المؤلفون: Tonolo, G., Velussi, M., Brocco, E., Abaterusso, C., Carraro, A., Morgia, G., Satta, A., Faedda, R., Abhyankar, Avinash, Luthman, Holger, Nosadini, R.

المصدر: Kidney International. 70(1):177-186

مصطلحات موضوعية: C-reactive protein, type II, diabetes, oxidized-LDL, slit diaphragm proteins, podocytes, rate, glomerular filtration, microalbuminuria, simvastatin, cholestyramine, Medicin och hälsovetenskap, Klinisk medicin, Urologi och njurmedicin, Medical and Health Sciences, Clinical Medicine, Urology and Nephrology

الوصف: The factors determining the course of glomerular fitration rate (GFR) and albumin excretion rate (AER) and the expression of mRNA of slit diaphragm (SD) and podocyte proteins in microalbuminuric, hypertensive type II diabetic patients are not fully understood. GFR, AER, and SD protein mRNA were studied in 86 microalbuminuric, hypertensive, type II diabetics at baseline and after 4-year random double-blind treatment either with 40 mg simvastatin (Group 1) or with 30 g cholestyramine (Group 2) per day. Both groups had at baseline a GFR decay per year in the previous 2-4 years of 3 ml/min/1.73 m(2). Both Groups 1 and 2 showed a significant decrease of low-density lipoprotein cholesterol levels after simvastatin and cholestyramine treatment (P < 0.01). No change from base line values was observed as for hs-C-reactive protein and interleukin-6. A significant decrease of 8-hydroxydeoxyguanosine urinary excretion was observed after simvastatin treatment. GFR did not change from baseline with simvstatin, whereas a decrease was observed with cholestyramine treatment ( simvastatin vs cholestyramine: -0.21 vs -2.75 ml/min/ 1.73 m(2), P < 0.01). AER decreased in Group 1 (P < 0.01), but not in Group 2 patients. Real-time polymerase chain reaction measurement of mRNA SD proteins (CD2AP, FAT, Actn 4, NPHS1, and NPHS2) significantly increased in kidney biopsy specimens after simvastatin, but not cholestyramine treatment. Simvastatin, but not cholestyramine, 4-year treatment maintains steady patterns of GFR, and improves AER and expression of SD proteins in type II diabetes, despite similar hypocholesterolemic effects in circulation.

الوصول الحر: https://lup.lub.lu.se/record/686389Test
http://dx.doi.org/10.1038/sj.ki.5001515Test

المؤلفون: Tonolo, G.¹, Melis, M. G.¹, Formato, M.², Angius, M. F.¹, Carboni, A.¹, Brizzi, P.¹, Ciccarese, M.¹, Cherchi, G. M.², Maioli, M.¹

المصدر: European Journal of Clinical Investigation. Nov2000, Vol. 30 Issue 11, p980-987. 8p.

مصطلحات موضوعية: *STATINS (Cardiovascular agents), *LOW density lipoproteins, *PEOPLE with diabetes

مستخلص: Background Experimental evidence indicates that statins might have direct vascular effects independently from low-density lipoprotein (LDL) cholesterol reduction and we reported that the reduction in urinary albumin excretion rate during Simvastatin treatment in type 2 diabetic patients was not correlated with LDL-cholesterol decrease. However in humans there are no data regarding possible additional effects of Simvastatin on blood pressure and urinary albumin excretion beyond its capacity to lower serum cholesterol. Patients and methods Twenty-six microalbuminuric hypertensive type 2 diabetic patients (diastolic blood pressure — after four months wash-out from the previous antihypertensive therapy — consistently > 90 and < 100 mmHg; plasma LDL-cholesterol > 3.9 and < 6.5 mmol L-1) were enrolled in the study. In random order, these patients received Simvastatin (20 mg day-1) or Cholestyramine (6 g three times a day) for a period of 10 months and after three months of wash-out (cross-over) the sequence was reversed for an additional 10 months. Blood pressure, lipid parameters, glycated haemoglobin and urinary albumin excretion were measured during the study. Additionally, in eight patients, urinary glycosaminoglycan excretion (GAG) was also measured during the study. Results Simvastatin and Cholestyramine were equally effective in reducing total and LDL cholesterol. Only during Simvastatin treatment a significant reduction in diastolic blood pressure and both 24 h urinary albumin and GAG excretion rates were observed, while no significant changes were seen with Cholestyramine treatment. Conclusions Our results clearly show for the first time that the reduction of blood pressure, together with 24 h urinary albumin excretion rate — two established cardiovascular risk factors, obtained during Simvastatin therapy in hypertensive type 2 diabetic patients — is in large part independent from the reduction of LDL Cholesterol. [ABSTRACT FROM AUTHOR]

المؤلفون: Ruggenenti, Piero, Cortinovis, Monica, Parvanova, Aneliya, Trillini, Matias, Iliev, Ilian P, Bossi, Antonio C, Belviso, Antonio, Aparicio, Maria C, Trevisan, Roberto, Rota, Stefano, Perna, Annalisa, Peracchi, Tobia, Rubis, Nadia, Martinetti, Davide, Prandini, Silvia, Gaspari, Flavio, Carrara, Fabiola, De Cosmo, Salvatore, Tonolo, Giancarlo, Mangili, Ruggero, Remuzzi, Giuseppe

المساهمون: Ruggenenti, P, Cortinovis, M, Parvanova, A, Trillini, M, Iliev, I, Bossi, A, Belviso, A, Aparicio, M, Trevisan, R, Rota, S, Perna, A, Peracchi, T, Rubis, N, Martinetti, D, Prandini, S, Gaspari, F, Carrara, F, De Cosmo, S, Tonolo, G, Mangili, R, Remuzzi, G

مصطلحات موضوعية: microalbuminuria, type 2 diabetes, ACE inhibitors, glomerular filtration rate, MED/13 - ENDOCRINOLOGIA

الوصف: Background: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. Methods and findings: VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. Conclusions: Risk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) ...

وصف الملف: ELETTRONICO

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/34260595; info:eu-repo/semantics/altIdentifier/wos/WOS:000677704400002; volume:18; issue:7; journal:PLOS MEDICINE; http://hdl.handle.net/10281/320153Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85110374036

الإتاحة: https://doi.org/10.1371/journal.pmed.1003691Test
http://hdl.handle.net/10281/320153Test

المؤلفون: Piero Ruggenenti, Monica Cortinovis, Aneliya Parvanova, Matias Trillini, Ilian P Iliev, Antonio C Bossi, Antonio Belviso, Maria C Aparicio, Roberto Trevisan, Stefano Rota, Annalisa Perna, Tobia Peracchi, Nadia Rubis, Davide Martinetti, Silvia Prandini, Flavio Gaspari, Fabiola Carrara, Salvatore De Cosmo, Giancarlo Tonolo, Ruggero Mangili, Giuseppe Remuzzi, VARIETY Study Organization

المساهمون: Ruggenenti, P, Cortinovis, M, Parvanova, A, Trillini, M, Iliev, I, Bossi, A, Belviso, A, Aparicio, M, Trevisan, R, Rota, S, Perna, A, Peracchi, T, Rubis, N, Martinetti, D, Prandini, S, Gaspari, F, Carrara, F, De Cosmo, S, Tonolo, G, Mangili, R, Remuzzi, G

المصدر: PLoS Medicine
PLoS Medicine, Vol 18, Iss 7, p e1003691 (2021)

مصطلحات موضوعية: Male, ACE inhibitors, Physiology, microalbuminuria, type 2 diabetes, ACE inhibitors, glomerular filtration rate, Angiotensin-Converting Enzyme Inhibitors, 030204 cardiovascular system & hematology, ACE inhibitor therapy, Biochemistry, Lung and Intrathoracic Tumors, Endocrinology, Medical Conditions, 0302 clinical medicine, Medicine, 030212 general & internal medicine, biology, Pharmaceutics, Drugs, Cardiovascular therapy, Enzyme inhibitors, General Medicine, Middle Aged, Type 2 Diabetes, Oncology, Valsartan, Nephrology, Drug Therapy, Combination, Female, Drug therapy, medicine.symptom, Research Article, Glomerular Filtration Rate, medicine.drug, medicine.medical_specialty, Combination therapy, Endocrine Disorders, Urology, Benazepril, 03 medical and health sciences, Diabetes Mellitus, Albuminuria, Humans, MED/13 - ENDOCRINOLOGIA, Aged, Medicine and health sciences, Pharmacology, Renal Physiology, Intention-to-treat analysis, business.industry, Biology and Life Sciences, Cancers and Neoplasms, Angiotensin-converting enzyme, Benzazepines, medicine.disease, Diabetes Mellitus, Type 2, Metabolic Disorders, ACE inhibitor, Enzymology, biology.protein, Microalbuminuria, business, Angiotensin II Type 1 Receptor Blockers

الوصف: Background Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. Methods and findings VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. Conclusions Risk/benefit profile of study treatments was similar. Dual renin–angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. Trial registration EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.
Piero Ruggenenti and co-workers study prevention of microalbuminuria in patients with type 2 diabetes.
Author summary Why was this study done? Renin–angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prevents the onset of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Some studies found that ACE inhibitor and ARB combination therapy reduced urinary albumin excretion (UAE) more effectively than ACE inhibitor or ARB monotherapy in type 2 diabetic patients with microalbuminuria or macroalbuminuria. Treatment effect was, however, associated with greater blood pressure (BP) reduction. Whether, at comparable BP control, dual RAS inhibition with an ACE inhibitor and an ARB could be more renoprotective than either monotherapy in diabetic patients with no evidence of kidney disease is unknown. What did the researchers do and find? In this prospective, randomized, open-label, blinded endpoint (PROBE) trial, we evaluated whether, at similar BP control, combination therapy with the ACE inhibitor benazepril and the ARB valsartan would reduce the incidence of microalbuminuria more effectively than benazepril or valsartan monotherapy in 612 patients with type 2 diabetes and high-normal albuminuria. Secondarily, we compared the effects of the 2 monotherapies on the primary prevention of microalbuminuria in this population. We found that during a median follow-up of 66 months, combined treatment with half of the standard manufacturer-recommended antihypertensive doses of benazepril and valsartan had no superior effect against progression to microalbuminuria as compared to monotherapy with full recommended doses of either benazepril or valsartan. The protective effects of benazepril and valsartan monotherapies against progression to microalbuminuria were also similar. All treatments were safe and well tolerated, with a slight excess of hyperkalemia and hypotension episodes in the combination therapy group. What do these findings mean? Dual RAS blockade should not be preferred to ACE inhibitor or ARB monotherapy for the primary prevention of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Recent studies showing that sodium–glucose co-transporter 2 (SGLT2) inhibitors may afford substantial nephro- and cardioprotection to patients with type 2 diabetes and varying degrees of albuminuria might pave the way to novel prevention strategies based upon the integrated use of these novel medications with an ACE inhibitor or an ARB, but not with their combination.

وصف الملف: ELETTRONICO

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f532fe597469725c51a3f7ae6f5eff27Test
https://doi.org/10.1371/journal.pmed.1003691Test