Temporal variation of renal function in people with type 2 diabetes mellitus: A retrospective UK clinical practice research datalink cohort study

Abstract

Aim To characterize the longitudinal variability of estimated glomerular filtration rate (eGFR) in people with type 2 diabetes mellitus (T2DM), including variation between categories and individuals. Methods People with T2DM and sufficient recorded serum creatinine measurements were identified from the Clinical Practice Research Datalink (T2DM diagnosis from 1 January 2009 to 1 January 2011 with 5 years follow‐up); eGFR was calculated using the CKD‐EPI equation. Results In total, 7766 individuals were included; 32.8%, 50.2%, 12.4%, 4.0% and 0.6% were in glomerular filtration rate (GFR) categories G1, G2, G3a, G3b and G4, respectively. Overall, eGFR decreased by 0.44 mL/min/1.73 m2 per year; eGFR increased by 0.80 mL/min/1.73 m2 between index and year 1, then decreased by 0.75 mL/min/1.73 m2 annually up to year 5. Category G1 showed a steady decline in eGFR over time; G2, G3a and G3b showed an increase between index and year 1, followed by a decline. Category G4 showed a mean eGFR increase of 1.85 mL/min/1.73 m2 annually. People in categories G3‐G4 moved across a greater number of GFR categories than those in G1 and G2. Individual patients' eGFR showed a wide range of values (change from baseline at year 5 varied from −80 to +59 mL/min/1.73 m2). Conclusion Overall, eGFR declined over time, although there was considerable variation between GFR categories and individuals. This highlights the difficulty in prescribing many glucose‐lowering therapies, which require dose adjustment for renal function. The study also emphasizes the importance of regular monitoring of renal impairment in people with T2DM.

Clonal Hematopoiesis of Indeterminate Potential and Diabetic Kidney Disease: A Nested Case-Control Study

“…1 J o u r n a l P r e -p r o o f 4 However, the course of the disease shows a considerably high inter-individual variability that often cannot be sufficiently explained by conventional risk factors. 5,6 Clonal hematopoiesis of indeterminate potential (CHIP) has recently emerged as a novel cardiovascular risk factor linking the innate immune system to specific clonal drivers, aging and subclinical chronic inflammation (microinflammation). 7,8 CHIP is defined as a clonal expansion in the hematopoietic lineages in the absence of a hematological malignancy.…”

“… 1 However, the course of the disease shows a considerably high interindividual variability that often cannot be sufficiently explained by conventional risk factors. 5 , 6 …”

Intra-individual variability of eGFR trajectories in early diabetic kidney disease and lack of performance of prognostic biomarkers

“…One explanation is the excessive competing risk of (mostly cardiovascular) mortality 4 , which increases in parallel to the decline in estimated glomerular filtration rate (eGFR) 5 . In addition, not all patients develop DKD 6 – 8 and even those who do, progress at a highly variable rate 9 . The KDIGO guidelines suggest using eGFR and urinary albumin excretion (UAE) for cross sectional categorization of chronic kidney disease into 5 eGFR and 3 UAE stages 10 .…”

“…During the last decades it became evident that the pathophysiology of DKD is complex 16 . Next to systemic co-morbidities or effects of medication, the cross-sectional inter- 17 , and longitudinal intra-individual 18 variability of pathways driving the disease leads to an unstable course over time 9 . This not only challenges the concept of a linear trajectory of eGFR decline but also conceptually creates a dilemma for biomarker research.…”

5-Hydroxymethylcytosines in Circulating Cell-Free DNA Reveal Vascular Complications of Type 2 Diabetes

“…The eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation: eGFR ϭ 141 ϫ min (Scr/, 1) ␣ ϫ max (Scr/, 1) -1.209 ϫ 0.993 Age ϫ (1.018 if female), (Scr, Serum creatinine; unit, mg/dL, 1 mg/dL ϭ 88.4 mol/L), where ϭ 0.7 for females or 0.9 for males; ␣ ϭ Ϫ0.329 for females or Ϫ0.411 for males; min indicates the minimum of Scr/ or 1; and max indicates the maximum of Scr/ or 1 (25 ).…”