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Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev 2023; 11:CD008176. [PMID: 37916745 PMCID: PMC10621004 DOI: 10.1002/14651858.cd008176.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2023]
Abstract
BACKGROUND Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. OBJECTIVES To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies until 15 November 2022 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA We included all randomised controlled trials investigating the use of antioxidants, compared with placebo, usual or standard care, no treatment, or other antioxidants, for adults with CKD on cardiovascular and kidney endpoints. DATA COLLECTION AND ANALYSIS Titles and abstracts were screened independently by two authors who also performed data extraction using standardised forms. Results were pooled using random effects models and expressed as risk ratios (RR) or mean difference (MD) with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS We included 95 studies (10,468 randomised patients) that evaluated antioxidant therapy in adults with non-dialysis-dependent CKD (31 studies, 5342 patients), dialysis-dependent CKD (41 studies, 3444 patients) and kidney transplant recipients (21 studies, 1529 patients). Two studies enrolled dialysis and non-dialysis patients (153 patients). Twenty-one studies assessed the effects of vitamin antioxidants, and 74 assessed the effects of non-vitamin antioxidants. Overall, the quality of included studies was moderate to low or very low due to unclear or high risk of bias for randomisation, allocation concealment, blinding, and loss to follow-up. Compared with placebo, usual care, or no treatment, antioxidant therapy may have little or no effect on cardiovascular death (8 studies, 3813 patients: RR 0.94, 95% CI 0.64 to 1.40; I² = 33%; low certainty of evidence) and probably has little to no effect on death (any cause) (45 studies, 7530 patients: RR 0.95, 95% CI 0.82 to 1.11; I² = 0%; moderate certainty of evidence), CVD (16 studies, 4768 patients: RR 0.79, 95% CI 0.63 to 0.99; I² = 23%; moderate certainty of evidence), or loss of kidney transplant (graft loss) (11 studies, 1053 patients: RR 0.88, 95% CI 0.67 to 1.17; I² = 0%; moderate certainty of evidence). Compared with placebo, usual care, or no treatment, antioxidants had little to no effect on the slope of urinary albumin/creatinine ratio (change in UACR) (7 studies, 1286 patients: MD -0.04 mg/mmol, 95% CI -0.55 to 0.47; I² = 37%; very low certainty of evidence) but the evidence is very uncertain. Antioxidants probably reduced the progression to kidney failure (10 studies, 3201 patients: RR 0.65, 95% CI 0.41 to 1.02; I² = 41%; moderate certainty of evidence), may improve the slope of estimated glomerular filtration rate (change in eGFR) (28 studies, 4128 patients: MD 3.65 mL/min/1.73 m², 95% CI 2.81 to 4.50; I² = 99%; low certainty of evidence), but had uncertain effects on the slope of serum creatinine (change in SCr) (16 studies, 3180 patients: MD -13.35 µmol/L, 95% CI -23.49 to -3.23; I² = 98%; very low certainty of evidence). Possible safety concerns are an observed increase in the risk of infection (14 studies, 3697 patients: RR 1.30, 95% CI 1.14 to 1.50; I² = 3%; moderate certainty of evidence) and heart failure (6 studies, 3733 patients: RR 1.40, 95% CI 1.11 to 1.75; I² = 0; moderate certainty of evidence) among antioxidant users. Results of studies with a low risk of bias or longer follow-ups generally were comparable to the main analyses. AUTHORS' CONCLUSIONS We found no evidence that antioxidants reduced death or improved kidney transplant outcomes or proteinuria in patients with CKD. Antioxidants likely reduce cardiovascular events and progression to kidney failure and may improve kidney function. Possible concerns are an increased risk of infections and heart failure among antioxidant users. However, most studies were of suboptimal quality and had limited follow-up, and few included people undergoing dialysis or kidney transplant recipients. Furthermore, the large heterogeneity in interventions hampers drawing conclusions on the efficacy and safety of individual agents.
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Affiliation(s)
- Julia Mt Colombijn
- Department of Nephrology and Hypertension, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
| | - Lotty Hooft
- Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
| | - Min Jun
- The George Institute for Global Health, UNSW, Sydney, Australia
| | - Angela C Webster
- Sydney School of Public Health, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- Westmead Applied Research Centre, The University of Sydney at Westmead, Westmead, Australia
- NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
- Department of Transplant and Renal Medicine, Westmead Hospital, Westmead, Australia
| | - Michiel L Bots
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, University of Utrecht, Utrecht, Netherlands
| | - Marianne C Verhaar
- Department of Nephrology and Hypertension, University of Utrecht, Utrecht, Netherlands
| | - Robin Wm Vernooij
- Department of Nephrology and Hypertension, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
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Peng L, Chen Y, Shi S, Wen H. Stem cell-derived and circulating exosomal microRNAs as new potential tools for diabetic nephropathy management. Stem Cell Res Ther 2022; 13:25. [PMID: 35073973 PMCID: PMC8785577 DOI: 10.1186/s13287-021-02696-w] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 12/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Despite major advances in the treatment of diabetic nephropathy (DN) in recent years, it remains the most common cause of end-stage renal disease. An early diagnosis and therapy may slow down the DN progression. Numerous potential biomarkers are currently being researched. Circulating levels of the kidney-released exosomes and biological molecules, which reflect the DN pathology including glomerular and tubular dysfunction as well as mesangial expansion and fibrosis, have shown the potential for predicting the occurrence and progression of DN. Moreover, many experimental therapies are currently being investigated, including stem cell therapy and medications targeting inflammatory, oxidant, or pro-fibrotic pathways activated during the DN progression. The therapeutic potential of stem cells is partly depending on their secretory capacity, particularly exosomal microRNAs (Exo-miRs). In recent years, a growing line of research has shown the participation of Exo-miRs in the pathophysiological processes of DN, which may provide effective therapeutic and biomarker tools for DN treatment. METHODS A systematic literature search was performed in MEDLINE, Scopus, and Google Scholar to collect published findings regarding therapeutic stem cell-derived Exo-miRs for DN treatment as well as circulating Exo-miRs as potential DN-associated biomarkers. FINDINGS Glomerular mesangial cells and podocytes are the most important culprits in the pathogenesis of DN and, thus, can be considered valuable therapeutic targets. Preclinical investigations have shown that stem cell-derived exosomes can exert beneficial effects in DN by transferring renoprotective miRs to the injured mesangial cells and podocytes. Of note, renoprotective Exo-miR-125a secreted by adipose-derived mesenchymal stem cells can improve the injured mesangial cells, while renoprotective Exo-miRs secreted by adipose-derived stem cells (Exo-miR-486 and Exo-miR-215-5p), human urine-derived stem cells (Exo-miR-16-5p), and bone marrow-derived mesenchymal stem cells (Exo-miR-let-7a) can improve the injured podocytes. On the other hand, clinical investigations have indicated that circulating Exo-miRs isolated from urine or serum hold great potential as promising biomarkers in DN.
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Affiliation(s)
- Lei Peng
- Department of Nephrology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, 610072, China
| | - Yu Chen
- Department of Cardiology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, 610072, China
| | - Shaoqing Shi
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
| | - Heling Wen
- Department of Cardiology, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, 610072, China.
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Zhang Q, Yang M, Xiao Y, Han Y, Yang S, Sun L. Towards Better Drug Repositioning: Targeted Immunoinflammatory Therapy for Diabetic Nephropathy. Curr Med Chem 2021; 28:1003-1024. [PMID: 31701843 DOI: 10.2174/0929867326666191108160643] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 09/23/2019] [Accepted: 09/26/2019] [Indexed: 11/22/2022]
Abstract
Diabetic nephropathy (DN) is one of the most common and important microvascular complications of diabetes mellitus (DM). The main clinical features of DN are proteinuria and a progressive decline in renal function, which are associated with structural and functional changes in the kidney. The pathogenesis of DN is multifactorial, including genetic, metabolic, and haemodynamic factors, which can trigger a sequence of events. Controlling metabolic risks such as hyperglycaemia, hypertension, and dyslipidaemia is not enough to slow the progression of DN. Recent studies emphasized immunoinflammation as a critical pathogenic factor in the progression of DN. Therefore, targeting inflammation is considered a potential and novel treatment strategy for DN. In this review, we will briefly introduce the inflammatory process of DN and discuss the anti-inflammatory effects of antidiabetic drugs when treating DN.
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Affiliation(s)
- Qin Zhang
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ming Yang
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ying Xiao
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yachun Han
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Shikun Yang
- Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Lin Sun
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Lacava V, Pellicanò V, Ferrajolo C, Cernaro V, Visconti L, Conti G, Buemi M, Santoro D. Novel avenues for treating diabetic nephropathy: new investigational drugs. Expert Opin Investig Drugs 2017; 26:445-462. [PMID: 28277032 DOI: 10.1080/13543784.2017.1293039] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2016] [Accepted: 02/06/2017] [Indexed: 01/01/2023]
Abstract
At present, treatment of diabetic kidney disease (DKD) is still mainly based on drugs acting on glycemic and blood pressure control, as there is no validated therapy able to halt the progression of renal failure. Because of the high incidence of DKD, due to the increase of diabetes mellitus in general population, new therapeutic strategies are needed. Areas covered: We analysed ongoing and already completed clinical trials, from clinicaltrials.gov and PubMed, dealing with new therapies for DKD. Expert opinion: Among the drugs currently being explored, the most promising molecules are those that interfere with glucose-dependent pathways, in particular polyol, protein kinase, hexosamine and AGEs metabolic pathways, and impaired renal vascular regulation. One of the recent goals achieved by molecular biology is the development of monoclonal antibodies able to interfere with extracellular matrix accumulation and fibrosis. Other interesting therapies are under investigation and further studies with a greater number of patients will establish a better approach for diabetic nephropathy.
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Affiliation(s)
- Viviana Lacava
- a Unit of Nephrology and Dialysis , University of Messina , Messina , Italy
| | - Vincenzo Pellicanò
- a Unit of Nephrology and Dialysis , University of Messina , Messina , Italy
| | - Carmen Ferrajolo
- b Department of Experimental Medicine , Second University of Naples , Napoli , Italy
| | - Valeria Cernaro
- a Unit of Nephrology and Dialysis , University of Messina , Messina , Italy
| | - Luca Visconti
- a Unit of Nephrology and Dialysis , University of Messina , Messina , Italy
| | - Giovanni Conti
- c Unit of Pediatric Nephrology and Rheumatology , University of Messina , Messina , Italy
| | - Michele Buemi
- a Unit of Nephrology and Dialysis , University of Messina , Messina , Italy
| | - Domenico Santoro
- a Unit of Nephrology and Dialysis , University of Messina , Messina , Italy
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Leporini C, Pisano A, Russo E, DArrigo G, de Sarro G, Coppolino G, Bolignano D. Effect of pentoxifylline on renal outcomes in chronic kidney disease patients: A systematic review and meta-analysis. Pharmacol Res 2016; 107:315-332. [DOI: 10.1016/j.phrs.2016.03.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 02/04/2016] [Accepted: 03/02/2016] [Indexed: 12/28/2022]
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Donate-Correa J, Martín-Núñez E, Muros-de-Fuentes M, Mora-Fernández C, Navarro-González JF. Inflammatory cytokines in diabetic nephropathy. J Diabetes Res 2015; 2015:948417. [PMID: 25785280 PMCID: PMC4345080 DOI: 10.1155/2015/948417] [Citation(s) in RCA: 172] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2014] [Revised: 01/17/2015] [Accepted: 01/31/2015] [Indexed: 12/12/2022] Open
Abstract
Probably, the most paradigmatic example of diabetic complication is diabetic nephropathy, which is the largest single cause of end-stage renal disease and a medical catastrophe of worldwide dimensions. Metabolic and hemodynamic alterations have been considered as the classical factors involved in the development of renal injury in patients with diabetes mellitus. However, the exact pathogenic mechanisms and the molecular events of diabetic nephropathy remain incompletely understood. Nowadays, there are convincing data that relate the diabetes inflammatory component with the development of renal disease. This review is focused on the inflammatory processes that develop diabetic nephropathy and on the new therapeutic approaches with anti-inflammatory effects for the treatment of chronic kidney disease in the setting of diabetic nephropathy.
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Affiliation(s)
- Javier Donate-Correa
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - Ernesto Martín-Núñez
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - Mercedes Muros-de-Fuentes
- Clinical Biochemistry Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - Carmen Mora-Fernández
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
| | - Juan F. Navarro-González
- Research Unit, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
- Nephrology Service, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain
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Agrawal NK, Kant S. Targeting inflammation in diabetes: Newer therapeutic options. World J Diabetes 2014; 5:697-710. [PMID: 25317247 PMCID: PMC4138593 DOI: 10.4239/wjd.v5.i5.697] [Citation(s) in RCA: 139] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 04/24/2014] [Accepted: 05/29/2014] [Indexed: 02/05/2023] Open
Abstract
Inflammation has been recognised to both decrease beta cell insulin secretion and increase insulin resistance. Circulating cytokines can affect beta cell function directly leading to secretory dysfunction and increased apoptosis. These cytokines can also indirectly affect beta cell function by increasing adipocyte inflammation.The resulting glucotoxicity and lipotoxicity further enhance the inflammatory process resulting in a vicious cycle. Weight reduction and drugs such as metformin have been shown to decrease the levels of C-Reactive Protein by 31% and 13%, respectively. Pioglitazone, insulin and statins have anti-inflammatory effects. Interleukin 1 and tumor necrosis factor-α antagonists are in trials and NSAIDs such as salsalate have shown an improvement in insulin sensitivity. Inhibition of 12-lipo-oxygenase, histone de-acetylases, and activation of sirtuin-1 are upcoming molecular targets to reduce inflammation. These therapies have also been shown to decrease the conversion of pre-diabetes state to diabetes. Drugs like glicazide, troglitazone, N-acetylcysteine and selective COX-2 inhibitors have shown benefit in diabetic neuropathy by decreasing inflammatory markers. Retinopathy drugs are used to target vascular endothelial growth factor, angiopoietin-2, various proteinases and chemokines. Drugs targeting the proteinases and various chemokines are pentoxifylline, inhibitors of nuclear factor-kappa B and mammalian target of rapamycin and are in clinical trials for diabetic nephropathy. Commonly used drugs such as insulin, metformin, peroxisome proliferator-activated receptors, glucagon like peptide-1 agonists and dipeptidyl peptidase-4 inhibitors also decrease inflammation. Anti-inflammatory therapies represent a potential approach for the therapy of diabetes and its complications.
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García-García PM, Getino-Melián MA, Domínguez-Pimentel V, Navarro-González JF. Inflammation in diabetic kidney disease. World J Diabetes 2014; 5:431-443. [PMID: 25126391 PMCID: PMC4127580 DOI: 10.4239/wjd.v5.i4.431] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2013] [Revised: 02/24/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
Diabetes mellitus entails significant health problems worldwide. The pathogenesis of diabetes is multifactorial, resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events, with metabolic and hemodynamic alterations. In this context, inflammation has emerged as a key pathophysiology mechanism. New pathogenic pathways will provide targets for prevention or future treatments. This review will focus on the implications of inflammation in diabetes mellitus, with special attention to inflammatory cytokines.
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Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, Chahin J, Méndez ML, Gallego E, Macía M, del Castillo N, Rivero A, Getino MA, García P, Jarque A, García J. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Am Soc Nephrol 2014; 26:220-9. [PMID: 24970885 DOI: 10.1681/asn.2014010012] [Citation(s) in RCA: 156] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
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 m(2) in the PTF group compared with 6.5±0.4 ml/min per 1.73 m(2) in the control group, with a between-group difference of 4.3 ml/min per 1.73 m(2) (95% confidence interval [95% CI], 3.1 to 5.5 ml/min per 1.73 m(2); 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 m(2) 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.
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Affiliation(s)
- Juan F Navarro-González
- Nephrology Service, Research Unit, GEENDIAB (Spanish Group for the Study of Diabetic Nephropathy), University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Carmen Mora-Fernández
- Research Unit, GEENDIAB (Spanish Group for the Study of Diabetic Nephropathy), University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Mercedes Muros de Fuentes
- GEENDIAB (Spanish Group for the Study of Diabetic Nephropathy), University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain Clinical Analysis Service, and
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Shan D, Wu HM, Yuan QY, Li J, Zhou RL, Liu GJ, Cochrane Kidney and Transplant Group. Pentoxifylline for diabetic kidney disease. Cochrane Database Syst Rev 2012; 2012:CD006800. [PMID: 22336824 PMCID: PMC11831249 DOI: 10.1002/14651858.cd006800.pub2] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Diabetic kidney disease (DKD) is associated with increased morbidity and mortality, mostly relating to cardiovascular complications. The relevance of inflammation in the pathogenesis of DKD has been investigated in recent years, and it has been shown that inflammatory markers are higher in people with DKD compared with the wider population. Pentoxifylline is a methylxanthine phosphodiesterase inhibitor with favourable anti-inflammatory effects and immunoregulatory properties. The anti-inflammatory effects conferred by pentoxifylline may be beneficial in the management of DKD. OBJECTIVES To assess the benefits and harms of pentoxifylline for treating people with DKD. SEARCH METHODS We searched the Cochrane Renal Group's specialised register (January 2012), CENTRAL (Issue 12, 2011), MEDLINE, EMBASE and four Chinese biomedical literature databases (CBM-disc, 1979 to July 2009), Chinese Science and Technique Journals Database (VIP, until July 2009), China National Knowledge Infrastructure (CNKI, until July 2009) and WanFang database (until July 2009). SELECTION CRITERIA All randomised controlled trials (RCTs) and quasi-RCTs studying the benefits and harms of pentoxifylline for DKD. DATA COLLECTION AND ANALYSIS Data were extracted independently by two authors. Meta-analyses were performed when more than one study provided data on a comparable outcome in sufficiently similar patients. Results of dichotomous outcomes were expressed as risk ratios (RR) with 95% confidence intervals (CI). Mean differences (MD) were calculated to assess the effects of treatment where outcomes were expressed on continuous scales, and standardised mean differences (SMD) calculated where different scales were used. Data was pooled using the random effects model. Adverse effects were assessed using descriptive techniques and where possible, risk differences (RD) with 95% CI. MAIN RESULTS We identified 17 studies that included a total of 991 participants with DKD which met our inclusion criteria. Overall, the methodological quality of included studies was low: 4/17 reported the method of randomisation, 13/17 did not; no study described the method of random allocation; 4/17 studies were considered to be at high risk of bias and 13/17 were considered to have unclear risk for incomplete outcome data reporting; 9/17 studies were at low risk bias and in 8/17 the risk of bias was unclear for selective outcome reporting.Compared with placebo, pentoxifylline significantly reduced serum creatinine (SCr) (MD -0.10 mg/dL, 95% CI -0.17 to -0.03), albuminuria (SMD -2.28, 95% CI -3.85 to -0.70) and overt proteinuria (MD -428.58 µg/min, 95% CI -661.65 to -195.50), but there was no difference in creatinine clearance (CrCl) (MD -5.18 mL/min, 95% CI -15.55 to 5.19). When compared with routine treatment alone, pentoxifylline did not significantly reduce SCr (MD 0.00 mg/dL, 95% CI -0.06 to 0.07) or blood pressure (systolic (SBP): MD -0.28 mm Hg, 95% CI -2.20 to 1.63; diastolic (DBP): MD -0.15 mm Hg, 95% CI -1.44 to 1.14), but did significantly reduce albuminuria (SMD 0.62, 95% CI 0.18 to 1.07) and proteinuria (MD 0.46 g/24 h, 95% CI 0.17 to 0.74). There was no significant difference in SCr (MD 0.00 mg/dL, 95% CI -0.08 to 0.07), albuminuria (MD -8.79 µg/min, 95% CI -27.18 to 9.59), proteinuria (MD -0.01 g/24 h, 95% CI -0.03 to 0.01) or blood pressure (SBP: MD 1.46 mm Hg, 95% CI -0.57 to 3.50; DBP: MD 1.37 mm Hg, 95% CI -0.23 to 2.98) between pentoxifylline and the active comparator (captopril or clonidine/methyldopa) for patients with type 1 and type 2 DKD. CrCl was significantly increased when pentoxifylline was compared to clonidine/methyldopa (MD 10.90 mL/min, 95% CI -1.40 to 20.40) but not with captopril (MD 3.26 mL/min, 95% CI -1.05 to 7.59). No data were available on the incidence of end-stage kidney disease (ESKD), time to ESKD, quality of life, or all-cause mortality. The adverse events of pentoxifylline were mild; no serious adverse events were reported in any of the included studies. AUTHORS' CONCLUSIONS From the available evidence, pentoxifylline seems to offer some beneficial effects in renal function improvement and reduction in albuminuria and proteinuria, with no obvious serious adverse effects for patients with DKD. However, most studies were poorly reported, small, and methodologically flawed. Evidence to support the use of pentoxifylline for DKD was insufficient to develop recommendations for its use in this patient population. Rigorously designed, randomised, multicentre, large scale studies of pentoxifylline for DKD are needed to further assess its therapeutic effects.
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Affiliation(s)
- Dan Shan
- West China Hospital, Sichuan UniversityDepartment of GeriatricsNo. 37 Guo Xue Xiang StreetChengduSichuanChina610041
| | - Hong Mei Wu
- West China Hospital, Sichuan UniversityDepartment of GeriatricsNo. 37 Guo Xue Xiang StreetChengduSichuanChina610041
| | - Qi Yuan Yuan
- No.5 People's Hospital of ChengduIntensive Care DepartmentChengduSichuanChina610041
| | - Jun Li
- West China Hospital, Sichuan UniversityDepartment of GeriatricsNo. 37 Guo Xue Xiang StreetChengduSichuanChina610041
| | - Rong Le Zhou
- Xi'an No.4 Hospital, Xi'an JiaoTong UniversityDepartment of OphthalmologyNo.21, Jie Fang RoadXi'anShaanxiChina710004
| | - Guan J Liu
- West China Hospital, Sichuan UniversityChinese Cochrane Centre, Chinese Evidence‐Based Medicine CentreNo. 37, Guo Xue XiangChengduSichuanChina610041
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Assem M, Yousri M. Impact of Pentoxifylline and Vitamin E on Ribavirin-induced Hemolytic Anemia in Chronic Hepatitis C Patients: An Egyptian Survey. Euroasian J Hepatogastroenterol 2012. [DOI: 10.5005/jp-journals-10018-1029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Auyanet I, Rodríguez LJ, Rodríguez LJ, Sánchez AY, Esparza N, Cabrera F, Bosch E, Cardona P, Checa MD. [Clinical and pharmacological factors related to the requirements of laser photocoagulation in patients with diabetic nephropathy due to type 2 diabetes mellitus]. Med Clin (Barc) 2011; 137:152-6. [PMID: 21507434 DOI: 10.1016/j.medcli.2010.11.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 11/08/2010] [Accepted: 11/09/2010] [Indexed: 10/18/2022]
Abstract
BACKGROUND AND OBJECTIVE Diabetic retinopathy is a microvascular complication of diabetes mellitus whose prevalence is closely related to the presence of nephropathy and hypertension. The aim was to study clinical and pharmacological factors that are associated with an increased need for laser photocoagulation in patients with diabetic nephropathy and retinopathy. PATIENTS AND METHODS Cross sectional study of 63 patients followed in the Diabetic Nephropathy consultation. Patients were divided into 2 groups according to whether or not previously have received photocoagulation. In each subgroup were studied demographic variables, anthropometric, laboratory, cardiovascular risk factors and treatment received by each patient for the control of hypertension, diabetes and others diseases. RESULTS We observed that the group had received photocoagulation had more years of diabetes evolution, more history of cardiovascular disease and a lower creatinine clearance. Similarly, the percentage of patients treated with carvedilol was significantly higher in the subgroup who had not received photocoagulation while the percentage of patients treated with beta-blockers was significantly higher in the subgroup that received photocoagulation; no significant differences was observed in the degree of control blood pressure. CONCLUSIONS Clinical and pharmacological factors related to the requirements of laser photocoagulation were years of diabetes evolution, history of cardiovascular disease, the stage of kidney disease and the treatment with beta-blockers.
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Affiliation(s)
- Ingrid Auyanet
- Servicio de Nefrología, Hospital Insular Universitario de Gran Canaria, Las Palmas, España.
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Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol 2011; 7:327-40. [DOI: 10.1038/nrneph.2011.51] [Citation(s) in RCA: 813] [Impact Index Per Article: 58.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Dash A, Maiti R, Bandakkanavar TKA, Pandey BL. Novel Drug Treatment for Diabetic Nephropathy. Int J Organ Transplant Med 2011. [DOI: 10.1016/s1561-5413(11)60003-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Pentosidina: un nuevo biomarcador de las complicaciones en la diabetes mellitus. Med Clin (Barc) 2011; 136:298-302. [DOI: 10.1016/j.medcli.2009.12.001] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2009] [Revised: 11/26/2009] [Accepted: 12/01/2009] [Indexed: 12/31/2022]
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Assem M, Yousri M. Impact of pentoxifylline and vitamin e on ribavirin-induced haemolytic anaemia in chronic hepatitis C patients: an egyptian survey. Int J Hepatol 2011; 2011:530949. [PMID: 21994862 PMCID: PMC3170830 DOI: 10.4061/2011/530949] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2010] [Revised: 01/22/2011] [Accepted: 02/28/2011] [Indexed: 11/30/2022] Open
Abstract
Background/Aim. We evaluate the impact of combined pentoxifylline and high-dose vitamins E to standard antiviral treatment on RBV-induced haemolytic anaemia. Patients and Methods. Selected 200 naïve chronic HCV patients, were randomized to receive either the standard antiviral therapy (peginterferon α-2b and RBV) plus pentoxifylline (800 mg) and high-dose vitamin E (1000 iu) daily (combined group) or received standard antiviral therapy plus placebo only (control group). They were followed up during treatment course and for 6 months posttreatment to assess the occurrence of anaemia and virological response, respectively. Results. RBV dose modification due to anaemia were significantly less in combined group (8.5 versus 21.5%. P < .05).Withdrawal, secondary to sever anemia (Hb < 8.5 gm%), was recorded only in 6 (28.6%) patients of the control group. Both (ETR) and (SVR) were significantly higher in combined group than control group by both intention-to-treat analysis (71 versus 56%, P < .05 and 66 versus 49%, P < .05) and per-protocol analysis (85.5 versus 70.9%, P < .05 and 79.5 versus 62%, P < .05). Conclusion. Pentoxifylline and vitamin E can ameliorate RBV-associated haemolysis; improve compliance and virologic clearance when combined with the standard antiviral therapy in patients with chronic hepatitis C.
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Affiliation(s)
- M. Assem
- Departments of Hepatology and Gastroenterology, National Liver Institute, Monoufiya University, Sheben Al kom 3211, Egypt,*M. Assem:
| | - M. Yousri
- Departments of Hepatology and Gastroenterology, National Liver Institute, Monoufiya University, Sheben Al kom 3211, Egypt
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