Aquaporin-2 (AQP-2) is known to be expressed in the renal collecting duct cells and participates in urinary concentration in response to arginine vasopressin (AVP). The present study was undertaken to determine whether progression of renal dysfunction affects urinary excretion of AQP-2 in diabetic nephropathy. The study was composed of 8 control subjects and 14 patients with type 2 diabetes classified into two groups according to serum creatinine level (cut-off point; 1.5 mg/dl). After an 8-hour water deprivation, both urinary osmolality (Uosm) and urinary excretion of AQP-2 significantly decreased in the diabetic patients with chronic renal failure as compared to the control subjects (p < 0.0001, p < 0.05, respectively). After a water load (10 ml/kg), no differences were found in plasma osmolality (Posm), AVP levels and Uosm, whereas urinary excretion of AQP-2 significantly decreased in the patients with chronic renal failure as compared to the control subjects (p < 0.05). These results indicate that the decreased urinary excretion of AQP-2 in diabetic nephropathy is due to the impaired cellular signaling of AVP in collecting duct cells, which may be partly involved in the urinary concentrating defect in renal failure.

1.
Ziyadeh FN, Goldfarb S: The renal tubulointerstitium in diabetes mellitus. Kidney Int 1991;39:464–475.
2.
Taft JL, Nolan CJ, Yeung SP, Hewitson TD, Martin FI: Clinical and histological correlations of decline in renal function in diabetic patients with proteinuria. Diabetes 1994;43:1046–1051.
3.
Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S: Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 1993;361:549–552.
4.
Sasaki S, Fushimi K, Saito H, Saito F, Uchida S, Ishibashi K, Kuwahara M, Ikeuchi T, Inui K, Nakajima K, Watanabe T, Marumo F: Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct. J Clin Invest 1994;93:1250–1256.
5.
Kanno K, Sasaki S, Hirata Y, Ishikawa S, Fushimi K, Nakanishi S, Bichet DG, Marumo F: Urinary excretion of aquaporin-2 in patients with diabetes insipidus. N Engl J Med 1995;332:1540–1545.
6.
Rai T, Sekine K, Kanno K, Hata K, Miura M, Mizushima A, Marumo F, Sasaki S: Urinary excretion of aquaporin-2 water channel protein in human and rat. J Am Soc Nephrol 1997;8:1357–1362.
7.
Ishikawa S, Saito T, Okada K, Tsutsui K, Kuzuya T: Effect of vasopressin antagonist on water excretion in inferior vena cava constriction. Kidney Int 1986;30:49–55.
8.
Saito T, Ishikawa S, Ando F, Okada N, Nakamura T, Kusaka I, Higashiyama M, Nagasaka S, Saito T: Exaggerated urinary excretion of aquaporin-2 in the pathological state of impaired water excretion dependent upon arginine vasopressin. J Clin Endocrinol Metab 1998;83:4034–4040.
9.
Fernandez LP, Andrews P, Nielsen S, Ecelbarger CA, Knepper MA: Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome. Kidney Int 1998;53:1244–1253.
10.
Jung JS, Lee RH, Koh SH, Kim YK: Changes in expression of sodium cotransporters and aquaporin-2 during ischemia-reperfusion injury in rabbit kidney. Ren Fail 2000;22:407–421.
11.
Kim SW, Lee JU, Nah MY, Kang DG, Ahn KY, Lee HS, Choi KC: Cisplatin decreases the abundance of aquaporin water channels in rat kidney. J Am Soc Nephrol 2001;12:875–882.
12.
Teitelbaum I, McGuinness S: Vasopressin resistance in chronic renal failure: Evidence for the role of decreased V2 receptor mRNA. J Clin Invest 1995;96:378–385.
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