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Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay‐guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti‐renal fibrotic lead. DA shows significant anti‐kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down‐regulates its downstream phospho‐protein kinase Cζ(p‐PKCζ)/phospho‐glycogen synthase kinase‐3β (p‐GSK‐3β), thereby promoting β‐catenin Ser33/37/Thr41 phosphorylation and ubiquitin‐dependent proteolysis to block classical pro‐fibrotic β‐catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: The aim of this study was to estimate the prevalence and risk factors of chronic kidney disease (CKD) in first-degree relatives (FDRs) of CKD patients. Methods: A cross-section study of first-degree relatives of CKD patients was conducted between November 2007 and March 2009 in southern China. A total of 1187 first-degree relatives (494 male and 693 female; mean age 41.26 years) of 419 CKD patients (194 male and 225 female; mean age 32.10 years) were reviewed and tested for haematuria, albuminuria and reduced glomerular filtration rate. CKD risk factors, including age, gender, body mass index, hypertension and the causes of index case were also investigated. CKD was diagnosed according to the criteria of the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative. Results: The prevalence of CKD in first-degree relatives of CKD patients was 29.7% (95% confidence interval [CI]: 27.1%-32.2%). After adjusting for all the potential confounders, older age, female gender, hypertension, hyperglycaemia, hyperuricaemia, hypertriglyceridemic, low level of high density lipoproteins, increased body mass index and nephrotoxic medications were independently associated with increased risk of CKD. Furthermore, relatives of index cases with chronic glomerulonephritis were at higher risk haematuria (ORs = 2.12, 95% CI: 1.45-3.10) compared with relatives of index cases with other kinds of renal diseases. Conclusion: The first-degree relatives of CKD patients are at high risk of CKD, especially those relatives of CKD patients with chronic glomerulonephritis. Screening in this high risk population might help to identify early CKD patients and make a proper intervention strategy to prevent the disease from quick progression. [ABSTRACT FROM AUTHOR]

Background. The prevalence of chronic kidney disease (CKD) at high altitude is not known. We conducted a population-based survey in Tibet to identify the prevalence and associated risk factors of CKD in subjects living at altitudes of > 3500 m.Methods. One thousand two hundred and eighty-nine Tibetans (≥ 18 years) from four districts of Lhasa city (altitude 3658 m) and eight villages of Dangxiong County (altitude 4200 m) were interviewed and tested for haematuria, albuminuria and estimated glomerular filtration rate (eGFR).Results. The adjusted prevalence of hypertension, albuminuria, haematuria and reduced eGFR were 38.8% (95% CI: 36.2–41.5%), 16.2% (95% CI: 14.1–18.2%), 3.9% (95% CI: 2.8–4.9%) and 2.1% (95% CI: 1.3–2.9%), respectively. Both the presence of hypertension and the presence of albuminuria were strongly and independently associated with hyperuricaemia and elevated haematocrit.Conclusions. This is the first population-based epidemiological study of CKD in the Tibetan population. We found a higher prevalence of CKD and associated high prevalence of albuminuria, hypertension, hyperuricaemia and high haematocrit in the Tibetan population. The present study indicates the urgent need to develop comprehensive strategies targeted at reducing the CKD burden in this area and may lead to a better understanding of CKD in high-altitude populations. [ABSTRACT FROM AUTHOR]