Hyporeninemic hypoaldosteronism and diabetes mellitus: Pathophysiology assumptions, clinical aspects and implications for management

Abstract

Patients with diabetes mellitus (DM) frequently develop electrolyte disorders, including hyperkalemia. The most important causal factor of chronic hyperkalemia in patients with diabetes is the syndrome of hyporeninemic hypoaldosteronism (HH), but other conditions may also contribute. Moreover, as hyperkalemia is related to the blockage of the renin-angiotensin-aldosterone system (RAAS) and HH is most common among patients with mild to moderate renal insufficiency due to diabetic nephropathy (DN), the proper evaluation and management of these patients is quite complex. Despite its obvious relationship with diabetic nephropathy, HH is also related to other microvascular complications, such as DN, particularly the autonomic type. To confirm the diagnosis, plasma aldosterone concentration and the levels of renin and cortisol are measured when the RAAS is activated. In addition, synthetic mineralocorticoid and/or diuretics are used for the treatment of this syndrome. However, few studies on the implications of HH in the treatment of patients with DM have been conducted in recent years, and therefore little, if any, progress has been made. This comprehensive review highlights the findings regarding the epidemiology, diagnosis, and management recommendations for HH in patients with DM to clarify the diagnosis of this clinical condition, which is often neglected, and to assist in the improvement of patient care.

Refractory Hypotension post Coronary Artery Bypass Graft Unmasking Hypoaldosteronism: Case Report and Literature Review

“…Hyporeninemic hypoaldosteronism itself is part of a heterogeneous group of clinical disorders rarely genetic [3,4] more often associated with mild to moderate renal insufficiency [5,6], and with diabetic nephropathy, as a form of RTA (type IV) [7]. In rare instances, no intrinsic renal disease is found, as in the case we are describing, and another process is behind the deficiency in aldosterone.…”

“…The second form is hyporeninemic hypoaldosteronism which occurs with prolonged type 2 diabetes [5,11], tubulointerstitial nephritis, type IV renal tubular acidosis [3,4], and chronic use of beta blockers and non-steroidal anti-inflammatory drugs. Hyponatremia and hyperkalemia generally occur in hypoaldosteronism.…”

Hyponatremia Associated with Prophylactic Low-Dose Trimethoprim during Systemic Corticosteroid Therapy for AQP4-Positive Optic Neuritis in a Diabetic Patient

“…A third factor for consideration is the co-existence of diabetes mellitus in this patient. It is clear that patients with diabetes mellitus are susceptible to hyperkalemic RTA for several reasons, including low renin resulting from damage to the juxtaglomerular apparatus, autonomic dysfunction due to neuropathy, volume expansion due to renal salt retention, and weakened prorenin to renin conversion [20]. The patient´s baseline renin profile was not known due to the effects of treatment with trimethoprim, prednisolone, and telmisartan on the renin-angiotensin-aldosterone system, but it is possible that her diabetes mellitus was conducive to the development of hyperkalemic RTA.…”

66-Year-Old Man With Light-headedness, Chest Pain, and Dyspnea

“…Type 2 diabetes mellitus may predispose individuals to hyperkalemia in various ways, including increased glucagon concentrations, hyperosmolality, insulin resistance, and the use of potassiumsparing medications. 9 It is also known to be associated with an increased propensity for type 4 renal tubular acidosis (hyporeninemic hypoaldosteronism), although typically only in the presence of underlying CKD. Similar to obesity, hyperlipidemia has no major effects on potassium clearance.…”