Clin J Am Soc Nephrol 3: 317-323, 2008
© 2008 American Society of Nephrology
doi: 10.2215/CJN.00400108
Cardiovascular Literature—Beyond Nephrology
Eberhard Ritz
Klinikum der Universitat/Heidelberg, Medizinische Klinik/Sektion Nephrologie, Heidelberg, Germany
Correspondence: Dr. Eberhard Ritz, Nierenzentrum, Im Neuenheimer Feld 162, D-69120 Heidelberg, Germany. Phone: 49-6221-601705; Fax: 49-6221-603302; E-mail: prof.e.ritz{at}t-online.de
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Cardiac Angiography in Renally Impaired Patients (CARE) study: A randomized, double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 115: 3189–3196, 2007 Solomon RJ, Natarajan MK, Doucet S, Sharma SK, Staniloae CS, Katholi RE, Gelormini JL, Labinaz M, Moreyra AE, Investigators of the CARE Study
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Although the occurrence of radiocontrast-induced nephropathy is relatively rare overall, approximately 2%, it is appreciable in high-risk individuals, particularly patients with chronic kidney disease (CKD) (1,2) and diabetic nephropathy (3), especially when undergoing percutaneous interventions (4) with reported rates as high as 20%.
In the past, it had been reported that the isosmolar dimeric nonionic radiocontrast agent iodixanol when compared with the low osmolar monomeric nonionic agent iohexol less frequently caused radiocontrast nephropathy in high-risk patients (5). A single-center trial, however, recently failed to show a difference in the incidence of radiocontrast-induced nephropathy when iodixanol was compared with the low osmolality but ionic ioxaglate in patients with CKD (6). This issue was reexamined in this multicenter, randomized, double-blind comparison of iodixanol and iopamidol in patients who had CKD (estimated GFR [eGFR] 20 to 59 ml/min per 1.73 m2) and underwent cardiac angiography or percutaneous coronary interventions.
Findings.
A total of 482 patients could be evaluated. The two groups were comparable with respect to all relevant parameters, particularly eGFR (49.3 ± 11.6 versus 50.2 ± 13.0 ml/min per 1.73 m2). The primary end point of an increase in serum creatinine >0.5 mg/dl was not significantly different between the two groups (6.7% iodixanol versus 4.4% iopamidol). The secondary end points of a >25% increase of serum creatinine occurred in 12.4% on iodixanol versus 9.8% on iopamidol (NS) and a decrease of eGFR in 10.0% on iodixanol versus in 5.9% on iopamidol. The secondary end points of postdose increase in serum creatinine and decrease of eGFR, respectively, were even in favor of iopamidol (serum creatinine 0.07 ± 0.22 mg/dl on iopamidol versus 0.12 ± 0.23 mg/dl on iodixanol; P < 0.03) particularly in the subgroup of patients with diabetes (0.07 ± 0.26 mg/dl versus 0.16 ± 0.27; P < 0.01). None of the patients required hemodialysis.
Commentary.
The sufficiently powered CARE study documents that the rate of radiocontrast nephropathy is no better with the isosmolar dimeric nonionic radiocontrast agent iodixanol compared with the nonionic monomer iopamidol after intra-arterial administration to patients with moderate to severe CKD. In the smaller previous RECOVER study (7), the rate of radiocontrast nephropathy was also not significantly different when the nonionic dimer iodixanol was compared with the low-osmolality ionic dimer ioxaglate. In contrast, the Nephrotoxicity in High-Risk Patients Study of Iso-Osmolar and Low-Osmolar Non-Ionic Contrast Media (NEPHRIC) (5) had found a significant difference in the mean peak postdose increase of serum creatinine: It was lower with iodixanol (0.13 ± 0.22 mg/dl) compared with iohexol (0.55 ± 0.98 mg/dl).
These results are also in contrast to a recent meta-analysis (8) of randomized, controlled trials that found a significantly smaller increase in serum creatinine 3 d postdose on iodixanol compared with a pooled group of other low-osmolality agents; one can criticize, however, that in these mostly smaller studies, the serum creatinine measurements were not standardized, the timing of the postdose measurements varied, and the two groups were not sufficiently balanced. It is therefore of note that in the one study (9) with a head-on comparison between iodixanol and iopamidol, a similar trend in favor of iopamidol was found, as observed in the above CARE study.
How can one reconcile the somewhat diverse findings? Systematic reviews and the analysis of renal adverse events in the Food and Drug Administration postmarketing safety database (10,11) are in agreement with the data of the CARE study and would be compatible with the interpretation that all depends on what is compared with what: When iodixanol is compared with these two low-osmolar compounds, iohexol is associated with a higher and iopamidol with a lower incidence of radiocontrast nephropathy. This is not without interest for the underlying pathophysiology. It has not been resolved whether it is ionicity, osmolality, or viscosity that is the main culprit: If the two equally low-osmolar agents differ with respect to renal risk, then it is unlikely that osmolality (which is comparable in the two groups) plays a major pathogenetic role.
It is remarkable that in an investigational environment with standardized pretreatment, the rate of adverse renal events was so remarkably low. All patients received prophylactic volume expansion with isotonic sodium bicarbonate (3 ml/kg per h for 1 h before angiography and 1 ml/kg per h for 6 h after angiography). Several studies had documented superiority of sodium bicarbonate over sodium chloride (saline) (12). Most patients had additionally received N-acetyl-cysteine (13), although its prophylactic value is debated, not the least because it apparently affects tubular transport of creatinine rather than GFR (14). If at least among the modern radiocontrast agents the selection of the radiocontrast agent has such small effect, then volume expansion as originally documented by Solomon et al. (15) with half-normal saline, possibly even better with normal saline (16) or sodium bicarbonate (12), remains the best and only solidly proven prophylactic measure in this important but underinvestigated area.
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Footnotes
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Published online ahead of print. Publication date available at www.cjasn.org.
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Serum concentrations of uric acid and the metabolic syndrome among US children and adolescents. Circulation 115: 2526–2532, 2007 Ford E, Li C, Cook S, Choi HK
Based mainly on the work of Johnson and colleagues (1–3), there has been much recent discussion of a potential pathogenetic role of hyperuricemia in the genesis of renal and endothelial damage and of cardiovascular events. A correlation is found among progression of renal disease, hypertension, and metabolic syndrome on the one hand and concentrations of uric acid on the other hand. It may be argued, however, that the issue is confounded by the fact that the concentration of uric acid may have risen, for instance, as a consequence of renal vascular involvement and malfunction (4). It would be a strong argument, however, against the hypothesis that hyperuricemia follows endothelial and renal injuries if it could be shown that hyperuricemia precedes endothelial and renal injuries. A recent study showed higher uric acid concentrations at the time of diagnosis in untreated children with primary hypertension, and it might therefore be that hyperuricemia even precedes the onset of hypertension (5,6). This cross-sectional study of children and adolescents that examined the relation of uric acid concentrations and factors of the metabolic syndrome (powerful cardiovascular risk factors) lends further weight to the hypothesis of a causal relationship, although not providing definite proof.
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Findings.
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A cross-sectional analysis was performed in the National Health and Nutrition Examination Survey (NHANES) of 1432 participants who were aged 12 to 17 yr and fasted <6 h. Serum uric acid was measured by colorimetry (oxidation of uric acid to allantoin by uricase), and components of the metabolic syndrome, appropriately adapted for juniors, were assessed. The data were mainly analyzed by logistic regression analysis adjusting for numerous confounders.
The salient findings were a high prevalence of the (age-modified) "metabolic syndrome" in 9.1% (SE 1.3%) with 5.4% in girls and 12.4% in boys. The concentrations of uric acid ranged from 1.9 to 12.1 mg/dl, with a mean of 5.1 mg/dl. The percentages of children and adolescents with concentrations of uric acid <5.5, 6, and 7 mg/dl were 30.2, 22.2, and 6.5%, respectively.
The prevalence of the metabolic syndrome was strongly correlated to the serum uric acid concentration: It rose from <1% in participants with serum uric acid <4.2 mg/dl to 21% in participants with values >5.2 mg/dl. A strong independent association was found between uric acid concentrations and the metabolic syndrome. The adjusted odds ratio was 2.52 (95% confidence interval 1.87 to 3.41) per 1 mg/dl.
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Commentary.
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The salient finding in this nationally representative sample of US children is the graded positive association between serum uric acid concentrations and the prevalence of a metabolic syndrome (with appropriate adjustment of the components for juniors). The significant association with all five components of the metabolic syndrome is of particular relevance because many factors that confound the interpretation in adults (e.g., impaired renal function, use of diuretics, alcohol consumption, diabetes or prediabetes, cardiovascular disease) do not interfere with the interpretation of the results in this age group. The data not only are of considerable concern with respect to cardiovascular risk and life expectancy at adult age (7,8) but also contribute to the discussion of the role of uric acid as a cardiovascular and renal risk factor. Admittedly, the data cannot definitely resolve the issue of whether high uric acid concentrations are merely a marker of insulin resistance and central obesity and thus an innocent bystander or are involved in the pathogenesis and thus a potential therapeutic target (9).
The higher uric acid concentrations may be the result of increased hepatic production (e.g., as a result of high fructose consumption [1]), which is associated with obesity in children (10) and has been shown to raise serum uric acid concentrations (2). A contributory factor may be impairment of oxidative phosphorylation by high intracellular concentrations of long-chain fatty acid CoA esters, which lead to elevated plasma adenosine concentrations, increasing urate production (11) and renal retention of urate (12).
Another possibility (which is not mutually exclusive) is impaired urate excretion by the kidney, for instance as the result of hyperinsulinemia affecting the urate-anion exchanger URAT1 (13) or the Na+-dependent anion co-transporter in the brush border membrane (14). There are a number of further possibilities. Clearly we do not yet have a "smoking gun," but these finding, which avoided a great number of confounders present in other studies, adds plausibility to a causal role of uric acid in the genesis of metabolic syndrome, hypertension, and renal malfunction.
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Change in salt intake affects blood pressure of chimpanzees implications for human populations. Circulation 116: 1563–1568, 2007 Elliott P, Walker LL, Little MP, Blair-West JR, Shade RE, Lee R, Rouquet P, Leroy E, Jeunemaitre X, Ardaillou R, Paillard F, Meneton P, Denton DA
Although the majority of guidelines on the management of hypertension recommend lowering sodium intake to 100 mmol/d (equivalent to 6 g of salt) (1–3) and although short- to intermediate-term interventions with reduced salt intake have convincingly shown BP lowering in humans (4,5), the desirability of reducing current intakes of salt in Western communities continues to be questioned by a minority of investigators (6–8) who argued that dietary quality, specifically the need for adequate intake of calcium and potassium, rather than sodium intake was the decisive factor in past studies (6,7) and that the evidence for benefit from low salt simply was not there (8). A further controversy is the issue of whether lowering of dietary salt intake is appropriate only in hypertensive individuals (9) or confers benefit if implemented on a population basis.
It is here that this study provides valuable new information. A past study in chimpanzees, the species closest to humans, showed as proof of principle that increasing amounts of salt—higher than comparable intakes in humans—increased BP (10). The present study extended this issue by examining the effects on BP of more modest alterations of salt intakes, more comparable to the intakes in Western societies. To this end, long-term feeding studies were carried out in two chimpanzee colonies in Gabon and in Bastrop (Texas), respectively. The diets contained adequate amounts of calcium and potassium.
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Findings.
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In Gabon, when sodium intake was reduced from 75 to 35 mmol/d, systolic BP decreased by –5.5 mmHg (95% confidence interval [CI]: –0.5 to –11.2); with intake increased to 120 mmol/d, it increased by 10.3 mmHg after 9 mo (95% CI 4.3 to 16.3). Multiple regression analysis with adjustment showed that lowering of sodium intake by 100 mmol/d was associated with a lowering of systolic BP by 12.7 mmHg and diastolic by 7.5 mmHg. The decrease was higher in female chimpanzees, in obese chimpanzees, and in chimpanzees with higher baseline BP.
In the Bastrop cohort, the reduction of sodium intake caused lower systolic (
–10.9 mmHg; 95% CI –18.9 to –2.9) and diastolic ( –9.3 mmHg; 95% CI –16.8 to –2.8) pressures for a sodium reduction by 122 mmol/d. When adjusted for age, gender, and baseline weight, the analogous differences were –5.7 mmHg systolic and –4.4 mmHg diastolic. Significant interactions existed between sodium intake and gender, baseline weight, and baseline BP (i.e., the BP decrease was greater in female chimpanzees, in obese chimpanzees, and chimpanzees with higher baseline BP).
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Commentary.
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These impressive data in the animal species that is phylogenetically closest to humans are certainly relevant for hypertension in humans, specifically in Western societies.
The decrease in BP was shown in the chimpanzees at sodium intakes comparable to intakes in humans below, at, or above current guidelines. The relationship was nonlinear, and the effect of lowering salt intake on BP was greater at low pressure values. Of particular importance with respect to past criticisms (6,7) is that this finding was obtained in a vegetarian "high potassium" (>350 mmol/d) and "high calcium" environment, refuting the argument that sodium intake is not relevant to BP in a mineral-replete state.
The data are particularly valuable because they were obtained in long-term, single-variable experiments that were not confounded by factors that complicate human studies, such as diet changes, alcohol intake, and smoking, and because in contrast to most human studies, they were long term over years. These findings extend the range of demonstrable effects of sodium intake beyond that addressed by the past experiment of Denton et al. (10), in which baseline sodium was 2 to 25 mmol/d (equivalent to the diet in preliterate societies) and diets with addition of 85, 170, and 257 mmol/d Na+. In this study, the highest intake had increased the mean systolic BP by 33 mmHg, but 20 wk after cessation of added salt, BP had fallen to baseline.
In the present study, the changes in BP were smaller in magnitude, but the protocol was more relevant to present-day discussions about optimal targets for dietary sodium reductions in humans. They will hopefully convince the last "doubting Thomases", after the Dietary Approaches to Stop Hypertension (DASH) study (5) had already demonstrated that in volunteers with normotension, prehypertension, and manifest hypertension, lower salt intake caused lower BP, albeit in combination with a diet rich in vegetables, fruit, and low-fat dairy products. The beauty of these studies in chimpanzees is that only one factor, sodium intake, was altered so that confounding by the other components of the diet can be safely excluded.
The implications of the study go beyond treatment of hypertension. It makes a lot of sense to reduce salt intake in the general population for several reasons. First, there is some evidence for BP-independent effects on survival (11) and target organ damage, including renal damage (12,13). Second, by age 80, more than 60% of the population has hypertension. Third, there is no lower limit of benefit from having a lower BP down to a level of 120 mmHg systolic (14). Fourth, the salt intake can be lowered to the universally recommended levels without impairing culinary quality and "bonne cuisine."
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Influence of albuminuria on cardiovascular risk in patients with stable coronary artery disease. Circulation 116: 2687–2693, 2007 Solomon SD, Lin J, Solomon CG, Jablonski KA, Rice MM, Steffes M, Domanski M, Hsia J, Gersh BJ, Arnold JM, Rouleau J, Braunwald E, Pfeffer MA
It has been one of the more relevant observations of renal research in recent years with substantial public health implications that microalbuminuria is a predictor of cardiovascular events and of renal risk in individuals with as well as in individuals without diabetes. It has been argued that the threshold values to define microalbuminuria (20 to 200 µg/min or 30 to 300 mg/d) were originally selected by diabetologists more based on the sensitivity of the available urinary test sticks for albuminuria and proteinuria, respectively, than on solid epidemiologic evidence. Be this as it may, in patients with type 2 diabetes, albuminuria values in the high normal range are associated with higher renal as well as cardiovascular risk (1). In individuals without diabetes and with high cardiovascular risk, it was recently observed, most convincingly in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) and Heart Outcomes Prevention Evaluation (HOPE) studies, that albumin excretion rates below the threshold value defining microalbuminuria are also correlated to cardiovascular risk (2–4). This was confirmed even in population based studies (e.g., Prevention of Renal and Vascular Endstage Disease [PREVEND] [5] and Health Survey of Nord-Trøndelag [HUNT] [6] studies). This situation has recently led to the very plausible postulate to abandon the separation between normo- and microalbuminuria (7) and to consider albumin excretion rate as a continuous variable, similar to the epidemiologic implications of serum cholesterol, which confers a graded risk even at concentrations conventionally regarded as normocholesterolemia.
Such rethinking about the validity of the very concept of microalbuminuria is supported by the findings in the PEACE trial (8), in which patients with relatively low cardiovascular risk were randomly assigned to receive trandolapril or placebo. In this post hoc analysis, the relationship between albuminuria and overall mortality as well as cardiovascular events was analyzed
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Findings.
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In this trial, 8290 patients who were aged >50 yr and had documented coronary heart disease but relatively well-preserved LV function (LV ejection fraction >40%) were examined at baseline. Spot urine was provided by 2977 patients. Patients were followed over a median of 4.8 yr. Follow-up urine samples were available for 1339 patients.
Higher baseline albumin concentrations (albumin-creatinine ratio [ACR]) were associated with the usual suspects: Older age, male gender, nonwhite race, history of angina, diabetes, hypertension, smoking, etc. Independent of the estimated GFR and other baseline covariates, higher ACR was associated with increased cardiovascular mortality (hazard ratio [HR] third quartile of normoalbuminuria 0.99, upper quartile of normoalbuminuria 1.35, low to medium microalbuminuria 1.89, high microalbuminuria/macroalbuminuria 1.68; P < 0.01) and with increased all-cause mortality (respective HR 1.77, 2.09, 2.08, and 1.99; P < 0.001).
Trandolapril treatment was associated with a significantly lower follow-up ACR (mean 12.5 versus 14.6 µg/ml; P = 0.0002). A baseline adjusted increase per unit log ACR was associated with increased risk of cardiovascular death (HR 1.74; 95% confidence interval 1.08 to 2.82).
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Commentary.
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This study underlines the prognostic validity of urinary albumin measurement as a predictor of adverse cardiovascular outcome in a population at relatively modest cardiovascular risk. This finding in patients who had chronically stable coronary disease and experienced relatively low event rates is remarkable. The authors proposed to regard albuminuria as an index of widespread vascular endothelial dysfunction and to quantify and measure routinely in such patients albumin concentrations as a risk indicator in spot urine samples (possibly even better, morning urine samples), because in this concentration range, albumin is not picked up by dipstick.
Another remarkable finding of this study is that the risk conferred by albuminuria was amplified by the simultaneous presence of low estimated GFR, similar to recent findings that the risk for progressive loss of GFR is amplified by the presence of proteinuria (9). The unpublished results of the HUNT study suggest that it is amplified even by microalbuminuria.
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References
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- Rachmani R, Levi Z, Lidar M, Slavachevski I, Half-Onn E, Ravid M: Considerations about the threshold value of microalbuminuria in patients with diabetes mellitus: Lessons from an 8-year follow-up study of 599 patients.
Diabetes Res Clin Pract49
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- Ibsen H, Olsen MH, Wachtell K, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlof B, Devereux RB, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wan Y: Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: Losartan intervention for endpoint reduction in hypertension study.
Hypertension45
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–202,2005[Abstract/Free Full Text]
- Ibsen H, Wachtell K, Olsen MH, Borch-Johnsen K, Lindholm LH, Mogensen CE, Dahlof B, Devereux RB, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wan Y: Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in hypertension with left ventricular hypertrophy? A LIFE substudy.
J Hypertens22
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- Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP, Young J, Rashkow A, Joyce C, Nawaz S, Yusuf S: Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals.
JAMA286
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- Hillege HL, Janssen WM, Bak AA, Diercks GF, Grobbee DE, Crijns HJ, Van Gilst WH, De Zeeuw D, De Jong PE: Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity.
J Intern Med249
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- Hallan S, Astor B, Romundstad S, Aasarod K, Kvenild K, Coresh J: Association of kidney function and albuminuria with cardiovascular mortality in older vs younger individuals: The HUNT II Study.
Arch Intern Med167
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- Ruggenenti P, Remuzzi G: Time to abandon microalbuminuria?
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- Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL: Angiotensin-converting-enzyme inhibition in stable coronary artery disease.
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The challenge of diagnosing atheroembolic renal disease clinical features and prognostic factors. Circulation 116: 298–304, 2007 Scolari F, Ravani P, Gaggi R, Santostefano M, Rollino C, Stabellini N, Colla L, Viola BF, Maiorca P, Ventrurelli C, Bonardelli S, Faggiano P, Barrett BJ
Although cholesterol embolism has been known for a long time and been the subject of many erudite reviews (1–3), there is a dearth of information on epidemiology, presentation, underlying comorbidities or triggers, and outcome. The underlying lesion is the occlusion of small arteries in kidney and other organs (e.g., intestine, skin, legs, retina) by cholesterol crystal emboli released spontaneously or after interventions from ulcerated atherosclerotic plaques mainly in the abdominal aorta. The resulting lesions distal to the cleft lodgement are both ischemic and inflammatory (4). The release of cholesterol may be spontaneous or triggered by vascular trauma (e.g., catheters, surgery) as well as the result of anticoagulants or thrombolytic agents. The condition was long regarded as a diagnostic curiosity, but it is underdiagnosed and is more frequent than thought. The disease is a great imitator with protean presentations, so it is easily misdiagnosed.
There is a great need for information from adequately sized cohorts providing quantitative information on causes, presentation, organ involvement, reliability of diagnostic procedures, and outcome. This need is satisfied by this multisite prospective study (with a small retrospective component) of 354 incident cases at 12 tertiary care centers in three major areas of Northern Italy.
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Findings.
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The salient characteristics of the cohort were male preponderance (83.3%), history of hypertension (82.7%, in half longstanding >10 yr), smoking (69.5%!), and a surprisingly low frequency of hypercholesterolemia (34.7%) and occurring in 29.3% despite statins. Associated cardiovascular disease was seen in 90.4%, particularly coronary heart disease (61.5%), peripheral artery disease (58%), and cerebrovascular disease (33.9%) as well as renal artery stenosis (34%). Average estimated GFR at presentation was 42 ± 18 ml/min per 1.73 m2; stage 4 to 5 chronic kidney disease was present in 27.1%.
In 77%, cholesterol embolism was iatrogenic and in 23% spontaneous. The two groups differed mainly by significantly lower estimated GFR in the spontaneous group (in the other group, the preceding intervention had presumably heightened awareness of the diagnosis). The onset was acute/subacute in 93.3% of the iatrogenic cases and only in 31.3% of the spontaneous form.
The diagnosis was confirmed by histology or ophthalmoscopy in all spontaneous cases and in 50% of the iatrogenic cases. Renal artery stenosis was present in 17% of all cases but accounted only for 8% of the cases with the spontaneous form.
The average GFR was 22.9 ± 13.2 ml/min per 1.73 m2 at onset and 12.2 ± 8.4 ml/min per 1.73 m2 at the time of peak serum creatinine; 32.7% required dialysis. The risk was especially high within 6 mo of the event. A total of 71% of patients who required dialysis ultimately required maintenance dialysis, whereas 28% could stop dialysis; nevertheless, 15% of these required maintenance dialysis again within 3 to 6 mo.
A total of 102 (29%) patients had died within 2 yr. Of those with a known cause of death, 80% died from cardiovascular causes; 10% from infections; and 10% from ischemic colitis, pancreatitis or cachexia.
The following were predictors of reduced renal survival: Heart failure, chronic kidney disease at baseline, diabetes, higher age, iatrogenic cause, acute/subacute onset, and involvement of leg and gastrointestinal tract. Remarkably, statin therapy was protective when it was in place at baseline or was initiated after diagnosis.
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Commentary.
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Although cholesterol microembolism was first described more than a century ago by Dahlerup (5) in the autopsy report of the Danish sculptor Thorwaldsen and described in greater detail by Panum (6), today, this condition is recognized with increasing frequency not the least because of the introduction of therapeutic procedures (e.g., anticoagulation, fibrinolysis) and interventions (e.g., vascular surgery, arteriography, angioplasty) (7,8). Most reports concern relatively small series from single institutions. Against this background, the documentation herein of the frequency and natural history of this important condition with complete capture of all cases observed in a large circumscribed area of Northern Italy with access to up-to-date medical interventions provides welcome new information on natural history and outcome. In autopsy series, frequencies up to 1 to 2% have been reported (9,10), considerably more than clinically diagnosed in the series reported here, suggesting that many cases are never diagnosed in vivo.
This report also confirms that invasive procedures, particularly arteriography, most frequently coronary angiography, percutaneous angioplasty, and cardiovascular surgery, account for most of the cases observed today, with anticoagulation the second most frequent trigger. The authors found that an acute/subacute onset argues more for an iatrogenic form resulting from the acute rupture of a plaque with a shower of cholesterol emboli, whereas a chronic course is more characteristic of the less frequent spontaneous form. The acute massive embolization in the iatrogenic form explains also the more malignant clinical course in patients with acute/subacute course.
The clinical presentation is notoriously protean and multifaceted, affecting tissues from toe to retina. It may masquerade as systemic vasculitis, subacute bacterial endocarditis, polymyositis, etc. The diagnosis requires a high level of suspicion, and the authors drew a profile of the typical high-risk patient: Elderly with a history of hypertension, smoking, and arterial disease with signs of peripheral emboli ("blue toe"). Of note, the diagnosis could be established in this study with surprisingly high frequency from skin biopsy and retinal evaluation, circumventing for many patients the necessity of renal biopsy. Another valuable piece of information is the elaboration of prognostic indicators detailed herein.
Such observational studies sadly fail to provide evidence for the efficacy of interventions. Steroid treatment, which was given to half of the patients, is controversial and would certainly necessitate a controlled trial (9). Of considerable interest is the finding that treatment with statins when present at the time of the event or administered immediately thereafter was associated with better outcome. This observation would argue for more widespread use of this intervention which—in contrast to steroids—has considerably fewer adverse effects.
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References
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- Panum PL: Experimental findings contributing to the understanding of embolism.
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- Theriault J, Agharazzi M, Dumont M, Pichette V, Ouimet D, Leblanc M: Atheroembolic renal failure requiring dialysis: Potential for renal recovery? A review of 43 cases.
Nephron Clin Pract94
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- Scolari F, Ravani P, Pola A, Guerini S, Zubani R, Movilli E, Savoldi S, Malberti F, Maiorca R: Predictors of renal and patient outcomes in atheroembolic renal disease: A prospective study.
J Am Soc Nephrol14
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- Stabellini N, Rizzioli E, Trapassi MR, Fabbian F, Catalano C, Gilli P: Renal cholesterol microembolism: Is steroid therapy effective?
Nephron86
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- Bellamy CO, Paul AB, Fleming S: Primary non-function of a renal allograft due to atheromatous emboli.
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Cardiac Angiography in Renally...
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