Interactions between kidney disease and diabetes: dangerous liaisons

Abstract

BackgroundType 2 diabetes mellitus (DM) globally affects 18–20 % of adults over the age of 65 years. Diabetic kidney disease (DKD) is one of the most frequent and dangerous complications of DM2, affecting about one-third of the patients with DM2. In addition to the pancreas, adipocytes, liver, and intestines, the kidneys also play an important role in glycemic control, particularly due to renal contribution to gluconeogenesis and tubular reabsorption of glucose.MethodsIn this review article, based on a report of discussions from an interdisciplinary group of experts in the areas of endocrinology, diabetology and nephrology, we detail the relationship between diabetes and kidney disease, addressing the care in the diagnosis, the difficulties in achieving glycemic control and possible treatments that can be applied according to the different degrees of impairment.DiscussionGlucose homeostasis is extremely altered in patients with DKD, who are exposed to a high risk of both hyperglycemia and hypoglycemia. Both high and low glycemic levels are associated with increased morbidity and shortened survival in this group of patients. Factors that are associated with an increased risk of hypoglycemia in DKD patients include decreased renal gluconeogenesis, deranged metabolic pathways (including altered metabolism of medications) and decreased insulin clearance. On the other hand, decrease glucose filtration and excretion, and inflammation-induce insulin resistance are predisposing factors to hyperglycemic episodes.ConclusionAppropriate glycaemic monitoring and control tailored for diabetic patients is required to avoid hypoglycaemia and other glycaemic disarrays in patients with DM2 and kidney disease. Understanding the renal physiology and pathophysiology of DKD has become essential to all specialties treating diabetic patients. Disseminating this knowledge and detailing the evidence will be important to initiate breakthrough research and to encourage proper treatment of this group of patients.

New‐onset diabetes mellitus among patients with glomerular diseases

“…postulated that proteinuria is a marker for systemic vascular endothelial dysfunction, which may also involve the pancreas, leading to impaired islet cell function and reduced insulin secretion . The role of renal dysfunction in diabetes is again controversial: while insulin resistance is common in CKD and thus predisposes individuals with CKD to hyperglycaemia, reduced glucose reabsorption and gluconeogenesis by kidney tubular cells in renal dysfunction lower the serum glucose concentration . We noted poorer renal function in patients who had incident diabetes, although the difference was not statistically significant.…”

“…Immunosuppressive therapy is often required to reduce inflammation and accrual damage that cause chronic kidney disease (CKD) or ESRD, but immunosuppressants such as glucocorticosteroid and calcineurin inhibitors can be diabetogenic. Current knowledge on diabetes mellitus after immunosuppressant treatment is generally derived from studies on steroid‐induced diabetes in non‐CKD populations, such as those with rheumatologic disease, but glucose homeostasis may be extremely altered in patients with renal disease . New‐onset diabetes after transplant is associated with ESRD and increased mortality, but data extrapolated from the extensive studies in transplant may not apply to patients with glomerulonephritis since immunosuppressive regimens to prevent and treat rejection in kidney transplant are generally more intensive and of longer duration.…”

Impact of drugs on hypoglycaemia in hospitalised patients

“…However, by considering age as a good proxy for renal function decrease, patients treated with heparin were found to be older than patients treated by enoxaparin (data not shown), supporting our hypothesis. Renal failure is known to induce hypoglycaemia by decreasing renal gluconeogenesis or clearance of some antidiabetic drugs 39. Thus, further studies are needed to better define the impact of heparin itself on hypoglycaemia.…”

Effectiveness and tolerability of therapy with exenatide once weekly vs basal insulin among injectable‐drug‐naïve elderly or renal impaired patients with type 2 diabetes in the United States

“…Approximately 20% to 30% of patients with T2DM will develop diabetic nephropathy over time, and a substantial proportion of these patients will progress to kidney failure . The kidneys play an important role in glycaemic control through gluconeogenesis and tubular reabsorption of glucose . Additionally, the kidneys play an important role in the clearance of antihyperglycaemic medications, including glucagon‐like protein‐1 receptor agonists (GLP‐1RAs) and long‐acting basal insulin (BI).…”

“…Additionally, the kidneys play an important role in the clearance of antihyperglycaemic medications, including glucagon‐like protein‐1 receptor agonists (GLP‐1RAs) and long‐acting basal insulin (BI). Renal impairment (RI) alters glycaemic control, placing patients at high risk of both hyperglycaemia and hypoglycaemia . Patients with T2DM and RI, specifically chronic kidney disease, are at increased risk of cardiovascular complications and death …”