scholarly journals Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study

2018 ◽  
Vol 314 (3) ◽  
pp. F412-F422 ◽  
Author(s):  
Harindra Rajasekeran ◽  
Heather N. Reich ◽  
Michelle A. Hladunewich ◽  
Daniel Cattran ◽  
Julie A. Lovshin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Short Term Treatment ◽  
Segmental Glomerulosclerosis ◽  
Renal Hemodynamic ◽  
Hemodynamic Function ◽  
The Impact

Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.

scholarly journals The Gomez equations and renal hemodynamic function in kidney disease research

2016 ◽  
Vol 311 (5) ◽  
pp. F967-F975 ◽  
Author(s):  
Petter Bjornstad ◽  
Marko Škrtić ◽  
Yuliya Lytvyn ◽  
David M. Maahs ◽  
Richard. J. Johnson ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Renal Plasma Flow ◽  
Pharmacological Agents ◽  
Additional Information ◽  
Renal Hemodynamic ◽  
Intratubular Pressure ◽  
Hemodynamic Function ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at a preclinical stage. Existing methods that are used to assess renal function, including albuminuria and eGFR, do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in vivo in humans, equations were developed by Gomez et al. in the 1950s. These equations used measurements of glomerular filtration rate, renal blood flow, effective renal plasma flow, renal vascular resistance, hematocrit, and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure, and filtration pressure. The Gomez equations are, however, indirect and based on physiological assumptions derived from animal models, which may not hold true in human pathophysiology, including the assumption of a normal gross filtration coefficient and not considering changes in intratubular pressure that may affect the pressure gradient across the glomerular capillaries. Nevertheless, the equations have the potential to improve researchers' ability to identify early preclinical changes in renal hemodynamic function in patients with a variety of conditions, including DKD, thereby offering potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of these techniques in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 and type 2 diabetes and hypertension.

scholarly journals Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis

2018 ◽  
Vol 94 (6) ◽  
pp. 1151-1159 ◽  
Author(s):  
Alla Mitrofanova ◽  
Judith Molina ◽  
Javier Varona Santos ◽  
Johanna Guzman ◽  
Ximena A. Morales ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Segmental Glomerulosclerosis

scholarly journals Assessing the Impact of Losmapimod on Proteinuria in Idiopathic Focal Segmental Glomerulosclerosis

2020 ◽  
Vol 5 (8) ◽  
pp. 1228-1239
Author(s):  
Debbie S. Gipson ◽  
Michelle A. Hladunewich ◽  
Richard Lafayette ◽  
John R. Sedor ◽  
Brad H. Rovin ◽  
...  
Keyword(s):  
Focal Segmental Glomerulosclerosis ◽  
Segmental Glomerulosclerosis ◽  
The Impact

scholarly journals Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Amir Taherkhani ◽  
Reyhaneh Farrokhi Yekta ◽  
Maede Mohseni ◽  
Massoud Saidijam ◽  
Afsaneh Arefi Oskouie
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iga Nephropathy ◽  
Focal Segmental Glomerulosclerosis ◽  
Membranous Glomerulonephritis ◽  
Renal Diseases ◽  
Segmental Glomerulosclerosis ◽  
Therapeutic Procedures ◽  
Definition Of ◽  
End Stage

AbstractChronic Kidney Disease (CKD) is a global health problem annually affecting millions of people around the world. It is a comprehensive syndrome, and various factors may contribute to its occurrence. In this study, it was attempted to provide an accurate definition of chronic kidney disease; followed by focusing and discussing on molecular pathogenesis, novel diagnosis approaches based on biomarkers, recent effective antigens and new therapeutic procedures related to high-risk chronic kidney disease such as membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy, which may lead to end-stage renal diseases. Additionally, a considerable number of metabolites and proteins that have previously been discovered and recommended as potential biomarkers of various CKDs using ‘-omics-’ technologies, proteomics, and metabolomics were reviewed.

Alterations in Cardiovascular and Renal Hemodynamic Function Following Hypophysectomy in the Dog

1957 ◽  
Vol 188 (3) ◽  
pp. 529-534 ◽  
Author(s):  
M. Jay Goodkind ◽  
James O. Davis ◽  
Wilmot C. Ball ◽  
Robert C. Bahn
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Renal Plasma Flow ◽  
Functional Change ◽  
Peripheral Vascular ◽  
Appreciable Change ◽  
Renal Hemodynamic ◽  
Hemodynamic Function ◽  
Renal Vascular ◽  
Oxygen Difference

In studies of unanesthetized dogs, hypophysectomy resulted in a decrease in cardiac output, oxygen consumption, and stroke volume. No appreciable change in arteriovenous oxygen difference, mean femoral arterial pressure, or heart rate was observed. Glomerular filtration rate, renal plasma flow and renal fraction of cardiac output were markedly reduced in the hypophysectomized animals. Renal vascular resistance increased two- to threefold in contrast to a 24% increase in total peripheral vascular resistance. Although a marked reduction in cardiovascular and renal hemodynamic function resulted following hypophysectomy, there was no correlation between the degree of functional change and either the amount of anterior pituitary tissue remaining or the degree of atrophy of the adrenal cortex.

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