Chapter 045. Azotemia and Urinary Abnormalities (Part 8) Approach to the patient with polyuria. ATN, acute tubular necrosis; ADH, antidiuretic hormone Excessive filtration of a poorly reabsorbed solute such as glucose, mannitol, or urea can depress reabsorption of NaCl and water in the proximal tubule and lead to enhanced excretion in the urine. Poorly controlled diabetes mellitus with glucosuria is the most common cause of a solute diuresis, leading to volume depletion and serum hypertonicity. Since the urine Na concentration is less than that of blood, more water than Na is lost, causing hypernatremia and hypertonicity. Common iatrogenic solute diuresis occurs from mannitol administration, radiocontrast media, and high-protein feedings (enterally or parenterally), leading to increased urea production and excretion. Less commonly, excessive Na loss may occur from cystic renal diseases, Bartter's syndrome, or during the course of a tubulointerstitial process (such as resolving ATN). In these so-called salt-wasting disorders, the tubule damage results in direct impairment of Na reabsorption and indirectly reduces the responsiveness of the tubule to aldosterone. Usually, the Na losses are mild, and the obligatory urine output is <2 L/d (resolving ATN and postobstructive diuresis are exceptions and may be associated with significant natriuresis and polyuria). Formation of large volumes of dilute urine represent polydipsic states or diabetes insipidus. Primary polydipsia can result from habit, psychiatric disorders, neurologic lesions, or medications. During deliberate polydipsia, extracellular fluid volume is normal or expanded and plasma vasopressin levels are reduced because serum osmolality tends to be near the lower limits of normal. Central diabetes insipidus may be idiopathic in origin or secondary to a variety of hypothalamic conditions including posthypophysectomy or trauma or neoplastic, inflammatory, vascular, or infectious hypothalamic diseases. Idiopathic central diabetes insipidus is associated with selective destruction of the vasopressin-secreting neurons in the supraoptic and paraventricular nuclei and can be inherited as an autosomal dominant trait or occur spontaneously. Nephrogenic diabetes insipidus can occur in a variety of clinical situations as summarized in Fig. 45-4. A plasma vasopressin level is recommended as the best method for distinguishing between central and nephrogenic diabetes insipidus. Alternatively, a water deprivation test plus exogenous vasopressin may also distinguish primary polydipsia from central and nephrogenic diabetes insipidus. For a detailed discussion, see Chap. 334. Further Readings Anderson S et al: Renal and systemic manifestations of glomerular disease, in Brenner & Rector's The Kidney, 7th ed, BM Brenner (ed). Philadelphia, Saunders, 2004, pp 1927–1954 Berl T, Verbalis J: Pathophysiology of water metabolism, in Brenner & Rector's The Kidney, 7th ed, BM Brenner (ed). Philadelphia, Saunders, 2004, pp 857–920 Kasiske BL, Keane WF: Laboratory assessment of renal disease: Clearance, urinalysis and renal biopsy, in Brenner & Rector's The Kidney, 7th ed, BM Brenner (ed). Philadelphia, Saunders, 2004, pp 1107–1150 Khadra MHet al: A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol 163:524, 2000 [PMID: 10647670] Rodrigo E et al: Measurement of renal function in pre-ESRD patients. Kidney Int Suppl 80:11, 2002 [PMID: 11982806] Sasaki S: Nephrogenic diabetes insipidus: Update of genetic and clinical aspects. Nephrol Dial Transplant 19:1351, 2004 [PMID: 15004257] Shrier RW et al: Acute renal failure: Definitions, diagnosis, pathogenesis and therapy. J Clin Invest 114:5, 2004 . Chapter 045. Azotemia and Urinary Abnormalities (Part 8) Approach to the patient with polyuria. ATN, acute tubular necrosis;. reabsorption and indirectly reduces the responsiveness of the tubule to aldosterone. Usually, the Na losses are mild, and the obligatory urine output is <2 L/d (resolving ATN and postobstructive. leading to volume depletion and serum hypertonicity. Since the urine Na concentration is less than that of blood, more water than Na is lost, causing hypernatremia and hypertonicity. Common