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.

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HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol

BMJ Open ◽

10.1136/bmjopen-2019-033923 ◽

2020 ◽

Vol 10 (9) ◽

pp. e033923

Author(s):

Kieran Mccafferty ◽

Ben Caplin ◽

Sinead Knight ◽

Paul Hockings ◽

David Wheeler ◽

...

Keyword(s):

Kidney Disease ◽

Observational Study ◽

Diabetic Kidney Disease ◽

Laboratory Data ◽

Premature Mortality ◽

Primary Objective ◽

Imaging Data ◽

Diabetic Kidney ◽

Number Of Patients

IntroductionDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment.Methods and analysisHEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR.Ethics and disseminationEthical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.

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Erratum Regarding “Insulin Sensitivity and Diabetic Kidney Disease in Children and Adolescents With Type 2 Diabetes: An Observational Analysis of Data From the TODAY Clinical Trial” (Am J Kidney Dis. 2018;71[1]:65-74)

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2019.02.001 ◽

2019 ◽

Vol 73 (4) ◽

pp. 580 ◽

Cited By ~ 1

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Insulin Sensitivity ◽

Kidney Disease ◽

Children And Adolescents ◽

Diabetic Kidney Disease ◽

Diabetic Kidney ◽

Observational Analysis

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Gemigliptin in Diabetic Kidney Disease in Asian Indians with Type 2 Diabetes in Real-Life Scenarios- Insights from Gem Study

Integrative Diabetes and Cardiovascular Diseases ◽

10.18314/idcd.v3i1.1494 ◽

2019 ◽

pp. 76-83

Author(s):

Kiran Shah ◽

Sonali A Patange ◽

Alka P Gandhi

Keyword(s):

Kidney Disease ◽

Goodness Of Fit ◽

Diabetic Kidney Disease ◽

Real Life ◽

Premature Mortality ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Diabetic Kidney ◽

Urine Albumin

Diabetic Kidney disease is strongly associated with cardiovascular events, premature mortality and ESRD. Gemigliptin can be used without dose adjustment in patients with renal failure. The current study aimed to assess the possible renoprotective effects of gemigliptin, using albuminuria and eGFR as indicators. This was a multi-center real-world retrospective analysis of 146 DPP-4 inhibitor naïve type 2 diabetic patients with established moderate DKD (eGFR between 30 to 45 ml/min/1.73 m2 over last 3 months) with diabetic retinopathy who received gemigliptin 50 mg once daily for 24 weeks in addition to anti-hyperglycemic, anti hypertensive’s and statins. Goodness of fit was examined using SPSS statistics 20 and ANOVA was conducted to interpret the results. Baseline characteristics were: 71 (48.6%) males and 75 (51.4%) females, the mean age was 60.81 ± 7.42 years, mean duration was 11.92 ± 3.3 years, mean BMI was 26.54 ± 2.59 kg/m2. Gemigliptin showed significant improvements in glycaemia, renal and lipid parameters with no deterioration in retinopathy, liver enzymes and with no hypoglycemic episodes and was weight neutral. In the present study, gemigliptin reduced albuminuria independent of age, gender, duration of diabetes, Hba1c, eGFR and SBP. It could ameliorate diabetic nephropathy by reducing urine albumin excretion and mitigating the reduction of eGFR in diabetic patients.

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Toll‐like receptor inflammatory cascade and the development of diabetic kidney disease in children and adolescents with type 1 diabetes

Journal of Paediatrics and Child Health ◽

10.1111/jpc.15884 ◽

2022 ◽

Author(s):

Thamara R Melo ◽

Karla S C Souza ◽

Marcela A G Ururahy ◽

Raul H Bortolin ◽

João F Bezerra ◽

...

Keyword(s):

Type 1 Diabetes ◽

Kidney Disease ◽

Children And Adolescents ◽

Diabetic Kidney Disease ◽

Toll Like Receptor ◽

Diabetic Kidney ◽

Inflammatory Cascade

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Elevated Urinary VEGF-A,Transferrin, and Angiotensinogen Levels in Normoalbuminuric Children and Adolescents with Type 1 Diabetes; Can They Be Early Markers of Diabetic Kidney Disease?

Hormone Research in Paediatrics ◽

10.1159/000521447 ◽

2021 ◽

Author(s):

Aydilek Dağdeviren Çakır ◽

Seha Kamil Saygılı ◽

Nur Canpolat ◽

Dildar Konukoğlu ◽

Hande Turan ◽

...

Keyword(s):

Risk Factors ◽

Type 1 Diabetes ◽

Kidney Disease ◽

Children And Adolescents ◽

Diabetic Kidney Disease ◽

Disease Duration ◽

Healthy Children ◽

Diabetic Kidney ◽

The Mean

Objective: We hypothesized that diabetic kidney disease (DKD) begins early, before albuminuria occurs. We therefore aimed to assess potential early urinary biomarkers of (DKD) in normoalbuminuric and normotensive children and adolescents with Type 1 Diabetes (T1D) to evaluate the relationship between these markers and clinical and laboratory risk factors for DKD. Methods: This cross-sectional study included 75 children and adolescents with T1D (62% females, mean age 13.9 ± 3.2 years) with normoalbuminuria [an albumin/creatinine ratio (ACR) below 30 mg/g creatinine]. Fifty-five age- and sex-matched healthy children and adolescents served as controls. For the assessment of early DKD, urinary levels of angiotensinogen (AGT), transferrin, nephrin, vascular endothelial growth factor-A (VEGF-A), and kidney injury molecule-1 (KIM-1) were measured in adequately collected 24-h urine samples using enzyme-linked immunoassays. Results: The mean disease duration was 7.3± 3.2 (ranged 2.1 - 15.7) years and the mean HbA1c level was 8.8±1.4%. The median levels of urine VEGF-A/Cr, AGT/Cr, and Transferrin/Cr were significantly higher in normoalbuminuric patients with T1D, compared with those of controls (p<0.001, p=0.02, and p=0.001, respectively), but there was no difference in nephrin/Cr and KIM-1/Cr between the two groups. Although, none of the patients had albuminuria, the median level of urine ACR was significantly higher in the patient group than the control group (p=0.003). The ACR was positively correlated with glomerular filtration rate (GFR). Urinary transferrin/Cr, AGT/Cr, and VEGF-A/Cr were significantly correlated with ACR, but not with either GFR or diabetic risk factors including HbA1c or disease duration. Conclusion: Normoalbuminuric and normotensive children and adolescents with T1D have elevated urinary VEGF, AGT and transferrin levels, which may indicate the development of DKD before albuminuria occurs.

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