Ignite Creation Date:
2024-06-16 @ 11:48 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06421870
Status:
RECRUITING
Last Update Posted:
2024-05-20
First Post:
2024-05-15
Brief Title:
Renoprotective Effects of Dapagliflozin Versus Pentoxiphylline in Chronic Kidney Disease Patients
Sponsor:
Ain Shams University
Organization:
Ain Shams University
Study Overview
Official Title:
Renoprotective Effects of Dapagliflozin Versus Pentoxiphylline in Chronic Kidney Disease Patients
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Kidneys have a vital role in glucose homeostasis by various mechanisms one of the major mechanisms is through SGLT2 This role was commonly overlooked till development of the new SGLT2 inhibitors Ni L et al 2020 The SGLT2 inhibitor class of glucose-lowering agents has recently shown beneficial effects to reduce the onset and progression of renal complications in people with and without diabetes through slow the decline in glomerular filtration rate GFR delaying the onset of microalbuminuria and slow or reverse the progression of proteinuria Nespoux J Vallon V 2020 The drug pentoxifylline is a methyl-xanthine derivative and a nonselective phosphodiesterase inhibitor with anti-inflammatory antiproliferative and antifibrotic actions currently indicated for peripheral artery disease Panchapakesan U et al2018 Chronic kidney disease is a progressive disorder in which patients are treated according to complications presented such as hypocalcemia hyperkalemia anemia and metabolic acidosis
Detailed Description:
It is only in recent years that the attention was drawn on the key role of the kidney in glucose homeostasis Nevertheless along with the liver the kidney has a key role in ensuring the energy needs during fasting periods This organ has a vital role in absorbing the entire quantity of the filtered glucose Having a glomerular filtration rate of 180 litres per day it filters approximately 180 grams of glucose per day bringing its contribution in maintaining normal fasting plasma glucose FPG levels Cersosimo Eet al 2014 The reabsorption of glucose is ensured by the sodium-glucose cotransporter SGLT 2 responsible for the reabsorption of 90 of glucose and SGLT1 that reabsorbs the remaining glucose Mota M et al 2015 Glomerular hyperfiltration is a common pathway of kidney injury both in diabetic and non-diabetic settings and is associated with progression of kidney function decline Hoogeveen E K 2022 Sodium-glucose co-transporter-2 SGLT2 inhibitors are glucose-lowering agents that eliminate excess glucose through a glucosuric effect by reducing glucose reabsorption from the renal filtrate Thomson S C et al 2019 It is indicated that the expression of high mobility group box 1 HMGB1 increased in patients with kidney disease and may result in renal injury through the activation of nuclear factor- κB NF- κB and an increase in receptor for advanced glycation end products RAGE expression It is suggested that Dapagliflozin achieves its reno-protective status through its antioxidative stress and anti-inflammatory action via inhibition of the HMGB1 - RAGE - NF- κB signalling pathway Yao D et al 2018 SGLT2 is found almost exclusively in the luminal membranes of epithelial cells lining the first and second segments of the proximal tubules where it mediates reabsorption of most typically 90 of filtered glucose Mudaliar S et al 2015 By inhibiting SGLT2 beneficial kidney effects are thought to be mediated by various mechanisms including restoration of tubule-glomerular feedback leading to a reduction in intraglomerular pressure and hyperfiltration Both conditions are considered core components of the pathophysiology contributing to progression of diabetic as well as nondiabetic CKD Reductions in intraglomerular pressure as shown by agents blocking the renin-angiotensin system are frequently accompanied by a hemodynamic acute decrease in GFR which is reversible after treatment cessation Wanner et al 2018
Common drug side effects of dapagliflozin include urinary tract infections cystitis hypotension dehydration and female genital mycotic infections Hypoglycemic episodes were reported in 6 to 10 of patients who administer dapagliflozin concurrently with insulin and insulin secretagogues Anderson SL et al 2014 Pentoxifylline PTF is a synthetic dimethylxanthine derivative that modulates the rheological properties of blood and has both anti-oxidant and anti-inflammatory properties PTF has been investigated for its possible use in diverse conditions including osteoradionecrosis diabetic kidney disease and generally any condition associated with fibrosis Wen WX et al 2017 PTF reduces levels of inflammatory markers high-sensitivity C-reactive protein hs-CRP serum fibrinogen and TNF-α this could reduce albuminuria and slow renal disease progression de Morales AM et al 2019
Thus we need to evaluate the effect of Dapagliflozin versus Pentoxifylline on GFR among CKD non-diabetic patients
Common drug side effects of dapagliflozin include urinary tract infections cystitis hypotension dehydration and female genital mycotic infections Hypoglycemic episodes were reported in 6 to 10 of patients who administer dapagliflozin concurrently with insulin and insulin secretagogues Anderson SL et al 2014 Pentoxifylline PTF is a synthetic dimethylxanthine derivative that modulates the rheological properties of blood and has both anti-oxidant and anti-inflammatory properties PTF has been investigated for its possible use in diverse conditions including osteoradionecrosis diabetic kidney disease and generally any condition associated with fibrosis Wen WX et al 2017 PTF reduces levels of inflammatory markers high-sensitivity C-reactive protein hs-CRP serum fibrinogen and TNF-α this could reduce albuminuria and slow renal disease progression de Morales AM et al 2019
Thus we need to evaluate the effect of Dapagliflozin versus Pentoxifylline on GFR among CKD non-diabetic patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None