Relationship between renal capacity to reabsorb glucose and renal status in patients with diabetes

Diabetes Metab. 2020 Nov;46(6):488-495. doi: 10.1016/j.diabet.2020.03.002. Epub 2020 Apr 4.

Abstract

Aims: Interindividual variability in capacity to reabsorb glucose at the proximal renal tubule could contribute to risk of diabetic kidney disease. Our present study investigated, in patients with diabetes, the association between fractional reabsorption of glucose (FRGLU) and degree of renal disease as assessed by urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR).

Methods: FRGLU [1-(glucose clearance/creatinine clearance)] was assessed in 637 diabetes patients attending our tertiary referral centre, looking for correlations between FRGLU and UAE (normo-, micro-, macro-albuminuria) and Kidney Disease: Improving Global Outcomes (KDIGO) eGFR categories: >90 (G1); 90-60 (G2); 59-30 (G3); and<30-16 (G4) mL/min/1.73 m2. Patients were stratified by admission fasting plasma glucose (FPG) into three groups: low (<6mmol/L); intermediate (6-11mmol/L); and high (>11mmol/L).

Results: Median (interquartile range, IQR) FRGLU levels were blood glucose-dependent: 99.90% (0.05) for low (n=106); 99.90% (0.41) for intermediate (n=288); and 96.36% (12.57) for high (n=243) blood glucose categories (P<0.0001). Also, FRGLU increased with renal disease severity in patients in the high FPG group: normoalbuminuria, 93.50% (17.74) (n=135); microalbuminuria, 96.56% (5.94) (n=77); macroalbuminuria, 99.12% (5.44) (n=31; P<0.001); eGFR G1, 94.13% (16.24) (n=111); G2, 96.35% (11.94) (n=72); G3 98.88% (7.59) (n=46); and G4, 99.11% (2.20) (n=14; P<0.01). On multiple regression analyses, FRGLU remained significantly and independently associated with UAE and eGFR in patients in the high blood glucose group.

Conclusion: High glucose reabsorption capacity in renal proximal tubules is associated with high UAE and low eGFR in patients with diabetes and blood glucose levels>11mmol/L.

Keywords: Diabetic kidney disease; Renal glucose transport; Tubuloglomerular feedback.

MeSH terms

  • Adult
  • Aged
  • Albuminuria / metabolism*
  • Blood Glucose / metabolism
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diabetic Nephropathies / metabolism*
  • Female
  • Glomerular Filtration Rate*
  • Glucose / metabolism*
  • Glycated Hemoglobin / metabolism
  • Glycosuria / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / metabolism
  • Renal Reabsorption / physiology*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Glucose