Discussion
Determining whether diabetes insipidus is central or nephrogenic is challenging in resource limited set-ups especially if a patient has pre-existing diabetes mellitus. We were able to diagnose NDI based on patient’s clinical presentation of excessive polyuria and severe hypokalaemia and hypomagnesemia and started the management on the second day with the resources available to us. Confirmatory tests like urine osmolality and plasma levels of arginine vasopressin (AVP) were not available, so the diagnosis was made based on the available diagnostic tools and clinical judgment.
The ability of kidneys to concentrate urine is regulated through water balancing activities mediated via a complex AVP/AVP V2 receptor/Aquaporin-2 axis. Aquaporin-2 (AQP2) are the principal water channel cells that regulate water permeability at the collecting duct epithelium mediated chiefly via AVP effects.(5) Both hereditary and acquired causes of NDI lead to decreased in the AQP2 expressions and AVP action, thus causing similar consequences of  . Acquired NDI is more frequently encountered than the hereditary form, usually being drug-induced or due to electrolyte disturbance. Lithium is not the only culprit, and there are a number of drugs (antibiotics, antifungals and antineoplastic) responsible in decreasing AQP2 expression and targeting, hence causing acquired NDI.(6)
In respect to metabolic causes of NDI, hypokalaemia and hypercalcemia have been identified from animal studies. It has been observed that hypokalaemia and hypercalcemia lead to autophagic degradation of AQP2 protein abundance in the inner medullary collecting ducts that impair urine concentrating ability. Within their studies it was observed that correcting hypokalaemia and hypercalcemia ameliorates autophagic activities on AQP2 reversing NDI within 24 – 48 hours.(7,8) In this patient, hypokalaemia induced NDI was refractory to therapy despite high doses of parenteral potassium supplementation until a coexistence of hypomagnesemia was sought. We corrected the hypokalaemia and hypomagnesemia concurrently, which eventually led to significant clinical improvement in correlation with ECG U-wave disappearance. (Fig.2)
Magnesium and potassium are cations which are predominantly intracellular. This distribution is what maintains the stability of the membrane potential and decreases cell excitability.(9) Deficiency of magnesium usually goes unrecognized thus exacerbating potassium wasting through the impairment of Na-K-ATPase activity.(4) Though hypomagnesaemia has been associated directly towards hypokalaemia, our knowledge is limited in identifying whether the former electrolyte has any obvious physiological impact in directly causing NDI.