A 28-year-old man is evaluated for a lifelong history of polyuria and polydipsia. Laboratory studies reveal hypokalemia and metabolic alkalosis. Genetic testing identifies a loss-of-function mutation in the gene encoding the Na+-K+-2Cl− cotransporter. During a water deprivation test, his urine osmolality remains low and fails to increase after administration of desmopressin. Which of the following best explains the defect leading to his inability to concentrate urine?
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