Renoprotection

Mutations in PKD1 and PKD2 cause autosomal dominant polycystic kidney disease (ADPKD), which is characterized by the formation of fluid-filled cysts in the kidney. In a subset of ADPKD patients, reduced blood calcium (Ca2+ ) and magnesium (Mg2+ ) concentrations are observed. As cystic fluid contains increased ATP concentrations and purinergic signaling reduces electrolyte reabsorption, we hypothesized that inhibiting ATP release could normalize blood Ca2+ and Mg2+ levels in ADPKD. Inducible kidney-specific Pkd1 knockout mice (iKsp-Pkd1-/- ) exhibit hypocalcemia and hypomagnesemia in a precystic stage and show increased expression of the ATP-release channel pannexin-1...

Ischemia-reperfusion (I/R) leads to tissue damage in transplanted kidneys, resulting in acute kidney injury (AKI) and chronic graft dysfunction, which critically compromises transplant outcomes, such as graft loss. Linaclotide, a guanylate cyclase C agonist clinically approved as a laxative, has recently been identified to exhibit renoprotective effects in a chronic kidney disease (CKD) model. This study evaluates the therapeutic effects of linaclotide on AKI triggered by I/R in a rat model with an initial comparison with other laxatives...

Curcumin is a naturally polyphenolic compound used for hepatoprotective, thrombosuppressive, neuroprotective, cardioprotective, antineoplastic, antiproliferative, hypoglycemic, and antiarthritic effects. Kidney disease is a major public health problem associated with severe clinical complications worldwide. The protective effects of curcumin against nephrotoxicity have been evaluated in several experimental models. In this review, we discussed how curcumin exerts its protective effect against renal toxicity and also illustrated the mechanisms of action such as anti-inflammatory, antioxidant, regulating cell death, and anti-fibrotic...

Acute kidney injury (AKI) is a serious health concern with high morbidity and high mortality worldwide. Recently, sexual dimorphism has become increasingly recognized as a factor influencing the severity of the disease. This study explores the gender-specific renoprotective pathways in αMUPA transgenic mice subjected to AKI. αMUPA transgenic male and female mice were subjected to ischemia-reperfusion (I/R)-AKI in the presence or absence of orchiectomy, oophorectomy, and L-NAME administration. Blood samples and kidneys were harvested 48 h following AKI for the biomarkers of kidney function, renal injury, inflammatory response and intracellular pathway sensing of or responding to AKI...

BACKGROUND: Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy. METHODS: 40 Wistar rats of either sex were randomly divided into four groups viz ...

The prevalence and burden of diabetes are on the rise in India, making it 'the diabetes capital of the world'. Comorbidities such as obesity, cardiovascular (CV) complications, chronic kidney disease (CKD), non-alcoholic fatty liver disease (NAFLD), and neurodegenerative diseases are common in patients with diabetes. Recent breakthroughs in diabetes medications and continuous glucose monitoring have resulted in a paradigm shift in diabetes care. Hence, a review in the Indian context is warranted. This review focuses on the existing evidence (gathered by a systematic literature search utilising online databases such as PubMed) on the metabolic, cardio-renoprotective, and hepatoprotective effects of sodium-glucose co-transporter 2 (SGLT2) inhibition, particularly in the Indian setting...

Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia-reperfusion injury (IRI) could prevent the progression to CKD. Forty-one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30 min (IR) or IR+RSV...

Transcription enhancers are genomic sequences regulating common and tissue-specific genes and their disruption can contribute to human disease development and progression. Klotho , a sexually dimorphic gene specifically expressed in kidney, is well-linked to kidney dysfunction and its deletion from the mouse genome leads to premature aging and death. However, the sexually dimorphic regulation of Klotho is not understood. Here, we characterize two candidate Klotho enhancers using H3K27ac epigenetic marks and transcription factor binding and investigate their functions, individually and combined, through CRISPR-Cas9 genome engineering...

BACKGROUND: High-dose methotrexate (HDMTX) as a cytotoxic agent might cause various side effects. Hyperhydration has been implemented as the major strategy to decrease the potential risk of toxicities induced by HDMTX. This study aims to assess the renoprotective effect of hydration with dextrose water (DW) 5% versus normal saline (N/S) 0.9% against methotrexate (MTX) induced nephrotoxicity. MATERIALS AND METHODS: This experimental animal study has been conducted on 36 Wistar rats (200-250 g) categorized into six groups, including male ( n = 6) and female ( n = 6) rats receiving sodium chloride 0...

CONTEXT: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. OBJECTIVE: To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. MATERIALS AND METHODS: Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks...

Proteinuria is a predictor of end-stage renal disease. The effectiveness of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker for the reduction in urinary protein excretion and renoprotection in proteinuric chronic kidney disease patients is well known, and coadministration of and sodium-glucose cotransporter inhibitor and the mineralocorticoid receptor blocker eplerenone has recently demonstrated an additive albuminuria-lowering effect in chronic kidney disease patients. Proteinuria is also an independent predictor of end-stage renal disease in kidney transplant recipients...

BACKGROUND AND AIMS: Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported...

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibition is recognized for its evident renoprotective benefits in diabetic renal disease. Recent data suggest that SGLT2 inhibition also slows down kidney disease progression and reduces the risk of acute kidney injury, regardless of whether the patient has diabetes or not, but the mechanism behind these observed effects remains elusive. The objective of this study is to utilize a mendelian randomization (MR) methodology to comprehensively examine the influence of metabolites in circulation regarding the impact of SGLT2 inhibition on kidney function...

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria...

OBJECTIVE: It is expected that antioxidants contribute to slow the progression of chronic kidney disease (CKD). However, there is no data on the protective effect of dietary antioxidant vitamins on CKD. The purpose of study was to evaluate the renoprotective effect of dietary antioxidant vitamins in the general population. DESIGN AND METHODS: The study participants were 127,081 Korean adults with preserved renal function with eGFR ≥ 60 ml/min/1.73 m2 . They were categorized into three groups by tertile levels of dietary antioxidant vitamins intake including vitamins C, E, and A...

This study focuses to investigate the pharmacological activities, botanical sources, and biopharmaceutical profile of the phytochemical fraxin based on different preclinical and non-clinical studies to show the scientific evidence and to evaluate the underlying molecular mechanisms of the therapeutic effects against various ailments. For this, data was searched and collected (as of February 15, 2024) in a variety of credible electronic databases, including PubMed/Medline, Scopus, Springer Link, ScienceDirect, Wiley Online, Web of Science, and Google Scholar...

BACKGROUND: The risk of contrast-associated acute kidney injury is relatively higher in patients with diabetes mellitus compared to non-diabetics. Recent trials have revealed the renoprotective effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors. We aimed to investigate the possible preventive effect of SGLT2 inhibitors against contrast-associated acute kidney injury in the diabetic population who underwent coronary angiography with a diagnosis of stable angina or acute coronary syndrome...

The tissue inhibitor of metalloproteinases 2 (TIMP2) has emerged as a promising biomarker for predicting the risk of sepsis-associated acute kidney injury (SA-AKI). However, its exact role in SA-AKI and the underlying mechanism remains unclear. In this study, we investigated the impact of kidney tubule-specific Timp2 knockout mice on kidney injury and inflammation. Our findings demonstrated that Timp2-knockout mice exhibited more severe kidney injury than wild-type mice, along with elevated levels of pyroptosis markers NLRP3, Caspase1, and GSDMD in the early stage of SA-AKI...

BACKGROUND: Renal ischemia-reperfusion injury (RIRI) is an inevitable complication in the process of kidney transplantation and lacks specific therapy. The study aims to determine the underlying mechanisms of RIRI to uncover a promising target for efficient renoprotection. METHOD: Four bulk RNA-seq datasets including 495 renal samples of pre- and post-reperfusion were collected from the GEO database. The machine learning algorithms were utilized to ascertain pivotal endoplasmic reticulum stress genes...

Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of end-stage kidney disease (ESKD). Vasopressin plays a pivotal role in ADPKD progression; therefore, the selective vasopressin V2 receptor antagonist tolvaptan is used as a key drug in the management of ADPKD. On the other hand, sodium-glucose cotransporter-2 inhibitors (SGLT2i), which may possibly stimulate vasopressin secretion due to the diuretic effect of the drug, have been shown to have both renal and cardioprotective effects in various populations, including those with non-diabetic chronic kidney disease...