Diabetic kidney disease in children and adolescents: an update

Abstract

Diabetic kidney disease (DKD), previously encountered predominantly in adult patients, is rapidly gaining center stage as a childhood morbidity and one that pediatric nephrologists are likely to encounter with increasing frequency. This is in large part due to the obesity epidemic and the consequent rise in type 2 diabetes in children and adolescents, as well as the more aggressive diabetes phenotype in today’s youth with more rapid β-cell decline and faster development and progression of diabetes-related complications along with lower responsiveness to the treatments used in adults. DKD, an end-organ complication of diabetes, is at the very least a marker of, and more likely a predisposing factor for, the development of adverse cardiovascular outcomes and premature mortality in children with diabetes. On an optimistic note, several new therapeutic approaches are now available for the management of diabetes in adults, such as GLP1 receptor agonists, SGLT2 inhibitors, and DPP4 inhibitors, that have also been shown to have a favorable impact on cardiorenal outcomes. Also promising is the success of very low-energy diets in inducing remission of diabetes in adults. However, the addition of these pharmacological and dietary approaches to the management toolbox of diabetes and DKD in children and adolescents awaits thorough assessment of their safety and efficacy in this population. This review outlines the scope of diabetes and DKD, and new developments that may favorably impact the management of children and young adults with diabetes and DKD.

Analysis of Apoptotic, Clinical, and Laboratory Parameters in Type 1 Diabetes and Early Diabetic Nephropathy: Clustering and Potential Groups Evaluation for Additional Therapeutic Interventions

“…Structural changes may be observed in kidney biopsies as early as the first few years after the onset of diabetes, but the disease has a long “silent period” in its development ( 18 ). Thus, our current understanding of the trajectory of DN in children and adolescents suggests that advanced CKD and kidney failure take decades to develop after the onset/diagnosis of diabetes, which means that the data on the prevalence and time course of these outcomes in childhood-onset diabetes is largely derived from adult studies ( 19 , 20 ). This presents a dilemma for any rigorous study of diabetic kidney disease (DKD) in children and adolescents because understanding any aspect of DN, for example biomarkers, risk factors for progression, and assessment of response to interventions, has had to rely on intermediate outcomes, such as albuminuria, and hyperfiltration.…”

Cystatin C, renal resistance index, and kidney injury molecule-1 are potential early predictors of diabetic kidney disease in children with type 1 diabetes

“…These three glomerular, vascular, and tubular markers are rarely simultaneously studied and are not part of the guidelines for screening for DKD in children with DM-T1 (5). The significant association between cystatin C and the latent variable indicating the risk for DKD is yet another confirmation of the probable value of cystatin C in the prediction of DKD, which has been documented (21)(22)(23)(24)(25).…”

“…Therefore, it is important to detect children at risk of developing diabetic kidney disease (DKD) as early as possible. Persistent microalbuminuria and reduced estimated glomerular filtration rate (eGFR) are contemporary methods of early detection for DKD (4)(5)(6). A high percentage of regression to normoalbuminuria in children with a history of albuminuria raises the question of whether albuminuria is an valid early indicator of DKD (7)(8)(9).…”

Diabetic kidney disease in pediatric patients: A current review

“…Hyperfiltration was noticed more frequently in females vs males in both T1DM and T2DM[ 32 , 35 ]. The estimated GFR (eGFR) in children and adolescents with T1DM or T2DM should be screened at diagnosis and then annually[ 36 ]. These ongoing changes help us to assess DKD stages, which are presented in Table 2 [ 20 , 21 , 37 ].…”

“…In T1DM pediatric patients, urine microalbumin to creatinine ratio (UACR) monitoring should start at puberty or 10 years of age (whichever is earlier), and when the child has had DM for 5 years this parameter should be checked annually. In T2DM the UACR should be checked at diagnosis and every year thereafter[ 36 ].…”