From the Guidelines
Nephrogenic diabetes insipidus (NDI) more closely resembles type 2 diabetes mellitus in terms of pathogenesis, as both conditions involve resistance to hormones rather than hormone deficiency. In NDI, the kidneys are resistant to the effects of antidiuretic hormone (ADH, also called vasopressin), which normally signals the kidneys to reabsorb water 1. Despite adequate or even elevated levels of ADH, the kidneys cannot respond appropriately, leading to excessive urine production and potential dehydration. Similarly, in type 2 diabetes mellitus, peripheral tissues become resistant to insulin, preventing proper glucose uptake despite normal or elevated insulin levels 1. This contrasts with type 1 diabetes mellitus, which results from an absolute deficiency of insulin due to autoimmune destruction of pancreatic beta cells. The parallel between NDI and type 2 diabetes lies in this fundamental mechanism of hormone resistance rather than hormone absence.
Some key features of NDI include:
- Polyuria, polydipsia, and the risk of hypertonic dehydration 1
- Insensitivity of the distal nephron to arginine vasopressin, leading to an inability to concentrate urine 1
- Serum osmolality is usually >300 mOsm/kg H2O owing to hypernatraemia, whereas urine is inappropriately diluted, with osmolality usually <200 mOsm/kg H2O 1
Treatment approaches for NDI focus on managing symptoms through:
- Increased water intake
- Low-salt diet
- Sometimes medications like thiazide diuretics, amiloride, or indomethacin that reduce urine output through various mechanisms, rather than hormone replacement which would be ineffective due to the underlying resistance 1.
It is essential to note that the diagnosis and management of NDI are very challenging and require an integrated, multidisciplinary approach 1. Further research on different aspects of this potentially life-threatening disorder is needed to support the development of evidence-based guidelines in the future 1.
From the Research
Pathogenesis of Nephrogenic Diabetes Insipidus (NDI)
- NDI is characterized by impaired urinary concentrating ability, despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP) 2, 3, 4.
- The condition can be inherited or acquired, with genetic abnormalities such as mutations in the vasopressin V2 receptor (AVPR2) or the aquaporin-2 (AQP2) water channel being common causes of congenital NDI 2, 4.
- Acquired NDI can result from chronic lithium therapy, kidney disorders, electrolyte imbalance, and various drugs 3, 4.
Comparison with Type 1 and Type 2 Diabetes Mellitus (DM)
- NDI does not closely resemble type 1 or type 2 DM in terms of pathogenesis, as it is primarily a disorder of water balance rather than glucose metabolism 2, 3, 4, 5.
- While type 1 and type 2 DM are characterized by impaired glucose regulation, NDI is characterized by impaired urinary concentrating ability due to resistance to AVP or defects in the AVP signaling pathway 2, 3, 4, 5.
Clinical Manifestations and Treatment
- The clinical manifestations of NDI vary according to the degree of dehydration and hyperosmolality, and can include polyuria, polydipsia, growth retardation, and dehydration 2, 3, 4.
- Treatment of NDI focuses on decreasing urine output, maintaining fluid balance, and ensuring an acceptable quality of life, and may include nonpharmacological interventions such as sufficient water intake and a low-sodium diet, as well as pharmacological treatment with thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride 2, 3, 6.