.1 [0.1] Post: 2.8 [0.2] | UVol (intervention group), Mean [sd] Pre: 0.9 [0.2] Post: 2.2 [0.3] UOsm (intervention group), Mean [sd] Pre: 721 [169] Post: 329 [117] | Benefit: 48% reduction in UTI recurrence in intervention group vs. control; increased time between episodes; reduction in antibiotic use |
Direct effect of increased water intake to increase urine flow
Kidney stones
Urinary tract infection
Take home points
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Increasing fluid intake is effective in the secondary prevention of kidney stones and urinary tract infection. Little is known about whether high fluid intake is also effective in primary prevention.
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Mechanistically, increasing fluid intake results in lower urine concentration and increased urine flow. The former may be important in preventing supersaturation and crystal formation, while the latter encourages frequent flushing of the urinary tract which may be helpful for both kidney stone and UTI prevention.
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European and American urological associations encourage maintaining a fluid intake sufficient to produce 2 to 2.5 L of urine per day to reduce risk of stone formation.
Indirect effect of increased water intake: mechanisms mediated by reducing circulating AVP
Author (year) Study type, cohort name, follow-up period Population | Fluid intake, urinary hydration biomarker or copeptin value associated with health outcome | Health Outcome (Risk or Benefit) | |||
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Total water intake, total fluid intake, or plain water intake (L·day−1) | 24-h urine volume (UVol, L·day−1) or concentration (UOsm, mOsm·kg−1 or USG, unitless) | Plasma copeptin (pmol·L−1) | |||
Abbasi et al. (2012) [57] Prospective, PREVEND cohort, 7.7-year follow-up General population | Median [25,75th percentile] Men Q4: 12.5 [10.5,15.5] Women Q3: 4.4 [4.0,4.9] Q4: 7.6 [6.3,9.8] | Risk: Increased multivariate-adjusted odds of incident T2D in women, but not men, during 7.7 year follow up, starting from the third quartile of baseline copeptin compared to Q1 (reference: 1.8 [1.4–2.1] pmol·L−1) Risk: Increased odds of incident T2DM in men (more marginally significant, depending on adjustment model) in the highest quartile of copeptin compared to Q1, 3.0 [2.3–3.5] pmol·L−1 | |||
Boertien et al. (2013) [118] Prospective, ZODIAC-33, 6-year follow up T2DM | Quintiles Q1 < 3.11 Q5 > 8.96 | Risk: Highest quartile of copeptin had the most rapid rate of eGFR decline and largest change in albumin:creatinine ratio compared to reference (Q1) | |||
Clark et al. (2011) [79] Prospective, Walkerton Health Study Cohort, 6-year follow up General population | UVol, quartiles < 1.0 1–1.9 2–2.9 ≥ 3.0 | Risk: urine volume (< 1.0 L·day−1) more likely to demonstrate mild to moderate kidney function decline, compared to reference (1–1.9 L·day−1), odds ratio multivariate adjusted Benefit: High urine volume ≥ 3 L·day−1 less likely to demonstrate mild to moderate or severe kidney function decline, compared to reference (1–1.9 L·day−1), odds ratios multivariate adjusted | |||
El Boustany et al. (2018) [54] Prospective, pooled analysis of 3 cohorts: DESIR, MDC-CC, PREVEND, 8.5–16.5-year follow-up General population | Tertiles, Median [IQR] Men T2: 5.9 [1.7] T3: 10.6 [4.6] Women: T2: 3.5 [1.0] T3: 6.5 [3.1] | Risk: Top tertile (T3): Higher fasting plasma glucose and triglycerides compared to T2, T1; Risk: Top two tertiles (T2 and T3): kidney function decline compared to T1 Reference copeptin T1 3.2 [1.4], 2.1 [0.8] pmol·L−1 for men and women, respectively | |||
Enhorning et al. (2010) [55] Prospective, MDC-CC, 12-year follow-up General population | Median [25,75th percentile] 6.74 [4.44,10.9] | Risk: Baseline copeptin in participants developing T2DM during 12-year follow-up; compared to 4.90 [3.03–7.65] pmol·L−1 in those not developing T2DM (all participants NFG at baseline) | |||
Enhorning et al. (2011) [52] Cross-sectional, MDC-CC General population | Men: ≥ 10.7 or Women: ≥ 6.47 | Risk: Higher likelihood of hypertension, high CRP or abdominal obesity, multivariate-adjusted | |||
Enhorning et al. (2011) [52] Cross-sectional, MDC-CC General population | Men: ≥ 4.61 or Women: ≥ 2.72 | Risk: Higher likelihood of Metabolic Syndrome (age and sex adjusted only) | |||
Enhorning et al. (2013) [119] Prospective, MDC-CC, 15.8-year follow up General population | Median [25,75th percentile] Men Q3: 8.44 [7.64,9.53] Q4: 13.5 [11.5,16.6] Women Q3: 5.14 [4.70,5.76] Q4: 8.41 [7.22,10.45] | Risk: Third and fourth quartiles of copeptin: more likely to develop abdominal obesity, T2DM (age- and sex-adjusted) Risk: Fourth quartile of copeptin: More likely to develop metabolic syndrome (age and sex adjusted); abdominal obesity, microalbuminuria (multivariate adjusted) | |||
Enhorning et al. (2018) [66] RCT, 6-week follow up General population | TWI, Median [25,75th percentile] Pre: 1.9 [1.6,2.1] Post: 2.7 [2.3,3.1] | UVol, Median [25,75th percentile] Pre: 1.06 [0.9,1.2] Post: 2.27 [1.52,2.67] UOsm, Median [25,75th percentile] Pre: 879 [705,996] Post: 384 [319,502] | Median [25,75th percentile] Pre: 12.9 [7.4,21.9] Post: 7.8 [4.6, 11.3] | Benefit: Increasing plain water intake by 0.9 L·day−1 resulted in a reduction in copeptin and was accompanied by a lowering of fasting plasma glucose: from (mean [sd] 5.94 [0.44] to 5.74 [0.51] mmol·L−1 over a 6-week follow-up | |
Meijer et al. (2010) [120] Cross-sectional, PREVEND General population | UVol, Mean by quintile of copeptin (Q2-Q4 estimated from figure) Men Q1: 1.74 Q2: 1.60 Q3: 1.55 Q4: 1.45 Q5: 1.36 Women Q1: 1.82 Q2: 1.70 Q3: 1.60 Q4: 1.55 Q5: 1.43 | Quintiles: Men Q1: 0.6–3.7 Q2: 3.8–5.3 Q3: 5.4–7.3 Q4: 7.4–10.5 Q5: 10.5–632 Women Q1: 0.1–2.1 Q2: 2.2–3.0 Q3: 3.1–4.2 Q4: 4.3–6.2 Q5: 6.3–131 | Risk: Higher copeptin was associated with higher urinary albumin excretion, greater prevalence of microalbuminuria, low urine volume and high urine osmolality in men and women, multivariate-adjusted. Higher copeptin also significantly associated with lower eGFR (men and women), and in men only, higher plasma glucose, prevalent T2DM, higher serum CRP, and higher serum creatinine | ||
Roussel et al. (2016) [56] Prospective, DESIR cohort, 9-year follow-up General population | Quartiles Q1: 0.91–2.92 Q2: 2.93–4.05 Q3: 4.06–6.57 Q4: 6.58–115 | Benefit: Cumulated incident IFG or T2DM by quartile: 11, 14.5, 17.0, 23.5%, respectively in men and women | |||
Sontrop et al. (2013) [77] Cross-sectional, NHANES General population | Plain water intake, Median of bottom 20% 0.5 L·day−1 | Risk: More likely to have moderate CKD (multivariate-adjusted OR), compared to those with high plain water intake (top 20%; median 2.6 L·day−1) | |||
Strippoli et al. (2011) [76] Cross-sectional, Blue Mountains, Australia General population | TFI, median of quintile Q1: 1.8 Q5: 3.2 | Benefit: Reduced risk of moderate CKD in the highest quintile compared to reference (Q1) | |||
Velho et al. (2018) [121] Prospective, pooled DIABHYCAR and SURDIAGENE cohorts, 4.7-year follow up T2DM | Tertiles median [IQR] T3: 13.5 [6.5] and 16.2 [12.2] in both cohorts, respectively | Risk: Highest tertile of copeptin had increased (multivariate-adjusted) risk of MI, coronary revascularization, CHF, cardiovascular events, cardiovascular death, rapid kidney function decline, doubling of serum creatinine or ESRD, over a median 4.7-year follow up, compared to the lowest copeptin tertile (reference 3.7 [2.0] and 3.1 [1.9] pmol·L−1, respectively) | |||
Wennamethee et al. (2015) [58] Prospective, BRHS, 13-year follow-up General population (men 60–79 years) | Quintiles Q1: < 2.18 Q2: 2.18–3.12 Q3: 3.13–4.45 Q4: 4.46–6.78 Q5: ≥ 6.79 | Risk: Higher incident T2DM in Q5 versus all other quintiles, multivariate-adjusted |
AVP and metabolic dysfunction
Lower AVP and renal water saving in chronic kidney disease (CKD)
Autosomal dominant polycystic kidney disease
Take home points
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AVP, or the antidiuretic hormone, is most well-known for its central role in maintaining body water balance. However, AVP can also stimulate hepatic gluconeogenesis and glycogenolysis and can moderate glucose-regulating and corticotrophic hormones through its V1a and V1b receptors. The AVP-V2 receptor is also implicated in the pathophysiology of a particular form of kidney disease (ADPKD).
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In epidemiological studies, higher circulating AVP, measured by its equimolar surrogate, copeptin, is associated both cross-sectionally and longitudinally with higher odds for kidney function decline, components of the metabolic syndrome, and incident T2DM.
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Short-term intervention studies suggest that in individuals with higher AVP, increasing water intake can have an AVP-lowering effect. However, it is unclear whether lowering AVP through increased water intake will reduce disease risk.