Jaap J. Beutler

Rosuvastatin and Cardiovascular Events in Patients Undergoing Hemodialysis

BACKGROUNDnStatins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved.nnnMETHODSnWe conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events.nnnRESULTSnAfter 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51).nnnCONCLUSIONSnIn patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)

Transluminal vascular stents for ostial atherosclerotic renal artery stenosis

We implanted transluminal stents in 24 hypertensive patients with a critical atherosclerotic ostial renal artery stenosis (28 arteries). Immediate revascularisation was successful in all. Follow-up angiography at 6 months, available in 18 patients, revealed restenosis twice. In another patient restenosis was suspected and confirmed by angiography at 2 months. Hence, the total restenosis rate was 3 of 19 patients (16%) and 3 of 23 arteries (13%). Two patients developed renal insufficiency due to cholesterol embolism. In the remaining 22 patients renal function improved (n = 8) or stabilised (n = 14). Although all had to resume antihypertensive treatment, blood pressure normalised in 15 patients, improved in one, remained unchanged in five and worsened in one.

Renal function as a risk indicator for cardiovascular events in 3216 patients with manifest arterial disease

AIMnTo establish whether impaired renal function is an independent predictor of cardiovascular disease (CVD) and death in an unselected high-risk population with CVD.nnnMETHODS AND RESULTSnIn 3216 patients with CVD, the estimated glomerular filtration rate (GFR) was assessed with the Modification of Diet in Renal Disease (MDRD)-equation. Primary outcomes were all vascular events (including stroke, myocardial infarction, end-stage renal disease and vascular death) and all cause death. During a median follow-up of 39 months, 378 patients had a vascular event (11.7%) and 337 patients died (10.5%). The adjusted hazard ratio (HR) of an estimated GFR<or=60 versus >90 ml/min per 1.73 m(2) was 1.8 (95% CI, 1.2-2.6) for vascular events and 1.4 (95% CI 0.9-2.0) for all cause death. For stroke and cardiac events as separate outcomes, similar HRs were found. Subgroup analysis according to localization of vascular disease at presentation or presence of the risk factors hypertension, diabetes and albuminuria had no influence on the hazard ratios.nnnCONCLUSIONSnThe presence of moderate to severe renal insufficiency is an independent risk factor for adverse CVD events in high-risk patients with a history of vascular disease. Localization of vascular disease or presence of other risk factors had no influence on the impact of renal function alone.

Influence of atherosclerosis on age-related changes in renal size and function

Background Renal size and function reflect the health of the kidney. These parameters are associated with age, gender and body weight. The kidneys are also influenced by micro‐ and macrovascular diseases. Atherosclerotic markers and risk factors may influence the age‐related changes of renal size and function.

Plasma concentration of von Willebrand factor predicts mortality in patients on chronic renal replacement therapy

BACKGROUNDnTraditional cardiovascular risk factors do not explain the high incidence of cardiovascular mortality and morbidity in patients with end-stage renal disease. A prothrombotic state could accelerate the process of vascular disease in these patients.nnnMETHODSnIn this study, four platelet activation markers (NAP-2, P-selectin, GP1b and RANTES) and two endothelial cell activation markers (von Willebrand factor and its propeptide) were measured in 671 haemodialysis patients and 275 patients on continuous ambulatory peritoneal dialysis (PD). All were long-term dialysis patients. The risk of all-cause and cardiovascular mortality was assessed in relation to these markers after a mean follow-up time of 2.5 years.nnnRESULTSnThe von Willebrand factor showed a positive correlation with total mortality in the haemodialysis patients. In an unadjusted model, the hazard rate (HR) of total mortality was 2.4 [95% confidence interval (95% CI) 1.7-3.4] in the upper quartile of von Willebrand factor compared with the lowest quartile. It remained statistically significant (HR 1.8; 95% CI 1.2-2.6) after adjustment for traditional risk factors. In contrast, no significant correlation was found between von Willebrand factor levels and total mortality in PD patients. Finally, no relationship between platelet activation markers and total mortality was found in either the haemodialysis or the PD patients.nnnCONCLUSIONnIt can be concluded that chronic endothelial cell activation, but not platelet activation, is related to all-cause mortality in end-stage renal disease patients on long-term dialysis.

The Clinical Course of Minimal Change Nephrotic Syndrome With Onset in Adulthood or Late Adolescence: A Case Series

BACKGROUNDnFew studies have examined the treatment and outcome of adult-onset minimal change nephrotic syndrome (MCNS). We retrospectively studied 125 patients who had MCNS with onset in either adulthood or late adolescence. Presenting characteristics, duration of initial treatment and response to treatment, relapse patterns, complications, and long-term outcome were studied.nnnSTUDY DESIGNnCase series.nnnSETTING & PARTICIPANTSnPatients with new-onset nephrotic syndrome 16 years or older and a histologic diagnosis of MCNS in 1985 to 2011 were identified from pathology records of 10 participating centers.nnnOUTCOMESnPartial and complete remission, treatment resistance, relapse, complications, renal survival.nnnRESULTSnCorticosteroids were given as initial treatment in 105 (84%) patients. After 16 weeks of corticosteroid treatment, 92 (88%) of these patients had reached remission. Median time to remission was 4 (IQR, 2-7) weeks. 7 (6%) patients initially received cyclophosphamide with or without corticosteroids, and all attained remission after a median of 4 (IQR, 3-11) weeks. 13 (10%) patients reached remission without immunosuppressive treatment. One or more relapses were observed in 57 (54%) patients who received initial corticosteroid treatment. Second-line cyclophosphamide resulted in stable remission in 57% of patients with relapsing MCNS. Acute kidney injury was observed in 50 (40%) patients. Recovery of kidney function occurred almost without exception. Arterial or venous thrombosis occurred in 11 (9%) patients. At the last follow-up, 113 (90%) patients were in remission and had preserved kidney function. 3 patients with steroid-resistant MCNS progressed to end-stage renal disease, which was associated with focal segmental glomerulosclerosis lesions on repeat biopsy.nnnLIMITATIONSnRetrospective design, variable treatment protocols.nnnCONCLUSIONSnThe large majority of patients who had MCNS with onset in adulthood or late adolescence were treated with corticosteroids and reached remission, but many had relapses. Cyclophosphamide resulted in stable remission in many patients with relapses. Significant morbidity was observed due to acute kidney injury and other complications. Progression to end-stage renal disease occurred in a few patients and was explained by focal segmental glomerulosclerosis.

Angiotensin Converting Enzyme Inhibitor-Induced Renal Dysfunction in Atherosclerotic Renovascular Disease

Angiotensin converting enzyme inhibitor-induced renal dysfunction in atherosclerotic renovascular disease. Ischemic nephropathy due to bilat- eral renovascular disease (RVD) is increasingly recognized as cause of end-stage renal failure in the elderly, but a reliable non-invasive method of detection is not available. Angiotensin converting enzyme inhibition (ACEi) may impair renal function in such patients, but a prospective study of its diagnostic validity has not been undertaken. We studied the effects of controlled exposure to ACEi on plasma creatinine in 108 patients at risk for severe bilateral atherosclerotic RVD, and compared the findings with subsequent angiography. ACEi was given for two weeks, or, to avoid acute renal failure, for four days if plasma creatinine had increased by 20% or more. If after two weeks of ACEi plasma creatinine had not increased by

Thoracic and abdominal pain in a 28-year-old woman with a failing kidney transplant

20%, while blood pressure was still elevated, plasma creatinine was remeasured after blood pressure control by addition of diuretics. The severity of RVD was scored by the stenosis grade of the best perfused kidney. Fifty-two patients had severe bilateral RVD, defined as

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50% stenosis to both kidneys (N 5 23) or a solitary functioning kidney (N 5 29). Of the others, 21 had less severe bilateral RVD, 20 unilateral RVD, and 15 no apparent RVD. Basal plasma creatinine was higher in severe bilateral RVD (median 170 mmol/liter, range 85 to 654 mmol/liter) than in the others (122 mmol/liter, 62 to 675 mmol/liter; P , 0.01), but not discriminative due to a large variability. The increase during ACEi was correlated with the degree of RVD (r 5 0.53, P , 0.001). In 69 patients ACEi caused at least a 20% increase in plasma creatinine, in 26 cases by four days, in 31 after two weeks, and in 12 only after blood pressure control by diuretics. Among these were all 52 patients with severe bilateral RVD, 15 of the 41 patients with lesser forms of RVD, and two with normal renal arteries. Thus, in this selected population the criterion of

The benefit of STent placement and blood pressure and lipid-lowering for the prevention of progression of renal dysfunction caused by Atherosclerotic ostial stenosis of the Renal artery. The STAR-study: rationale and study design.

20% rise in plasma creatinine upon ACEi was 100% sensitive to detect severe bilateral RVD, while its specificity was 70%. No case of acute renal failure was encountered, and plasma creatinine always recovered after stopping ACEi. In conclusion, controlled exposure to ACEi in these patients is safe, and ACEi-induced increase in plasma creatinine is a very sensitive detector of severe bilateral RVD in a high risk population.