This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.

The underlying mechanisms of proteinuria, a main characteristic of preeclampsia (PE), have not yet been fully elucidated. Evidence indicates that the renin-angiotensin system (RAS) is involved in the pathogenesis of this disease, including decreased angiotensin-(1-7) [Ang-(1-7)] levels in the circulation and urine. In the present study, we examined the damage to podocytes induced by preeclamptic serum and the effects of Ang-(1-7) on podocytes treated with preeclamptic serum, as well as the underlying mechanisms. The podocytes were incubated with serum obtained from women with PE or with serum from women with normal pregnancies for different periods of time. Cell viability was determined by CCK-8 assay. The cells were treated with various concentrations of Ang-(1-7) and A779 [an (Ang-(1-7) antagonist]. The effects of Ang-(1-7) on the expression of podocyte-specific proteins [nephrin, Wilms tumor‑1 (WT-1) and podocin] and the phosphorylation of mitogen-activated protein kinases (MAPKs) were investigated by western blot analysis. Changes in F-actin rearrangement were determined by immunofluorescence. Podocyte apoptosis was determined by flow cytometry. The results revealed that in the cultured podocytes incubated with preeclamptic serum, there was a decrease in the expression of podocyte-specific proteins (nephrin and WT-1 but not podocin), a rearrangement of F-actin and apoptosis compared with the control group. However, treatment with Ang-(1-7) attenuated podocyte injury in the preeclamptic group, which may be mediated through the downregulation of MAPK (p38, ERK1/2 and JNK) phosphorylation. Thus, our data suggest that Ang-(1-7) plays a protective role in PE through the downregulation of MAPK phosphorylation.

We examined the effect of total and afferent renal denervation (RDN) on hypertension and the renin-angiotensin system (RAS) in a rodent model of juvenile-onset polycystic kidney disease (PKD). Lewis Polycystic Kidney (LPK) and control rats received total, afferent or sham RDN by periaxonal application of phenol, capsaicin or normal saline, respectively, and were monitored for 4-weeks. Afferent RDN did not affect systolic blood pressure (SBP) determined by radiotelemetry in either strain (n = 19) while total RDN significantly reduced SBP in Lewis rats 4-weeks post-denervation (total vs. sham, 122 ± 1 vs. 130 ± 2 mmHg, P = 0.002, n = 25). Plasma and kidney renin content determined by radioimmunoassay were significantly lower in LPK vs. Lewis (plasma: 278.2 ± 6.7 vs. 376.5 ± 11.9 ng Ang I/ml/h; kidney: 260.1 ± 6.3 vs. 753.2 ± 37.9 ng Ang I/mg/h, P < 0.001, n = 26). These parameters were not affected by RDN. Intrarenal mRNA expression levels of renin, angiotensinogen, angiotensin-converting enzyme (ACE)2, and angiotensin II receptor type 1a were significantly lower, whereas ACE1 expression was significantly higher in the LPK vs. Lewis (all P < 0.05, n = 26). This pattern of intrarenal RAS expression was not changed by RDN. In conclusion, RDN does not affect hypertension or the RAS in the LPK model and indicates RDN might not be a suitable antihypertensive strategy for individuals with juvenile-onset PKD.

Renal denervation (RDN) as a therapeutic intervention in patients with hypertension has been intensively studied for over a decade, yet a critical question remains unanswered: what kind of patients are the ideal target population for RDN to achieve its maximum clinical benefit? We herein provide a review of current literature to answer questions related to patient selection to identify populations that will benefit most from RDN, drawing first from human studies but also important clues derived from preclinical animal models. Different aspects that may influence the selection of patients such as the cause of hypertension, the severity of hypertension, concurrent pharmaceutical treatment, renal function, and renal artery anatomy are discussed. Based on current evidence, patients who have severe primary hypertension, regardless of medication or degree of renal dysfunction, who have an accessible accessory renal artery, can achieve a desirable response if a thorough ablation is achieved. In preclinical models, as in humans, RDN shows variable impact, with evidence indicating it does not work in specific conditions such as reduced renal mass, salt-sensitive hypertension, and autosomal recessive polycystic kidney disease. The thresholds, however, for indicators are such that it is still not possible to reliably predict which patients could benefit from the technique. Confirmation of predictive factors and identification of biomarkers are needed before RDN can be integrated in clinical practice on clear and reliable grounds.

No abstract

Renal denervation is a novel device based therapy promoted to reduce high blood pressure. We examined the impact of renal denervation on systolic blood pressure, renal function, and arterial stiffness in the Lewis Polycystic Kidney disease (LPK) rodent model of kidney disease. Animals were subjected to bilateral renal denervation or sham surgeries at age 6 and 12 weeks. Systolic blood pressure was monitored by tail-cuff plethysmography and renal function by urinalysis and creatinine clearance. At age 16 weeks, beat-to-beat aortic pulse wave velocity as a functional indicator of arterial stiffness was determined. Renal denervation produced an overall reduction in blood pressure in the LPK [(denervated 164±4 vs. sham-operated 180±6 mmHg, n = 6 per group, P=0.003)] and delayed, but did not prevent, the decline in renal function. Aortic pulse wave velocity was markedly elevated in the LPK compared with Lewis and was not altered by renal denervation in the LPK however a reduction was seen in the control Lewis animals. These results support the hypothesis that renal nerves contribute to secondary hypertension in conditions such as kidney disease.

No abstract

Objective: Our study aims to evaluate the association between heart rate variability (HRV) and short and long-term prognosis in patients admitted to intensive care unit (ICU). Methods and Results: Adult patients continuously monitored for over 24h in ICUs from the MIMIC-IV Waveform Database were recruited in our study. Twenty HRV-related variables (8 time-domain, 6 frequency-domain; and 6 nonlinear variables) were calculated based on RR intervals. The association between HRV and 30-day all-cause mortality was assessed. Ninety-three patients met the inclusion criteria and were classified into 30-day survivor group and non-survivor groups based on their survival status. The 30-day all-cause mortality rate was 17.2%. NN50 and pNN50 were both significantly higher in non-survivors compared to survivors, whereas the rest of the time-domain, frequency domain and non-linear HRV parameters did not differ significantly between the two groups (all P >0.05). In addition, at 180 days after admission, non-survivors had significantly higher levels of NN50 and rMSSD than the survivors. However, NN50 was not an independent predictor of 30-day all-cause mortality in patients by multivariate COX regression analysis (HR, 1.0; 95% CI, 1.000 - 1.001; P =0.594). The Area Under the Curve (AUC), cut-off value, sensitivity and specificity of NN50 for predicting 30-day all-cause mortality using ROC were 0.67, 799, 0.813 and 0.584, respectively. Plotting Kaplan-Meier analysis using this cut-off value showed that patients with high NN50 had considerably greater 30-day all-cause mortality than those with low NN50 (P < 0.001). Conclusion: NN50 and pNN50 are associated with elevated 30-day all-cause mortality in ICU patients but are not independent predictors of all-cause mortality using multivariate COX regression analysis.