Charlyne Carpentier1,2, Séverine Dubois1,2, Kamel Mohammedi3,4,5, Narimène Belhatem6, Béatrice Bouhanick7,8, Vincent Rohmer1,2, Claire Briet1,2, Anisoara Bumbu6, Samy Hadjadj9,10,11,12, Ronan Roussel6,13,14, Louis Potier6,13,14, Gilberto Velho14, Michel Marre6,13,14. 1. Centre Hospitalier Universitaire d'Angers, Service EDN, Angers, France. 2. INSERM, UMRS 1063, SOPAM, Université d'Angers, Angers, France. 3. Hôpital Haut-Lévêque, Service d'Endocrinologie, Diabétologie, Nutrition, Bordeaux, France. 4. Université de Bordeaux, Faculté de Médecine Paul Broca, Bordeaux, France. 5. Centre de Recherche INSERM-Université de Bordeaux U1219 'Bordeaux Population Health', Bordeaux, France. 6. Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat Hospital, DHU FIRE, Department of Diabetology, Endocrinology and Nutrition, Paris, France. 7. Centre Hospitalier Universitaire Rangueil, Service d'Hypertension et de Thérapeutique, TSA, Toulouse, France. 8. INSERM UMRS 1027, Université Toulouse 3, Toulouse, France. 9. INSERM, CIC 0802, Poitiers, France. 10. Université de Poitiers, UFR de Médecine et Pharmacie, Poitiers, France. 11. INSERM, Research Unit 1082, Poitiers, France. 12. Centre Hospitalier Universitaire de Poitiers, Department of Endocrinology and Diabetology, Poitiers, France. 13. Université Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France. 14. Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France.
Abstract
BACKGROUND: Hyperglycaemia impairs tubulo-glomerular feedback. We tested whether variable tubulo-glomerular feedback during hyperglycaemia contributes to renal risk heterogeneity seen in Type 1 diabetes. METHODS: During the period 1990-92, we studied the tubulo-glomerular feedback in Type 1 diabetic patients at high or low renal risk [21 of 54 with glomerular hyperfiltration and/or microalbuminuria against 11 of 55 with normal glomerular filtration rate (GFR) and urinary albumin despite uncontrolled diabetes]. The GFR, effective renal plasma flow, mean arterial pressure and fractional reabsorptions of glucose, osmols, sodium and lithium were measured sequentially during normo- and hyperglycaemia. All patients were followed up until 2016 for incident proteinuria, estimated GFR <60 mL/min/1.73 m2, doubling of serum creatinine, end-stage renal disease or all-cause death. RESULTS: Glycaemia increased from 6.1 ± 1.3 to 15.1 ± 1.9 mmol/L in both high-risk and low-risk patients. Glycosuria was lower in the high- versus low-risk patients: 0.34 ± 0.25 versus 0.64 ± 0.44 mmol/min (P = 0.03). Both groups displayed similar kidney function during normoglycaemia. Hyperglycaemia increased more importantly GFR and fractional reabsorptions, and pre-glomerular vasodilatation in the high- than in the low-risk patients (all P < 0.05). Over 21 years, 31.5% high- versus 12.7% low-risk patients developed endpoints (adjusted P = 0.006). In a multi-adjusted survival analysis of patients having undergone renal tests, each 0.10 mmol/min glycosuria during hyperglycaemia reduced the outcome risk by 0.72 (95% confidence interval 0.49-0.97, P = 0.03). CONCLUSIONS: Reduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabetic patients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes.
BACKGROUND:Hyperglycaemia impairs tubulo-glomerular feedback. We tested whether variable tubulo-glomerular feedback during hyperglycaemia contributes to renal risk heterogeneity seen in Type 1 diabetes. METHODS: During the period 1990-92, we studied the tubulo-glomerular feedback in Type 1 diabeticpatients at high or low renal risk [21 of 54 with glomerular hyperfiltration and/or microalbuminuria against 11 of 55 with normal glomerular filtration rate (GFR) and urinary albumin despite uncontrolled diabetes]. The GFR, effective renal plasma flow, mean arterial pressure and fractional reabsorptions of glucose, osmols, sodium and lithium were measured sequentially during normo- and hyperglycaemia. All patients were followed up until 2016 for incident proteinuria, estimated GFR <60 mL/min/1.73 m2, doubling of serum creatinine, end-stage renal disease or all-cause death. RESULTS: Glycaemia increased from 6.1 ± 1.3 to 15.1 ± 1.9 mmol/L in both high-risk and low-risk patients. Glycosuria was lower in the high- versus low-risk patients: 0.34 ± 0.25 versus 0.64 ± 0.44 mmol/min (P = 0.03). Both groups displayed similar kidney function during normoglycaemia. Hyperglycaemia increased more importantly GFR and fractional reabsorptions, and pre-glomerular vasodilatation in the high- than in the low-risk patients (all P < 0.05). Over 21 years, 31.5% high- versus 12.7% low-risk patients developed endpoints (adjusted P = 0.006). In a multi-adjusted survival analysis of patients having undergone renal tests, each 0.10 mmol/min glycosuria during hyperglycaemia reduced the outcome risk by 0.72 (95% confidence interval 0.49-0.97, P = 0.03). CONCLUSIONS: Reduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabeticpatients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes.
Authors: Katina D Hulme; Limin Yan; Rebecca J Marshall; Conor J Bloxham; Kyle R Upton; Sumaira Z Hasnain; Helle Bielefeldt-Ohmann; Zhixuan Loh; Katharina Ronacher; Keng Yih Chew; Linda A Gallo; Kirsty R Short Journal: Elife Date: 2020-07-22 Impact factor: 8.140