Evaluation of cystatin C for the detection of chronic kidney disease in cats

BackgroundSerum cystatin C (sCysC) and urinary cystatin C (uCysC) are potential biomarkers for early detection of chronic kidney disease (CKD) in cats. An in-depth clinical validation is required. ObjectivesTo evaluate CysC as a marker for CKD in cats and to compare assay performance of the turbidimetric assay (PETIA) with the previously validated nephelometric assay (PENIA). AnimalsNinety cats were included: 49 CKD and 41 healthy cats. MethodsSerum CysC and uCysC concentrations were prospectively evaluated in cats with CKD and healthy cats. Based on plasma exo-iohexol clearance test (PexICT), sCysC was evaluated to distinguish normal, borderline, and low GFR. Sensitivity and specificity to detect PexICT<1.7mL/min/kg were calculated. Serum CysC results of PENIA and PETIA were correlated with GFR. Statistical analysis was performed using general linear modeling. ResultsCats with CKD had significantly higher meanSD sCysC (1.4 +/- 0.5mg/L) (P<.001) and uCysC/urinary creatinine (uCr) (291 +/- 411mg/mol) (P<.001) compared to healthy cats (sCysC 1.0 +/- 0.3 and uCysC/uCr 0.32 +/- 0.97). UCysC was detected in 35/49 CKD cats. R-2 values between GFR and sCysC or sCr were 0.39 and 0.71, respectively (sCysC or sCr=+GFR+epsilon). Sensitivity and specificity were 22 and 100% for sCysC and 83 and 93% for sCr. Serum CysC could not distinguish healthy from CKD cats, nor normal from borderline or low GFR, in contrast with sCr. ConclusionSerum CysC is not a reliable marker of reduced GFR in cats and uCysC could not be detected in all CKD cats

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Heart rate variability and target organ damage in hypertensive patients

Background: We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD). Methods: A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index. Results: Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors. Conclusions: Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD

Prevalence, predictors and prognostic implications of PR interval prolongation in patients with heart failure

Aims: To determine the prevalence, incidence, predictors and prognostic implications of PR interval prolongation in patients referred with suspected heart failure. Methods and Results: Consecutive patients referred with suspected heart failure were prospectively enrolled. After excluding patients with implantable cardiac devices and atrial fibrillation, 1420 patients with heart failure and reduced ejection fraction (HeFREF) [age: median 71 (interquartile range IQR: 63-78) years; men: 71%; NT-ProBNP: 1319 (583-3378) ng/L], 1094 with heart failure and normal ejection fraction (HeFNEF) [age: 76 (70-82) years; men: 47%; NT-ProBNP: 547 (321-1171) ng/L], and 1150 without heart failure [age: 68 (60-75) years; men: 51%; NT-ProBNP: 86 (46-140) ng/L] were included. The prevalence of first degree heart block [heart-rate corrected PR interval (PRc) >200 ms] was higher in patients with heart failure (21% HeFREF, 20% HeFNEF, 9% without heart failure). In patients with HeFREF or HeFNEF, longer baseline PRc was associated with greater age, male sex, and longer QRS duration and, in those with HeFREF, treatment with amiodarone or digoxin. Patients with heart failure in the longest PRc quartile had worse survival compared to shorter PRc quartiles but PRc was not independently associated with survival in multivariable analysis. For patients without heart failure, shorter baseline PRc was independently associated with worse survival. Conclusion: PRc prolongation is common in patients with HeFREF or HeFNEF and associated with worse survival, although not an independent predictor of outcome. The results of clinical trials investigating the therapeutic potential of shortening the PR interval by pacing are awaited

Emergent Properties of Patch Shapes Affect Edge Permeability to Animals

Animal travel between habitat patches affects populations, communities and ecosystems. There are three levels of organization of edge properties, and each of these can affect animals. At the lowest level are the different habitats on each side of an edge, then there is the edge itself, and finally, at the highest level of organization, is the geometry or structure of the edge. This study used computer simulations to (1) find out whether effects of edge shapes on animal behavior can arise as emergent properties solely due to reactions to edges in general, without the animals reacting to the shapes of the edges, and to (2) generate predictions to allow field and experimental studies to test mechanisms of edge shape response. Individual animals were modeled traveling inside a habitat patch that had different kinds of edge shapes (convex, concave and straight). When animals responded edges of patches, this created an emergent property of responding to the shape of the edge. The response was mostly to absolute width of the shapes, and not the narrowness of them. When animals were attracted to edges, then they tended to collect in convexities and disperse from concavities, and the opposite happened when animals avoided edges. Most of the responses occurred within a distance of 40% of the perceptual range from the tip of the shapes. Predictions were produced for directionality at various locations and combinations of treatments, to be used for testing edge behavior mechanisms. These results suggest that edge shapes tend to either concentrate or disperse animals, simply because the animals are either attracted to or avoid edges, with an effect as great as 3 times the normal density. Thus edge shape could affect processes like pollination, seed predation and dispersal and predator abundance

Increased Urinary Angiotensin-Converting Enzyme 2 in Renal Transplant Patients with Diabetes

Angiotensin-converting enzyme 2 (ACE2) is expressed in the kidney and may be a renoprotective enzyme, since it converts angiotensin (Ang) II to Ang-(1-7). ACE2 has been detected in urine from patients with chronic kidney disease. We measured urinary ACE2 activity and protein levels in renal transplant patients (age 54 yrs, 65% male, 38% diabetes, n = 100) and healthy controls (age 45 yrs, 26% male, n = 50), and determined factors associated with elevated urinary ACE2 in the patients. Urine from transplant subjects was also assayed for ACE mRNA and protein. No subjects were taking inhibitors of the renin-angiotensin system. Urinary ACE2 levels were significantly higher in transplant patients compared to controls (p = 0.003 for ACE2 activity, and p≤0.001 for ACE2 protein by ELISA or western analysis). Transplant patients with diabetes mellitus had significantly increased urinary ACE2 activity and protein levels compared to non-diabetics (p<0.001), while ACE2 mRNA levels did not differ. Urinary ACE activity and protein were significantly increased in diabetic transplant subjects, while ACE mRNA levels did not differ from non-diabetic subjects. After adjusting for confounding variables, diabetes was significantly associated with urinary ACE2 activity (p = 0.003) and protein levels (p<0.001), while female gender was associated with urinary mRNA levels for both ACE2 and ACE. These data indicate that urinary ACE2 is increased in renal transplant recipients with diabetes, possibly due to increased shedding from tubular cells. Urinary ACE2 could be a marker of renal renin-angiotensin system activation in these patients

Chronic kidney disease and use of dental services in a united states public healthcare system: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>As several studies have shown an association between periodontal disease and chronic kidney disease (CKD), regular dental care may be an important strategy for reducing the burden of CKD. Access to dental care may be limited in the US public health system.</p> <p>Methods</p> <p>In this retrospective cohort study of 6,498 adult patients with (n = 2,235) and without (n = 4,263) CKD and at least 12 months of follow-up within the San Francisco Department of Public Health Community Health Network clinical databases, we examined the likelihood of having a dental visit within the observation period (2005-2010) using Cox proportional hazards models. To determine whether dental visits reflected a uniform approach to preventive service use in this setting, we similarly examined the likelihood of having an eye visit among those with diabetes, for whom regular retinopathy screening is recommended. We defined CKD status by average estimated glomerular filtration rate based on two or more creatinine measurements ≥ 3 months apart (no CKD, ≥ 60 ml/min/1.73 m²; CKD, < 60 ml/min/1.73 m²).</p> <p>Results</p> <p>Only 11.0% and 17.4% of patients with and without CKD, respectively, had at least one dental visit. Those with CKD had a 25% lower likelihood of having a dental visit [HR = 0.75, 95% CI (0.64-0.88)] than those without CKD after adjustment for confounders. Among the subgroup of patients with diabetes, 11.8% vs. 17.2% of those with and without CKD had a dental visit, while 58.8% vs. 57.8% had an eye visit.</p> <p>Conclusions</p> <p>Dental visits, but not eye visits, in a US public healthcare setting are extremely low, particularly among patients with CKD. Given the emerging association between oral health and CKD, addressing factors that impede dental access may be important for reducing the disparate burden of CKD in this population.</p