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Seasonal influence on the renal function in hospitalized elderly patients
European Geriatric Medicine 6 (2015) 232–236
Available online at
ScienceDirect www.sciencedirect.com
Research paper
Seasonal influence on the renal function in hospitalized elderly patients L. Barski a,*, C. Bartal b,1, I. Sagy a,2, A. Jotkowitz a,3, R. Nevzorov a,4, L. Zeller a,5, V. Dizengof a,6, B. Rogachev c,7 a b c
Department of Internal Medicine F, Soroka University Medical Center, PO Box 151, 84101 Beer-Sheva, Israel Department of Emergency Medicine, Soroka University Medical Center, PO Box 151, 84101 Beer-Sheva, Israel Department of Nephrology, Soroka University Medical Center, Beer-Sheva, Israel
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 September 2014 Accepted 13 October 2014 Available online 17 January 2015
Background: Elderly adults are more vulnerable to heat-induced illness because of dysfunctional thermoregulatory mechanisms, chronic dehydration, medications, and diseases involving the systems that regulate body temperature. We hypothesized that extensive loss of fluids in a hot and dry climate in the summer months may lead to impaired renal function in elderly patients. The aim of the study was to determine the impact of the season of admission on renal function and the development of acute kidney injury in elderly patients. Methods: A retrospective observational cohort study on all patients older than 65 with creatinine level 2.0 mg/dL who were hospitalized twice (in the summer and in winter) in 2010–2011. The outcome was incidence of acute kidney injury. Results: The study cohort included 1107 consecutive patients hospitalized in the summer and in the winter months. The biochemical parameters of impaired renal function were more prominent in the summer as compared to the winter months in the whole cohort of patients and especially in patients with hypertension, diabetes mellitus and heart failure, and in patients treated with thiazide diuretics, ACE-inhibitors and ARBs. The most common reason for hospitalization in patients developing AKI in the summer was febrile disease and sepsis and in the winter heart, failure. Conclusions: Extensive fluids loss in a hot and dry climate in the summer months leads to mild impaired renal function in elderly patients. However, this influence is not clinically significant probably due to compensatory mechanisms for the preservation of renal function. ß 2015 Published by Elsevier Masson SAS.
Keywords: Impaired renal function Dehydration Acute kidney injury Elderly patient Seasonal influence
1. Abbreviations * Corresponding author. Department of Medicine F, Soroka University Medical Center, PO Box 151, Beer-Sheva 84101, Israel. Tel.: +972 8 6403 431, Cellular phone: +972 50 5 966 807; fax: +972 8 6400 097. E-mail addresses: [email protected] (L. Barski), [email protected] (C. Bartal), [email protected] (I. Sagy), [email protected] (A. Jotkowitz), [email protected] (R. Nevzorov), [email protected] (L. Zeller), [email protected] (V. Dizengof), [email protected] (B. Rogachev). 1 Cellular phone: +972 50 6 260 541. 2 Cellular phone: +972 54 9 344 704. 3 Cellular phone: +972 50 3 331 585. 4 Cellular phone: +972 36 5 561 952. 5 Cellular phone: +972 54 4 709 553. 6 Cellular phone: +972 54 6 056 488. 7 Cellular phone: +972 52 3 475 965. http://dx.doi.org/10.1016/j.eurger.2014.10.007 1878-7649/ß 2015 Published by Elsevier Masson SAS.
ACE-I ADH ARBs AKI GFR CHF COPD DM IQR RAAS
Angiotensin converting enzyme inhibitors Antidiuretic hormone Angiotensin receptor blockers Acute kidney injury Glomerullar filtration rate Congestive heart failure Chronic obstructive pulmonary disease Diabetes mellitus Inter quartile range (25th percentile; 75th percentile) Renin–angiotensin–aldosterone system
L. Barski et al. / European Geriatric Medicine 6 (2015) 232–236
2. Introduction One of the most serious problems of the 21th century is global warming. Since the early 20th century, earth’s average surface temperature has increased by about 0.8 8C (1.4 F), with about two thirds of the increase occurring since 1980. Climate model projections indicate that during the 21st century, the global surface temperature is likely to rise a further 1.1 to 2.9 8C (2 to 5.2 F) for their lowest emissions scenario and 2.4 to 6.4 8C (4.3 to 11.5 F) for their highest [1]. There is a dearth of data on the influence of this warming trend on human health. The climate of southern Negev in Israel is very hot and dry, especially in the summer period and therefore, it is an advantageous place to study the effect of high temperatures on human health. Elderly debilitated patients are especially sensitive to the influence of environmental factors on their health [2,3]. Also, older adults are more vulnerable to heat-induced illness than younger people because of dysfunctional thermoregulatory mechanisms, chronic dehydration, medications, and diseases involving the systems that regulate body temperature [4]. When core temperature rises, the hypothalamus initiates corrective measures. The processes that produce body heat, such as shivering and chemical thermogenesis, are inhibited. Simultaneously, renal and splanchnic vasoconstriction and peripheral vasodilation occur, shunting blood to the periphery. Heart rate and cardiac output increase to distribute large quantities of blood to the skin where heat is dissipated. Sweating increases and facilitates the loss of even more heat through evaporation [4]. Age dependent decline in cardiac reserve and an age-related reduction in vascularity decrease peripheral blood flow and reduce the efficiency with which heat can be removed. When such conditions as hypertension, atherosclerosis, and heart failure are present, the body’s ability to respond to heat is compromised further. It is a clear that in these conditions, the renal function may be impaired due to blood redistribution and diminishing of renal blood flow. Increased sweating in hot weather in elderly patients requires a good hydration, adequate water intake and urine concentrating ability. Without these conditions, elderly patients may to develop additional renal function impairment [4–6]. Early detection of heat illness and prompt treatment are crucial to survival in this population of peoples [3,4,7,8]. In addition, several factors predisposed elderly patients to water depletion and dehydration: a decrease of functional status with limitation of mobility, visual problems, confusion or other cognitive alterations, certain medications that greatly increase dehydration risk, such as diuretics, laxatives, and sedatives, all acute pathologies with fever and those that cause difficulties in swallowing or provoke diarrhea and/or vomiting [3,9]. Also, a fear of incontinence leads some elderly people to diminish their intake of fluids [3]. The following risk factors of water depletion and dehydration were identified in a study among acutely ill nursing home residents: female gender, age > 85 years, more than four chronic conditions, more than four medications, bedridden status, laxative use, chronic infections [10]. The number of deaths of elderly people that occurred due to dehydration during the heat wave of the summer of 2003 in Europe illustrates the importance of this problem [3]. Mortality associated with disturbances of water balance in the elderly may be as high as 40–70%, depending on the treatment [5,6]. Findings consistently support the conclusion that the elderly do not become as thirsty as younger persons following water deprivation and subsequently do not drink enough to rehydrate themselves [11].
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Maintaining hydration is important because of the close relationship between cell hydration and cell function. Appropriate water and electrolyte concentrations are essential for proper metabolic function and survival [12]. Several changes that occur with aging in renal function predisposed to kidney injury by various environmental factors [13–15]. For example, insensible loss can cause consecutive dehydration, pre-renal azotemia and the development of acute kidney injury (AKI) in this population [3,14,15]. Structural as well as functional changes occur as the kidneys age. Nephrons are lost and/or remaining ones perform less effectively, and the glomerular filtration rate (GFR) decreases [16]. Lessened responsiveness to hormonal signals causes the kidneys to function less efficiently in concentrating urine and correcting water loss [11,16]. There is evidence that impaired renal response to vasopressin causes the kidneys to be less able to concentrate urine [16]. AKI has been reported among 2–7% of hospitalized patients and these rates are increasing due to the aggressive treatment of elderly patients and the impact of nephrotoxic medications and invasive diagnostic procedures [17–21]. Many elderly patients use for the treatment of hypertension and diabetes mellitus thiazide diuretics, ACE-inhibitors and ARBs [22–27]. These medications may provoke or aggravate dehydration, volume depletion and decline renal perfusion in predisposed elderly patients [28]. The aim of the study was to determine the impact of the season of admission (winter or summer) in hospitalized elderly patients on the development of impaired renal function and AKI. 3. Materials and methods We performed a retrospective observational cohort study on all patients older than 65 with creatinine level 2.0 mg/dL who were hospitalized twice (in the summer and in winter) in 2010–2011 at Soroka University Medical Center. In this study, we enrolled patients with serum level of creatinine less than 2.0. The RIFLE classification is the current standard for stratifying renal injury and failure and gives 5 stages of AKI according to creatinine elevation:
risk – 1.5-fold increase in the serum creatinine; injury – 2-fold increase in the serum creatinine; failure – 3-fold increase in the serum creatinine; loss – complete loss of kidney function for more than 4 weeks; ESRD – complete loss of kidney function for more than 3 months [29].
A creatinine level of less than 2 gives us a pool of patients ranging from normal kidney function to failure (groups 1–3) and excludes the loss and ESKD groups (complete loss of kidney function 4–5). Patients were allocated to groups according to their seasonal hospitalization: ‘‘summer’’ or ‘‘winter’’ months of the year. In our study, the periods of the year were defined as a ‘‘winter’’ – November, December, January and February and as a ‘‘summer’’ – June, July, August and September according to significant difference in temperatures in these periods of the year in southern Israel. The exclusion criteria were diagnosis of previously known renal insufficiency and creatinine level > 2.0 mg/dL before the hospitalization. The clinical and biochemical characteristics of patients hospitalized in the summer months were compared with those hospitalized in the winter months. For estimation of renal function and diagnosis of AKI in the winter period, we used comparison of renal function in admission to the hospital
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with previous renal function in past 3 months prior to the hospitalization. The outcomes were incidence of acute kidney injury according to RIFLE classification [29] and parameters related to renal function that was determined by urea, creatinine, sodium plasma levels and blood hematocrit level. In addition, we performed sub-group analysis for patients with arterial hypertension, diabetes mellitus and congestive heart failure and for patients treated by thiazide diuretics, ACEinhibitors and ARBs. For calculation of GFR, we used modification of diet in renal disease formula (MDRD): MDRD = 186 SCr 1.154 age 0.203 (1.2010 if black), 0.742 if female. The study was approved by the Institutional Review Board prior to its initiation. Confidentiality was maintained throughout the study.
4. Statistical analysis The results are presented as the mean standard deviation (SD) for continuous variables with normal distribution and as the median (IQR; 25th, 75th percentiles) if the distribution is not normal. Categorical data is presented as the total patients (percentage of total patients). Paired-samples t-test was used for comparison of the continuous variables with normal distribution and Wilcoxon test for two related samples of continuous variables with not normal distribution. A two-sided P value < 0.05 was considered as statistically significant. Data summaries were performed using the Statistical Package for Social Sciences (SPSS, Chicago Inc.) windows version 16.0.
5. Results The study cohort included 1107 consecutive patients older than 65 hospitalized both in the ‘‘summer’’ and in the ‘‘winter’’ periods of 2010 and 2011. The average age of patients in this study was 78.9 7.5. In total, 48.1% of patients were men gender, 54.7% of patients had hypertension, 31.6% had diabetes and 11.1% had congestive heart failure. In this study, 43.8% of patients treated prior hospitalization with ACE-I, 15.6% with ARBs and 13.9% of patients with thiazide diuretics. In the whole cohort of patients, the urea and creatinine levels were significantly higher in the summer as compared to the winter period (urea 50 mg/dL 29 vs. 55 mg/dL 33, P < 0.001, creatinine 1.01 mg/dL 0.37 vs. 1.07 mg/dL 0.44, P < 0.001) (Table 1). Serum urea levels were higher in the summer as compared to winter period in patients with hypertension (53 mg/dL 32 vs. 47 mg/dL 28, P < 0.001), patients with DM (60 mg/dL 40 vs. 53 mg/dL 30, P < 0.001) and in patients with CHF (66 mg/dL (45– 86) vs. 56 mg/dL (40–77), P = 0.001). Serum creatinine was higher in summer compared to the winter period in patients with CHF (1.27 mg/dL 0.49 vs. 1.19 mg/dL 0.47, P = 0.007). Table 1 Laboratory tests on admission and estimated GFR of the whole cohort. Tests
Winter (n = 1107)
Summer (n = 1107)
P value
Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Sodium (meq/L), mean SD Uric acid (mg/dL), mean SD Hct (%), mean SD GFR (mL/min/1.73 m2)
50 29 1.01 0.37 137 10 5.4 2.8 37.8 6.2 75.5 28.9
55 33 1.07 0.44 137 11 5.4 3.1 36.5 6.4 73.3 32.1
< 0.001 < 0.001 0.7 0.8 < 0.001 < 0.001
No significant differences in plasma sodium level according to season of the year were observed. However, the hematocrit level was significantly lower in the summer as compared to the winter period. Results of sub-group analysis are shown in the Table 2. All patients treated with thiazide diuretics and ACE-inhibitors demonstrated significantly higher levels of urea and creatinine in the serum in the summer as compared to the winter period. Patients treated with ARBs demonstrated significantly higher level of creatinine in the serum in the summer as compared to the winter period. There was a significantly higher incidence of acute kidney injury in early stage in patients hospitalized in summer than in winter, 22.1% vs. 18.6 relatively, P = 0.04 (Table 3). No significant difference in the incidence of AKI in later stages between summer and winter periods was observed in this study, 4.3% vs. 3.1%, P = 0.14. Only a small proportion of patients (0.2% and 0.4%, relatively in both groups) developed decreased GFR by 75% or stage of failure according to RIFLE classification. The most common reasons for hospitalization in patients who developed AKI in the summer were febrile disease and sepsis, heart failure, diarrhoea and vomiting accounting for 30%, 25% and 15% of hospitalizations. In the winter, the most common reasons for admission of patients that developed AKI were heart failure, respiratory disease predominantly COPD or asthma exacerbation, febrile disease and sepsis accounting for 25%, 20% and 16%, respectively. 6. Discussion It is known that older adults are more vulnerable to heat influence and complications than younger people because of dysfunctional thermoregulatory mechanisms, chronic dehydration, medications, and diseases involving the systems that regulate body temperature [3,4]. Extensive fluid loss in the summer period compared to the winter in hot and dry climate may be significant factor for deviations from normal ranges of fluid balance especially in elderly debilitated patients and it may to provoke renal function impairment in this category of patients. Therefore, according to this hypothesis, the impairment of renal function due to extensive fluid loss would be more frequent in the summer period compared to the winter in a hot and dry climate in this population. The past medical literature provides some support for this hypothesis [30]. Patients, operated during the warmest season, have higher levels of serum creatinine and lower levels of estimated GFR, without a correspondent increase in the AKI rate. Different hypotheses underlying this pattern are generated by this study, including a dehydration status, concomitant anaemia, and a higher transfusion rate [30]. Notwithstanding the above, the fluid homeostasis normally functions automatically and effectively. Almost every organ and system in the body helps in some way to maintain fluid homeostasis. When serum osmolality rises, antidiuretic hormone (ADH) is produced, causing the collecting ducts to become more permeable to water. This increased permeability allows more water to be reabsorbed into the blood. As more water is reabsorbed, urine output falls and serum osmolality decreases because the water dilutes body fluid. Other factor for maintaining fluid homeostasis is renin– angiotensin–aldosterone system that restores blood volume (and renal perfusion) through sodium and water retention. In spite the aging kidney undergoes a number of important anatomic and physiologic changes that impaired functioning of these mechanisms, it yet remains significant compensatory mechanisms in this population of patients [7,10,15] and [31].
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Table 2 Difference in laboratory tests results in patients hospitalized both in winter and in summer months stratified by hypertension, diabetes mellitus and heart failure and by antihypertensive therapy. Disease
Laboratory tests
Winter
Summer
P value
Hypertension (n = 605)
Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Uric acid (mg/dL), mean SD Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Uric acid (mg/dl), mean SD Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), median (IQR) Creatinine (mg/dL), mean SD Uric acid (mg/dL), median (IQR) Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), median (IQR) Creatinine (mg/dL), median (IQR) Uric acid (mg/dL), median (IQR) Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Uric acid (mg/dL), mean SD Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), median (IQR) Creatinine (mg/dL), median (IQR) Uric acid (mg/dL), median (IQR) Hct (%), mean SD Sodium (meq/L), mean SD
47 28 0.99 0.72 5.7 2.4 38.1 5.6 137 6 53 30 1.11 0.83 6.1 2.4 37.7 5.8 137 3 56 (40–77) 1.19 0.47 7.2(5.6–9.0) 36.4 5.3 137 4 45 (34–60) 0.89 (0.73–1.14) 5.7 (4.3–6.9) 37.9 5.9 138 3 46 21 0.97 0.51 5.3 2.8 38.2 6.3 137 9 50 (36–71) 1.03 (0.79–1.38) 6.2 (4.7–7.8) 37.1 4.9 137 4
53 32 1.02 0.46 5.4 3.0 36.5 6.4 136 13 60 40 1.16 0.73 5.7 3.1 36.0 6.9 136 13 66 (45–86) 1.27 0.49 7.4 (5.2–9.1) 35.5 6.4 135 17 49 (39–65) 0.99 (0.75–1.30) 6.0 (4.5–7.3) 36.9 4.7 138 4 54 30 1.07 0.64 5.4 3.1 37.1 5.8 137 10 54 (40–73) 1.10 (0.78–1.47) 6.2 (4.7–7.6) 36.5 5.5 137 11
< 0.001 0.4 0.001 < 0.001 0.3 < 0.001 0.08 0.038 < 0.001 0.3 0.001 0.007 0.8 0.03 0.3 0.005 0.001 0.6 0.009 1 < 0.001 < 0.001 0.5 < 0.001 0.7 0.1 0.015 0.4 0.08 0.7
Diabetes mellitus (n = 350)
Heart failure (n = 123)
Thiazide diuretics (n = 154)
ACE-inhibitors (n = 481)
ARBs (n = 173)
In our study, the plasma urea and creatinine levels were statistically significantly higher in the summer as compared to the winter period of the year. But clinically this difference does not seem significant. This is probably due to compensatory mechanisms, which prevents further impairment of renal function. In our study, the sodium level was not increased in the summer compared to the winter period. This may also be explained by compensatory mechanisms, which prevent significant water depletion in these patients. Other explanation of these results is that patients enrolled in this study presumably had nearly enough or enough water consumption prior to hospitalization. In southern Israel, the elderly population receives information from many sources, including health care professionals about the necessity to drink enough in the hot summer period. And many of the patients probably followed these recommendations. Elevated blood hematocrit reflects the hemoconcentration associated with water depletion and global dehydration [4,8]. In this study, we did find mild statistically but not clinically significant differences in blood hematocrit concentration in the two groups of patients. Therefore, this data confirms that physiologic compensatory mechanisms for preserving adequate
Table 3 Incidence of acute kidney injury (according to RIFLE criteria) in patients hospitalized both in winter and in summer months. Acute kidney injury according to RIFLE criteria
Winter
Summer
P value
Risk (GFR decrease by 25%), n (%) Injury (GFR decrease by 50%), n (%) Failure (GFR decrease by 75%), n (%)
206 (18.6) 34 (3.1) 2 (0.2)
245 (22.1) 48 (4.3) 4 (0.4)
0.04 0.14 0.6
renal blood flow and the maintenance of normal renal function are enough for the prevention of the development of AKI. Sub-groups analysis in this study revealed that laboratory signs of impaired renal function were significantly more prominent in the summer compared to the winter period in the sub-groups of patients with CHF and DM. In these groups of patients, the influence of extensive fluid loss on renal function in the summer period compared to the winter may be more clinically significant. Therefore, these groups of patients required additional attention by medical providers in the summer months in order to prevent impairment of renal function and the possible development of AKI. In patients treated with ACE-I, ARBs and thiazides, we also observed statistically significant laboratory signs of impaired renal function in the summer as compared to the winter period. But the clinical significance of these findings is probably not important. These findings probably also reflect enough compensatory renal mechanisms in the older population of patients, however, this category of patients require attention by healthcare providers. In some elderly debilitated patients who live in hot and dry climates and are treated with these medications, the therapeutic approach must be individualized with a possible reduction of dosage or maybe even changing their medications to another class free from RAAS influence. The present study demonstrates significantly higher incidence of acute kidney injury in the early stage according to RIFLE classification in patients hospitalized in the summer compared to winter. In the later stages of AKI (injury, failure), we did not reveal any significant differences between two groups of patients. Explanation of this finding may be due to compensatory mechanisms, which preserve renal function and well-timed medical attention and early correction of the volume status. In this study, the reasons for hospitalization in patients who developed AKI in the summer and winter periods were different. The most common reasons for hospitalization in patients who
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developed AKI in the summer period were febrile diseases and sepsis, heart failure, diarrhoea and vomiting. In the winter, the most common reasons for admission of patients that developed AKI were heart failure, respiratory disease, predominantly COPD or asthma exacerbation, febrile diseases and sepsis. These differences might partially be associated with a seasonal distribution of morbidity causes. Therefore, timely attention, and if needed appropriate and aggressive rehydration in this population of patients is an important component of the management. In addition, particular attention must be paid to patients with heart failure, treated with drugs with potential nephrotoxic effect. The strengths of this study are that more than a thousand elderly consecutive patients were included in the study and seasonal changes in renal function have rarely been studied previously. The limitations of this study are that it was a retrospective study performed at one large medical centre. In conclusion, extensive fluids loss in a hot and dry climate in the summer months leads to mild impaired renal function in elderly patients. However, this influence is not clinically significant probably due to compensatory mechanisms for the preservation of renal function. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgments We thank Professor Mark Clarfield for his insightful comments. References [1] Meehl GA. StockerTF. Global Climate Projections (Sec. 10.ES). Mean Temperature in IPCC AR4 WG1; (Chap. 10); 2007. [2] Juhlin T, Bjo¨rkman S, Ho¨glund P. Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors. Eur J Heart Fail 2005;7(6):1049–56. [3] Ferry M. Strategies for ensuring good hydration in the elderly. Nutr Rev 2005;63(6 Pt 2):S22–9. [4] Worfolk JB. Heat waves: their impact on the health of elders. Geriatr Nurs 2014;21(2):70–7. [5] Warren JL, Bacon E, Harris T, McBean AM, Foley DJ, Phillips C. The burden and outcomes associated with dehydration among US elderly. Am J Public Health 2000;84:1265–9. [6] Kleiner SM. Water: an essential but overlooked nutrient. J Am Diet Assoc 1999;99:200–6. [7] Coca SG. Acute kidney injury in elderly persons. Am J Kidney Dis 2010;56:122–31. [8] Davidhizar R, Dunn CL, Hart AN. A review of the literature on how important water is to the world’s elderly population. Int Nurs Rev 2004;51(3):159–66.
[9] Haussinger D, Lang F, Gerok W. Regulation of cell function by the cellular hydration state. Am J Physiol 1994;267(3 part 1):E343–55. [10] Lavizzo-Mourey R, Johnson J, Stolley P. Risk factors for dehydration among elderly nursing home residents. J Am Geriatr Soc 1988;36:213. [11] Gross CR, Lindquist RD, Woolley AC, Granieri R, Allard K, Webster B. Clinical indicators of dehydration severity in elderly patients. J Emerg Med 1992;10:267–74. [12] Porth CM, Erickson M. Physiology of thirst and drinking: implications for nursing practice. Heart Lung 1992;21:273–82. [13] Chronopoulos A, Rosner MH, Cruz DN. Acute kidney injury in the elderly. Contrib Nephrol 2010;165:315–21. [14] Yilmaz R, Erdem Y. Acute kidney injury in the elderly population. Int Urol Nephrol 2010;42(1):259–71. [15] Abdel-Kader K, Palevsky PM. Acute kidney injury in the elderly. Clin Geriatr Med 2009;25(3):331–58. [16] Erkert JD. Dehydration in the elderly. J Am Acad Phys Assist 1988;1:261–9. [17] Singri N, Ahja SN, Levin ML. Acute renal failure. JAMA 2003;289:747–51. [18] Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 2005;16:3365–70. [19] Shema L, Ore L, Kristal B. Hospital-acquired acute kidney injury in Israel. IMAJ 2009;269–74. [20] Xue JL, Daniels F, Star RA, Kimmel PL, Eggers PW, Molitoris BA, et al. Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. JASN 2006;1135–42. [21] Hoste EAJ, Kellum JA. RIFLE criteria provide robust assessment of kidney dysfunction and correlate with hospital mortality. Crit Care Med 2006;34:2016–7. [22] Staessen JA, Gasowski J, Wang JG, Thijs L, Den Hond E, Boissel JP, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: metaanalysis of outcome trials. Lancet 2000;355:865. [23] Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887. [24] Staessen JA, Richart T, Verdecchia P. Reducing blood pressure in people of different ages. BMJ 2008;336:1080. [25] Staessen JA, Richart T, Birkenhager WH. Less atherosclerosis and lower blood pressure for a meaningful life perspective with more brain. Hypertension 2007;49:389. [26] Furberg CD, Wright JT, Davis BR, Cutler JA, Alderman M, Black H, (the ALLHAT research group). Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981. [27] Jamerson K, Weber MA, Bakris GL, Dahlo¨f B, Pitt B, Shi V, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008;359:2417. [28] Jerkic´ M, Vojvodic´ S, Lo´pez-Novoa JM. The mechanism of increased renal susceptibility to toxic substances in the elderly. Part I. The role of increased vasoconstriction. Int Urol Nephrol 2001;32(4):539–47. [29] Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failuredefinition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204. [30] Ranucci M, Castelvecchio S, La Rovere MT, Surgical and Clinical Outcome Research (SCORE) Group. Renal function changes and seasonal temperature in patients undergoing cardiac surgery. Chronobiol Int 2014;31(2):175–81. http://dx.doi.org/10.3109/07420528.2013.836533. Epub 2013 Oct 28. [31] Mulder WJ, Hillen HFP. Renal function and renal disease in the elderly: part 1. Eur J Int Med 2001;12:86–97.
Available online at
ScienceDirect www.sciencedirect.com
Research paper
Seasonal influence on the renal function in hospitalized elderly patients L. Barski a,*, C. Bartal b,1, I. Sagy a,2, A. Jotkowitz a,3, R. Nevzorov a,4, L. Zeller a,5, V. Dizengof a,6, B. Rogachev c,7 a b c
Department of Internal Medicine F, Soroka University Medical Center, PO Box 151, 84101 Beer-Sheva, Israel Department of Emergency Medicine, Soroka University Medical Center, PO Box 151, 84101 Beer-Sheva, Israel Department of Nephrology, Soroka University Medical Center, Beer-Sheva, Israel
A R T I C L E I N F O
A B S T R A C T
Article history: Received 7 September 2014 Accepted 13 October 2014 Available online 17 January 2015
Background: Elderly adults are more vulnerable to heat-induced illness because of dysfunctional thermoregulatory mechanisms, chronic dehydration, medications, and diseases involving the systems that regulate body temperature. We hypothesized that extensive loss of fluids in a hot and dry climate in the summer months may lead to impaired renal function in elderly patients. The aim of the study was to determine the impact of the season of admission on renal function and the development of acute kidney injury in elderly patients. Methods: A retrospective observational cohort study on all patients older than 65 with creatinine level 2.0 mg/dL who were hospitalized twice (in the summer and in winter) in 2010–2011. The outcome was incidence of acute kidney injury. Results: The study cohort included 1107 consecutive patients hospitalized in the summer and in the winter months. The biochemical parameters of impaired renal function were more prominent in the summer as compared to the winter months in the whole cohort of patients and especially in patients with hypertension, diabetes mellitus and heart failure, and in patients treated with thiazide diuretics, ACE-inhibitors and ARBs. The most common reason for hospitalization in patients developing AKI in the summer was febrile disease and sepsis and in the winter heart, failure. Conclusions: Extensive fluids loss in a hot and dry climate in the summer months leads to mild impaired renal function in elderly patients. However, this influence is not clinically significant probably due to compensatory mechanisms for the preservation of renal function. ß 2015 Published by Elsevier Masson SAS.
Keywords: Impaired renal function Dehydration Acute kidney injury Elderly patient Seasonal influence
1. Abbreviations * Corresponding author. Department of Medicine F, Soroka University Medical Center, PO Box 151, Beer-Sheva 84101, Israel. Tel.: +972 8 6403 431, Cellular phone: +972 50 5 966 807; fax: +972 8 6400 097. E-mail addresses: [email protected] (L. Barski), [email protected] (C. Bartal), [email protected] (I. Sagy), [email protected] (A. Jotkowitz), [email protected] (R. Nevzorov), [email protected] (L. Zeller), [email protected] (V. Dizengof), [email protected] (B. Rogachev). 1 Cellular phone: +972 50 6 260 541. 2 Cellular phone: +972 54 9 344 704. 3 Cellular phone: +972 50 3 331 585. 4 Cellular phone: +972 36 5 561 952. 5 Cellular phone: +972 54 4 709 553. 6 Cellular phone: +972 54 6 056 488. 7 Cellular phone: +972 52 3 475 965. http://dx.doi.org/10.1016/j.eurger.2014.10.007 1878-7649/ß 2015 Published by Elsevier Masson SAS.
ACE-I ADH ARBs AKI GFR CHF COPD DM IQR RAAS
Angiotensin converting enzyme inhibitors Antidiuretic hormone Angiotensin receptor blockers Acute kidney injury Glomerullar filtration rate Congestive heart failure Chronic obstructive pulmonary disease Diabetes mellitus Inter quartile range (25th percentile; 75th percentile) Renin–angiotensin–aldosterone system
L. Barski et al. / European Geriatric Medicine 6 (2015) 232–236
2. Introduction One of the most serious problems of the 21th century is global warming. Since the early 20th century, earth’s average surface temperature has increased by about 0.8 8C (1.4 F), with about two thirds of the increase occurring since 1980. Climate model projections indicate that during the 21st century, the global surface temperature is likely to rise a further 1.1 to 2.9 8C (2 to 5.2 F) for their lowest emissions scenario and 2.4 to 6.4 8C (4.3 to 11.5 F) for their highest [1]. There is a dearth of data on the influence of this warming trend on human health. The climate of southern Negev in Israel is very hot and dry, especially in the summer period and therefore, it is an advantageous place to study the effect of high temperatures on human health. Elderly debilitated patients are especially sensitive to the influence of environmental factors on their health [2,3]. Also, older adults are more vulnerable to heat-induced illness than younger people because of dysfunctional thermoregulatory mechanisms, chronic dehydration, medications, and diseases involving the systems that regulate body temperature [4]. When core temperature rises, the hypothalamus initiates corrective measures. The processes that produce body heat, such as shivering and chemical thermogenesis, are inhibited. Simultaneously, renal and splanchnic vasoconstriction and peripheral vasodilation occur, shunting blood to the periphery. Heart rate and cardiac output increase to distribute large quantities of blood to the skin where heat is dissipated. Sweating increases and facilitates the loss of even more heat through evaporation [4]. Age dependent decline in cardiac reserve and an age-related reduction in vascularity decrease peripheral blood flow and reduce the efficiency with which heat can be removed. When such conditions as hypertension, atherosclerosis, and heart failure are present, the body’s ability to respond to heat is compromised further. It is a clear that in these conditions, the renal function may be impaired due to blood redistribution and diminishing of renal blood flow. Increased sweating in hot weather in elderly patients requires a good hydration, adequate water intake and urine concentrating ability. Without these conditions, elderly patients may to develop additional renal function impairment [4–6]. Early detection of heat illness and prompt treatment are crucial to survival in this population of peoples [3,4,7,8]. In addition, several factors predisposed elderly patients to water depletion and dehydration: a decrease of functional status with limitation of mobility, visual problems, confusion or other cognitive alterations, certain medications that greatly increase dehydration risk, such as diuretics, laxatives, and sedatives, all acute pathologies with fever and those that cause difficulties in swallowing or provoke diarrhea and/or vomiting [3,9]. Also, a fear of incontinence leads some elderly people to diminish their intake of fluids [3]. The following risk factors of water depletion and dehydration were identified in a study among acutely ill nursing home residents: female gender, age > 85 years, more than four chronic conditions, more than four medications, bedridden status, laxative use, chronic infections [10]. The number of deaths of elderly people that occurred due to dehydration during the heat wave of the summer of 2003 in Europe illustrates the importance of this problem [3]. Mortality associated with disturbances of water balance in the elderly may be as high as 40–70%, depending on the treatment [5,6]. Findings consistently support the conclusion that the elderly do not become as thirsty as younger persons following water deprivation and subsequently do not drink enough to rehydrate themselves [11].
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Maintaining hydration is important because of the close relationship between cell hydration and cell function. Appropriate water and electrolyte concentrations are essential for proper metabolic function and survival [12]. Several changes that occur with aging in renal function predisposed to kidney injury by various environmental factors [13–15]. For example, insensible loss can cause consecutive dehydration, pre-renal azotemia and the development of acute kidney injury (AKI) in this population [3,14,15]. Structural as well as functional changes occur as the kidneys age. Nephrons are lost and/or remaining ones perform less effectively, and the glomerular filtration rate (GFR) decreases [16]. Lessened responsiveness to hormonal signals causes the kidneys to function less efficiently in concentrating urine and correcting water loss [11,16]. There is evidence that impaired renal response to vasopressin causes the kidneys to be less able to concentrate urine [16]. AKI has been reported among 2–7% of hospitalized patients and these rates are increasing due to the aggressive treatment of elderly patients and the impact of nephrotoxic medications and invasive diagnostic procedures [17–21]. Many elderly patients use for the treatment of hypertension and diabetes mellitus thiazide diuretics, ACE-inhibitors and ARBs [22–27]. These medications may provoke or aggravate dehydration, volume depletion and decline renal perfusion in predisposed elderly patients [28]. The aim of the study was to determine the impact of the season of admission (winter or summer) in hospitalized elderly patients on the development of impaired renal function and AKI. 3. Materials and methods We performed a retrospective observational cohort study on all patients older than 65 with creatinine level 2.0 mg/dL who were hospitalized twice (in the summer and in winter) in 2010–2011 at Soroka University Medical Center. In this study, we enrolled patients with serum level of creatinine less than 2.0. The RIFLE classification is the current standard for stratifying renal injury and failure and gives 5 stages of AKI according to creatinine elevation:
risk – 1.5-fold increase in the serum creatinine; injury – 2-fold increase in the serum creatinine; failure – 3-fold increase in the serum creatinine; loss – complete loss of kidney function for more than 4 weeks; ESRD – complete loss of kidney function for more than 3 months [29].
A creatinine level of less than 2 gives us a pool of patients ranging from normal kidney function to failure (groups 1–3) and excludes the loss and ESKD groups (complete loss of kidney function 4–5). Patients were allocated to groups according to their seasonal hospitalization: ‘‘summer’’ or ‘‘winter’’ months of the year. In our study, the periods of the year were defined as a ‘‘winter’’ – November, December, January and February and as a ‘‘summer’’ – June, July, August and September according to significant difference in temperatures in these periods of the year in southern Israel. The exclusion criteria were diagnosis of previously known renal insufficiency and creatinine level > 2.0 mg/dL before the hospitalization. The clinical and biochemical characteristics of patients hospitalized in the summer months were compared with those hospitalized in the winter months. For estimation of renal function and diagnosis of AKI in the winter period, we used comparison of renal function in admission to the hospital
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with previous renal function in past 3 months prior to the hospitalization. The outcomes were incidence of acute kidney injury according to RIFLE classification [29] and parameters related to renal function that was determined by urea, creatinine, sodium plasma levels and blood hematocrit level. In addition, we performed sub-group analysis for patients with arterial hypertension, diabetes mellitus and congestive heart failure and for patients treated by thiazide diuretics, ACEinhibitors and ARBs. For calculation of GFR, we used modification of diet in renal disease formula (MDRD): MDRD = 186 SCr 1.154 age 0.203 (1.2010 if black), 0.742 if female. The study was approved by the Institutional Review Board prior to its initiation. Confidentiality was maintained throughout the study.
4. Statistical analysis The results are presented as the mean standard deviation (SD) for continuous variables with normal distribution and as the median (IQR; 25th, 75th percentiles) if the distribution is not normal. Categorical data is presented as the total patients (percentage of total patients). Paired-samples t-test was used for comparison of the continuous variables with normal distribution and Wilcoxon test for two related samples of continuous variables with not normal distribution. A two-sided P value < 0.05 was considered as statistically significant. Data summaries were performed using the Statistical Package for Social Sciences (SPSS, Chicago Inc.) windows version 16.0.
5. Results The study cohort included 1107 consecutive patients older than 65 hospitalized both in the ‘‘summer’’ and in the ‘‘winter’’ periods of 2010 and 2011. The average age of patients in this study was 78.9 7.5. In total, 48.1% of patients were men gender, 54.7% of patients had hypertension, 31.6% had diabetes and 11.1% had congestive heart failure. In this study, 43.8% of patients treated prior hospitalization with ACE-I, 15.6% with ARBs and 13.9% of patients with thiazide diuretics. In the whole cohort of patients, the urea and creatinine levels were significantly higher in the summer as compared to the winter period (urea 50 mg/dL 29 vs. 55 mg/dL 33, P < 0.001, creatinine 1.01 mg/dL 0.37 vs. 1.07 mg/dL 0.44, P < 0.001) (Table 1). Serum urea levels were higher in the summer as compared to winter period in patients with hypertension (53 mg/dL 32 vs. 47 mg/dL 28, P < 0.001), patients with DM (60 mg/dL 40 vs. 53 mg/dL 30, P < 0.001) and in patients with CHF (66 mg/dL (45– 86) vs. 56 mg/dL (40–77), P = 0.001). Serum creatinine was higher in summer compared to the winter period in patients with CHF (1.27 mg/dL 0.49 vs. 1.19 mg/dL 0.47, P = 0.007). Table 1 Laboratory tests on admission and estimated GFR of the whole cohort. Tests
Winter (n = 1107)
Summer (n = 1107)
P value
Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Sodium (meq/L), mean SD Uric acid (mg/dL), mean SD Hct (%), mean SD GFR (mL/min/1.73 m2)
50 29 1.01 0.37 137 10 5.4 2.8 37.8 6.2 75.5 28.9
55 33 1.07 0.44 137 11 5.4 3.1 36.5 6.4 73.3 32.1
< 0.001 < 0.001 0.7 0.8 < 0.001 < 0.001
No significant differences in plasma sodium level according to season of the year were observed. However, the hematocrit level was significantly lower in the summer as compared to the winter period. Results of sub-group analysis are shown in the Table 2. All patients treated with thiazide diuretics and ACE-inhibitors demonstrated significantly higher levels of urea and creatinine in the serum in the summer as compared to the winter period. Patients treated with ARBs demonstrated significantly higher level of creatinine in the serum in the summer as compared to the winter period. There was a significantly higher incidence of acute kidney injury in early stage in patients hospitalized in summer than in winter, 22.1% vs. 18.6 relatively, P = 0.04 (Table 3). No significant difference in the incidence of AKI in later stages between summer and winter periods was observed in this study, 4.3% vs. 3.1%, P = 0.14. Only a small proportion of patients (0.2% and 0.4%, relatively in both groups) developed decreased GFR by 75% or stage of failure according to RIFLE classification. The most common reasons for hospitalization in patients who developed AKI in the summer were febrile disease and sepsis, heart failure, diarrhoea and vomiting accounting for 30%, 25% and 15% of hospitalizations. In the winter, the most common reasons for admission of patients that developed AKI were heart failure, respiratory disease predominantly COPD or asthma exacerbation, febrile disease and sepsis accounting for 25%, 20% and 16%, respectively. 6. Discussion It is known that older adults are more vulnerable to heat influence and complications than younger people because of dysfunctional thermoregulatory mechanisms, chronic dehydration, medications, and diseases involving the systems that regulate body temperature [3,4]. Extensive fluid loss in the summer period compared to the winter in hot and dry climate may be significant factor for deviations from normal ranges of fluid balance especially in elderly debilitated patients and it may to provoke renal function impairment in this category of patients. Therefore, according to this hypothesis, the impairment of renal function due to extensive fluid loss would be more frequent in the summer period compared to the winter in a hot and dry climate in this population. The past medical literature provides some support for this hypothesis [30]. Patients, operated during the warmest season, have higher levels of serum creatinine and lower levels of estimated GFR, without a correspondent increase in the AKI rate. Different hypotheses underlying this pattern are generated by this study, including a dehydration status, concomitant anaemia, and a higher transfusion rate [30]. Notwithstanding the above, the fluid homeostasis normally functions automatically and effectively. Almost every organ and system in the body helps in some way to maintain fluid homeostasis. When serum osmolality rises, antidiuretic hormone (ADH) is produced, causing the collecting ducts to become more permeable to water. This increased permeability allows more water to be reabsorbed into the blood. As more water is reabsorbed, urine output falls and serum osmolality decreases because the water dilutes body fluid. Other factor for maintaining fluid homeostasis is renin– angiotensin–aldosterone system that restores blood volume (and renal perfusion) through sodium and water retention. In spite the aging kidney undergoes a number of important anatomic and physiologic changes that impaired functioning of these mechanisms, it yet remains significant compensatory mechanisms in this population of patients [7,10,15] and [31].
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Table 2 Difference in laboratory tests results in patients hospitalized both in winter and in summer months stratified by hypertension, diabetes mellitus and heart failure and by antihypertensive therapy. Disease
Laboratory tests
Winter
Summer
P value
Hypertension (n = 605)
Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Uric acid (mg/dL), mean SD Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Uric acid (mg/dl), mean SD Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), median (IQR) Creatinine (mg/dL), mean SD Uric acid (mg/dL), median (IQR) Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), median (IQR) Creatinine (mg/dL), median (IQR) Uric acid (mg/dL), median (IQR) Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), mean SD Creatinine (mg/dL), mean SD Uric acid (mg/dL), mean SD Hct (%), mean SD Sodium (meq/L), mean SD Urea (mg/dL), median (IQR) Creatinine (mg/dL), median (IQR) Uric acid (mg/dL), median (IQR) Hct (%), mean SD Sodium (meq/L), mean SD
47 28 0.99 0.72 5.7 2.4 38.1 5.6 137 6 53 30 1.11 0.83 6.1 2.4 37.7 5.8 137 3 56 (40–77) 1.19 0.47 7.2(5.6–9.0) 36.4 5.3 137 4 45 (34–60) 0.89 (0.73–1.14) 5.7 (4.3–6.9) 37.9 5.9 138 3 46 21 0.97 0.51 5.3 2.8 38.2 6.3 137 9 50 (36–71) 1.03 (0.79–1.38) 6.2 (4.7–7.8) 37.1 4.9 137 4
53 32 1.02 0.46 5.4 3.0 36.5 6.4 136 13 60 40 1.16 0.73 5.7 3.1 36.0 6.9 136 13 66 (45–86) 1.27 0.49 7.4 (5.2–9.1) 35.5 6.4 135 17 49 (39–65) 0.99 (0.75–1.30) 6.0 (4.5–7.3) 36.9 4.7 138 4 54 30 1.07 0.64 5.4 3.1 37.1 5.8 137 10 54 (40–73) 1.10 (0.78–1.47) 6.2 (4.7–7.6) 36.5 5.5 137 11
< 0.001 0.4 0.001 < 0.001 0.3 < 0.001 0.08 0.038 < 0.001 0.3 0.001 0.007 0.8 0.03 0.3 0.005 0.001 0.6 0.009 1 < 0.001 < 0.001 0.5 < 0.001 0.7 0.1 0.015 0.4 0.08 0.7
Diabetes mellitus (n = 350)
Heart failure (n = 123)
Thiazide diuretics (n = 154)
ACE-inhibitors (n = 481)
ARBs (n = 173)
In our study, the plasma urea and creatinine levels were statistically significantly higher in the summer as compared to the winter period of the year. But clinically this difference does not seem significant. This is probably due to compensatory mechanisms, which prevents further impairment of renal function. In our study, the sodium level was not increased in the summer compared to the winter period. This may also be explained by compensatory mechanisms, which prevent significant water depletion in these patients. Other explanation of these results is that patients enrolled in this study presumably had nearly enough or enough water consumption prior to hospitalization. In southern Israel, the elderly population receives information from many sources, including health care professionals about the necessity to drink enough in the hot summer period. And many of the patients probably followed these recommendations. Elevated blood hematocrit reflects the hemoconcentration associated with water depletion and global dehydration [4,8]. In this study, we did find mild statistically but not clinically significant differences in blood hematocrit concentration in the two groups of patients. Therefore, this data confirms that physiologic compensatory mechanisms for preserving adequate
Table 3 Incidence of acute kidney injury (according to RIFLE criteria) in patients hospitalized both in winter and in summer months. Acute kidney injury according to RIFLE criteria
Winter
Summer
P value
Risk (GFR decrease by 25%), n (%) Injury (GFR decrease by 50%), n (%) Failure (GFR decrease by 75%), n (%)
206 (18.6) 34 (3.1) 2 (0.2)
245 (22.1) 48 (4.3) 4 (0.4)
0.04 0.14 0.6
renal blood flow and the maintenance of normal renal function are enough for the prevention of the development of AKI. Sub-groups analysis in this study revealed that laboratory signs of impaired renal function were significantly more prominent in the summer compared to the winter period in the sub-groups of patients with CHF and DM. In these groups of patients, the influence of extensive fluid loss on renal function in the summer period compared to the winter may be more clinically significant. Therefore, these groups of patients required additional attention by medical providers in the summer months in order to prevent impairment of renal function and the possible development of AKI. In patients treated with ACE-I, ARBs and thiazides, we also observed statistically significant laboratory signs of impaired renal function in the summer as compared to the winter period. But the clinical significance of these findings is probably not important. These findings probably also reflect enough compensatory renal mechanisms in the older population of patients, however, this category of patients require attention by healthcare providers. In some elderly debilitated patients who live in hot and dry climates and are treated with these medications, the therapeutic approach must be individualized with a possible reduction of dosage or maybe even changing their medications to another class free from RAAS influence. The present study demonstrates significantly higher incidence of acute kidney injury in the early stage according to RIFLE classification in patients hospitalized in the summer compared to winter. In the later stages of AKI (injury, failure), we did not reveal any significant differences between two groups of patients. Explanation of this finding may be due to compensatory mechanisms, which preserve renal function and well-timed medical attention and early correction of the volume status. In this study, the reasons for hospitalization in patients who developed AKI in the summer and winter periods were different. The most common reasons for hospitalization in patients who
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developed AKI in the summer period were febrile diseases and sepsis, heart failure, diarrhoea and vomiting. In the winter, the most common reasons for admission of patients that developed AKI were heart failure, respiratory disease, predominantly COPD or asthma exacerbation, febrile diseases and sepsis. These differences might partially be associated with a seasonal distribution of morbidity causes. Therefore, timely attention, and if needed appropriate and aggressive rehydration in this population of patients is an important component of the management. In addition, particular attention must be paid to patients with heart failure, treated with drugs with potential nephrotoxic effect. The strengths of this study are that more than a thousand elderly consecutive patients were included in the study and seasonal changes in renal function have rarely been studied previously. The limitations of this study are that it was a retrospective study performed at one large medical centre. In conclusion, extensive fluids loss in a hot and dry climate in the summer months leads to mild impaired renal function in elderly patients. However, this influence is not clinically significant probably due to compensatory mechanisms for the preservation of renal function. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. Acknowledgments We thank Professor Mark Clarfield for his insightful comments. References [1] Meehl GA. StockerTF. Global Climate Projections (Sec. 10.ES). Mean Temperature in IPCC AR4 WG1; (Chap. 10); 2007. [2] Juhlin T, Bjo¨rkman S, Ho¨glund P. Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors. Eur J Heart Fail 2005;7(6):1049–56. [3] Ferry M. Strategies for ensuring good hydration in the elderly. Nutr Rev 2005;63(6 Pt 2):S22–9. [4] Worfolk JB. Heat waves: their impact on the health of elders. Geriatr Nurs 2014;21(2):70–7. [5] Warren JL, Bacon E, Harris T, McBean AM, Foley DJ, Phillips C. The burden and outcomes associated with dehydration among US elderly. Am J Public Health 2000;84:1265–9. [6] Kleiner SM. Water: an essential but overlooked nutrient. J Am Diet Assoc 1999;99:200–6. [7] Coca SG. Acute kidney injury in elderly persons. Am J Kidney Dis 2010;56:122–31. [8] Davidhizar R, Dunn CL, Hart AN. A review of the literature on how important water is to the world’s elderly population. Int Nurs Rev 2004;51(3):159–66.
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