Dysglycemia after renal transplantation: Definition, pathogenesis, outcomes and implications for management

Abstract

New-onset diabetes after transplantation (NODAT) is major complication following renal transplantation. It commonly develops within 3-6 mo post-transplantation. The development of NODAT is associated with significant increase in risk of major cardiovascular events and cardiovascular death. Other dysglycemic states, such as impaired glucose tolerance are also associated with increasing risk of cardiovascular events. The pathogenesis of these dysglycemic states is complex. Older recipient age is a consistent major risk factor and the impact of calcineurin inhibitors and glucocorticoids has been well described. Glucocorticoids likely cause insulin resistance and calcineurin inhibitors likely cause β-cell toxicity. The impact of transplantation in incretin hormones remains to be clarified. The oral glucose tolerance test remains the best diagnostic test but other tests may be validated as screening tests. Possibly, NODAT can be prevented by administering insulin early in patients identified as high risk for NODAT. Once NODAT has been diagnosed altering immunosuppression may be acceptable, but creates the difficulty of balancing immunological with metabolic risk. With regard to hypoglycemic use, metformin may be the best option. Further research is needed to better understand the pathogenesis, identify high risk patients and to improve management options given the significant increased risk of major cardiovascular events and death.

Metabolic consequences of modern immunosuppressive agents in solid organ transplantation

“…In addition, a greater number of metabolic syndrome components increases the likelihood of developing NODAT [Perito et al 2016]. Hence pretransplant screening for detection of modifiable metabolic events is an appropriate preventive strategy [Juan Khong and Ping Chong, 2014;Langsford and Dwyer, 2015].…”

Impact of renal transplantation on glucose tolerance in Japanese recipients with impaired glucose tolerance

“…This leads to the question of what are the factors affecting the improvement in glucose tolerance, insulin secretion and insulin sensitivity. Considering the risk factors for NODAT, recipient characteristics such as age, sex and the use of immunosuppression and glucocorticoids might affect glucose tolerance [8,10]. In the present study, there were no differences in age, sex or glucocorticoid dosage between the non-amelioration group and the amelioration group (Table 4), and no significant differences in the changes in glucose tolerance were observed between the tacrolimus group and the cyclosporin A group (Tables S1 and S2).…”

“…In the present study, there were no differences in age, sex or glucocorticoid dosage between the non‐amelioration group and the amelioration group (Table ), and no significant differences in the changes in glucose tolerance were observed between the tacrolimus group and the cyclosporin A group (Tables S1 and S2). Although pre‐transplant weight and post‐transplant weight gain have significant impacts on the development of NODAT , no significant differences in BMI before or after transplantation were observed between the non‐amelioration group and the amelioration group (Table and Table S3). Also, tissue insensitivity to the action of insulin is reportedly present in people with advanced chronic renal failure and is the predominant factor contributing to glucose tolerance in uraemia ; however, no significant differences in renal function before and after transplantation were observed between the non‐amelioration group and the amelioration group (Table and Table S3).…”

“…The development of NODAT is associated with an increased risk of cardiovascular disease and mortality in transplant recipients and is also associated with graft failure [2][3][4][5][6]. Accordingly, many researchers have investigated the diagnosis, risk factors, management and prevention of NODAT [7][8][9][10][11]. The pathophysiology underlying NODAT is at present only poorly understood.…”

Böbrek Nakli Sonrası Hepatit C Virüs Enfeksiyonu Tedavisi ve İlaç Etkileşimleri; Olgu ve Literatürün Gözden Geçirilmesi

“…Takibini geciktirmesiyle, takrolimus dozu azaltılıp, diltiazem (orta derece CYP3A4 inhibitörü) kullanımı durdurulduğu halde ritonavir ilişkili takrolimus toksisitesi gelişti. Olguda takrolimus toksisitesinin bütün özellikleri mevcuttu; gastrointestinal yakınmalar, insülin bağımlı diyabetes mellitus (insülin salınımını azalması), akut böbrek hasarı (renal vazokonstriksiyon, hipoksi), hiperkalemi, hipertansiyon (endotelin artışı) ve nörotoksisite (direkt nöron hasarı, endotel disfonksiyonu) (11,15,16). Bu nedenle hem antiviral tedavi hem de kalsinorin inhibitörü alımının durdurulması gerekti.…”