scholarly journals Dietary protein restriction in established renal injury in the rat. Selective role of glomerular capillary pressure in progressive glomerular dysfunction.

1986 ◽  
Vol 78 (5) ◽  
pp. 1199-1205 ◽  
Author(s):  
K A Nath ◽  
S M Kren ◽  
T H Hostetter
Keyword(s):  
Capillary Pressure ◽  
Dietary Protein ◽  
Renal Injury ◽  
Protein Restriction ◽  
Dietary Protein Restriction ◽  
Glomerular Capillary ◽  
Glomerular Capillary Pressure

Role of FGF21 and GCN2 in mediating the metabolic response to dietary protein restriction

2016 ◽  
Vol 11 (S 01) ◽  
Author(s):  
T Laeger ◽  
DC Albarado ◽  
L Trosclair ◽  
J Hedgepeth ◽  
CD Morrison
Keyword(s):  
Dietary Protein ◽  
Metabolic Response ◽  
Protein Restriction ◽  
Dietary Protein Restriction

scholarly journals Impaired renal hemodynamics and glomerular hyperfiltration contribute to hypertension-induced renal injury

2020 ◽  
Vol 319 (4) ◽  
pp. F624-F635 ◽  
Author(s):  
Letao Fan ◽  
Wenjun Gao ◽  
Bond V. Nguyen ◽  
Joshua R. Jefferson ◽  
Yedan Liu ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Capillary Pressure ◽  
Renal Injury ◽  
Filtration Rate ◽  
Time Course ◽  
Renal Hemodynamics ◽  
Myogenic Response ◽  
Glomerular Capillary ◽  
Glomerular Capillary Pressure

Recently, we reported a mutation in γ-adducin (ADD3) was associated with an impaired myogenic response of the afferent arteriole and hypertension-induced chronic kidney disease (CKD) in fawn hooded hypertensive (FHH) rats. However, the mechanisms by which altered renal blood flow (RBF) autoregulation promotes hypertension-induced renal injury remain to be determined. The present study compared the time course of changes in renal hemodynamics and the progression of CKD during the development of DOCA-salt hypertension in FHH 1BN congenic rats [wild-type (WT)] with an intact myogenic response versus FHH 1BN Add3KO ( Add3KO) rats, which have impaired myogenic response. RBF was well autoregulated in WT rats but not in Add3KO rats. Glomerular capillary pressure rose by 6 versus 14 mmHg in WT versus Add3KO rats when blood pressure increased from 100 to 150 mmHg. After 1 wk of hypertension, glomerular filtration rate increased by 38% and glomerular nephrin expression decreased by 20% in Add3KO rats. Neither were altered in WT rats. Proteinuria doubled in WT rats versus a sixfold increase in Add3KO rats. The degree of renal injury was greater in Add3KO than WT rats after 3 wk of hypertension. RBF, glomerular filtration rate, and glomerular capillary pressure were lower by 20%, 28%, and 19% in Add3KO rats than in WT rats, which was associated with glomerular matrix expansion and loss of capillary filtration area. The results indicated that impaired RBF autoregulation and eutrophic remodeling of preglomerular arterioles increase the transmission of pressure to glomeruli, which induces podocyte loss and accelerates the progression of CKD in hypertensive Add3KO rats.

scholarly journals The role of TRPC6 calcium channels and P2 purinergic receptors in podocyte mechanical and metabolic sensing

2021 ◽  
Keyword(s):  
Capillary Pressure ◽  
Plasma Glucose ◽  
Purinergic Receptors ◽  
P2 Receptors ◽  
Glomerular Capillary ◽  
Glomerular Capillary Pressure ◽  
Metabolic Sensing

Abstract Podocyte calcium (Ca2+) signaling plays important roles in the (patho)physiology of the glomerular filtration barrier. Overactivation of podocyte transient receptor potential canonical (TRPC) channels including TRPC6 and purinergic signaling via P2 receptors that are known mechanosensors can increase podocyte intracellular Ca2+ levels ([Ca2+]i) and cause cell injury, proteinuria and glomerular disease including in diabetes. However, important mechanistic details of the trigger and activation of these pathways in vivo in the intact glomerular environment are lacking. Here we show direct visual evidence that podocytes can sense mechanical overload (increased glomerular capillary pressure) and metabolic alterations (increased plasma glucose) via TRPC6 and purinergic receptors including P2Y2. Multiphoton microscopy of podocyte [Ca2+]i was performed in vivo using wild-type and TRPC6 or P2Y2 knockout (KO) mice expressing the calcium reporter GCaMP3/5 only in podocytes and in vitro using freshly dissected microperfused glomeruli. Single-nephron intra-glomerular capillary pressure elevations induced by obstructing the efferent arteriole lumen with laser-induced microthrombus in vivo and by a micropipette in vitro triggered >2-fold increases in podocyte [Ca2+]i. These responses were blocked in TRPC6 and P2Y2 KO mice. Acute elevations of plasma glucose caused >4-fold increases in podocyte [Ca2+]i that were abolished by pharmacological inhibition of TRPC6 or P2 receptors using SAR7334 or suramin treatment, respectively. This study established the role of Ca2+ signaling via TRPC6 channels and P2 receptors in mechanical and metabolic sensing of podocytes in vivo, which are promising therapeutic targets in conditions with high intra-glomerular capillary pressure and plasma glucose, such as diabetic and hypertensive nephropathy.

Abstract MP46: Knockout Of Add3 Impairs Autoregulation Of Renal Blood Flow And Promotes Hypertension-induced Renal Injury By Increasing Glomerular Capillary Pressure And Podocyte Loss

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Letao Fan ◽  
Wenjun Gao ◽  
Yedan Liu ◽  
Bond V Nguyen ◽  
Joshua R Jefferson ◽  
...  
Keyword(s):  
Capillary Pressure ◽  
Renal Injury ◽  
Time Course ◽  
Interstitial Fibrosis ◽  
Myogenic Response ◽  
Mesenchymal Transition ◽  
Glomerular Capillary ◽  
Glomerular Capillary Pressure ◽  
Podocyte Loss ◽  
Salt Hypertension

Recently, we reported that a mutation in γ-Adducin (ADD3) alters the actin cytoskeleton and is associated with an impaired myogenic response of the afferent arteriole and enhanced hypertension-induced renal disease. However, it remains to be determined whether the loss of ADD3 function promotes renal injury by increasing glomerular capillary pressure (Pgc) and podocyte loss or other mechanisms. The present study compared the time course of changes in renal hemodynamics and the progression of renal injury during the development of DOCA-salt hypertension in FHH 1 BN rats (WT) with an intact myogenic response vs. FHH 1 BN Add3KO rats (Add3KO) in which the myogenic response is impaired. When transmural pressure rose from 40 to 100 mmHg, the inner diameter of the preglomerular artery constricted by 19% (47.7 ± 4.3 to 38.4 ± 3.4 μm, n = 5) in WT, but it dilated by 28% (53.0 ± 2.2 to 67.9 ± 4.3 μm, n = 7) in Add3KO. Pgc was similar (50.1 ± 0.4 vs. 51.2 ± 0.8 mmHg, n = 6) at 100 mmHg, but rose by 6 and 14 mmHg in WT vs. Add3KO when perfusion pressure rose to 150 mmHg. Mean arterial pressure increased similarly and reached 177.7 ± 3.5 vs. 182.6 ± 2.3 mmHg (n = 9) after 3 weeks of DOCA-salt hypertension in WT vs. Add3KO. After 1 week of DOCA-salt hypertension, glomerular filtration rate (GFR) increased by 38% (1.2 ± 0.1 to 1.6 ± 0.1 ml/min/kidney, n = 6) and glomerular nephrin expression decreased by 20% (165.4 ± 4.5 to 131.614 ± 5.2 RFU, n = 7) in Add3KO. Both were unaltered in WT. Proteinuria increased 2 folds in WT (56.9 ± 4.7 to 168.6 ± 26.7 mg/day, n = 12) in the first week of hypertension vs. a 6-fold increase in Add3KO (64.6 ± 4.1 to 446.0 ± 41.9 mg/day, n = 9). After 3 weeks of hypertension, the degree of glomerulosclerosis (3.4 ± 0.1 vs. 2.4 ± 0.1 glomerular injury score, n = 9~12), protein cast formation (9.0% ± 0.8% vs. 4.8% ± 0.4% of area, n = 6), epithelial-mesenchymal transition, interstitial fibrosis (17.9% ± 0.8% vs. 9.5% ± 0.3% of area, n = 6), and inflammation was significantly greater in Add3KO vs. WT. GFR and Pgc were 28% and 19% lower in Add3KO than WT. These results indicate that the impaired myogenic response increases the transmission of pressure to the glomerulus to induce the loss of podocytes, which accelerates the progression of renal injury during the development of hypertension in Add3KO.

scholarly journals Glomerular preload and afterload reduction as a tool to lower urinary protein leakage: will such treatments also help to improve renal function outcome?

1993 ◽  
Vol 3 (7) ◽  
pp. 1333-1341 ◽  
Author(s):  
P E de Jong ◽  
S Anderson ◽  
D de Zeeuw
Keyword(s):  
Ace Inhibitors ◽  
Dietary Protein ◽  
Protein Restriction ◽  
Urinary Protein ◽  
Hydraulic Pressure ◽  
Protein Loss ◽  
Afterload Reduction ◽  
Dietary Protein Restriction ◽  
Glomerular Capillary ◽  
Lower Urinary

It has been well documented that different therapeutic strategies, including angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, and dietary protein restriction, lower urinary protein excretion in patients with diabetic and non-diabetic nephropathy. Experimental evidence suggests that this antiproteinuric effect is, at least in part, related to a reduction in the glomerular capillary hydraulic pressure. ACE inhibitors appear to achieve this reduction in glomerular capillary pressure, mainly through a fall in postglomerular arteriolar resistance, whereas dietary protein restriction and non-steroidal antiinflammatory drugs appear to invoke the response predominantly through an increase in preglomerular resistance. This leads to the suggestion that both "glomerular preload reduction" (afferent vasoconstriction) and "glomerular afterload reduction" (efferent vasodilation) will result in an anti-proteinuric response. Interestingly, these same therapeutic regimens, particularly the ACE inhibitors and low-protein diets, have been proven to prevent progressive glomerulosclerosis in animal models. This concept of influencing glomerular hemodynamics both at the afferent and efferent arteriolar level may open new perspectives in the treatment of patients with renal protein loss and renal failure. At present, however, it is too early to conclude whether the fall in proteinuria induced by these treatments will also contribute to a better renal survival of these patients.

Neuronal FGF-21 Signaling–A Sensor of Dietary Protein Restriction

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 261-LB
Author(s):  
CRISTAL M. HILL ◽  
MADELEINE V. DEHNER ◽  
DAVID MCDOUGAL ◽  
HANS-RUDOLF BERTHOUD ◽  
HEIKE MUENZBERG ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Protein Restriction ◽  
Dietary Protein Restriction

238-LB: Dietary Protein Restriction Induces Myocardial Dysfunction Despite Reducing Body Weight in Aged C57BL/6J Mice

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 238-LB
Author(s):  
CHRISTOPHER L. AXELROD ◽  
WAGNER S. DANTAS ◽  
GANGARAO DAVULURI ◽  
WILLIAM T. KING ◽  
CRISTAL M. HILL ◽  
...  
Keyword(s):  
Body Weight ◽  
Dietary Protein ◽  
Myocardial Dysfunction ◽  
Protein Restriction ◽  
Dietary Protein Restriction
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