Progressive kidney dysfunction is often observed in children with bilateral hypoplastic kidneys. While glomerulopathy can exacerbate hypoplastic kidney progression, only IgA nephropathy and post-streptococcal acute glomerulonephritis have been noted in such cases. Herein, we present a case of a four-year-old female patient with bilateral hypoplastic kidney, kidney dysfunction, and significant proteinuria (urinary protein/creatinine ratio > 1 g/gCr), prompting referral owing to persistent hematuria since two years of age. Enalapril was initiated; however, urinary findings exhibited no improvement despite stable symptoms and kidney function. Subsequently, a kidney biopsy was performed at six years of age, and C1q nephropathy was diagnosed. Given the presence of only mild mesangial proliferation, steroids were not administered; enalapril treatment was continued. By seven years of age, the patient\'s hematuria had resolved, and proteinuria levels had decreased. On the latest follow-up at 12 years of age, kidney function was preserved with only mild proteinuria. This case report highlights the favorable prognosis of asymptomatic C1q nephropathy characterized by mild mesangial proliferation, even in patients with hypoplastic kidneys, renal dysfunction, and significant proteinuria. It emphasizes the significance of timely pathological evaluation for guiding appropriate interventions in such patients.

Muscle atrophy due to limb immobilization and inactivity is a common consequence of many diseases and treatment processes. One of the systems activated in inflammatory conditions is the renin-angiotensin system (RAS). The present study was conducted with the aim of investigating the effects of one of the angiotensin-converting enzyme (ACE) inhibitors, enalapril, on improving muscle atrophy caused by immobility. The study was conducted in three groups: a control, an atrophy, and an atrophy group treated with enalapril on Balb/c mice. After tying a splint to cause atrophy in one of the legs, daily treatment with enalapril intraperitoneally (dissolved in DMSO) at a dose of 10 mg/kg/day was done for 7 days. On the eighth day, the splint was opened and half of the mice were evaluated. Then, in the recovery phase, treatment with enalapril was continued in the remaining mice for 10 days without a splint. At the end of each phase, the mice were examined for the muscle strength of the lower limb muscles, and histological and biochemical analyses were subsequently carried out. The tissue level of the oxidative stress index MDA was evaluated, which showed a significantly lower level in the enalapril group compared to the atrophy group (*P<0.1). Also, inflammatory factors in the enalapril group showed a decrease compared to the atrophy group. The strength of four limbs in the mice of the treatment group (-18.36 ± 1.70 %) was significantly higher than that of the atrophy group (-30.33 ± 3 %) at the end of the atrophy phase and also after 10 days of recovery. The results suggest that the use of enalapril that reduces the activation of angiotensin II-dependent pro-oxidant and pro-inflammatory pathways may improve the functional disorder and muscle necrosis in the murine model of muscle atrophy.

BACKGROUND: Adult nephrotic syndrome is a well-known kidney disease that causes heavy proteinuria, hypoalbuminemia, hypercholesterolemia, edema, and hypertension. The treatment varies according to its underlying cause but often faces medication resistance or adverse drug effects.
METHODS: A Japanese woman in her 80s presented with nephrotic syndrome after a 3 year latent period of urinary protein and occult blood. She did not have any secondary causes of nephrotic syndrome. Renal biopsy revealed thin glomerular basement membrane, partial foot process fusion on electron microscopy with minor glomerular change on light microscopy, and slight coarse immunoglobulin M deposition in the mesangium on immunofluorescence microscopy, which was inconsistent with any other glomerular diseases. Without steroid treatment, she dramatically remitted from proteinuria after the administration of the renal protective agents enalapril, ezetimibe, rosuvastatin, and dapagliflozin. Recurrence after 8 months of follow-up subsided with the administration of additional doses of the agents.
CONCLUSIONS: This case illustrated the novel outcomes of combining medical treatment without steroid use for nephrotic syndrome with thin glomerular basement membrane disease. At the time of writing this report, the patient\'s renal function was stable and she was free of edema, although moderate proteinuria and occult hematuria persisted. The final diagnosis was uncertain because of the lack of genetic investigation; however, the response to the aforementioned medical treatment suggests the effectiveness of the supportive therapy.

Obesity over-activates the classical arm of the renin-angiotensin system (RAS), impairing skeletal muscle remodeling. We aimed to compare the effect of exercise training and enalapril, an angiotensin-converting enzyme inhibitor, on RAS modulation in the skeletal muscle of obese animals. Thus, we divided C57BL/6 mice into two groups: standard chow (SC) and high-fat (HF) diet for 16 weeks. At the eighth week, the HF-fed animals were divided into four subgroups-sedentary (HF), treated with enalapril (HF-E), exercise training protocol (HF-T), and combined interventions (HF-ET). After 8 weeks of treatment, we evaluated body mass and index (BMI), body composition, exercise capacity, muscle morphology, and skeletal muscle molecular markers. All interventions resulted in lower BMI and attenuation of overactivation in the classical arm, while favoring the B2R in the bradykinin receptors profile. This was associated with reduced apoptosis markers in obese skeletal muscles. The HF-T group showed an increase in muscle mass and expression of biosynthesis markers and a reduction in expression of degradation markers and muscle fiber atrophy due to obesity. These findings suggest that the combination intervention did not have a synergistic effect against obesity-induced muscle remodeling. Additionally, the use of enalapril impaired muscle\'s physiological adaptations to exercise training.

Renal artery stenosis can complicate the management of heart failure with reduced ejection fraction, as it is a conventional contraindication to the use of ACE inhibitors. We report a case in which bilateral renal artery revascularisation allowed the safe reintroduction of enalapril (and subsequently sacubitril valsartan) in a patient with severe left ventricular systolic dysfunction. There is a role for renal artery angioplasty in selected patients to allow optimal medical therapy for patients with heart failure due to impaired systolic function.

OBJECTIVE: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19.
METHODS: We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated.
RESULTS: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]).
CONCLUSIONS: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Renin-angiotensin-aldosterone system (RAAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are commonly used in the management of hypertension. High blood pressure is a vital risk factor for cardiovascular disease. This study aims to establish any significant difference in using ACEIs and ARBs in managing hypertension. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct this systematic review. We searched PubMed, MEDLINE, and ScienceDirect for articles published in the last 20 years (2003 to 2023). Our search was last done on the 27th of June, 2023. Following the initial search, 8,313 articles were found on PubMed. After screening the articles selected from the databases, 10 articles examining 1,621,445 patients were selected for the final study. Three articles were identified that compared ACEI and ARB in their capacity to lower blood pressure. Six articles compared both medications\' capacity to reduce cardiovascular events and mortality. Five articles were identified that compared both classes of drugs for adverse effects. This study was made to determine whether or not there is a difference between the use of ACEIs and ARBs in the treatment of hypertension. The study showed that both ACEIs and ARBs are similar in their efficacy in lowering blood pressure. However, ACEI was revealed to be superior to ARB in reducing cardiovascular events and all-cause mortality. ARB was shown to be better tolerated by patients than ACEI.

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes.
METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment.
RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering.
CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg.
RESULTS:
UNASSIGNED: NCT03472508 (Registration Date: March 21, 2018).

BACKGROUND: Myxomatous mitral valve degeneration is the most common canine heart disease. Several clinical trials have investigated various treatments. The latest recommendations are published in the ACVIM consensus guidelines (2019). Our study aimed to investigate how closely veterinary practitioners apply the treatment recommendations of these guidelines and the latest clinical trials.
METHODS: An online survey was sent to Dutch and Belgian veterinary practices via digital channels.
RESULTS: The data from 363 fully completed surveys were analyzed. For stage B1 disease, 93% recommended, correctly, no treatment. For stage B2 disease, 67% of the respondents recommended starting pimobendan as monotherapy. For chronic treatment of stage C disease, 16 different drug combinations were mentioned, but nobody recommended surgery. Only 48% of the respondents recommended the only evidence-based drug combination: a loop diuretic with pimobendan. A concerning finding was the simultaneous prescription of two loop diuretics, by 19% of the respondents.
CONCLUSIONS: Treatment recommendations showed an increasing variation with more advanced disease stages from B1 through B2 to C. This reflects the increasing disagreement among the panelists who prepared the ACVIM consensus guidelines. Practitioners of our study seem to practice more evidence-based medicine than veterinary cardiologists, as it was reported in a recent survey-based study.

BACKGROUND: We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI).
OBJECTIVE: To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function and molecular signaling in the brain of MI rats in comparison with the effect of enalapril.
METHODS: Male rats were assigned to either sham or MI operation. In the MI group, rats with an ejection Fraction less than 50% were included, and then they received one of the following treatments for 5 weeks: vehicle, enalapril, Mdivi-1, or M1. Cognitive function was tested, and the brains were used for molecular study.
RESULTS: MI rats exhibited cardiac dysfunction with systemic oxidative stress. Cognitive impairment was found in MI rats, along with dendritic spine loss, blood-brain barrier (BBB) breakdown, brain mitochondrial dysfunction, and decreased mitochondrial and increased glycolysis metabolism, without the alteration of APP, BACE-1, Tau and p-Tau proteins. Treatment with Mdivi-1, M1, and enalapril equally improved cognitive function in MI rats. All treatments decreased dendritic spine loss, brain mitochondrial oxidative stress, and restored mitochondrial metabolism. Brain mitochondrial fusion was recovered only in the Mdivi-1-treated group.
CONCLUSIONS: Mitochondrial dynamics modulators improved cognitive function in MI rats through a reduction of systemic oxidative stress and brain mitochondrial dysfunction and the enhancement of mitochondrial metabolism. In addition, this mitochondrial fission inhibitor increased mitochondrial fusion in MI rats.