Compelling evidence suggests that the age of diabetes diagnosis may be linked to the risk of end-stage kidney disease.
The rarity of its occurrence is the predominant factor that limits approximating the long-term risk of end-stage renal disease in patients with type 2 diabetes. Therefore, to achieve consistent approximations of end-stage renal disease incidence, studies must be of significant magnitude and duration, comprised of a patient population with diffuse ages of diabetes onset. Consequently, only one clinical trial has been conducted that was adequately large enough to provide an estimate of the long-term risk of end-stage kidney disease in type 2 diabetes. In the 2019 study, “Cumulative Risk of End-Stage Renal Disease Among Patients with Type 2 Diabetes: A Nationwide Inception Cohort Study,” Finne and associates assessed an accumulative end-stage kidney disease risk of 0.74% after 20 years in patients with type 2 diabetes. This trial demarcated end-stage kidney disease as the initiation of renal replacement therapy. It was concluded that the risk of end-stage kidney disease is low in patients with type 2 diabetes. However, one-third of the patients in their cohort were greater than 70 years of age when a diabetes diagnosis was received, and renal replacement therapy initiation at end-stage renal disease onset decreases drastically as age increases. Moreover, this study precluded individuals diagnosed with type 2 diabetes at less than 40 years of age, who may be at an increased risk for end-stage kidney disease, with notably longer durations. Hence, the long-term risk of end-stage kidney disease in patients with type 2 diabetes may be significantly higher than this trial’s findings would insinuate.
The differences in diabetic nephropathy pathophysiology between younger-onset and older-onset of type 2 diabetes are ambiguous. It is also uncertain whether longer survival durations in young-onset diabetes merely permit more time for diabetic nephropathy progression to end-stage renal disease, than in an older-onset cohort. While an increased risk of end-stage kidney disease in younger-onset type 2 diabetes has been well established, when the duration of diabetes is controlled, findings of onset age effects have been contradictory. This may be due to the disregard of renal replacement therapy non-initiation and the contending risk of mortality, both of which are significantly contingent on age. Therefore, they are particularly influential in exemplifying the effects that the age of disease onset has on long-term end-stage renal disease risk. There is an apparent need for further information on the long-term risk of end-stage renal disease in patients with type 2 diabetes, and the impact that a younger-onset age has on this risk.
Researchers of the 2020 study, “The Association Between Age of Onset of Type 2 Diabetes and the Long-Term Risk of End-Stage Kidney Disease: A National Registry Study,“ linked nationwide type 2 diabetes, end-stage kidney disease, and death registries to yield a study population of 1,113,201 individuals. Participants were registered on the Australian National Diabetes Services Scheme (NDSS) and observed from 2002 until 2013. Australia and New Zealand Dialysis and Transplant Registry and the Australian National Death Index were connected to the NDSS to estimate the occurrence of end-stage kidney disease from the age of onset of type 2 diabetes in this cohort.
During 2002 – 2013, there were 7,592 cases of end-stage kidney disease during 7,839,075 person-years of follow up. Throughout the first 10-15 subsequent years of type 2 diabetes onset, the incidence of end-stage kidney disease was highest in those with older-onset diabetes; while over longer diabetes durations, the incidence of end-stage kidney disease developed more in those with younger-onset diabetes. In the young-onset category (less than 30 years of age), the risk of end-stage kidney disease was substantially higher in men than women after 40 years of diabetes (more than twofold). After 40 years of diabetes, the aggregate incidence of end-stage renal disease was 11.8% in patients diagnosed with type 2 diabetes at ages 10-29 years and 9.3% in those diagnosed between 30-39 years. The incidence of end-stage renal disease continued to be higher for the initial 20 years in older-onset diabetes when death from the end-stage renal disease without renal replacement therapy was incorporated, with no distinct effect of age seen after that. The resulting data obtained from this trial suggest that the long-term risk of end-stage kidney disease is high in patients with type 2 diabetes; those with a younger diabetes onset age are excessively affected, as survival to lengthier diabetes durations is more probable in this patient demographic. The authors of this study concluded that the prevalence of end-stage kidney disease in type 2 diabetes escalates with lengthening duration of diabetes as well as age, culminating in the association between age of diabetes onset and long-term risk of end-stage kidney disease.
- The long-term risk of end-stage kidney disease is high in patients with type 2 diabetes.
- The incidence of end-stage kidney disease in type 2 diabetes escalates with lengthening duration of diabetes as well as age.
- Diabetes duration is a primary determinant of end-stage kidney disease risk. With the survival of longer diabetes durations being more feasible in individuals with a younger age of diabetes onset, this patient demographic undoubtedly presents a higher long-term risk of developing end-stage kidney disease.
Finne P, Groop PH, Arffman M, et al. Cumulative risk of end-stage renal disease among patients with type 2 diabetes: A nationwide inception cohort study. Diabetes Care. 2019;42(4):539-544. doi:10.2337/dc18-1485 https://care.diabetesjournals.org/content/42/4/539?ijkey=787d760a0435250c078c15d72991d06e0cfb38e9&keytype2=tf_ipsecsha
The Association Between Age of Onset of Type 2 Diabetes and the Long-term Risk of End-Stage Kidney Disease: A National Registry Study. 2020. doi:10.2337/dc20-0352 https://care.diabetesjournals.org/content/43/8/1788.full-text.pdf
Bernice Ford, 2021 PharmD Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences