scholarly journals Proteinuria in frasier syndrome

2013 ◽  
Vol 141 (9-10) ◽  
pp. 685-688
Author(s):  
Amira Peco-Antic ◽  
Fatih Ozaltin ◽  
Vojislav Parezanovic ◽  
Gordana Milosevski-Lomic ◽  
Verica Zdravkovic
Keyword(s):  
Renin Angiotensin System ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Frasier Syndrome ◽  
Angiotensin System ◽  
Increased Risk ◽  
Risk Of Malignancy ◽  
End Stage ◽  
Ras Inhibitors

Introduction. Frasier syndrome (FS) is a genetic form of glomerulopathy, which results from mutations in the Wilms? tumour suppressor gene (WT1). Proteinuria in FS has been traditionally considered unresponsive to any medication and FS inevitably progresses to end stage renal failure. Case Outline. We present a patient with FS who had atypical clinical manifestation and unusual beneficial antiproteinuric response to renin-angiotensin system (RAS) inhibitors given in combination with indomethacin. After 13 years of follow-up, the patient is now 17-year old with normal renal functions and no proteinuria. Conclusion. RAS inhibitors combined with indomethacin showed beneficial effect in our patient. Thus, this combination might be the initial treatment of patients with FS. If this treatment strategy was not satisfied for at least 3 months, then CsA would be considered to be administered taking account of the nephrotoxicity and the increased risk of malignancy. Further prospective study is required to clarify this issue.

scholarly journals Real-world Evidence of Time-varying Effects of Renin-angiotensin System Inhibitors on Pneumonia and Related Deaths: A Territory-wide Cohort Study in 252,616 Patients With Diabetes (2002-2019)

2021 ◽  
Author(s):  
Aimin Yang ◽  
Mai Shi ◽  
Hongjiang Wu ◽  
Eric SH Lau ◽  
Baoqi Fan ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Chinese Patients ◽  
Cumulative Exposure ◽  
Time Varying ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Reduced Risk

Abstract BackgroundDiabetes is associated with increased risk of respiratory infections. Renin-angiotensin system (RAS) inhibition with anti-fibrotic, anti-inflammatory effects may reduce pneumonia risk. Prior studies did not account for time-varying and cumulative exposure to RAS inhibitors (RASi), with short follow-up periods, nor compared angiotensin converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use in Asians. We investigated the association of long-term use of RASi with risk of pneumonia and related death in Chinese people with diabetes using electronic medical record (EMR) data.MethodsThis was a prospective analysis of EMR with overlap propensity-score weighting of a territory-wide cohort (n=252,616, 1.7 million person-years) and a register-based cohort (n=13,017, 0.1 million person-years) in Hong Kong. We compared new-users of RASi (ACEi/ARBs) following baseline assessment with non-RASi users and new-users of calcium-channel blockers as active comparator. The main outcome was first hospitalization and death from pneumonia. ResultsAmongst 252,616 patients with diabetes in the population-based cohort (mean age=61.0 [SD=12.2] years), 73,161 were new-ACEi-only users; 20,907 new-ARBs-only users; 38,778 ACEi/ARBs users; and 119,770 never-ACEi/ARBs users. Over a mean follow-up period of 6.7 years, 5.2% (n=13,057) of patients had pneumonia and 2.2% (n=5,480) died with pneumonia. Compared with non-RASi use, time-varying RASi exposure was associated with reduced risk of pneumonia (hazard ratio, HR, 95% CI): 0.78 (0.75-0.82) and pneumonia-related death (HR=0.49, 0.46-0.53). The respective HRs for ARBs-only were 0.70 (0.62-0.78) and 0.41 (0.33-0.52) and that of ACEi-only were 0.98 (0.91-1.05) and 0.77 (0.68-86). In the Aalen-additive hazards model, the effect of RASi use was time-invariant for pneumonia (P=0.340) and time-varying for related death (P<0.001) with prevention of 0.6 (0.2-0.9) and 1.4 (1.0-1.6) per-1000-person-years pneumonia events and related deaths, respectively.ConclusionsLong-term use of RASi, notably ARB, was associated with reduced risk of pneumonia and related deaths in Chinese patients with diabetes.

scholarly journals Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction

2019 ◽  
Vol 316 (3) ◽  
pp. H446-H458 ◽  
Author(s):  
Viktoriya Mozolevska ◽  
Anna Schwartz ◽  
David Cheung ◽  
Vineet Goyal ◽  
Bilal Shaikh ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Prophylactic Treatment ◽  
Cell Cancer ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Prophylactic Administration ◽  
Increased Risk ◽  
Ras Inhibitors

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg−1·wk−1), or 3) SNT (40 mg·kg−1·day−1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

Sex Difference in the Ambulatory Blood Pressure Control Associates with Risk of Eskd and Death

2021 ◽  
Author(s):  
Roberto Minutolo ◽  
Francis B Gabbai ◽  
Rajiv Agarwal ◽  
Carlo Garofalo ◽  
Silvio Borrelli ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Sex Difference ◽  
Ambulatory Blood Pressure ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Increased Risk ◽  
End Stage ◽  
Adjusted Model

Abstract Background It is unknown whether faster progression of chronic kidney disease (CKD) in men than in women relates to differences in ambulatory blood pressure (ABP) levels. Methods We prospectively evaluated 906 hypertensive CKD patients (553 men) regularly followed in renal clinics to compare men vs women in terms of ABP control (daytime&lt;135/85 and nighttime BP &lt; 120/70 mmHg) and risk of all-cause mortality and end-stage kidney disease (ESKD) Results Age, eGFR and use of renin-angiotensin system inhibitors were similar in men and women while proteinuria was lower in women (0.30 g/24h IQR 0.10-1.00 vs 0.42 g/24h, IQR 0.10-1.28, P = 0.025). No sex-difference was detected in office BP levels; conversely, daytime and nighttime BP were higher in men (134±17/78±11 and 127±19/70±11 mmHg) than in women (131±16/75±11, P = 0.005/P&lt;0.001 and 123±20/67±12, P = 0.006/P&lt;0.001) with ABP goal achieved more frequently in women (39.1% vs 25.1%, P &lt; 0.001). During a median follow-up of 10.7 years, 275 patients reached ESKD (60.7% men) and 245 died (62.4% men). Risks of ESKD and mortality (Hazard Ratio and 95% CI), adjusted for demographic and clinical variables, were higher in men (1.34, 1.02-1.76 and 1.36, 1.02-1.83, respectively). Adjustment for office BP at goal did not modify this association. In contrast, adjustment for ABP at goal attenuated the increased risk in men for ESKD (1.29, 0.98-1.70) and death (1.31, 0.98-1.77). In the fully adjusted model, ABP at goal was associated with reduced risk of ESKD (0.49, 0.34-0.70) and death (0.59, 0.43-0.80). No interaction between sex and ABP at goal on the risk of ESKD and death was found, suggesting that ABP-driven risks are consistent in males and females. Conclusions Our study highlights that higher ABP significantly contributes to higher risks of ESKD and mortality in men.

scholarly journals DICER1 mutation and pituitary prolactinoma

2018 ◽  
Vol 2018 ◽  
Author(s):  
Ellena Cotton ◽  
David Ray
Keyword(s):  
Case Reports ◽  
Early Death ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
List Type ◽  
Non Coding Rna ◽  
Increased Risk ◽  
Non Coding Rnas ◽  
Learning Points

Summary A young woman carrying germline DICER1 mutation was discovered to have a pituitary microprolactinoma when she became amenorrhoic. The mutation was identified as a result of family screening following the early death of the patient’s daughter with ovarian cancer. The patient was in follow-up screening for thyroid disease, and investigations were initiated when she became amenorrhoic. MR scan revealed a 6 mm diameter pituitary microadenoma and raised prolactin. The prolactin was efficiently suppressed with low-dose cabergoline, and her menstrual cycles resumed. Dicer is an RNase enzyme, which is essential for processing small non-coding RNAs. These molecules play pleiotropic roles in regulating gene expression, by targeting mRNA sequences for degradation. DICER1 plays different roles depending on cell context, but is thought to be a functional tumour suppressor gene. Accordingly, germline mutation in one DICER1 allele is insufficient for oncogenesis, and a second hit on the other allele is required, as a result of postnatal somatic mutation. Loss of DICER1 is linked to multiple tumours, with prominent endocrine representation. Multinodular goitre is frequent, with increased risk of differentiated thyroid cancer. Rare, developmental pituitary tumours are reported, including pituitary blastoma, but not reports of functional pituitary adenomas. As DICER1 mutations are rare, case reports are the only means to identify new manifestations and to inform appropriate screening protocols. Learning points: DICER1 mutations lead to endocrine tumours. DICER1 is required for small non-coding RNA expression. DICER1 carriage and microprolactinoma are both rare, but here are reported in the same individual, suggesting association. Endocrine follow-up of patients carrying DICER1 mutations should consider pituitary disease.

P5448Enzymatic regulation of the myocardial tissue renin-angiotensin-system of the failing heart

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
N Pavo ◽  
R Wurm ◽  
S Prausmueller ◽  
G Spinka ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Failing Heart ◽  
Conversion Rates ◽  
Neprilysin Inhibitor ◽  
Metabolic Activities ◽  
End Stage ◽  
The Impact ◽  
Ras Inhibitors

Abstract Background In heart failure with reduced ejection fraction (HFrEF) the renin-angiotensin-system (RAS) is dysregulated and serves as therapeutic target. Research has been focusing on plasma RAS. Information on tissue RAS is scarce although assumedly more crucial for myocardial function. Among known angiotensins, only AngII and AngIII are detectable in the failing heart. Plasma samples in HFrEF show high AngI and AngII levels with clearly distinguishable AngI/AngII ratios for different RAS-inhibitors. AngII and AngIII levels in the myocardium were comparable for different RAS-inhibitors, i.e. no RAS-blocker, ACE-inhibitor, ARB or angiotensin-receptor neprilysin-inhibitor (ARNI). Here we aimed to elucidate the metabolic regulation of tissue RAS enzymes for these four different modalities of RAS-inhibition. Methods Enzyme regulation and metabolic activities were investigated in myocardial samples of end-stage HFrEF patients undergoing heart transplantation with a mass-spectrometry based method. Concentrations of respective angiotensin metabolites AngI, AngII, Ang1–7, AngIII, Ang1–5 and AngIV (RAS-fingerprints) were investigated after adding AngI or AngII and incubation to display metabolic patterns of the main plasma angiotensins. Metabolic activities of distinct enzymes have been assessed for the no therapy and ACE-I subgroups. Patients were stratified according to background therapy with RAS-inhibitors. Results A total of 30 patients were included (n=6 without RAS-blockade, n=16 with ACE-I, n=6 with ARB, n=2 with ARNI). Median age was 55 (IQR 45–63) years, 87%were male. Etiology of HF was ischemic in 40%, median NT-proBNP levels were 3498pg/ml (IQR 1761–8400). Patterns for tissue RAS metabolism of AngI and AngII was visually similar for all groups, indicating comparable regulation of tissue RAS enzymes independent from therapy (Figure 1). The formation of AngII from AngI was mainly chymase dependent with conversion rates of 99.4 (IQR 77.0–254.1) (pg/μg protein)/h for ACE-I and 141.8 (IQR 67.9–369.2) (pg/μg protein)/h for no RAS-blockade, whereas ACE-related generation of AngII was under the detection limit. The formation of Ang1–7 from AngI was mediated by NEP and PEP. The contribution of NEP was significantly higher [5022 (IQR 5002–5286) (pg/μg)/h vs 3555 (IQR 3351–3849) (pg/μg)/h, p=0.005 for the ACE-I group and 4729 (IQR 4438–6135) (pg/μg)/h vs 3601 (IQR 3052–4182) (pg/μg)/h, p=0.012 for no RAS-blockade]. No differences in tissue enzymatic activities between ACE-I and no therapy, as already indicated by the metabolization patterns occurred. Figure 1 Conclusions Enzymatic tissue RAS regulation in end-stage HF seems to be independent from the mode of established RAS-inhibitor therapy.In contrast to plasma, AngII formation of the tissue is mainly chymase dependent, whereas ACE seems to play an unsignificant role. NEP has a substantial role in generating beneficial Ang1–7 from AngI. The impact of NEP inhibition by ARNI on tissue RAS and mechanism of action have to be further investigated.

COVID-19, Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Inhibition: Implications for Practice

2021 ◽  
Vol 17 ◽  
Author(s):  
Vasiliki Katsi ◽  
George Pavlidis ◽  
George Charalambous ◽  
Dimitrios Tousoulis ◽  
Konstantinos Toutouzas
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Viral Entry ◽  
Enzyme Inhibitor ◽  
Experimental Studies ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Increased Risk ◽  
Ras Inhibitors

Background : Recent studies suggested that patients with coronavirus disease 2019 (COVID-19) who use renin-angiotensin system (RAS) inhibitors have an increased risk of respiratory failure and death. The hypothesis was that angiotensin-converting enzyme inhibitor (ACEIs) or angiotensin receptor blocker (ARBs) may up-regulate ACE2 expression that is used as receptor for viral entry into cells. Objective: The purpose of this review is to discuss the existing evidence on the interaction between COVID-19 infection, ACE2 and ACEIs or ARBs and to examine the main implications for clinical practice. In addition, novel therapeutic strategies for blocking ACE2-mediated COVID-19 infection will be displayed. Methods : We performed a comprehensive review of the literature to identify data from clinical and experimental studies for the association between COVID-19 infection, ACE2 and RAS inhibition. Results: The current clinical and experimental evidence for ACEIs or ARBs to facilitate severe acute respiratory distress syndrome-coronavirus-2 (SARS-CoV-2) is insufficient to suggest discontinuing these drugs. Several observational studies arrive at the conclusion that the continued use of RAS inhibitors is unlike to be harmful in COVID-19-positive patients. Conclusions: Further randomized trials are needed to answer definitely the question of whether RAS inhibitors are harmful or beneficial to patients with COVID-19.

scholarly journals Renin-angiotensin system blocker and outcomes of COVID-19: a systematic review and meta-analysis

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215322
Author(s):  
Hyun Woo Lee ◽  
Chang-Hwan Yoon ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Angiotensin Ii Receptor ◽  
Angiotensin System ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Receptor Blockers

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.

scholarly journals Clinical Outcomes of Patients With Primary Membranous Nephropathy and Subnephrotic Proteinuria

2021 ◽  
Vol 8 ◽  
Author(s):  
Peng He ◽  
Yang Zha ◽  
Jing Liu ◽  
Hanmin Wang ◽  
Lijie He
Keyword(s):  
Kidney Function ◽  
Membranous Nephropathy ◽  
Independent Predictor ◽  
Effective Management ◽  
Nephrotic Proteinuria ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Course Outcomes ◽  
End Stage

Objectives: To update the information about the prognosis of patients with primary membranous nephropathy (MN) and subnephrotic proteinuria and identify the relevant predictors.Methods: In total, 474 cases of biopsy-proven primary MN with at least 18 months of follow-up were reviewed to determine the outcomes of the subgroup of patients that presented with subnephrotic proteinuria. Clinical data included initial proteinuria and microhematuria, defined as the average proteinuria/microhematuria of the first 6 months during the course. Outcomes included partial remission (PR), complete remission (CR), nephrotic proteinuria progression, and kidney function progression, defined as ≥50% loss of kidney function or end-stage kidney disease.Results: In total, 205 patients with primary MN and subnephrotic proteinuria at biopsy were eligible. During a median follow-up of 43 months, 200 (97.56%), 167 (81.46%), and 53 (25.85%) patients attained PR, CR, and nephrotic proteinuria progression, respectively. Only one patient (0.49%) progressed to the kidney function progression. By multivariate Cox hazards regression analyses, the initial proteinuria was identified as the independent predictor for PR, CR, and nephrotic proteinuria progression with adjusted hazard ratios (aHRs) of 0.67 (95% confidence interval, 0.56–0.80), 0.50 (95% CI, 0.40–0.63), and 2.97 (95% CI, 2.23–3.97), respectively. A higher level of initial microhematuria was also associated with an increased risk of nephrotic proteinuria progression. The corresponding aHR was 1.11 (95% CI, 1.05–1.17).Conclusion: Among patients with primary MN and subnephrotic proteinuria, although the overall prognosis is excellent, dynamic detection and effective management of proteinuria remain important. In addition, initial microhematuria may be another predictor of nephrotic proteinuria progression.

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