letter to the editor
http://www.kidney-international.org & 2009 International Society of Nephrology
Causative vascular abnormalities for renal ischemia Kidney International (2009) 75, 1354; doi:10.1038/ki.2009.106
To the Editor: As a case of The Renal Consult, Sperati et al.1 presented a 46-year-old man with renal infarctions and renal artery stenoses (RASs). Although their clinical diagnosis was bilateral intimal fibromuscular dysplasia (FMD) complicated by dissection, several distinctions of the case would indicate other causative abnormalities for the RASs, such as atherosclerosis and arteritis. Although the renal arteriographic image is characteristic of intimal FMD, either atherosclerosis or arteritis can present arteriographic images similar to those seen in intimal FMD.2 A middle-aged man could have atherosclerosis, especially if he were a smoker. The intravascular ultrasound image, a crescent-shaped hypoechoic lesion with an echogenic layer on its vascular surface, would indicate lipid-laden atherosclerosis with a thin fibrous cap.3 Several echogenic clefts inside the hypoechoic lesion would be fibrous or calcified components of atherosclerosis rather than dissection flaps. It would be unlikely that dissection flaps had been embedded in a thick thrombus covered by a fibrous cap. Furthermore, the episodes of fever and spontaneous improvement in vascular lesions while taking prednisone might indicate superimposed inflammatory changes; these episodes are rarely noted in FMD.2 1. Sperati CJ, Aggarwal N, Arepally A et al. Fibromuscular dysplasia. Kidney Int 2009; 75: 333–336. 2. Luscher TF, Lie JT, Stanson AW et al. Arterial fibromuscular dysplasia. Mayo Clin Proc 1987; 62: 931–952. 3. Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiological insights and current clinical applications. Circulation 2001; 103: 604–616.
Masayuki Tanemoto1 1 Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan Correspondence: Masayuki Tanemoto, Division of Nephrology, Hypertension, and Endocrinology, Department of Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi 980-8574, Japan. E-mail:
[email protected]
Response to ‘Causative vascular abnormalities for renal ischemia’ Kidney International (2009) 75, 1354; doi:10.1038/ki.2009.110
Dr Tanemoto suggests that the intravascular ultrasound image may be more consistent with a lipid-laden atheroma, indicating that the patient may have actually had atherosclerotic renal artery stenosis (RAS) rather than intimal fibromuscular dysplasia (FMD). In addition, Dr Tanemoto proposes that the improvement in vascular lesions and fever after the administration of prednisone might suggest an inflammatory etiology to the vascular lesions.1 We agree 1354
that intimal FMD can be difficult to distinguish angiographically from atherosclerotic disease.2 The features of this case, however, strongly supports FMD rather than RAS. The patient had multiple areas of stenosis in the distal, smaller renal vessels—angiographic findings typical for FMD and unusual in RAS.3 The intravascular ultrasound image shows low-intensity echoes without significant calcification—findings more typical of a dissection than atherosclerotic RAS. Moreover, the relatively young age of this patient who did not smoke, and the absence of peripheral arterial disease, places him at low risk for RAS. The low-grade fevers before admission are consistent with renal infarction, and the absence of significant markers of infla mmation is consistent with a diagnosis of FMD. Importantly, his clinical improvement without ongoing immunosuppressive therapy essentially excludes a diagnosis of polyarteritis nodosa. 1. 2. 3.
Tanemoto M. Causative vascular abnormalities for the renal ischemia. Kidney Int 2009; 75: 1354. Luscher TF, Lie JT, Stanson AW et al. Arterial fibromuscular dysplasia. Mayo Clin Proc 1987; 62: 931–952. Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med 2001; 344: 431–442.
C. John Sperati1, Nisha Aggarwal2, Aravind Arepally3 and Mohamed G. Atta1 1 Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; 2Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA and 3 Piedmont Radiology, Atlanta, Georgia, USA Correspondence: C. John Sperati, 1830 E Monument Street, Room 416, Baltimore, Maryland 21205, USA. Email:
[email protected]
Treatment with statins may be considered in ESRD patients for primary prevention of cardiovascular disease Kidney International (2009) 75, 1354–1355; doi:10.1038/ki.2009.107
To the Editor: In their elegant review, Cachofeiro et al.1 related cardiovascular risk to oxidative stress, inflammation, and atherogenesis and report the results of treatment with statins on the prevention of cardiovascular disease (CVD) in the general population and in chronic kidney disease patients. Peripheral blood mononuclear cell (PBMC) 5-lipoxygenase (5-Lox) activity is involved in low-density lipoprotein oxidation during the early phases of atherogenesis. 5-Lox activity and expression are upregulated in PBMC of uremic patients under maintenance hemodialysis (MHD).2 The subsequent increase in membrane lipid peroxidation, reactive oxygen species production, and lowdensity lipoprotein oxidation seems to contribute to the susceptibility of uremic patients to atherosclerosis and CVD. Antioxidant and anti-inflammatory ‘pleiotropic’ actions of Kidney International (2009) 75, 1354–1358
letter to the editor
statins have been widely investigated, and their use is usually recommended in the secondary prevention of acute coronary syndrome (ACS). To investigate the use of statins for the primary prevention of ACS, between April 2004 and February 2005 we enrolled a total of 31 end-stage renal disease patients on MHD, with neither history nor clinical and instrumental signs of earlier major adverse cardiac events (MACEs). We started each patient on atorvastatin (10 mg) daily regardless of serum low-density lipoprotein cholesterol associated with conventional pharmacologic control of blood pressure, serum glucose, and calcium–phosphate balance. During a 4-year follow-up overall 3-year actuarial survival was 67%,3 compared with a 20–40% 5-year survival reported earlier.4 Cardiovascular mortality was 12.9%, (4 patients). ‘MACE’ free’ (lethal and non-lethal) 3-year actuarial survival was 53%. Treatment with statins may be considered in the primary prevention of MACEs in hemodialysis patients. 1. Cachofeiro V, Goicochea M, Gracia de Vinuesa S et al. Oxidative stress and inflammation, a link between chronic kidney disease and cardiovascular disease. Kidney Int 2008; 74(suppl 111): S4–S9. 2. Maccarrone M, Taccone Gallucci M, Meloni C et al. ‘Activation of 5-lipoxygenase and related lipid peroxidation in hemodialysis patients’. J Am Soc Nephrol 1999; 10: 1991–1996. 3. Lonzi M, Manca di Villahermosa S, Summaria F et al. Cardiovascular outcome in asymptomatic haemodialysis patients submitted to aggressive medical therapy: a 30-month follow-up. Nephrol Dial Transplant 2007; 22s6: vi322–vi323. 4. Akmal M. Hemodialysis in diabetic patients. Am J Kidney Dis 2001; 38(suppl 1): S195–S199.
associated with cardiovascular mortality reduction, which accounts for half the deaths in such patients.2 Moreover, this occurs independently of the presence or absence of high c-reactive protein levels that are associated with cardiovascular event risk.3 Reasons for this discrepancy are not evident, as statins exert anti-inflammatory, antioxidant, and lipid-lowering effects as effective as those observed in normal renal function participants. End-stage renal disease patients are at high risk for cardiovascular complications, in whom cardiovascular disease is considered complex and aggravated by coexisting factors, including malnutrition, accelerated atherosclerosis, left ventricular hypertrophy, cardiac fibrosis, and sympathetic overactivity. In the 4-D study, most of cardiovascular deaths were caused by sudden death and not by coronary heart disease.2 Data for two ongoing large trials (AURORA and SHARP) would help put into perspective statin’s beneficial effect in chronic kidney disease with respect to cardiovascular mortality. Apart from this, it has been reported that statin use is associated with sepsis incidence reduction—a major cause of morbimortality in chronic kidney disease.4 This protective benefit could contribute to total mortality reduction in peritoneal dialysis and hemodialysis patients using statins reported by some observational studies (e.g., DOPPS).5 1.
Simone Manca-di-Villahermosa1, Massimo Taccone-Gallucci1 and Mauro Maccarrone2
2.
1
Department of Internal Medicine, Tor Vergata University, Rome, Italy, and Nephrology and Dialysis Unit, Tor Vergata University Hospital, Rome, Italy and 2Department of Biomedical Sciences, University of Teramo, Italy, and European Center for Brain Research (CERC)/S. Lucia Foundation, Rome, Italy Correspondence: Massimo Taccone-Gallucci, Unita` Operativa di Nefrologia e Dialisi Policlinico Tor Vergata; Viale Oxford 81, Rome 00133, Italy. E-mail:
[email protected]
Response to ‘Treatment with statins may be considered in ESRD patients for primary prevention of cardiovascular disease’
3.
4. 5.
Manca-di-Villahermosa S, Maccarrone M, Taccone-Gallucci M. Treatment with statins may be considered in ESRD patients for primary prevention of cardiovascular disease. Kidney Int 2009; 75: 1354–1355. Wanner C, Krane V, Ma¨rz W et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005; 353: 238–248. Krane V, Winkler K, Drechsler C et al. Effect of atorvastatin on inflammation and outcome in patients with type 2 diabetes mellitus on hemodialysis. Kidney Int 2008; 74: 1261–1467. Gupta R, Plantita L, Fink NE et al. Statin use and hospitalization for sepsis in patients with chronic kidney disease. JAMA 2007; 297: 1455–1464. Mason NA, Bailie GR, Satyathum S et al. HMG-coenzyme A reductase inhibitor use is associated with mortality reduction in hemodialysis patients. Am J Kidney Dis 2005; 45: 119–126.
Victoria Cachofeiro1, Vicente Lahera1, Marian Goicochea2, Soledad Garcia de Vinuesa2 and Jose´ Lun˜o2 1
Department of Physiology, School of Medicine, Universidad Complutense, Madrid 28040 and 2Department of Nephrology, Hospital General Universitario Gregorio Maran˜on, C/ Dr Esquerdo 47, Madrid 28007 Correspondence: Victoria Cachofeiro, School of Medicine, Universidad Complutense, Physiology, Departamento de Fisiologia, Facultad de Medicina, UCM, Madrid 28040, Spain. E-mail:
[email protected]
Kidney International (2009) 75, 1355; doi:10.1038/ki.2009.111
Considering the clinical benefits of statins for primary and secondary cardiovascular event prevention in normal renal function patients, one can assume a similar benefit for patients with chronic kidney disease. Accordingly, Manca-di-Villahermosa’s letter1 reports that a small group of end-stage renal disease patients receiving atorvastatin show low cardiovascular mortality after 3 years of followup. However, in the 4-D study—the only randomized placebo-controlled statin trial done to date, which included 1255 patients with type 2 diabetes undergoing hemodialysis—atorvastatin administration was not Kidney International (2009) 75, 1354–1358
On vascular calcification prevention with phosphonoformate and bisphosphonates Kidney International (2009) 75, 1355–1356; doi:10.1038/ki.2009.108
To the Editor: Phosphonoformic acid (PFA) is a nonhydrolyzeable inorganic pyrophosphate analog, and it has been used as an experimental inhibitor of renal and 1355