Original Report: Patient-Oriented, Translational Research
Validation of Surrogates of Urine Osmolality in Population StudiesYouhanna S.a · Bankir L.b, c · Jungers P.d · Porteous D.e · Polasek O.f · Bochud M.g · Hayward C.h · Devuyst O.a
aInstitute of Physiology, University of Zurich, Zurich, Switzerland; bINSERM UMRS 1138, Centre de Recherche des Cordeliers, Paris, France; cUniversité Pierre et Marie Curie, Paris, France; dService de Néphrologie, Hôpital Necker, Paris, France; eCentre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland; fDepartment of Public Health, University of Split, Split, Croatia; gInstitute of Social and Preventive Medicine, Lausanne University Hospital Center, Lausanne, Switzerland; hMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, Scotland
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Article / Publication Details
Background: The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (Uosm), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. Methods: We analyzed 2 possible surrogates of Uosm in 4 large population-based cohorts (total n = 4,247) and in patients with chronic kidney disease (CKD, n = 146). An estimated Uosm (eUosm) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured Uosm (mUosm). Results: eUosm is an excellent surrogate of mUosm, with a highly significant linear relationship and values within 5% of mUosm (r = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eUosm and mUosm with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mUosm is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mUosm in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mUosm. Conclusion: The eUosm is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function.
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- Torres VE: Vasopressin in chronic kidney disease: an elephant in the room? Kidney Int 2009;76:925-928.
- Bolignano D, Zoccali C: Vasopressin beyond water: implications for renal diseases. Curr Opin Nephrol Hypertens 2010;19:499-504.
- Cirillo M: Determinants of kidney dysfunction: is vasopressin a new player in the arena? Kidney Int 2010;77:5-6.
- Devuyst O, Torres VE: Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease. Curr Opin Nephrol Hypertens 2013;22:459-470.
- Greenberg A, Verbalis JG: Vasopressin receptor antagonists. Kidney Int 2006;69:2124-2130.
- Decaux G, Soupart A, Vassart G: Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet 2008;371:1624-1632.
- Morgenthaler NG: Copeptin: a biomarker of cardiovascular and renal function. Congest Heart Fail 2010;16(suppl 1):S37-S44.
- Roussel R, Fezeu L, Marre M, Velho G, Fumeron F, Jungers P, Lantieri O, Balkau B, Bouby N, Bankir L, Bichet DG: Comparison between copeptin and vasopressin in a population from the community and in people with chronic kidney disease. J Clin Endocrinol Metab 2014;99:4656-4663.
- Bankir L, Bouby N, Ritz E: Vasopressin: a novel target for the prevention and retardation of kidney disease? Nat Rev Nephrol 2013;9:223-239.
- Bardoux P, Bichet DG, Martin H, Gallois Y, Marre M, Arthus MF, Lonergan M, Ruel N, Bouby N, Bankir L: Vasopressin increases urinary albumin excretion in rats and humans: involvement of V2 receptors and the renin-angiotensin system. Nephrol Dial Transplant 2003;18:497-506.
- Meijer E, Bakker SJ, Halbesma N, de Jong PE, Struck J, Gansevoort RT: Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. Kidney Int 2010;77:29-36.
- Enhorning S, Struck J, Wirfalt E, Hedblad B, Morgenthaler NG, Melander O: Plasma copeptin, a unifying factor behind the metabolic syndrome. J Clin Endocrinol Metab 2011;96:E1065-E1072.
- Roussel R, Fezeu L, Bouby N, Balkau B, Lantieri O, Alhenc-Gelas F, Marre M, Bankir L: Low water intake and risk for new-onset hyperglycemia. Diabetes Care 2011;34:2551-2554.
- Ho TA, Godefroid N, Gruzon D, Haymann JP, Marechal C, Wang X, Serra A, Pirson Y, Devuyst O: Autosomal dominant polycystic kidney disease is associated with central and nephrogenic defects in osmoregulation. Kidney Int 2012;82:1121-1129.
- Schoen T, Blum J, Paccaud F, Burnier M, Bochud M, Conen D: Factors associated with 24-hour urinary volume: the Swiss salt survey. BMC Nephrol 2013;14:246.
- Velho G, Bouby N, Hadjadj S, Matallah N, Mohammedi K, Fumeron F, Potier L, Bellili-Munoz N, Taveau C, Alhenc-Gelas F, Bankir L, Marre M, Roussel R: Plasma copeptin and renal outcomes in patients with type 2 diabetes and albuminuria. Diabetes Care 2013;36:3639-3645.
- Ong AC, Devuyst O, Knebelmann B, Walz G: Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet 2015;385:1993-2002.
- Ponte B, Pruijm M, Ackermann D, Vuistiner P, Guessous I, Ehret G, Alwan H, Youhanna S, Paccaud F, Mohaupt M, Pechere-Bertschi A, Vogt B, Burnier M, Martin PY, Devuyst O, Bochud M: Copeptin is associated with kidney length, renal function, and prevalence of simple cysts in a population-based study. J Am Soc Nephrol 2015;26:1415-1425.
- Roussel R, Matallah N, Bouby N, El Boustany R, Potier L, Fumeron F, Mohammedi K, Balkau B, Marre M, Bankir L, Velho G: Plasma copeptin and decline in renal function in a Cohort from the Community: the Prospective D.E.S.I.R. Study. Am J Nephrol 2015;42:107-114.
- Pruijm M, Ponte B, Ackermann D, Paccaud F, Guessous I, Ehret G, Pechere-Bertschi A, Vogt B, Mohaupt MG, Martin PY, Youhanna SC, Nagele N, Vollenweider P, Waeber G, Burnier M, Devuyst O, Bochud M: Associations of urinary uromodulin with clinical characteristics and markers of tubular function in the general population. Clin J Am Soc Nephrol 2016;11:70-80.
- Roussel R, El Boustany R, Bouby N, Potier L, Fumeron F, Mohammedi K, Balkau B, Tichet J, Bankir L, Marre M, Velho G: Plasma copeptin, AVP gene variants, and incidence of type 2 diabetes in a cohort from the community. J Clin Endocrinol Metab 2016;101:2432-2439.
- Bouby N, Bachmann S, Bichet D, Bankir L: Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat. Am J Physiol 1990;258(4 pt 2):F973-F979.
- Ahrabi AK, Terryn S, Valenti G, Caron N, Serradeil-Le Gal C, Raufaste D, Nielsen S, Horie S, Verbavatz JM, Devuyst O: PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice. J Am Soc Nephrol 2007;18:1740-1753.
- Perico N, Zoja C, Corna D, Rottoli D, Gaspari F, Haskell L, Remuzzi G: V1/V2 Vasopressin receptor antagonism potentiates the renoprotection of renin-angiotensin system inhibition in rats with renal mass reduction. Kidney Int 2009;76:960-967.
- Koshimizu TA, Nakamura K, Egashira N, Hiroyama M, Nonoguchi H, Tanoue A: Vasopressin V1a and V1b receptors: from molecules to physiological systems. Physiol Rev 2012;92:1813-1864.
- Taveau C, Chollet C, Waeckel L, Desposito D, Bichet DG, Arthus MF, Magnan C, Philippe E, Paradis V, Foufelle F, Hainault I, Enhorning S, Velho G, Roussel R, Bankir L, Melander O, Bouby N: Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats. Diabetologia 2015;58:1081-1090.
- Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS: Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012;367:2407-2418.
- Clark WF, Sontrop JM, Macnab JJ, Suri RS, Moist L, Salvadori M, Garg AX: Urine volume and change in estimated GFR in a community-based cohort study. Clin J Am Soc Nephrol 2011;6:2634-2641.
- 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.
- Bankir L, Perucca J, Weinberger MH: Ethnic differences in urine concentration: possible relationship to blood pressure. Clin J Am Soc Nephrol 2007;2:304-312.
- Perucca J, Bouby N, Valeix P, Bankir L: Sex difference in urine concentration across differing ages, sodium intake, and level of kidney disease. Am J Physiol Regul Integr Comp Physiol 2007;292:R700-R705.
- Zittema D, van den Berg E, Meijer E, Boertien WE, Muller Kobold AC, Franssen CF, de Jong PE, Bakker SJ, Navis G, Gansevoort RT: Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients. Clin J Am Soc Nephrol 2014;9:1553-1562.
- Smith BH, Campbell H, Blackwood D, Connell J, Connor M, Deary IJ, Dominiczak AF, Fitzpatrick B, Ford I, Jackson C, Haddow G, Kerr S, Lindsay R, McGilchrist M, Morton R, Murray G, Palmer CN, Pell JP, Ralston SH, St Clair D, Sullivan F, Watt G, Wolf R, Wright A, Porteous D, Morris AD: Generation Scotland: the Scottish Family Health Study; a new resource for researching genes and heritability. BMC Med Genet 2006;7:74.
- Olden M, Corre T, Hayward C, Toniolo D, Ulivi S, Gasparini P, Pistis G, Hwang SJ, Bergmann S, Campbell H, Cocca M, Gandin I, Girotto G, Glaudemans B, Hastie ND, Loffing J, Polasek O, Rampoldi L, Rudan I, Sala C, Traglia M, Vollenweider P, Vuckovic D, Youhanna S, Weber J, Wright AF, Kutalik Z, Bochud M, Fox CS, Devuyst O: Common variants in UMOD associate with urinary uromodulin levels: a meta-analysis. J Am Soc Nephrol 2014;25:1869-1882.
- Polasek O, Marusic A, Rotim K, Hayward C, Vitart V, Huffman J, Campbell S, Jankovic S, Boban M, Biloglav Z, Kolcic I, Krzelj V, Terzic J, Matec L, Tometic G, Nonkovic D, Nincevic J, Pehlic M, Zedelj J, Velagic V, Juricic D, Kirac I, Belak Kovacevic S, Wright AF, Campbell H, Rudan I: Genome-wide association study of anthropometric traits in Korcula Island, Croatia. Croat Med J 2009;50:7-16.
- Pruijm M, Ponte B, Ackermann D, Vuistiner P, Paccaud F, Guessous I, Ehret G, Eisenberger U, Mohaupt M, Burnier M, Martin PY, Bochud M: Heritability, determinants and reference values of renal length: a family-based population study. Eur Radiol 2013;23:2899-2905.
- Ponte B, Pruijm M, Ackermann D, Vuistiner P, Eisenberger U, Guessous I, Rousson V, Mohaupt MG, Alwan H, Ehret G, Pechere-Bertschi A, Paccaud F, Staessen JA, Vogt B, Burnier M, Martin PY, Bochud M: Reference values and factors associated with renal resistive index in a family-based population study. Hypertension 2014;63:136-142.
- Jungers P, Hannedouche T, Itakura Y, Albouze G, Descamps-Latscha B, Man NK: Progression rate to end-stage renal failure in non-diabetic kidney diseases: a multivariate analysis of determinant factors. Nephrol Dial Transplant 1995;10:1353-1360.
- van den Brand JA, van Boekel GA, Willems HL, Kiemeney LA, den Heijer M, Wetzels JF: Introduction of the CKD-EPI equation to estimate glomerular filtration rate in a Caucasian population. Nephrol Dial Transplant 2011;26:3176-3181.
- Sweeney TE, Beuchat CA: Limitations of methods of osmometry: measuring the osmolality of biological fluids. Am J Physiol 1993;264(3 pt 2):R469-R480.
- Vallon V, Komers R: Pathophysiology of the diabetic kidney. Compr Physiol 2011;1:1175-1232.
- Perrier E, Demazieres A, Girard N, Pross N, Osbild D, Metzger D, Guelinckx I, Klein A: Circadian variation and responsiveness of hydration biomarkers to changes in daily water intake. Eur J Appl Physiol 2013;113:2143-2151.
- Perrier ET, Buendia-Jimenez I, Vecchio M, Armstrong LE, Tack I, Klein A: Twenty-four-hour urine osmolality as a physiological index of adequate water intake. Dis Markers 2015;2015:231063.
- Bouby N, Ahloulay M, Nsegbe E, Dechaux M, Schmitt F, Bankir L: Vasopressin increases glomerular filtration rate in conscious rats through its antidiuretic action. J Am Soc Nephrol 1996;7:842-851.
- Bottin JH, Lemetais G, Poupin M, Jimenez L, Perrier ET: Equivalence of afternoon spot and 24-h urinary hydration biomarkers in free-living healthy adults. Eur J Clin Nutr 2016;70:904-907.
- Souza AC, Zatz R, de Oliveira RB, Santinho MA, Ribalta M, Romao JE Jr, Elias RM: Is urinary density an adequate predictor of urinary osmolality? BMC Nephrol 2015;16:46.
- Leech S, Penney MD: Correlation of specific gravity and osmolality of urine in neonates and adults. Arch Dis Child 1987;62:671-673.
- Berl T: Impact of solute intake on urine flow and water excretion. J Am Soc Nephrol 2008;19:1076-1078.
- Zerbe RL, Miller JZ, Robertson GL: The reproducibility and heritability of individual differences in osmoregulatory function in normal human subjects. J Lab Clin Med 1991;117:51-59.
- Share L, Crofton JT, Ouchi Y: Vasopressin: sexual dimorphism in secretion, cardiovascular actions and hypertension. Am J Med Sci 1988;295:314-319.
- Perinpam M, Ware EB, Smith JA, Turner ST, Kardia SL, Lieske JC: Key influence of sex on urine volume and osmolality. Biol Sex Differ 2016;7:12.
- Cowley AW Jr, Skelton MM, Velasquez MT: Sex differences in the endocrine predictors of essential hypertension. Vasopressin versus renin. Hypertension 1985;7(3 pt 2):I151-I160.
- Chun TY, Bankir L, Eckert GJ, Bichet DG, Saha C, Zaidi SA, Wagner MA, Pratt JH: Ethnic differences in renal responses to furosemide. Hypertension 2008;52:241-248.
- Katz AI, Massry S, Agmon J, Toor M: Concentration and dilution of urine in permanent inhabitants of hot regions. Isr J Med Sci 1965;1:968-978.
- Johnson RH, Corbett JL, Wilkinson RH: Desert journeys by Bedouin: sweating and concentration of urine during travel by camel and on foot. Nature 1968;219:953-954.
- Berlyne GM, Yagil R, Goodwin S, Morag M: Drinking habits and urine concentration of man in southern Israel. Isr J Med Sci 1976;12:765-769.
- Taylor GO, Oyediran AB, Saliu I: Effects of haemoglobin electrophoretic pattern and seasonal changes on urine concentration in young adult Nigerian males. Afr J Med Med Sci 1978;7:201-205.
- Kristal-Boneh E, Glusman JG, Chaemovitz C, Cassuto Y: Improved thermoregulation caused by forced water intake in human desert dwellers. Eur J Appl Physiol Occup Physiol 1988;57:220-224.
- Bankir L, Bochud M, Maillard M, Bovet P, Gabriel A, Burnier M: Nighttime blood pressure and nocturnal dipping are associated with daytime urinary sodium excretion in African subjects. Hypertension 2008;51:891-898.
- Kimura G, Dohi Y, Fukuda M: Salt sensitivity and circadian rhythm of blood pressure: the keys to connect CKD with cardiovascular events. Hypertens Res 2010;33:515-520.
- Guerrot D, Hansel B, Perucca J, Roussel R, Bouby N, Girerd X, Bankir L: Reduced insulin secretion and nocturnal dipping of blood pressure are associated with a disturbed circadian pattern of urine excretion in metabolic syndrome. J Clin Endocrinol Metab 2011;96:E929-E933.
- Burnier M, Coltamai L, Maillard M, Bochud M: Renal sodium handling and nighttime blood pressure. Semin Nephrol 2007;27:565-571.
- Fezeu L, Bankir L, Hansel B, Guerrot D: Differential circadian pattern of water and Na excretion rates in the metabolic syndrome. Chronobiol Int 2014;31:861-867.
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