Glucagon-like peptide-1 receptors in the kidney: impact on renal autoregulation

Glucagon-like peptide-1 (GLP-1) and strategies based on this blood sugar-reducing and appetite-suppressing hormone are used to treat obesity and type 2 diabetes. However, the GLP-1 receptor (GLP-1R) is also present in the kidney, where it influences renal function. The effect of GLP-1 on the kidney varies between humans and rodents. The effect of GLP-1 on kidney function also seems to vary depending on its concentration and the physiological or pathological state of the kidney. In studies with rodents or humans, acute infusion of pharmacological doses of GLP-1 stimulates natriuresis and diuresis. However, the effect on the renal vasculature is less clear. In rodents, GLP-1 infusion increases renal plasma flow and glomerular filtration rate, suggesting renal vasodilation. In humans, only a subset of the study participants exhibits increased renal plasma flow and glomerular filtration rate. Differential status of kidney function and changes in renal vascular resistance of the preglomerular arterioles may account for the different responses of the human study participants. Because renal function in patients with type 2 diabetes is already at risk or compromised, understanding the effects of GLP-1R activation on kidney function in these patients is particularly important. This review examines the distribution of GLP-1R in the kidney and the effects elicited by GLP-1 or GLP-1R agonists. By integrating results from acute and chronic studies in healthy individuals and patients with type 2 diabetes along with those from rodent studies, we provide insight into how GLP-1R activation affects renal function and autoregulation.

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Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00518.2015 ◽

2016 ◽

Vol 310 (9) ◽

pp. E744-E753 ◽

Cited By ~ 16

Author(s):

Ali Asmar ◽

Lene Simonsen ◽

Meena Asmar ◽

Sten Madsbad ◽

Jens J. Holst ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiac Output ◽

Glomerular Filtration ◽

Filtration Rate ◽

Renal Plasma Flow ◽

Renal Hemodynamics ◽

Acute Administration ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

During acute administration of native glucagon-like peptide-1 (GLP-1), we previously demonstrated central hemodynamic effects in healthy males, whereas renal hemodynamics, despite renal uptake of GLP-1 in excess of glomerular filtration, was unaffected. In the present study, we studied hemodynamic effects of GLP-1 in patients with type 2 diabetes under fixed sodium intake. During a 3-h infusion of GLP-1 (1.5 pmol·kg−1·min−1) or saline, intra-arterial blood pressure and heart rate were measured continuously, concomitantly with cardiac output estimated by pulse contour analysis. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured using Fick's Principle after catheterization of a renal vein. Urine collection was conducted throughout the experiments at voluntary voiding, and patients remained supine during the experiments. During the GLP-1 infusion, systolic and diastolic blood pressure and cardiac output remained unchanged, whereas heart rate increased significantly. Arterio-venous gradients for GLP-1 exceeded glomerular filtrations significantly, but renal plasma flow and glomerular filtration rate as well as renal sodium and lithium excretion were not affected. In conclusion, acute administration of GLP-1 in patients with type 2 diabetes leads to a positive chronotropic effect, but in contrast to healthy individuals, cardiac output does not increase in patients with type 2 diabetes. Renal hemodynamics and sodium excretion are not affected.

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STUDY OF RADIATION CHARACTERISTICS THE RENAL FUNCTION IN PATIENTS WITH TYPE 2 DIABETES

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2014.2.12 ◽

2014 ◽

pp. 73-77

Author(s):

Van Chuong Nguyen ◽

Thi Kim Anh Nguyen

Keyword(s):

Type 2 Diabetes ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Disease Duration ◽

Left Kidney ◽

Cross Sectional ◽

The Right

Background: A Research glomerular filtration rate (GFR) of 61 patients with type 2 diabetes mellitus with renal scanning 99mTc-DTPA glomerular filtration rate at the hospital 175. Objective: (1) To study characteristics of imaging of renal function. (2) Understanding the relationship between GFR with blood sugar, HbA1c, blood pressure and albuminuria in patients with type 2 diabetes. Methods: Descriptive, prospective, cross-sectional study. Clinical examination, Clinical tests and 99mTc-DTPA GFR gamma - camera renography for patients. Result: GFR of the study group was 75,4 ± 22,3 ml/phut/1,73m2, the left kidney was 35,0 ± 13,0 is lower than the right kidney and 39,8 ± 11,9; p <0,01. There is no correlation between GFR with blood glucose and HbA1c, the risk of reduced GFR in hypertensive group associated is OR = 6,5 with p<0,01; albuminuria (+) is OR = 4,2 with p <0,01; and disease duration > 10 years is OR = 3,5 with p <0.01. Conclusion: GFR of the left kidneys is lower than the right kidney; correlation decreased GFR associated with hypertension, albuminuria and disease duration. Keywords: GFR, diabetes, albuminuria

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Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2015.04.004 ◽

2015 ◽

Vol 29 (5) ◽

pp. 670-674 ◽

Cited By ~ 36

Author(s):

Bernt Johan von Scholten ◽

Tine Willum Hansen ◽

Jens Peter Goetze ◽

Frederik Persson ◽

Peter Rossing

Keyword(s):

Type 2 Diabetes ◽

Kidney Function ◽

Receptor Agonist ◽

Term Effect ◽

Long Term Effect ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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Comparative Cardio-Renal Outcomes of Type 2 Diabetes Patients Administered Glucagon-Like Peptide-1 Receptor Agonists: A Network Meta-Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.759262 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chuanjun Zhuo ◽

Chongguang Lin ◽

Chunhua Zhou ◽

Xiangyang Gao ◽

Hailin Shao ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Type 2 Diabetes ◽

Thyroid Carcinoma ◽

Kidney Function ◽

Cardiovascular Outcome Trials ◽

Secondary Outcomes ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Background: Cardio-renal profiles are available from cardiovascular outcome trials of glucagon-like peptide-1 receptor agonists (GLP-1 RAs).Methods: A comprehensive systematic review of Embase, Medline, Web of Knowledge, and CENTRAL databases was conducted. Randomized controlled cardiovascular outcome trials of type 2 diabetes mellitus (T2DM) patients administered GLP-1 RAs were included. The following primary outcomes were examined: cardiovascular death, major adverse cardiovascular events (MACE), myocardial infarction, stroke, mortality, heart failure, hypoglycemia, pancreatitis, and thyroid carcinoma. Secondary outcomes included: composite kidney outcome, worsening kidney function, macroalbuminuria, and retinopathy.Results: Seven trials involving 56,004 patients and eight interventions were identified. Albiglutide was associated with fewer MACE and myocardial infarction events compared with lixisenatide. Lixisenatide was related to a greater number of stroke events and cardiovascular deaths compared to once-weekly semaglutide and oral semaglutide, respectively. Improved mortality was associated with oral semaglutide compared with once-weekly semaglutide, albiglutide, dulaglutide, exenatide, or lixisenatide. Risks of heart failure, thyroid carcinoma, and pancreatitis were similar among all the treatments. Weighting of the nine primary outcomes identified oral semaglutide as first among the eight treatments examined. Among three of the secondary outcomes, once-weekly semaglutide ranked first. Better composite kidney outcome was observed with once-weekly semaglutide than with dulaglutide or exenatide; once-weekly semaglutide improved macroalbuminuria compared with exenatide or lixisenatide; and albiglutide, exenatide, and placebo was associated with fewer cases of retinopathy compared with once-weekly semaglutide. Meanwhile, kidney function was less likely to worsen with dulaglutide than with lixisenatide or placebo.Conclusion: Semaglutide should be considered when GLP-1 RAs are indicated for T2DM patients.

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The Error of Estimated GFR in Type 2 Diabetes Mellitus

Journal of Clinical Medicine ◽

10.3390/jcm8101543 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1543 ◽

Cited By ~ 2

Author(s):

Sergio Luis-Lima ◽

Tomás Higueras Linares ◽

Laura Henríquez-Gómez ◽

Raquel Alonso-Pescoso ◽

Angeles Jimenez ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Kidney Disease ◽

Glomerular Filtration ◽

Cystatin C ◽

Filtration Rate

Type 2 diabetes mellitus represents 30–50% of the cases of end stage renal disease worldwide. Thus, a correct evaluation of renal function in patients with diabetes is crucial to prevent or ameliorate diabetes-associated kidney disease. The reliability of formulas to estimate renal function is still unclear, in particular, those new equations based on cystatin-C or the combination of creatinine and cystatin-C. We aimed to assess the error of the available formulas to estimate glomerular filtration rate in diabetic patients. We evaluated the error of creatinine and/or cystatin-C based formulas in reflecting real renal function over a wide range of glomerular filtration rate (from advanced chronic kidney disease to hyperfiltration). The error of estimated glomerular filtration rate by any equation was common and wide averaging 30% of real renal function, and larger in patients with measured glomerular filtration rate below 60 mL/min. This led to chronic kidney disease stages misclassification in about 30% of the individuals and failed to detect 25% of the cases with hyperfiltration. Cystatin-C based formulas did not outperform creatinine based equations, and the reliability of more modern algorithms proved to be as poor as older equations. Formulas failed in reflecting renal function in type 2 diabetes mellitus. Caution is needed with the use of these formulas in patients with diabetes, a population at high risk for kidney disease. Whenever possible, the use of a gold standard method to measure renal function is recommended.

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The effects of Glucagon‐like Peptide‐1 receptor agonists on kidney function and safety in type 2 diabetes

Journal of Diabetes Investigation ◽

10.1111/jdi.13552 ◽

2021 ◽

Author(s):

Min Kyung Kim ◽

Doo‐Man Kim

Keyword(s):

Type 2 Diabetes ◽

Kidney Function ◽

Receptor Agonists ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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SERIAL RENAL CLEARANCES IN DOGS WITH NEPHROGENIC AND SPONTANEOUS HYPERTENSION

Journal of Experimental Medicine ◽

10.1084/jem.90.6.511 ◽

1949 ◽

Vol 90 (6) ◽

pp. 511-524 ◽

Cited By ~ 16

Author(s):

J. Stamler ◽

L. N. Katz ◽

S. Rodbard

Keyword(s):

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Kidney Function ◽

Plasma Flow ◽

Filtration Rate ◽

Renal Plasma Flow ◽

Spontaneous Hypertension ◽

Focal Lesions ◽

Renal Clearances

Evidence is presented on the occurrence of spontaneous hypertension in dogs. All dogs with spontaneous hypertension exhibited normal renal plasma flow and glomerular filtration rate. Clearances on nephrogenic hypertensive dogs revealed that some exhibited normal kidney function, while others had significant depression of renal plasma flow and glomerular filtration rate. In the latter, the filtration fraction may or may not be elevated. Serial renal clearances were done at intervals on 3 dogs with spontaneous hypertension during their 3rd year of known hypertension. They exhibited no tendency to develop impaired renal function in the face of prolonged benign hypertension. Serial renal clearances on nephrogenic hypertensive dogs revealed no tendency for kidney function to become progressively impaired. This was true, whether the immediate postoperative clearance values were normal or depressed. It was also true regardless of the duration of the hypertension. It is suggested that mechanisms other than elevated blood pressure per se operate to produce progressive kidney damage and impairment of renal function. No tendency was revealed over the course of a year or more for the kidney function to improve in Goldblatt dogs exhibiting depressed clearances immediately postoperatively. This is interpreted as evidence against the postoperative development in persistently hypertensive Goldblatt dogs of a renal collateral circulation sufficient to augment significantly effective renal blood flow. Pathological studies on 2 dogs with spontaneous hypertension revealed slight to moderate chronic focal lesions in the kidneys, and bilateral adrenal cortical adenomatous hyperplasia. Both lesions may have no pathogenetic significance. In accord with previous observations, autopsies on 3 Goldblatt dogs revealed minimal renal changes in one, and unilateral kidney atrophy with contralateral hypertrophy in the 2 others. The adrenals were normal. In general, data on renal clearances showed correlation with postmortem kidney findings. However, normal renal clearances are found in the presence of anatomically abnormal kidneys. The findings in canine spontaneous and nephrogenic hypertension are compared and contrasted with data obtained in human essential hypertension. Pathogenetic relationships are discussed.

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Impact of glucagon like peptide-1 receptor agonist and sodium glucose cotransporter 2 inhibitors on type 2 diabetes patients with renal impairment

Diabetes and Vascular Disease Research ◽

10.1177/1479164120971220 ◽

2020 ◽

Vol 17 (6) ◽

pp. 147916412097122

Author(s):

Takeyuki Hiramatsu ◽

Hiroki Ito ◽

Shota Okumura ◽

Yuko Asano ◽

Daiki Iguchi ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Renal Function ◽

Renal Impairment ◽

Cardiac Function ◽

Receptor Agonist ◽

Sodium Glucose Cotransporter ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Introduction: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. Materials and methods: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)—dapagliflozin ( n = 52) or empagliflozin ( n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. Results: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups ( p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e′ or left atrial volume index, decreased only in Group G at 36 months. Conclusions: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.

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РARTICULAR QUALITIES OF THE RENAL OSMOREGULATORY FUNCTION IN PATIENTS WITH TYPE 2 DIABETES

Ukrainian Journal of Nephrology and Dialysis ◽

10.31450/ukrjnd.4(48).2015.03 ◽

2015 ◽

pp. 21-26 ◽

Cited By ~ 1

Author(s):

E.S. Kuznetsova ◽

A.S. Kuznetsova ◽

V.V. Shuhtin ◽

A.I. Gozhenko

Keyword(s):

Type 2 Diabetes ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Glomerular Filtration ◽

Filtration Rate ◽

Freezing Point ◽

Insulin Dependent ◽

Insulin Dependent Diabetic ◽

Osmoregulatory Function

The aim of the study was to examine the osmoregulatory state of renal function in patients with type 2 diabetes in a water - salt load with 0,5% NaCl in the amount of 0.5% of body weight. Materials and methods. The study involved 56patients with insulin - dependent diabetic nephropathy,24 men (42.9%) and 32 women (57.1%), aged from 38 to 81 years. The osmolality was measured by freezing point depression on osmomat 030 - D (USA). Glomerular filtration rate (GFR) was calculated by the formula GFR - EPI with subsequent determination of renal functional reserve. Results. It demonstrated that renal osmoregulatory function provides effective regulation of osmotic homeostasis even in a reduced amount of nephrons, but as the glomerular filtration rate decreses to 30 ml/min, the excretion of osmotically active substances gradually decrease too. Conclusion. Osmoregulatory disturbances in the renal function in patients with 2 types diabetes depend both on the reduction in GFR, - and on changes in the functional capacity of nephron's tubules.

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