Axel Pflueger

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (15)61.95 Total impact

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    ABSTRACT: Objective: Increasing evidence links TGF-β1 to progression of renal fibrosis including its association with diabetic nephropathy (DN). Current ELISA assays are not sensitive enough to measure TGF-β1 in the urine of many clinically healthy individuals, even those with established renal disease. The objective of this study was to validate a sensitive urinary assay for TGF-β1 and compare levels between healthy controls and patients with established DN. Design and methods: An ELISA method (R&D Systems) was utilized together with an amplification step to assay TGF-β1 in urine samples from 190 patients with DN and 80 healthy controls. Results: Using an ELAST (Perkin Elmer, Inc) amplification step, the ELISA for urinary TGF-β1 had a limit of quantification of 15.6 pg/mL and limit of detection of 7 pg/mL. Preliminary studies demonstrated that TGF-β1 was stable if urine was frozen promptly at -70°C without preservatives. Using this assay, 22/80 controls (27%) had detectable levels of urinary TGF-β1 (range <7 to 40.9 pg/mL; mean±SD 6.4±11.1 pg/mL). This was significantly lower (p<0.0001) than in the DN group in whom 114/190 (60%) had detectable levels of urinary TGF-β1 (range <7 to 526.4 pg/mL; mean±SD 20.4±45.8 pg/mL). Urinary protein and TGF-β1 concentrations demonstrated modest correlation in patients with DN (r=0.47, P<0.001). TGF-β1 measurement in patients with DN did not demonstrate significant association with progression of proteinuria or increase in serum creatinine during the next 12 months of follow-up. Conclusion: We have validated a sensitive ELISA assay for urinary TGF-β1, and demonstrated correlations with the degree of proteinuria and higher levels in patients with DN compared to controls. Additional study will be necessary in order to determine if serial testing can predict renal prognosis independent of known prognostic factors for patients with DN.
    Clinical biochemistry 05/2013; 46(15). DOI:10.1016/j.clinbiochem.2013.05.041 · 2.28 Impact Factor
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    ABSTRACT: To compare the clinical outcomes in patients with chronic renal insufficiency (CRI) and renal artery stenosis (RAS) following renal artery (RA) stent placement with and without embolic protection device (EPD) usage. Eighteen patients who had RA stent placement with EPD were matched to control patients (RA stent only). Blood pressure, number of hypertensive medications, and estimated glomerular filtration rate (eGFR) at 3 months before the procedure and after 12 months were determined. An increase of ≥ 20% in eGFR at 12 months from baseline was defined as "improvement," decrease of ≥ 20% as "deterioration," and an eGFR change between those values as "stabilization" at 12 months. At 12 months, stage 4 patients treated with EPD had significantly higher eGFR than controls (P = .01). There was no statistical difference in blood pressure outcomes between the 2 groups. Patients with stage 4 CRI did significantly better with EPD than those treated without it.
    Vascular and Endovascular Surgery 06/2012; 46(6):447-54. DOI:10.1177/1538574412449911 · 0.66 Impact Factor
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    Alina Livshits · Axel Pflueger
    Diseases of Renal Parenchyma, 03/2012; , ISBN: 978-953-51-0245-8
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    ABSTRACT: Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m²). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (+3.3 ± 8.5 ml/min per 1.73 m²) whereas the mean eGFR decreased in the placebo group (-2.2 ± 4.8 ml/min per 1.73 m²; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 ± 6.7 ml/min per 1.73 m²). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.
    Journal of the American Society of Nephrology 06/2011; 22(6):1144-51. DOI:10.1681/ASN.2010101049 · 9.34 Impact Factor
  • American Journal of Kidney Diseases 04/2011; 57(4). DOI:10.1053/j.ajkd.2011.02.331 · 5.90 Impact Factor
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    Andrew D Calvin · Sanjay Misra · Axel Pflueger
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    ABSTRACT: Contrast-induced acute kidney injury (CIAKI) is a leading cause of iatrogenic renal failure. Multiple studies have shown that patients with diabetic nephropathy are at high risk of CIAKI. This Review presents an overview of the pathogenesis of CIAKI in patients with diabetic nephropathy and discusses the currently available and potential future strategies for CIAKI prevention.
    Nature Reviews Nephrology 09/2010; 6(11):679-88. DOI:10.1038/nrneph.2010.116 · 8.54 Impact Factor
  • Fayaz A Hakim · Axel Pflueger
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    ABSTRACT: Diabetes mellitus has become a worldwide epidemic affecting nearly all areas of developing and developed countries. Nearly half of all patients with diabetes, type 1 and 2, will develop diabetic kidney disease (DKD) if they do not die prematurely from cardiovascular disease. Diabetic kidney disease is associated with a high cardiovascular mortality even in its early stages and about a third of patients with DKD will progress to end stage renal disease (ESRD). Presently, therapy for DKD is limited primarily to inhibitors of the renin angiotensin system, treatment of comorbidities, and life style modifications. The role of reactive oxidant species (ROS) in the pathogenesis of DKD has been demonstrated in numerous studies. However, the implementation of antioxidant therapy for DKD has been inadequate. The current review addresses the role of ROS in the pathogenesis of DKD and discusses current and potential novel treatment modalities. Methodology: A comprehensive search of the literature was performed using MEDLINE and PubMed covering the period between 1966 and September 2009. The search for literature included only articles written in English. An article was rejected if it was clearly a letter or case report. The terms used for PubMed and Medline searches were: oxidative stress, reactive oxidant species, oxygen free radicals, diabetic nephropathy, and diabetic kidney disease. Formal inclusion and exclusion criteria were not defined for this review. The authors performed the analyses and statistical judgments in this review, and evaluated and identified articles for eligibility based on 4 criteria: 1) scientific relevance, 2) study design, 3) target population and 4) outcome.
    Medical science monitor: international medical journal of experimental and clinical research 02/2010; 16(2):RA37-48. · 1.43 Impact Factor
  • Axel Pflueger · David Abramowitz · Andrew D Calvin
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    ABSTRACT: Contrast-induced acute kidney injury (CIAKI) is the most-common form of in-hospital drug-induced acute kidney injury and occurs in 1 to over 50% of patients undergoing intravascular contrast media (CM) administration. Numerous risk factors for CIAKI have been described, the most prominent among them is pre-existing kidney disease such as diabetic nephropathy. The pathogenesis of CIAKI appears to be caused, at least in part, by renal vasoconstriction and renal ischemia leading to the generation of reactive oxygen species (ROS). Diabetes is associated with increased sensitivity to renal vasoconstrictors including CM agents and is also associated with dysfunctional renal handling of ROS, making diabetics particularly susceptible to CIAKI. At present, there are limited srtategies for the prevention of CIAKI among them the administration of the antioxidant N-acetylcysteine (NAC) and intravenous hydration. In light of the rising prevalence of diabetes worldwide and the high risk it represents for the development of CIAKI and CIAKI-associated cardiovascular mortality, a lucid understanding of the pathogenesis of CIAKI and diabetic nephropathy is indispensable. The current review addresses the role of ROS in the pathogenesis of CIAKI in the diabetic renal milieu and discusses current and potential novel treatment modalities for the prevention of CIAKI in diabetic patients.
    Medical science monitor: international medical journal of experimental and clinical research 07/2009; 15(6):RA125-36. · 1.43 Impact Factor
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    ABSTRACT: Various forms of renal replacement therapies (RRT) are available to treat acute kidney injury (AKI) after cardiac surgery. The objective of this review is to assess the incidence of postoperative AKI that necessitates the application of haemofiltration in adult patients undergoing cardiac operations with cardiopulmonary bypass (CPB), to determine the factors that influence the outcome in these patients. In addition, the review aims to assess the outcomes of postoperative early haemofiltration as compared to late intensive haemofiltration. Different forms of RRT such as intermittent haemodialysis, continuous haemofiltration, or hybrid forms which combine advantages of both are now available for application in cardiac surgery patients, and will be discussed in this article. The underlying disease, its severity and stage, the aetiology of AKI, clinical and haemodynamic status of the patient, the resources available, and different costs of therapy may all influence the choice of the RRT strategy. AKI, with its risk of uraemic complications, represents an independent risk factor for adverse outcomes in critically ill patients after cardiac surgery. Whether early initiation of RRT is associated with improved survival is unknown, and also clear guidelines on RRT durations are still lacking. In particular, it remains unclear whether haemodynamically unstable patients who develop septic shock pre- and postoperatively can benefit from early RRT initiation. In addition, it is not known whether in AKI patients undergoing cardiac surgery RRT modalities can eliminate significant amounts of clinically relevant inflammatory mediators. This review gives an update of information available in the literature on possible mechanisms underlying AKI and the recent developments in continuous renal replacement treatment modalities.
    European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 05/2009; 35(5-35):854-863. DOI:10.1016/j.ejcts.2008.12.019 · 3.30 Impact Factor
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    ABSTRACT: To describe restenosis and clinical outcomes with drug-eluting stents (DESs) and compare them to those of bare metal stents (BMSs) in the treatment of symptomatic atherosclerotic renal artery stenosis (RAS) in the same patients. A retrospective study was performed of all patients with RAS treated with a DES (Taxus Express 2 or Cypher). DESs were used for RASs with luminal vessel diameters of 4 mm or smaller and BMSs were used for those larger than 4 mm. Sixteen patients (eight women; mean age, 72 years +/- 8) underwent treatment of 27 RASs for worsening renal function (n = 10) and uncontrolled hypertension (n = 6). Eighteen RASs were treated with 23 DESs (Cypher, n = 12; Taxus, n = 11) and nine were treated with BMSs. The average follow-up was 22 months +/- 10. After the procedure, the mean systolic blood pressure decreased significantly (P < .05), with no change in the mean diastolic pressure, serum creatinine, or number of antihypertensive medications. By Kaplan-Meier estimates, the 1- and 2-year patency rates for DESs were 78% and 68%, respectively; and for BMSs, the respective rates were 58% and 47% (P = NS). The average diameters of RASs were 3.4 mm +/- 0.6 in the DES group and 5.3 mm +/- 0.6 in the BMS group (P < .05). There were two technical failures (7.7%) in the DES group. There was one minor complication and a non-flow-limiting dissection. DESs were used to treat RASs with good technical results and low restenosis rates compared with BMSs despite the smaller artery diameters in the DES group.
    Journal of Vascular and Interventional Radiology 06/2008; 19(6):833-9. DOI:10.1016/j.jvir.2008.03.017 · 2.41 Impact Factor
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    ABSTRACT: The role of sodium bicarbonate in preventing contrast nephropathy needs to be evaluated in clinical settings. We performed a retrospective cohort study at Mayo Clinic in Rochester, Minnesota, to assess the risk of contrast nephropathy associated with the use of sodium bicarbonate, N-acetylcysteine, and the combination of sodium bicarbonate with N-acetylcysteine from April 2004 to May 2005. Contrast nephropathy was defined as postexposure creatinine elevation of > or =25% or >0.5 mg/dl within 7 d of contrast exposure. A total of 11,516 contrast exposures in 7977 patients had creatinine values available for review before and after contrast exposure. More than 90% of exposures to agents prophylactic for contrast nephropathy were available for analysis. Sodium bicarbonate was used in 268 cases, N-acetylcysteine was used in 616 cases, and both agents were used in combination in 221 cases of contrast exposure. After adjustment for total volume of hydration, medications, age, gender, prior creatinine, contrast iodine load, prior exposure to contrast material, type of imaging study, heart failure, hypertension, renal failure, multiple myeloma, and diabetes mellitus, use of sodium bicarbonate alone was associated with an increased risk of contrast nephropathy compared with no treatment (odds ratio 3.10, 95% confidence interval 2.28 to 4.18; P < 0.001). N-acetylcysteine alone and in combination with sodium bicarbonate was not associated with any significant difference in the incidence of contrast nephropathy. The use of intravenous sodium bicarbonate was associated with increased incidence of contrast nephropathy. Use of sodium bicarbonate to prevent contrast nephropathy should be evaluated further rather than adopted into clinical practice.
    Clinical Journal of the American Society of Nephrology 01/2008; 3(1):10-8. DOI:10.2215/CJN.03100707 · 4.61 Impact Factor
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    ABSTRACT: ANG II induces vasoconstriction, at least in part, by stimulating NADPH oxidase and generating reactive oxygen species. ANG II also induces heme oxygenase activity, and bilirubin, a product of such activity, possesses antioxidant properties. We hypothesized that bilirubin, because of its antioxidant properties, may reduce the pressor and prooxidant effects of ANG II. Our in vivo studies used the hyperbilirubinemic Gunn rat which is deficient in the enzyme uridine diphosphate glucuronosyl transferase, the latter enabling the excretion of bilirubin into bile. ANG II (0.5 mg x kg(-1) x day(-1)) or saline vehicle was administered by osmotic minipump to control and Gunn rats for 4 wk. The rise in systolic blood pressure induced by ANG II, as observed in control rats, was markedly reduced in Gunn rats, the latter approximately 50% less at 3 and 4 wk after the initiation of ANG II infusion. The chronic administration of ANG II also impaired endothelium-dependent relaxation responses in control rats but not in Gunn rats. As assessed by the tetrahydrobiopterin/dihydrobiopterin ratio, ANG II induced oxidative stress in the aorta in control rats but not in Gunn rats. Heightened generation of superoxide anion in aortic rings in ANG II-infused rats and by vascular smooth muscle cells exposed to ANG II was normalized by bilirubin in vitro. We conclude that the pressor and prooxidant effects of ANG II are attenuated in the hyperbilirubinemic Gunn rat, an effect which, we speculate, may reflect, at least in part, the scavenging of superoxide anion by bilirubin.
    American journal of physiology. Renal physiology 03/2005; 288(3):F552-8. DOI:10.1152/ajprenal.00278.2004 · 3.25 Impact Factor
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    Mayo Clinic Proceedings 02/2005; 80(1):111-4. DOI:10.1016/S0025-6196(11)62967-4 · 6.26 Impact Factor
  • Mayo Clinic Proceedings 01/2005; 80(1):111-114. DOI:10.4065/80.1.111 · 6.26 Impact Factor
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    ABSTRACT: Increased release of renal adenosine and stimulation of renal adenosine receptors have been proposed to be major mechanisms in the development of contrast media-induced acute renal failure (CM-ARF). Patients with diabetes mellitus or preexisting renal disease who have reduced renal function have a markedly increased risk to develop CM-ARF. This increased risk to develop CM-ARF in patients with diabetes mellitus is linked to a higher sensitivity of the renal vasculature to adenosine, since experimental studies have shown increased adenosine-induced vasoconstriction in the kidneys of diabetic animals. Furthermore, recent evidence suggests that administration of adenosine receptor antagonists reduces the risk of development of CM-ARF in both diabetic and nondiabetic patients. The purpose of this review is to discuss the role of adenosine in the development of CM-ARF, particularly in the kidneys of diabetic patients, and to evaluate the therapeutic potential of adenosine receptor antagonists in the prevention of CM-ARF. Selective adenosine A1 receptor antagonists may provide a therapeutic tool to prevent CM-ARF in patients with diabetes mellitus and reduced renal function.
    Mayo Clinic Proceedings 01/2001; 75(12):1275-83. DOI:10.4065/75.12.1275 · 6.26 Impact Factor