Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Mar;59(3):309-317.
doi: 10.1007/s00592-021-01804-9. Epub 2021 Oct 14.

Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial

Fabiola Carrara #  1 , Piero Ruggenenti #  2   3 , Annalisa Perna  1 , Ilian Petrov Iliev  1 , Flavio Gaspari  1 , Silvia Ferrari  1 , Nadia Stucchi  1 , Antonio Bossi  4 , Roberto Trevisan  5 , Giuseppe Remuzzi  1   6 , Aneliya Parvanova  1
Affiliations
Clinical Trial

Glomerular resistances predict long-term GFR decline in type 2 diabetic patients without overt nephropathy: a longitudinal subgroup analysis of the DEMAND trial

Fabiola Carrara et al. Acta Diabetol. 2022 Mar.

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.

Keywords: Arterial hypertension; GFR decline; Glomerular hypoperfusion; Pre- and post-glomerular resistances; Type 2 diabetes.

PubMed Disclaimer

References

    1. Tuttle KR, Bakris GL, Bilous RW et al (2014) Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care 37:2864–2883. https://doi.org/10.2337/dc14-1296 - DOI - PubMed - PMC
    1. Pugliese G, Penno G, Natali A et al (2019) Diabetic kidney disease: New clinical and therapeutic issues. Joint position statement of the Italian Diabetes Society and the Italian Society of Nephrology on “The natural history of diabetic kidney disease and treatment of hyperglycemia in patients with type 2 diabetes and impaired renal function.” Nutr Metab Cardiovasc Dis 29:1127–1150. https://doi.org/10.1016/j.numecd.2019.07.017 - DOI - PubMed
    1. Warren AM, Knudsen ST, Cooper ME (2019) Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies. Expert Opin Ther Targets 23:579–591. https://doi.org/10.1080/14728222.2019.1624721 - DOI - PubMed
    1. Mogensen CE (1986) Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scand J Clin Lab Invest 46:201–206. https://doi.org/10.3109/00365518609083660 - DOI - PubMed
    1. Tonneijck L, Muskiet MHA, Smits MM et al (2017) Glomerular hyperfiltration in diabetes: mechanisms, clinical significance, and treatment. J Am Soc Nephrol 28:1023–1039. https://doi.org/10.1681/ASN.2016060666 - DOI - PubMed - PMC

Publication types

Associated data

LinkOut - more resources