Abstract
Background and Aims
Pre-emptive therapy, screen for and treat asymptomatic cytomegalovirus (CMV) viremia, is an important preventive strategy for CMV disease in kidney transplant (KT) ...recipients. Oral valganciclovir is the most commonly used as preventive strategy. However, the optimal dose and treatment duration of valganciclovir remains elusive.
Method
We retrospectively evaluated the efficacy and toxicity of low-dose of oral valganciclovir (450 mg twice daily) as pre-emptive therapy in KT recipients who underwent KT between January 2015 and December 2021. CMV viral load was measured by polymerase chain reaction. Pre-emptive therapy with valganciclovir was applied for 2 weeks.
Results
of 33 kidney transplant recipients who received pre-emptive CMV therapy with valganciclovir (55 therapy cases), 32 (97.0%) were CMV seropositive except 1 patient who had no related information. Thirty-two (97.0%) received T-cell depleting agent, thymoglobulin as an induction immunosuppressive treatment. Treatment failure, defined as a CMV DNA load more than or equal to 1000 copies/mL after 2 weeks of treatment, occurred in 3 (5.45 %) patients. No patient developed CMV disease during pre-emptive therapy. The median viral copies in patients treated successfully was 487.50 (311.24 – 826.25), whereas 4420.00 (2535.00 – 137450.00) in patients who undergone treatment failure.
Conclusion
These results suggest that pre-emptive therapy with low dose oral valganciclovir for 2 weeks can be successfully used for preventing CMV disease among KT recipients with low-level CMV viremia. Further research is needed to replicate these findings in larger samples and assess long-term outcomes.
Abstract
Background
The effect of a high-protein diet with renal hyperfiltration (RHF) on decline of kidney function has rarely been explored. We investigated the association between a high-protein ...diet, RHF and declining kidney function.
Methods
A total of 9226 subjects from the Korean Genome and Epidemiology Study, a community-based prospective study (2001–14), were enrolled and classified into quartiles according to daily amount of protein intake based on food frequency questionnaires. RHF was defined as estimated glomerular filtration rate (eGFR) with residuals of >95th percentile after adjustment for age, sex, history of hypertension or diabetes, height and weight. Rapid decline of renal function was defined as decline rate of eGFR >3 mL/min/1.73 m2/year.
Results
The relative risk of RHF was 3.48-fold higher in the highest than in the lowest protein intake quartile after adjustment for confounding factors 95% confidence interval (CI) 1.39–8.71. The mean eGFR decline rate was faster as quartiles of protein intake increased. Furthermore, the highest quartile was associated with 1.32-fold increased risk of rapid eGFR decline (95% CI 1.02–1.73). When subjects were divided into two groups with or without RHF, the highest quartile was associated with a rapid decline in renal function only in RHF subjects (odds ratio 3.35; 95% CI 1.07–10.51). The sensitivity analysis using the Korean National Health and Nutrition Examination Survey (2008–15) data with 40 113 subjects showed that higher quartile was associated with increased risk for RHF.
Conclusions
A high-protein diet increases the risk of RHF and a rapid renal function decline in the general population. These findings suggest that a high-protein diet has a deleterious effect on renal function in the general population.
Abstract Background and Aims Genetic risk for elevated blood pressure (BP) has been associated with a higher risk of hypertension and cardiovascular disease. However, the generalizability of previous ...findings has been limited due to a lack of studies among Asian populations. This study aimed to investigate whether genetic risk for BP predicts the incidence of hypertension and chronic kidney disease (CKD) in Asian populations. Method We performed genome-wide association studies for systolic and diastolic BP (SBP and DBP, respectively) using data from the Korean Genome and Epidemiology Study (KoGES). We then meta-analyzed these results with summary statistics from Biobank Japan to construct polygenic risk scores (PRSs) and examined the association between BP PRSs and incident hypertension or CKD. This study included participants without hypertension, cardiovascular disease, or CKD at baseline (n=4349, median age 48.5 years, 48.8% men). Participants were categorized into four groups based on their PRS percentile (<5, 5–50, 50–95, >95). Results As the PRS percentile increases, the median SBP and DBP at baseline also increase. Compared to the lowest SBP PRS percentile, higher PRS percentile was associated with increased risk of hypertension (hazard ratio HR 1.49, 95% confidence interval CI 1.22–1.83 for PRS percentile 5–50, HR 1.94, 95% CI 1.58–2.38 for PRS percentile 50–95, and HR 2.35, 95% CI 1.80–3.07 for PRS percentile >95). Elevated DBP PRS was also associated with higher risk of hypertension (HR 1.27, 95% CI 1.04–1.54 for PRS percentile 5–50, HR 1.72, 95% CI 1.41–2.09 for PRS percentile 50-95, and HR 2.09, 95% CI 1.60–2.72 for PRS percentile >95). The highest PRS percentile for SBP and DBP was associated with earlier onsets of hypertension by median 11 and 9 years, respectively, compared to the lowest PRS percentile for SBP and DBP. However, both SBP and DBP RPSs were not associated with incident CKD. Conclusion Genetic risk for elevated BP was associated with a higher risk of incident hypertension and earlier onset of hypertension in the Asian population. However, there was no association between PRS for elevated BP and the incidence of CKD.
Abstract
Background and Aims
Recent studies showed that the fibroblast growth factor 21 (FGF21) and angiotensin-converting enzyme 2 (ACE2)/Angiotensin 1-7 (Ang (1-7))/MAS axis of the ...renin-angiotensin system counteract to the negative role of Ang II in various disease. In this study, we examed FGF21 and ACE2/Ang (1-7) in obesity and its change after bariatric surgery.
Method
We prospectively enrolled obese patient who performed bariatric surgery and age-sex matched healthy volunteers (HV) (n=12 each). We obtained their clinical information and serum samples. Serum FGF-21, Ang II, ACE2, and Ang (1-7) levels were measured by enzyme-linked immunosorbent assay kits. We measured also FGF-21, Ang II, ACE2, and Ang (1-7) 6 months after bariatric surgery in obese patients (n=12).
Results
FGF21, Ang II, and ACE2 levels were significantly higher in obese patients compared with HV (p= 0.045, < 0.001, and 0.020, respectively). FGF21, Ang II, and ACE2 levels were significantly decreased after bariatric surgery (p = 0.002, 0.005, and 0.023, respectively). There was no significant difference in Ang (1-7) levels between obese patients and HV (p = 0.887) (Figure 1). Although Ang (1-7) levels did not change after bariatric surgery (p = 0.480), changes in Ang (1-7) levels were positively correlated with changes in body mass index (BMI) (R2 = 0.580, p = 0.048) (Figure 2).
Conclusion
FGF21 and ACE2 were upregulated in obese patients and they are reduced after bariatric surgery. A decrease in BMI after bariatric surgery could lead to decrease in Ang (1-7).
Figure 1. Changes in FGF21, Ang II, ACE2, and Ang (1-7) levels after bariatric surgery. Data were analyzed by *Mann-Whitney and **Wilcoxon matched-pairs signed rank tests. ACE2, angiotensin-converting enzyme 2; Ang (1-7), Angiotensin 1-7; Ang II, angiotensin II; FGF21, fibroblast growth factor 21; HV, healthy volunteers.
Figure 2. Relationships among changes in FGF21, Ang II, ACE2, Ang (1-7) levels and BMI after bariatric surgery. Data were analyzed by Spearman’s rank correlation coefficient. ACE2, angiotensin-converting enzyme 2; Ang (1-7), Angiotensin 1-7; Ang II, angiotensin II; BMI, body mass index; FGF21, fibroblast growth factor 21.
Mesenchymal stem cells (MSCs) are promising source of cell‐based regenerative therapy. In consideration of the risk of allosensitization, autologous MSC‐based therapy is preferred over allogenic ...transplantation in patients with chronic kidney disease (CKD). However, it remains uncertain whether adequate cell functionality is maintained under uremic conditions. As chronic inflammation and oxidative stress in CKD may lead to the accumulation of senescent cells, we investigated cellular senescence of CKD MSCs and determined the effects of metformin on CKD‐associated cellular senescence in bone marrow MSCs from sham‐operated and subtotal nephrectomized mice and further explored in adipose tissue‐derived MSCs from healthy kidney donors and patients with CKD. CKD MSCs showed reduced proliferation, accelerated senescence, and increased DNA damage as compared to control MSCs. These changes were significantly attenuated following metformin treatment. Lipopolysaccharide and transforming growth factor β1‐treated HK2 cells showed lower tubular expression of proinflammatory and fibrogenesis markers upon co‐culture with metformin‐treated CKD MSCs than with untreated CKD MSCs, suggestive of enhanced paracrine action of CKD MSCs mediated by metformin. In unilateral ureteral obstruction kidneys, metformin‐treated CKD MSCs more effectively attenuated inflammation and fibrosis as compared to untreated CKD MSCs. Thus, metformin preconditioning may exhibit a therapeutic benefit by targeting accelerated senescence of CKD MSCs.
Increased senescence of CKD MSCs may contribute to poor regenerative potential. Metformin decreased CKD‐induced prelamin A accumulation and DNA damage signaling, which may lead to cellular senescence. We suggest metformin preconditioning as an effective strategy to overcome the senescence‐associated barrier to autologous patient‐derived MSC therapy in CKD.
Changes in the perivascular adipose tissue (PVAT) are associated with the risk of metabolic syndrome (MetS). We hypothesized that the quantity and quality of PVAT measured by computed tomography (CT) ...are associated with cardiometabolic risk.
This study analyzed the data of 505 participants (men, 72.7%) who underwent general health checkups, including abdominal and pelvic CT. We measured the volume and fat attenuation index (FAI) of the abdominal periaortic (APA) and renal sinus (RS) adipose tissues. Participants were categorized into three groups according to the number of MetS components they had based on the modified ATP III criteria (0, 1–2, and ≥3).
Moving stepwise from the no MetS component group to the 1–2 components group to the ≥3 components group, all PVAT volumes increased and all PVAT FAIs decreased consistently. Greater PVAT volume was independently associated with greater prevalence of MetS components in the ≥3 components group (P = 0.002 for right RS, P = 0.027 for left RS, and P = 0.001 for APA), whereas lower FAI in all PVATs was associated with greater prevalence of MetS components in the 1–2 components group after adjusting for the corresponding adipose tissue volumes (P = 0.007 for right RS, P = 0.002 for left RS, and P = 0.001 for APA).
Higher abdominal PVAT volume was independently associated with prevalent MetS. Moreover, lower abdominal PVAT FAI was associated with mild metabolic derangement. Image-based assessment of abdominal PVAT may be a potential biomarker for cardiometabolic risk.
Although dyslipidemia is a major risk factor for chronic kidney disease (CKD), the relationship between dietary cholesterol and CKD remains unknown. We investigated the association between ...cholesterol intake and CKD risk.
The Korea National Health and Nutrition Examination Survey (KNHANES) 2019–2021 (n = 13,769) and the Korean Genome and Epidemiology Study (KoGES) (n = 9225) data were used for this study. Cholesterol intake was assessed using a 24-h recall food frequency questionnaire, and participants were categorized into three groups (T1, T2, and T3) based on cholesterol intake. Primary outcomes were prevalence and incidence of CKD. Higher cholesterol intake was modestly associated with increased serum levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol in the KNHANES. However, we found no significant association between cholesterol intake and CKD prevalence in the KNHANES, regardless of a history of hypercholesterolemia. In the KoGES, during a median follow-up of 11.4 years, cholesterol intake was not associated with incident CKD in participants without hypercholesterolemia (hazard ratio HR per 10 mg increase, 1.00; 95 % confidence interval CI, 0.99–1.01) and in those with hypercholesterolemia (HR, 1.01; 95 % CI, 0.98–1.04). Egg consumption also showed no significant association with the risk of incident CKD. Additionally, cholesterol intake had no significant interaction on the relationships between serum cholesterol levels and incident CKD.
Although cholesterol intake was associated with increased serum cholesterol levels, it was not associated with CKD prevalence and incidence. Our findings suggest that reducing cholesterol intake alone may not be sufficient to prevent CKD.
•Dyslipidemia is a well-known risk factor for chronic kidney disease (CKD).•Cholesterol intake was not associated with CKD prevalence and incidence.•The daily intake of eggs was not associated with incident CKD.•Simply lowering cholesterol intake may not be enough to prevent CKD.
Objective
Exosomal microRNAs (miRNAs) are potential biomarkers for obesity, in which they regulate biological processes. Bariatric surgery has health benefits for patients with obesity; however, the ...mechanisms of these benefits are not clear. This study attempted to identify the exosomal miRNA signature associated with obesity and how it changed after bariatric surgery.
Methods
Healthy volunteers (HVs) and nondiabetic patients with obesity were prospectively enrolled in the study. The study assessed the serum exosomal miRNA profiles of HVs and patients with obesity using RNA sequencing. To evaluate the effects of bariatric surgery, the study also analyzed exosomal miRNAs in patients 6 months after surgery.
Results
RNA sequencing revealed differential expression of 72 exosomal miRNAs in patients with obesity compared with HVs and differential expression of 41 miRNAs in post‐ versus presurgery blood. Among the differentially expressed miRNAs, the study identified nine surgery‐responsive miRNAs that were highly expressed in patients before surgery compared with HVs. Biological pathway analysis of the nine miRNAs indicated that they are likely involved in WNT, neurotrophin, and insulin signaling; the insulin receptor signaling cascade; and focal adhesion.
Conclusions
Patients with obesity have a distinct exosomal miRNA expression profile compared with HVs. In addition, weight loss after surgery alters the exosomal miRNA profile of patients with obesity.
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