Association between serum indoxyl sulfate levels with carotid-femoral pulse wave velocity in patients with chronic kidney disease

BackgroundThe role of indoxyl sulfate (IS), an important protein-bound uremic toxin, in arterial stiffness (AS) in patients with chronic kidney disease (CKD) is unclear.Materials and methodsWe investigated the association between serum IS levels and AS in a cross-sectional study of 155 patients with CKD. Patients in the AS group was defined as carotid-femoral pulse wave velocity (cfPWV) value >10 m/s measured by a validated tonometry system (SphygmoCor), while values ≤10 m/s were regarded as without AS group Serum IS was measured by liquid chromatography–mass spectrometry analysis.ResultsOf these CKD patients, AS was present in 51 (32.9%) patients, who were older, had a higher rate of diabetes, higher systolic blood pressure (SBP), and higher IS levels compared to those without AS. By multivariable logistic regression analysis, IS (adjusted odds ratio [aOR] 1.436, 95% confidence interval [CI] 1.085–1.901, p = 0.011), age (aOR 1.058, 95% CI 1.021–1.097, p = 0.002), and SBP (aOR 1.019, 95%CI 1.000–1.038, p = 0.049) were independent predictors of AS. By multivariable stepwise linear regression analysis, logarithmically transformed IS, age, DM, and SBP were significantly correlated with cfPWV. The area under the receiver-operating characteristic curve for serum log-IS was 0.677 (95%CI 0.598–0.750, p = 0.0001) to predict the development of AS in patients with CKD.ConclusionThese finding demonstrate that in addition to older and higher SBP, a high serum IS level is a significant biomarker associated with AS in patients with CKD.     

Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden

Trimethlyamine-N-oxide (TMAO) was recently identified as a promoter of atherosclerosis. Patients with CKD exhibit accelerated development of atherosclerosis; however, no studies have explored the relationship between TMAO and atherosclerosis formation in this group. This study measured serum concentrations and urinary excretion of TMAO in a CKD cohort (n=104), identified the effect of renal transplant on serum TMAO concentration in a subset of these patients (n=6), and explored the cross-sectional relationship between serum TMAO and coronary atherosclerosis burden in a separate CKD cohort (n=220) undergoing coronary angiography. Additional exploratory analyses examined the relationship between baseline serum TMAO and long-term survival after coronary angiography. Serum TMAO concentrations demonstrated a strong inverse association with eGFR (r²=0.31, P<0.001). TMAO concentrations were markedly higher in patients receiving dialysis (median [interquartile range], 94.4 μM [54.8–133.0 μM] for dialysis-dependent patients versus 3.3 μM [3.1–6.0 μM] for healthy controls; P<0.001); whereas renal transplantation resulted in substantial reductions in TMAO concentrations (median [min–max] 71.2 μM [29.2–189.7 μM] pretransplant versus 11.4 μM [8.9–20.2 μM] post-transplant; P=0.03). TMAO concentration was an independent predictor for coronary atherosclerosis burden (P=0.02) and predicted long-term mortality independent of traditional cardiac risk factors (hazard ratio, 1.26 per 10 μM increment in TMAO concentration; 95% confidence interval, 1.13 to 1.40; P<0.001). In conclusion, serum TMAO concentrations substantially increase with decrements in kidney function, and this effect is reversed by renal transplantation. Increased TMAO concentrations correlate with coronary atherosclerosis burden and may associate with long-term mortality in patients with CKD undergoing coronary angiography.     

Safety and effectiveness of lanthanum carbonate for hyperphosphatemia in chronic kidney disease (CKD) patients: a meta-analysis

ObjectiveThe aim of this study was to determine the efficacy and safety of lanthanum carbonate (LC) versus calcium salts, non-LC phosphate binders (PBs), sevelamer, or placebo in patients with chronic kidney disease (CKD).Materials and methodsA literature search on PubMed, Embase, and Cochrane Library databases was conducted up to 18 June 2021. Data acquisition and quality assessment were performed by two reviewers. Meta-analysis was performed to evaluate the serum biochemical parameters, adverse events, and patient-level outcomes of LC, non-LC PBs, and sevelamer for hyperphosphatemia in patients with CKD. Heterogeneity across studies was assessed utilizing the I² statistic and Q-test, and a random effect model was selected to calculate the pooled effect size.ResultsA total of 26 randomized, controlled trials and 3 observational studies were included. Compared to the other groups, better control effect of serum phosphorus (RR = 2.68, p < 0.001), reduction in serum phosphorus (95%CI = −1.93, −0.99; p < 0.001), Ca × P (95%CI = −13.89, −2.99; p = 0.002), serum intact parathyroid hormone levels (95%CI = −181.17, −3.96, p = 0.041) were found in LC group. Besides, reduced risk of various adverse effects, such as hypotension, abdominal pain, diarrhea, dyspepsia, and a score of coronary artery calcification were identified with LC in comparison to calcium salt, non-LC PBs, or placebo group. Significantly lower risk in mortality with LC treatment vs. non-LC PBs was observed, while no significant difference was identified between LC and calcium salt groups.ConclusionLC might be an alternative treatment for hyperphosphatemia in patients with CKD considering its comprehensive curative effect.     

Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiency—genetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor–23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-β1–, angiotensin II–, or high phosphate–induced fibrosis and abolished TGF-β1– or angiotensin II–induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor–23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.     

Longitudinal Changes of Cardiac Structure and Function in CKD (CASCADE Study)

Little is known regarding the natural longitudinal changes in cardiac structure and function in CKD. We hypothesized that baseline CKD stage is associated with progressive worsening in cardiac structure and function. We conducted a prospective longitudinal study, recruiting 300 patients with stages 3–5 CKD from a major regional tertiary center and university teaching hospital in Hong Kong. Baseline CKD stages were studied in relation to natural longitudinal changes in echocardiographic and tissue Doppler imaging–derived parameters. Over 1 year, the prevalence of left ventricular (LV) hypertrophy increased from 40.3% to 48.9%, median left atrial volume index increased 4.8 (interquartile range [IQR], 2.1, 7.7) ml/m² (P<0.001), peak systolic mitral annular velocity decreased 0.5 (IQR, −1.5, 0.5) cm/s (P<0.001), early diastolic mitral annular velocity decreased 0.5 (IQR, −1.5, 0.5) cm/s (P<0.001), and eGFR declined 2.0 (IQR, −5.0, 0.0) ml/min per 1.73 m². CKD stages 4 and 5 were associated with more baseline abnormalities in cardiac structure and function and predicted greater longitudinal progression in LV mass index (odds ratio [OR], 3.02; 95% confidence interval [95% CI], 1.39 to 6.58), volume index (OR, 2.58; 95% CI, 1.18 to 5.62), and left atrial volume index (OR, 2.61; 95% CI, 1.20 to 5.69) and worse diastolic dysfunction grade (OR, 3.17; 95% CI, 1.16 to 8.69) compared with stage 3a in the fully adjusted analysis. In conclusion, more advanced CKD at baseline may be associated with larger longitudinal increases in LV mass and volume and greater deterioration in diastolic function.     

Balance,Falls Risk,and Related Disability in Untreated Vestibular Schwannoma Patients

Background Many vestibular schwannoma (VS) patients complain of balance dysfunction; however, validated standardized assessments are lacking. The relative contribution of imbalance and factors like anxiety to disability is unknown. Because imbalance significantly affects quality of life in this group and vestibular rehabilitation may improve outcomes, determining the severity of balance dysfunction is important to understand long-term rehabilitation needs. Aim To assess functional balance (Vertigo Symptom Scale-Vertigo [VSS-VER] and Functional Gait Assessment [FGA]) and the relative contribution of symptom severity (VSS-VER), ambulant posture (FGA), and anxiety symptoms (Vertigo Symptom Scale-Anxiety [VSS-SA]) to disability in untreated patients. Methods Patients not exposed to surgery completed the VSS, Vertigo Handicap Questionnaire (VHQ), and FGA. VSS scores were compared with migrainous vertigo (MV) patients, a mixed neuro-otological group, and healthy controls. Results A correlation was found between decreased FGA and increasing age (r = − 0.35; p < 0.01), female sex (r = 0.42; p = 0.001), increasing handicap (r = − 0.55; p < 0.001), and symptom severity (r = − 0.52; p < 0.001). In 12 of 21 patients (57%) > 60 years of age the FGA score was ≤ 22 suggesting increased falls risk.VSS-VER scores were higher than in healthy controls (p < 0.001) but lower than MV (p < 0.001) and mixed neuro-otology controls (p < 0.001).VSS-SA scores in VS patients with balance symptoms were higher than normal controls (p < 0.05) and correlated with handicap (r = 0.59; p < 0.001) and symptom severity (r = 0.74; p < 0.001).After controlling for age and sex, the VSS-VER, VSS-SA, and FGA explained 47% of the variation in VHQ scores. Conclusion Older VS patients are at significant risk of falls. Balance symptoms are more severe than in healthy controls but less than other neuro-otological patients. Balance symptom severity, anxiety symptoms, and ambulant posture were significant contributors to disability and should be the focus of vestibular rehabilitation strategies.     

Fibroblast Growth Factor 23 and Klotho as Cardiovascular Risk Factors in Heart Transplant Recipients

Background

Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for FGF23 and at the same time it is known as a “longevity” hormone. There are no data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The aim of this study was to assess Klotho and FGF23 serum concentration in heart transplant recipients depending on immunosuppressive therapy regimen and comorbidities.

Methods

Eighty-four stable heart transplant recipients were enrolled in the study; 22 healthy volunteers served as control subjects. FGF23 and Klotho protein concentration, markers of renal function, such as cystatin C and neutrophil gelatinase–associated lipocalin (NGAL), and heart failure markers, such as copeptine and N-termiinal pro–B-type natriuretic peptide (NT-proBNP), were evaluated.

Results

FGF23 concentration was significantly higher in the HT group whereas Klotho protein was significantly lower. FGF23 correlated with creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate (eGFR; r = −0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P < .001), hemoglobin (r = −0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high-density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05). Klotho protein correlated only with age (r = −0.21; P < .05), creatinine (r = −0.21; P < .05), and eGFR (r = −0.31; P < .01). FGF23 concentration was significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was significantly lower. FGF23 predictors were renal function (creatinine concentration; β = 0.45; P = .0001), HDL (β = 0.33; P = .003), intraventricular septum thickness (β = 0.38; P = .0003), and right ventricular systolic pressure (β = 0.34; P = .003), explaining 70% of FGF23 variability.

Conclusions

FGF23/Klotho system disorders in HT recipients are related to cardiovascular system function and kidney failure and could cause increased risk of cardiovascular disease.     

New Clues that May Link Osteoporosis to the Circulating Lipid Profile

Bone Mineral Density (BMD) is a gold standard for the diagnosis of osteoporosis and is also important in the assessment of fracture risk. Other risk factors have been identified that together make up fracture risk assessment tools such as FRAX. Another potential factor, circulating lipids, has been suggested because of reports linking statins to fracture risk reduction. We analyzed the lipid profile in a cohort of women diagnosed with postmenopausal osteoporosis based on bone density determination: 610 women with osteoporosis (mean lumbar spine T-score −3.16±0.81, mean yrs. since menopause 15.79±8.9) were grouped according to age at evaluation (< 50 years, 51–60 years, 61–70 years, > 70 years), the presence/absence of a history of a fragility fracture, statin and/or antiresorptive drug use. There was no correlation between BMD and Body Mass Index (BMI: P>0.05, r²<0.02). However, when BMD was correlated with both BMI and the lipid profile (Triglycerides, Cholesterol, LDLc, HDLc), significant correlations were found in 5 cohorts: 51–60 years with fractures (n=61, r²=0.14, P<0.01), 61–70 years (n=201, r²=0.09, P<0.01) with fractures (n=88, r²=0.14, P<0.01) or without fractures (n=113, r²=0.24, P=0.02) and over 70 years (n=247, r²=0.11, P<0.01).     

Language barriers in Hispanic patients: relation to upper-extremity disability

BackgroundAlthough upper-extremity disability has been shown to correlate highly with various psychosocial aspects of illness (e.g., self-efficacy, depression, kinesiophobia, and pain catastrophizing), the role of language in musculoskeletal health status is less certain. In an English-speaking outpatient hand surgery office setting, we sought to determine (1) whether a patient’s primary native language (English or Spanish) is an independent predictor of upper-extremity disability and (2) whether there are any differences in the contribution of measures of psychological distress to disability between native English- and Spanish-speaking patients.MethodsA total of 122 patients (61 native English speakers and 61 Spanish speakers) presenting to an orthopaedic hand clinic completed sociodemographic information and three Patient-Reported Outcomes Measurement Information System (PROMIS)-based computerized adaptive testing questionnaires: PROMIS Pain Interference, PROMIS Depression, and PROMIS Upper-Extremity Physical Function. Bivariate and multivariable linear regression modeling were performed.ResultsSpanish-speaking patients reported greater upper-extremity disability, pain interference, and symptoms of depression than English-speaking patients. After adjusting for sociodemographic covariates and measures of psychological distress using multivariable regression modeling, the patient’s primary language was not retained as an independent predictor of disability. PROMIS Depression showed a medium correlation (r = −0.35; p < 0.001) with disability in English-speaking patients, while the correlation was large (r = −0.52; p < 0.001) in Spanish-speaking patients. PROMIS Pain Interference had a large correlation with disability in both patient cohorts (Spanish-speaking: r = −0.66; p < 0.001; English-speaking: r = −0.77; p < 0.001). The length of time since immigration to the USA did not correlate with disability among Spanish speakers.ConclusionPrimary language has less influence on symptom intensity and magnitude of disability than psychological distress and ineffective coping strategies. Interventions to optimize mood and to reduce pain interference should be considered in patients of all nationalities.Type of study/level of evidence: Prognostic II.     

Effect of Pentoxifylline on Renal Function and Urinary Albumin Excretion in Patients with Diabetic Kidney Disease: The PREDIAN Trial

Diabetic kidney disease (DKD) is the leading cause of ESRD. We conducted an open-label, prospective, randomized trial to determine whether pentoxifylline (PTF), which reduces albuminuria, in addition to renin-angiotensin system (RAS) blockade, can slow progression of renal disease in patients with type 2 diabetes and stages 3–4 CKD. Participants were assigned to receive PTF (1200 mg/d) (n=82) or to a control group (n=87) for 2 years. All patients received similar doses of RAS inhibitors. At study end, eGFR had decreased by a mean±SEM of 2.1±0.4 ml/min per 1.73 m² in the PTF group compared with 6.5±0.4 ml/min per 1.73 m² in the control group, with a between-group difference of 4.3 ml/min per 1.73 m² (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m²; P<0.001) in favor of PTF. The proportion of patients with a rate of eGFR decline greater than the median rate of decline (0.16 ml/min per 1.73 m² per month) was lower in the PTF group than in the control group (33.3% versus 68.2%; P<0.001). Percentage change in urinary albumin excretion was 5.7% (95% CI, −0.3% to 11.1%) in the control group and −14.9% (95% CI, −20.4% to −9.4%) in the PTF group (P=0.001). Urine TNF-α decreased from a median 16 ng/g (interquartile range, 11–20.1 ng/g) to 14.3 ng/g (interquartile range, 9.2–18.4 ng/g) in the PTF group (P<0.01), with no changes in the control group. In this population, addition of PTF to RAS inhibitors resulted in a smaller decrease in eGFR and a greater reduction of residual albuminuria.     

The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer: who can benefit from ketoconazole therapy?

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer (mCRPC). In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200–400 mg three times daily with replacement doses of prednisone. Progression-free survival (PFS) was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months (0.5–8.6 months) for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen (PSA) declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following: 1.4 and 3.5 months for a nadir PSA of ≥0.2 and <0.2 ng ml⁻¹, respectively (hazard rate (HR)=4.767, P<0.001); 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and <0.1 ng ml⁻¹, respectively (HR=2.865, P=0.012); 2.8 and 1.9 months for a baseline haemoglobin of ≥120 and <120 g l⁻¹, respectively (HR=1.605, P<0.001); and 3.0 and 1.9 months for a PSA doubling time (PSADT) of ≥2.0 and <2.0 months, respectively (HR=1.454, P=0.017). A risk model was constructed according to the four factors that divided patients into three subgroups of low risk (0–1 factors), moderate risk (2 factors) and high risk (3–4 factors) with PFS values of 3.6, 3.0 and 1.4 months, respectively (HR=1.619, P<0.001). A nadir PSA of ≥0.2 ng ml⁻¹, a baseline testosterone of <0.1 ng ml⁻¹, a baseline haemoglobin of <120 g l⁻¹ and a PSADT of <2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.     

Serum level of soluble (pro)renin receptor is modulated in chronic kidney disease

Background

Prorenin, the precursor of renin, binds to the (pro)renin receptor [(P)RR] and triggers intracellular signaling. The ligand binding sites of (P)RR are disconnected and are present in the soluble form of the receptor in serum. Given that the clinical significance of serum prorenin and soluble (P)RR in chronic kidney disease (CKD) is unclear, we investigated the relationship between serum prorenin, soluble (P)RR, and various clinical parameters in patients with CKD.

Methods

A total of 374 patients with CKD were enrolled. Serum samples were collected, and the levels of soluble (P)RR and prorenin were measured using ELISA kits. Serum creatinine (Cr), blood urea nitrogen (BUN), uric acid (UA), hemoglobin (Hb), soluble secreted α-Klotho, and the urine protein/Cr ratio were also measured. Similarly, clinical parameters were also evaluated using serum and urine sample collected after 1 year (n = 204).

Results

Soluble (P)RR levels were positively associated with serum Cr (P < 0.0001, r = 0.263), BUN (P < 0.0001, r = 0.267), UA (P < 0.005, r = 0.168) levels, CKD stage (P < 0.0001, r = 0.311) and urine protein/Cr ratio (P < 0.01, r = 0.157), and inversely with estimated glomerular infiltration rate (eGFR) (P < 0.0001, r = ?0.275) and Hb (P < 0.005, r = ?0.156). Soluble (P)RR levels were inversely associated with α-Klotho levels (P < 0.001, r = ?0.174) but did not correlate with prorenin levels. With respect to antihypertensive drugs, soluble (P)RR levels were significantly lower in patients treated with an angiotensin II receptor blocker (ARB) than in those without ARB therapy (P < 0.005). Soluble (P)RR levels were significantly lower in CKD patients with diabetes mellitus or primary hypertension than in those without these conditions (P < 0.05). In contrast, serum levels of prorenin did not correlate with parameters related to renal function. Serum prorenin levels were significantly higher in CKD patients with diabetes mellitus than in nondiabetic patients (P < 0.05), but not in CKD patients with hypertension (P = 0.09). Finally, with respect to the relationship between basal soluble (P)RR levels and the progression rates of renal function, soluble (P)RR levels were positively associated with ΔCr (P < 0.05, r = 0.159) and inversely associated with ΔeGFR (P < 0.05, r = ?0.148).

Conclusion

Serum levels of soluble (P)RR correlated with the stage of CKD. Our findings suggest that soluble (P)RR may be involved in renal injury and influence the progression of CKD.     

Physical exercise is associated with better fat mass distribution and lower insulin resistance in spinal cord injured individuals

Objectives

The aim of the study was to compare total and regional body composition and their relationship with glucose homeostasis in physically active and non-active individuals with cervical spinal cord injury (c-SCI).

Methods

Individuals with lesion level between C5–C7 were divided into two groups: physically active (PA; n = 14; who practiced physical exercise for at least 3 months, three times per week or more, minimum of 150 minutes/week): and non-physically active (N-PA n = 8). Total fat mass (t-FM) and regional fat mass (r-FM) were assessed by dual energy X-ray absorptiometry. Fasting plasma insulin (FPI) was determined by enzyme-linked immunosorbent assay.

Results

PA group present lower (P < 0.01) total fat mass (t-FM), % and kg, regional fat mass (r-FM), % and kg, FPI levels and HOMA index, while they had higher (P < 0.001) total free fat mass (t-FFM), %, and regional free fat mass (r-FFM), %, compared to the N-PA group. In the N-PA group, FPI and HOMA index were negatively (P < 0.05) correlated with FFM% (r = −0.71, −0.69, respectively) and positively correlated to trunk-FM (r = 0.71, 0.69, respectively) and trunk-FM:t-FM (kg) ratio (r = 0.83, 0.79, respectively).

Conclusion

Physical exercise is associated with lower t-FM, r-FM, and insulin resistance, which could contribute to the decrease of the risk of cardiovascular and metabolic conditions in individuals with c-SCI.     

Is thioredoxin reductase involved in the defense against DNA fragmentation in varicocele?

We aimed to investigate the role of thioredoxin reductase (TR) and inducible heat shock protein 70 (iHsp70) and their relationship with sperm quality in varicocele (VAR) patients. Semen samples were obtained from 16 subfertile men diagnosed as VAR and 10 fertile men who applied to the Andrology Laboratory of Istanbul Medical Faculty of Istanbul University. The sperm TR and iHsp 70 expression levels were determined using Western blot analysis. The TR activity of the sperm was assayed spectrophometrically. The sperm quality was evaluated both by conventional sperm analysis and by a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique that assayed DNA-fragmented spermatozoa in semen samples. The percentage of TUNEL-positive spermatozoa in the VAR group (16.3%±5.6%) was higher than that in the fertile group (5.5%±1.9%). Significant inverse correlations were detected between the percentage of TUNEL-positive cells and both the concentration (r=−0.609; P=0.001) and motility (r=−0.550; P=0.004) of spermatozoa. Both the TR expression and activity were increased significantly in the VAR group (U=22.0; P=0.001 and U=33.5; P=0.012, respectively) as analyzed using the Mann–Whitney U Wilcoxon rank sum W test. Furthermore, significant positive correlations were found between TR expression and activity (r=0.406; P=0.040) and between TR expression and the percentage of TUNEL-positive cells (r=0.665; P=0.001). Sperm iHsp70 expression did not differ between the VAR and fertile groups. In conclusion, increased sperm TR expression might be a defense mechanism against apoptosis in the spermatozoa of men with VAR.     

Effects of intensive blood pressure control on mortality and cardiorenal function in chronic kidney disease patients

BackgroundBlood pressure (BP) variability is highly correlated with cardiovascular and kidney outcomes in patients with chronic kidney disease (CKD). However, appropriate BP targets in patients with CKD remain uncertain.MethodsWe searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of CKD patients who underwent intensive BP management. Kappa score was used to assess inter-rater agreement. A good agreement between the authors was observed to inter-rater reliability of RCTs selection (kappa = 0.77; P = 0.005).ResultsTen relevant studies involving 20 059 patients were included in the meta-analysis. Overall, intensive BP management may reduce the incidence of cardiovascular disease mortality (RR: 0.69, 95% CI: 0.53 to 0.90, P: 0.01), all-cause mortality (RR: 0.77, 95% CI: 0.67 to 0.88, P < 0.01) and composite cardiovascular events (RR: 0.84 95% CI: 0.75 to 0.95, P < 0.01) in patients with CKD. However, reducing BP has no significant effect on the incidence of doubling of serum creatinine level or 50% reduction in GFR (RR: 1.26, 95% CI: 0.66 to 2.40, P = 0.48), composite renal events (RR 1.07, 95% CI: 0.81 to 1.41, P = 0.64) or SAEs (RR: 0.97, 95% CI: 0.90 to 1.05, P = 0.48).ConclusionIn patients with CKD, enhanced BP management is associated with reduced all-cause mortality, cardiovascular mortality, and incidence of composite cardiovascular events.     

Importance of Initial Peak Torque of the Supraspinatus Muscle during Shoulder Flexion

BackgroundMost previous studies have evaluated flexion strength to assess recovery after arthroscopic rotator cuff (RC) repair. However, limited data are available regarding peak torque at the initial angle (iPT) because most studies have measured flexion strength for peak torque (PT), particularly in small- and medium-sized supraspinatus tears. The purpose of this study was to compare conventional PT and iPT to evaluate supraspinatus muscle strength after arthroscopic RC repair in patients with small- and medium-sized supraspinatus tears.MethodsIsokinetic muscle performance testing was performed in 42 patients with small tears and in 47 patients with medium-sized tears. PT and iPT were evaluated before and 1 year after surgery and were recorded at an angular velocity of 60°/sec and 180°/sec with an isokinetic test.ResultsPT and iPT were significantly lower in the involved-side shoulders than in the uninvolved-side shoulders (PT: small tear, p < 0.001; medium tear, p < 0.001; iPT: small tear, p < 0.001; medium tear, p < 0.001) in both groups, preoperatively. However, postoperatively, in the involved-side shoulders, PTs were not different in both small- and medium-sized tears (all p > 0.05), but iPTs were significantly lower in the involved-side shoulders (small tear, p < 0.001; medium tear, p < 0.001). iPT was significantly lower in the involved side shoulders in the medium-sized tear group than in the small-sized tear group before and after surgery (p < 0.05). In the small- and medium-sized tear groups, tear size was significantly correlated with preoperative iPT in the involved-side shoulders (small tear: r = −0.304, p = 0.046; medium tear: r = −0.323, p = 0.027). However, pain visual analog scale was significantly correlated with preoperative (small tear: r = −0.455, p = 0.002; medium tear: r = −0.286, p = 0.044) and postoperative (small tear: r = −0.430, p = 0.005; medium tear: r = −0.354, p = 0.021) iPT in the involved-side shoulders. Furthermore, fatty infiltration grade of the supraspinatus muscle and global fatty degeneration index were not associated with preoperative and postoperative PT and iPT in each group (all p > 0.05).ConclusionsiPT is as important as conventional PT in isokinetic testing to assess supraspinatus muscle strength before and after RC repair.     

The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid

In CKD, uremic solutes may induce endothelial dysfunction, inflammation, and oxidative stress, leading to increased cardiovascular risk. We investigated whether the uremic solute indole-3 acetic acid (IAA) predicts clinical outcomes in patients with CKD and has prooxidant and proinflammatory effects. We studied 120 patients with CKD. During the median study period of 966 days, 29 patients died and 35 experienced a major cardiovascular event. Kaplan–Meier analysis revealed that mortality and cardiovascular events were significantly higher in the higher IAA group (IAA>3.73 µM) than in the lower IAA group (IAA<3.73 µM). Multivariate Cox regression analysis demonstrated that serum IAA was a significant predictor of mortality and cardiovascular events after adjustments for age and sex; cholesterol, systolic BP, and smoking; C-reactive protein, phosphate, body mass index, and albumin; diastolic BP and history of cardiovascular disease; and uremic toxins p-cresyl sulfate and indoxyl sulfate. Notably, IAA level remained predictive of mortality when adjusted for CKD stage. IAA levels were positively correlated with markers of inflammation and oxidative stress: C-reactive protein and malondialdehyde, respectively. In cultured human endothelial cells, IAA activated an inflammatory nongenomic aryl hydrocarbon receptor (AhR)/p38MAPK/NF-κB pathway that induced the proinflammatory enzyme cyclooxygenase-2. Additionally, IAA increased production of endothelial reactive oxygen species. In conclusion, serum IAA may be an independent predictor of mortality and cardiovascular events in patients with CKD. In vitro, IAA induces endothelial inflammation and oxidative stress and activates an inflammatory AhR/p38MAPK/NF-κB pathway.     

Efficacy of statins on renal function in patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundStudies have shown that the use of statins could significantly improve lipid profiles; however, it remains controversial whether the use of statins could improve renal function in patients with chronic kidney disease (CKD). Therefore, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of statins on renal function in patients with CKD.MethodsWe systematically searched PubMed, EMBASE, and the Cochrane Library databases for eligible RCTs from inception to October 2020. Pooled effect estimates were assigned as weighted mean differences (WMDs) with 95% confidence intervals (CIs) using the random-effects model.ResultsWe selected 33 RCTs that recruited 37,391 patients with CKD patients. The summary results suggested that statin use significantly reduced urinary albumin (WMD: −2.04; 95%CI: −3.53 to −0.56; p = .007) and protein (WMD: −0.58; 95%CI: −0.95 to −0.21; p = .002) excretions and increased creatinine clearance (WMD: 0.86; 95%CI: 0.32–1.41; p = .002). However, there were no significant differences between statin and control groups in terms of changes in estimated glomerular filtration rate (WMD: 0.38; 95%CI: −0.04 to 0.79; p = .075), and serum creatinine levels (WMD: −0.07; 95%CI: −0.25, 0.12; p = .475).ConclusionsWe found that statin use in patients with CKD may slow CKD progression by lowering urinary albumin and protein excretions or increasing creatinine clearance. Further large-scale RCTs should be conducted to evaluate the long-term effects of statins on renal outcomes. Abbreviations: CKD: chronic kidney disease; RCT: randomized controlled trials; WMD: weighted mean differences; CI: confidence intervals; ACEI: angiotensin-converting enzyme inhibitors; eGFR: estimated glomerular filtration rate     

Left Ventricular Hypertrophy Is More Prevalent in Type B than Type A Aortic Dissection

Objectives: Several factors determining differences between types A and B aortic dissection (AD) have been reported; however, little data exist examining their differences in left ventricular hypertrophy (LVH). We compared the prevalence of LVH in patients with types A and B AD.Methods: We retrospectively analyzed 334 patients with acute AD (227 type A; 107 type B). Concentric hypertrophy (CH; increased left ventricular mass index [LVMI] and relative wall thickness [RWT]) is one of four types of left ventricular (LV) geometry thought to be most associated with hypertension. We compared LVMI and the prevalence of CH in patients with types A or B AD. Multivariate logistic regression analyses of variables associated with type B AD were performed.Results: Comparing type A and B AD, LVMI (95 ± 26 vs.107 ± 28, p <0.001) and prevalence of CH (26% vs. 44%, p = 0.001) were higher in type B AD. In multivariate analysis, CH was an independent factor associated with type B AD (odds ratio: 2.62, confidence interval: 1.54–4.47, p <0.001).Conclusions: Our data suggested LVH was more prevalent in type B than in type A AD. Considering LVH usually results from hypertension, patients with type B AD may be more affected by hypertension than those with type A.