Aims: Investigating whether and to what extent changes in glomerular hemodynamic parameters, beyond glomerular hyperfiltration, could predict glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients. Materials and methods: We estimated baseline afferent (Ra) and efferent (Re) arteriolar resistances and glomerular hydrostatic pressure in 60 consecutive patients from DEMAND study, using the Gomez’ equations. Baseline renal plasma flow was measured by para-aminohippurate plasma clearance, and GFR was measured by iohexol plasma clearance at baseline and every 6 months for a median of 4.0 years [IQR 3.5–4.0 years]. Patients with a GFR decline > or ≤ 3 mL/min/1.73 m2/year were categorized as “Progressors” and “Non-progressors,” respectively. Predictors of GFR decline were studied by univariable and multivariable logistic regression analysis. Results: •The GFR declined by a median [IQR] of 4.06 [5.46–2.00] mL/min/1.73 m2/year in the study group as a whole and by 5.35 [6.60–4.48] mL/min/1.73 m2/year and 1.71 [2.14–1.33] mL/min/1.73 m2/year in Progressors and Non-progressors, considered separately. Progressors had a higher baseline Ra (3487.3 ± 1349.3 dyne•sec•cm−5 vs. 2877.0 ± 668.9 dyne•sec•cm−5, p < 0.05) and higher Ra/Re ratio (1.4 ± 0.5 vs. 1.1 ± 0.3, p < 0.01) than Non-progressors. At multivariable logistic regression analysis, Ra/Re ratio and arterial hypertension duration were independently associated with GFR decline (odds ratio [95% CI] 8.50 [1.56–46.28] and 1.14 [1.01–1.28]), respectively. Conclusions: Increased Ra/Re ratio and arterial hypertension duration predict early GFR decline in hypertensive non-proteinuric type 2 diabetic patients. These findings could be explained by glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing. Clinical trial registration: DEMAND, NCT00157586, September 12, 2005.
Carrara, F., Ruggenenti, P., Perna, A., Iliev, I., Gaspari, F., Ferrari, S., et al. (2022). Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial. ACTA DIABETOLOGICA, 59(3), 309-317 [10.1007/s00592-021-01804-9].
Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial
Ruggenenti, Piero
Membro del Collaboration Group
;Trevisan, RobertoMembro del Collaboration Group
;
2022
Abstract
Aims: Investigating whether and to what extent changes in glomerular hemodynamic parameters, beyond glomerular hyperfiltration, could predict glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients. Materials and methods: We estimated baseline afferent (Ra) and efferent (Re) arteriolar resistances and glomerular hydrostatic pressure in 60 consecutive patients from DEMAND study, using the Gomez’ equations. Baseline renal plasma flow was measured by para-aminohippurate plasma clearance, and GFR was measured by iohexol plasma clearance at baseline and every 6 months for a median of 4.0 years [IQR 3.5–4.0 years]. Patients with a GFR decline > or ≤ 3 mL/min/1.73 m2/year were categorized as “Progressors” and “Non-progressors,” respectively. Predictors of GFR decline were studied by univariable and multivariable logistic regression analysis. Results: •The GFR declined by a median [IQR] of 4.06 [5.46–2.00] mL/min/1.73 m2/year in the study group as a whole and by 5.35 [6.60–4.48] mL/min/1.73 m2/year and 1.71 [2.14–1.33] mL/min/1.73 m2/year in Progressors and Non-progressors, considered separately. Progressors had a higher baseline Ra (3487.3 ± 1349.3 dyne•sec•cm−5 vs. 2877.0 ± 668.9 dyne•sec•cm−5, p < 0.05) and higher Ra/Re ratio (1.4 ± 0.5 vs. 1.1 ± 0.3, p < 0.01) than Non-progressors. At multivariable logistic regression analysis, Ra/Re ratio and arterial hypertension duration were independently associated with GFR decline (odds ratio [95% CI] 8.50 [1.56–46.28] and 1.14 [1.01–1.28]), respectively. Conclusions: Increased Ra/Re ratio and arterial hypertension duration predict early GFR decline in hypertensive non-proteinuric type 2 diabetic patients. These findings could be explained by glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing. Clinical trial registration: DEMAND, NCT00157586, September 12, 2005.
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