Original Article
Brief Report
Defective Urinary Concentrating Ability Due to a Complete Deficiency of Aquaporin-1
N Engl J Med 2001; 345:175-179July 19, 2001
- Article
Aquaporin-1, the archetypal water-channel protein,1 was initially identified in red cells and renal proximal tubular epithelium.2 The gene for aquaporin-1 (AQP1) on chromosome 7 colocalizes with the Colton blood-group antigen,3,4 and the Colton blood-group antigen polymorphism was identified as a substitution of a single amino acid in an extracellular domain of aquaporin-1.5 The International Blood Group Reference Laboratory has confirmed the existence of only six kindreds who lack the Colton blood group. Members of three of these kindreds were found to be homozygous for different mutations in the AQP1 gene, and their red-cell membranes had a complete absence or a marked reduction of aquaporin-1.6,7 Surprisingly, aquaporin-1 deficiency had no obvious clinical consequence in these people.
Since aquaporin-1 is abundant in renal proximal tubular epithelium, the thin descending limb of the loop of Henle, and the descending vasa recta of the kidney,8,9 we hypothesized that people with a deficiency of aquaporin-1 have defects in water homeostasis in the kidneys that can be identified only under conditions of stress. We studied two unrelated subjects with a deficiency of aquaporin-1 and found that they had impaired urinary concentrating ability, suggesting that aquaporin-1 has a physiologic role in renal function.
Case Reports
Subject 1
Subject 1 was a 37-year-old woman who had no active medical problems but was homozygous for a deletion of exon 1 of the AQP1 gene.6 In 1980 she had a miscarriage during the first trimester of her first pregnancy. During her second pregnancy, routine testing demonstrated the presence of antibodies against the Colton blood group. She gave birth to a healthy baby at 34 weeks of gestation, but the infant subsequently required three blood transfusions. In 1987, a third pregnancy was complicated by marked hemolysis in the fetus, which necessitated five intrauterine transfusions. After delivery at 31 weeks of gestation, the baby required two transfusions.
Subject 1 had occasional edema of the lower legs, for which she infrequently took furosemide or indapamide; neither diuretic had been taken within the previous month at the time of our study. She drank three to four liters of fluid per day. The results of a physical examination were normal, except for trace nonpitting edema of the lower legs.
Subject 2
Subject 2 was a 57-year-old woman who was homozygous for a frame-shift mutation in exon 1 of the AQP1 gene.6 Her medical history was unremarkable. She had had four uncomplicated pregnancies. Antibodies against the Colton blood group were detected on routine blood screening. She drank two liters of fluid per day and urinated two to three times daily, without nocturia. The results of a physical examination were normal.
Methods
Subjects were evaluated in the Johns Hopkins General Clinical Research Center. Both subjects provided written informed consent. Blood chemical and hematologic studies and urinalyses were performed; the urine of Subject 1 was screened for diuretics. During a base-line period of 24 hours, vital signs, weight, serum and urine osmolality, and plasma vasopressin levels were measured at regular intervals, and fluid intake was recorded. The daily urine volume and creatinine clearance were measured in a 24-hour collection, and the glomerular filtration rate was measured with [99mTc]diethylenetriamine pentaacetic acid (DTPA). Renal and bladder ultrasonography was performed.
Water deprivation was initiated at 9 a.m. on the day after the base-line evaluation. After 21 to 23 hours of water deprivation, subjects received 1 μg of desmopressin subcutaneously, and urine osmolality was determined hourly for 2 hours. Subject 2 then received intravenous desmopressin (30 mU per kilogram of body weight per hour) and 3 percent sodium chloride (10 ml per minute). Serum and urine sodium levels and osmolality were measured every 30 minutes. Subject 1 received hypertonic saline after 15 hours of water deprivation in a second study but did not receive desmopressin because of a possible allergic rash during the first study. Safety end points, including changes in blood chemical values, development of symptoms, and duration of the study, were predefined; studies were discontinued when established safety end points were met.
After three days of ad libitum intake of fluids, lithium clearance, maximal rate of urine flow, and free-water clearance were measured as described.10 On the morning after an evening dose of lithium chloride (300 mg in the case of Subject 1 and 600 mg in the case of Subject 2), the subjects drank 20 ml of tap water per kilogram over a period of 30 minutes. The hourly urine output during the four-hour study was replaced with an equal amount of water. Lithium clearance was calculated according to the following equation: lithium clearance = (ULi ÷ PLi)V̇, where ULi is the lithium level of the pooled urine sample, PLi the plasma lithium level, and V̇ the urinary flow rate; the serum lithium level was calculated according to the following formula: (P1 – P2) ÷ (2.3 × log [P1 ÷ P2]), where P1 and P2 are the initial and final serum lithium levels, respectively. The steady-state values of maximal urinary flow rate and free-water clearance are reported.
Osmolal clearance during infusion of hypertonic saline was calculated according to the following equation: osmolal clearance = (Uosm ÷ Posm)V̇, where Uosm and Posm are the urine and plasma osmolality, respectively. Free-water clearance was calculated according to the following equation: free-water clearance = V̇(1 – [Uosm ÷ Posm]); negative values represent free-water reabsorption.
Laboratory studies were performed in Johns Hopkins clinical laboratories. Arginine vasopressin, renin, and aldosterone levels were measured by radioimmunoassay (Quest Diagnostic Laboratories, Baltimore). Immunoblots of red-cell membranes and urine sediment were performed as described previously11 and probed with antibodies against aquaporin-112 or aquaporin-2.13
Results
Blood chemical and hematologic values, results of urinalyses, creatinine clearance rates, glomerular filtration rates, and kidney and bladder sizes were normal in both subjects. Ad libitum intake of fluid was 1.9 liters per day in Subject 1 and 1.6 liters per day in Subject 2. The urine volume was 1.5 liters per 24 hours in Subject 1 and 1.2 liters per 24 hours in Subject 2.
After water deprivation, Subject 1 lost 2.7 kg (3.3 percent of body weight) and Subject 2 lost 2.0 kg (2.7 percent of body weight). Serum osmolality increased from 280 mOsm per kilogram to 287 mOsm per kilogram after water deprivation in Subject 1 and from 288 mOsm per kilogram to 294 mOsm per kilogram in Subject 2 (Figure 1Figure 1
Water Deprivation in Two Subjects with a Complete Deficiency of Aquaporin-1.). Correspondingly, vasopressin levels increased from 1.5 pg per milliliter to 4.7 pg per milliliter in Subject 1 and from 1.6 pg per milliliter to 5.3 pg per milliliter in Subject 2; these increases were within the range reported for normal persons.14 Despite these changes, urine osmolality failed to increase normally after water deprivation, reaching only 431 mOsm per kilogram in Subject 1 and 460 mOsm per kilogram in Subject 2. Urine osmolality was not increased in either subject by the administration of desmopressin.After water loading, urine became maximally dilute (less than 80 mOsm per kilogram) in both subjects (Table 1Table 1
Maximal Free-Water Diuresis and Lithium Clearance.). Maximal urinary flow rate and the ratio of maximal urinary flow rate to creatinine clearance were within the range reported for normal persons.15,16 Both the clearance and fractional excretion of lithium10,17,18 were normal in Subject 2 but could not be calculated in Subject 1 because of undetectable serum levels of lithium.During hypertonic saline loading, free-water reabsorption increased in both subjects as solute excretion (osmolal clearance) increased (Figure 2Figure 2
Free-Water Reabsorption Plotted against Osmolal Clearance in the Two Subjects and Three Historical Controls.). However, as compared with normal controls,19 free-water reabsorption was reduced at all values of osmolal clearance in the two subjects.Immunoblots confirmed the absence of aquaporin-1 from red-cell membranes and urine sediment6 and the presence of aquaporin-2 in the urine sediment of both subjects (data not shown).
Discussion
The pathophysiology associated with the aquaporin family of water-channel proteins includes mutations in some patients with nephrogenic diabetes insipidus (AQP2)20 and cataracts (AQP0)21 and abnormal transport of aquaporin-5 in patients with Sjögren's syndrome.22,23 We found that aquaporin-1 is essential for maximal urinary concentrating ability.
Although the two subjects with a complete deficiency of aquaporin-1 did not have polyuria, both had an impaired ability to concentrate their urine maximally when deprived of water. Despite normal increases in serum osmolality and plasma vasopressin levels in both subjects, urine osmolality after water deprivation was in the range reported for patients with partial nephrogenic diabetes insipidus. At vasopressin levels of 4 to 5 pg per milliliter, urine osmolality reaches 775 to 1200 mOsm per kilogram in normal persons,24 as compared with a maximal urine osmolality of approximately 460 mOsm per kilogram in our subjects. Unlike patients with central or nephrogenic diabetes insipidus,25 our subjects had aquaporin-2 in their urine sediment. The low daily fluid intake and urine output exclude the possibility that urine concentration was impaired because of the medullary washout that occurs in patients with primary polydipsia.24
Aquaporin-1 is normally abundant in renal proximal tubular epithelium,8 but our data suggest that impaired water reabsorption due to the absence of aquaporin-1 does not account for the impaired urinary concentrating ability in our subjects. During water diuresis, the maximal urinary flow rate and the fractional excretion of water, as well as lithium clearance, are indexes of the reabsorption of fluid in the proximal tubule.10,15,16,18 These measurements were normal in our subjects, who also had normal glomerular filtration rates. The preservation of glomerular filtration also suggests that reabsorption of fluid in the proximal tubule was not affected; if reabsorption were decreased, increased delivery of chloride to the macula densa would secondarily decrease the glomerular filtration rate through tubuloglomerular feedback. Our findings in subjects with a complete deficiency of aquaporin-1 contrast with observations in mice with a complete deficiency of aquaporin-1, since such mice have polyuria, severe dehydration in response to fluid deprivation, defects in the reabsorption of fluid in the proximal tubule, and a reduced glomerular filtration rate.26,27 This suggests that people with a complete deficiency of aquaporin-1 have unidentified mechanisms of fluid reabsorption in the proximal tubules that compensate for the deficiency of aquaporin-1.
Urinary concentration depends on normal function of the countercurrent multiplier, which requires both active transport of sodium chloride in the thick ascending limb of the loop of Henle and osmotic equilibration of water across the epithelium of the descending limb into the interstitium. The latter process is almost certainly mediated by aquaporin-1. Two measurements of the reabsorption of sodium chloride in the distal nephron that were made during water diuresis, the rate of formation of free water (the ratio of free-water clearance to maximal urinary flow rate, 77 percent in Subject 1 and 86 percent in Subject 2) and the difference between lithium clearance and sodium clearance (28 ml per minute in Subject 2), were normal.17,28,29 This suggests that reabsorption of sodium chloride in the distal nephron is intact in our subjects and, therefore, does not contribute to the defect in urinary concentrating ability.
The calculated free-water reabsorption represents the rate of osmotically driven transfer of solute-free water out of the medullary collecting duct. When measured during water deprivation at increased osmolar loads, free-water reabsorption depends on the reabsorption of sodium chloride in the distal nephron, as well as the maintenance of a hypertonic interstitial gradient and an intact response of the collecting duct to vasopressin. In our subjects, free-water reabsorption during hypertonic saline loading increased with increasing solute clearance; this increase was largely parallel to that reported for normal persons but at a lower level (Figure 2). Although the range of solute clearance was somewhat narrow, the results suggest that the absence of aquaporin-1 in our subjects impairs the small fraction of free-water reabsorption required to produce maximally concentrated urine at the papilla.
In mice with a complete deficiency of aquaporin-1, the absence of aquaporin-1 in the thin descending limb of the loop of Henle impairs water transfer into the interstitium and limits the maximal urinary concentrating ability. In addition, aquaporin-1–mediated osmotic transfer of water from the descending vasa recta into the interstitium reduces blood flow into the papillary tip and prevents washout of solute in that region.30 The absence of aquaporin-1 may consequently increase both medullary blood flow and papillary washout, resulting in decreased maximal urinary concentrating ability.
Our observations show an important physiologic role for aquaporin-1 in renal concentrating ability and provide an example of an impairment in maximal urinary concentration arising from a molecular defect in transport in the thin descending limb of the loop of Henle, the descending vasa recta, or both.
Supported by grants from the National Institutes of Health and the Cystic Fibrosis Foundation (to Drs. King and Agre) and by a General Clinical Research Center Grant (MO1 RR00052) from the National Center for Research Resources of the National Institutes of Health.
We are indebted to Drs. Melanie Bonhivers (Paris) and Jacques Carrières (Aurillac, France) as well as the staff of Osler 5 and the General Clinical Research Center (Baltimore) for assistance with these studies; to Drs. Jerry Krishnan and Greg Diette for assistance with statistical analysis; and to Dr. Mark Knepper (Bethesda, Md.) for a critical review of the manuscript.
Source Information
From the Divisions of Pulmonary and Critical Care Medicine (L.S.K.) and Nephrology (M.C.) and the Departments of Medicine (P.A.) and Biological Chemistry (L.S.K., P.A.), Johns Hopkins School of Medicine, Baltimore; the Penn Center for Molecular Kidney Diseases, University of Pennsylvania School of Medicine, Philadelphia (P.C.F.); and INSERM Unité 76, Paris (J.-P.C.).
Address reprint requests to Dr. King at the Division of Pulmonary and Critical Care Medicine, 600 N. Wolfe St., Blalock 910, Baltimore, MD 21287, or at lsking@welch.jhu.edu.
- References
References
1
Preston GM ,Carroll TP ,Guggino WB ,Agre P . Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 1992;256:385-387
CrossRef | Web of Science | Medline2
Denker BM ,Smith BL ,Kuhajda FP ,Agre P . Identification, purification, and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules. J Biol Chem 1988;263:15634-15642
Web of Science | Medline3
Moon C ,Preston GM ,Griffin CA ,Jabs EW ,Agre P . The human aquaporin-CHIP gene: structure, organization, and chromosomal localization. J Biol Chem 1993;268:15772-15778
Web of Science | Medline4
Zelinski T ,Kaita H ,Gilson T ,Coghlan G ,Philipps S ,Lewis M . Linkage between the Colton blood group locus and ASSP11 on chromosome 7. Genomics 1990;6:623-625
CrossRef | Web of Science | Medline5
Smith BL ,Preston GM ,Spring FA ,Anstee DJ ,Agre P . Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton blood group antigens. J Clin Invest 1994;94:1043-1049
CrossRef | Web of Science | Medline6
Preston GM ,Smith BL ,Zeidel ML ,Moulds JJ ,Agre P . Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels. Science 1994;265:1585-1587
CrossRef | Web of Science | Medline7
Mathai JC ,Mori S ,Smith BL , et al. Functional analysis of aquaporin-1 deficient red cells: the Colton-null phenotype. J Biol Chem 1996;271:1309-1313
CrossRef | Web of Science | Medline8
Nielsen S ,Smith BL ,Christensen EI ,Knepper MA ,Agre P . CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. J Cell Biol 1993;120:371-383
CrossRef | Web of Science | Medline9
Nielsen S ,Pallone T ,Smith BL ,Christensen EI ,Agre P ,Maunsbach AB . Aquaporin-1 water channels in short and long loop descending thin limbs and in descending vasa recta in rat kidney. Am J Physiol 1995;268:F1023-F1037
Web of Science | Medline10
Rombola G ,Colussi G ,De Ferrari ME ,Surian M ,Malberti F ,Minetti L . Clinical evaluation of segmental tubular reabsorption of sodium and fluid in man: lithium vs. free water clearances. Nephrol Dial Transplant 1987;2:212-218
Medline11
King LS ,Nielsen S ,Agre P . Aquaporin-1 water channel protein in lung: ontogeny, steroid-induced expression, and distribution in rat. J Clin Invest 1996;97:2183-2191
CrossRef | Web of Science | Medline12
Smith BL ,Agre P . Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins. J Biol Chem 1991;266:6407-6415
Web of Science | Medline13
DiGiovanni SR ,Nielsen S ,Christensen EI ,Knepper MA . Regulation of collecting duct water channel expression by vasopressin in Brattleboro rat. Proc Natl Acad Sci U S A 1994;91:8984-8988
CrossRef | Web of Science | Medline14
Robertson GL . Vasopressin in osmotic regulation in man. Annu Rev Med 1974;25:315-322
CrossRef | Web of Science | Medline15
Kleeman CR ,Epstein FH ,White C . The effect of variations in solute excretion and glomerular filtration on water diuresis. J Clin Invest 1956;35:749-756
CrossRef | Web of Science | Medline16
Levinsky NG, Lieberthal W. Clearance techniques. In: Windhager EE, ed. Handbook of physiology: a critical, comprehensive presentation of physiological knowledge and concepts. Section 8. Renal physiology. Vol. 1. New York: Oxford University Press, 1992:227-47.
17
Thomsen K . Lithium clearance as a measure of sodium and water delivery from the proximal tubules. Kidney Int Suppl 1990;28:S10-S16
Medline18
Thomsen K . Lithium clearance: a new method for determining proximal and distal tubular reabsorption of sodium and water. Nephron 1984;37:217-223
CrossRef | Medline19
Hatch FE ,Culbertson JW ,Diggs LW . The nature of the renal concentrating defect in sickle cell disease. J Clin Invest 1967;46:336-345
CrossRef | Web of Science | Medline20
Deen PMT ,Verdijk MAJ ,Knoers NVAM , et al. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science 1994;264:92-95
CrossRef | Web of Science | Medline21
Berry V ,Francis P ,Kaushal S ,Moore A ,Bhattacharya S . Missense mutations in MIP underlie autosomal dominant `polymorphic' and lamellar cataracts linked to 12q. Nat Genet 2000;25:15-17
CrossRef | Web of Science | Medline22
Tsubota K ,Hirai S ,King LS ,Agre P ,Ishida N . Defective cellular trafficking of lacrimal gland aquaporin-5 in Sjögren's syndrome. Lancet 2001;357:688-689
CrossRef | Web of Science | Medline23
Steinfeld S ,Cogan E ,King LS ,Agre P ,Kiss R ,Delporte C . Abnormal distribution of aquaporin-5 water channel protein in salivary glands from Sjögren's syndrome patients. Lab Invest 2001;81:143-148
CrossRef | Web of Science | Medline24
Robertson GL . Differential diagnosis of polyuria. Annu Rev Med 1988;39:425-442
CrossRef | Web of Science | Medline25
Kanno K ,Sasaki S ,Hirata Y , et al. Urinary excretion of aquaporin-2 in subjects with diabetes insipidus. N Engl J Med 1995;332:1540-1545
Full Text | Web of Science | Medline26
Ma T ,Yang B ,Gillespie A ,Carlson EJ ,Epstein CJ ,Verkman AS . Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem 1998;273:4296-4299
CrossRef | Web of Science | Medline27
Schnermann J ,Chou C-L ,Ma T ,Traynor T ,Knepper MA ,Verkman AS . Defective proximal tubular fluid reabsorption in transgenic aquaporin-1 null mice. Proc Natl Acad Sci U S A 1998;95:9660-9664
CrossRef | Web of Science | Medline28
Steinmetz PR ,Eisinger RP ,Gombos EA ,Chasis H ,Baldwin DS . Excretion of free water and solute during maximal water diuresis in normal and hypertensive subjects. J Lab Clin Med 1964;64:238-256
Medline29
Atherton JC ,Hussain R ,Jones R . Assessment of proximal and distal nephron water and sodium reabsorption in man. Renal Physiol 1986;9:74-7430
Pallone TL ,Edwards A ,Ma T ,Silldorff EP ,Verkman AS . Requirement of aquaporin-1 for NaCl-driven water transport across descending vasa recta. J Clin Invest 2000;105:215-222
CrossRef | Web of Science | Medline
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J. H. Robben, N. V. A. M. Knoers, P. M. T. Deen. (2006) Aquaporines in de nier en hun rol in nefrogene diabetes insipidus. Tijdschrift voor kindergeneeskunde 74:2, 79-83
CrossRef29
A S Verkman. (2006) Aquaporins in endothelia. Kidney International 69:7, 1120-1123
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CrossRef33
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David Kozono, Masato Yasui, Landon S. King, Peter Agre. (2002) Aquaporin water channels: atomic structure molecular dynamics meet clinical medicine. Journal of Clinical Investigation 109:11, 1395-1399
CrossRef49
Rachid Sougrat, Maryse Morand, Catherine Gondran, Patrick Barre, R. Gobin, Frediric Bonte, Mara Dumas, Jean-Marc Verbavatz. (2002) Functional Expression of AQP3 in Human Skin Epidermis and Reconstructed Epidermis. Journal of Investigative Dermatology 118:4, 678-685
CrossRef50
Tim Cheetham, Peter H. Baylis. (2002) Diabetes Insipidus in Children. Pediatric Drugs 4:12, 785-796
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