Uric acid lowering therapies for preventing or delaying the progression of chronic kidney disease

Zhu

et al. 2020

IJMS

Hyperuricemia (HUA) is a risk factor for chronic kidney disease (CKD). Serum uric acid (SUA) levels in CKD stage 3–4 patients closely correlate with hyperuricemic nephropathy (HN) morbidity. New uric acid (UA)-lowering strategies are required to prevent CKD. The multiple-purpose connectivity map (CMAP) was used to discover potential molecules against HUA and renal fibrosis. We used HUA and unilateral ureteral occlusion (UUO) model mice to verify renoprotective effects of molecules and explore related mechanisms. In vitro experiments were performed in HepG2 and NRK-52E cells induced by UA. Esculetin was the top scoring compound and lowered serum uric acid (SUA) levels with dual functions on UA excretion. Esculetin exerted these effects by inhibiting expression and activity of xanthine oxidase (XO) in liver, and modulating UA transporters in kidney. The mechanism by which esculetin suppressed XO was related to inhibiting the nuclear translocation of hexokinase 2 (HK2). Esculetin was anti-fibrotic in HUA and UUO mice through inhibiting TGF-β1-activated profibrotic signals. The renoprotection effects of esculetin in HUA mice were associated with lower SUA, alleviation of oxidative stress, and inhibition of fibrosis. Esculetin is a candidate urate-lowering drug with renoprotective activity and the ability to inhibit XO, promote excretion of UA, protect oxidative stress injury, and reduce renal fibrosis.

Section: Discussionmentioning

confidence: 99%

Multiple-Purpose Connectivity Map Analysis Reveals the Benefits of Esculetin to Hyperuricemia and Renal Fibrosis

Zhu

et al. 2020

IJMS

“…Elevated levels of serum uric acid have been associated with increased cardiovascular risk and CKD (63)(64)(65) . In this context, it has been suggested that lowering serum uric acid may improve kidney function (66,67) .…”

Section: Discussionmentioning

confidence: 99%

A higher ratio of refined grain to whole grain is associated with a greater likelihood of chronic kidney disease: a population-based study

et al. 2018

A growing number of studies suggest that diet and renal function are related. However, little is known about the link between both whole grain (WG) and refined grain (RG) consumption and kidney function parameters. Thus, we investigated the association of WG and RG with urinary albumin to creatinine ratio (ACR) and prevalent chronic kidney disease (CKD). Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were collected. Estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation. Survey design and sample weights were taken into consideration for statistical analyses. Finally, we included 16 325 participants from NHANES, 6·9 % of whom had prevalent CKD. In models adjusted for age, sex, race, fasting blood glucose, blood pressure, adiposity, hypertension and diabetes status, mean eGFR significantly increased across increasing quartiles of WG (Q1: 88·2 v. Q4: 95·4 ml/min per 1·73 m2, P<0·001), whereas it significantly decreased across increasing quartiles of RG (Q1: 97·2 v. Q4: 88·4 ml/min per 1·73 m2, P<0·001). Furthermore, serum uric acid levels and ACR significantly decreased across quartiles of WG (both P<0·001). In multivariable-adjusted logistic regression models, the likelihood of prevalent CKD was 21 % lower in the highest WG quartile compared with the lowest one. In conclusion, our results shed light on the beneficial impact of WG on kidney function and CKD, whereas RG is adversely associated with eGFR.

“…51 At present, there is insufficient evidence to recommend treatment of asymptomatic hyperuricemia with the purpose of delaying the progression of CKD. 52,53…”

Section: Step 7 Initiation Titration and Optimization Of Tolvaptanmentioning

confidence: 99%

A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan

Chebib

Perrone

Chapman

et al. 2018

JASN

192

184

In the past, the treatment of autosomal dominant polycystic kidney disease (ADPKD) has been limited to the management of its symptoms and complications. Recently, the US Food and Drug Administration (FDA) approved tolvaptan as the first drug treatment to slow kidney function decline in adults at risk of rapidly progressing ADPKD. Full prescribing information approved by the FDA provides helpful guidelines but does not address practical questions that are being raised by nephrologists, internists, and general practitioners taking care of patients with ADPKD, and by the patients themselves. In this review, we provide practical guidance and discuss steps that require consideration before and after prescribing tolvaptan to patients with ADPKD to ensure that this treatment is implemented safely and effectively. These steps include confirmation of diagnosis; identification of rapidly progressive disease; implementation of basic renal protective measures; counseling of patients on potential benefits and harms; exclusions to use; education of patients on aquaresis and its expected consequences; initiation, titration, and optimization of tolvaptan treatment; prevention of aquaresis-related complications; evaluation and management of liver enzyme elevations; and monitoring of treatment efficacy. Our recommendations are made on the basis of published evidence and our collective experiences during the randomized, clinical trials and open-label extension studies of tolvaptan in ADPKD.