Estimated glomerular filtration rate as a measurement of kidney function. / Estimert glomerulær filtrasjonshastighet som mål på nyrefunksjon.

Estimated glomerular filtration rate is an established, routine clinical measurement for kidney function, but the estimate has limitations and cannot be used in all clinical situations. Estimated glomerular filtration rate has a high coefficient of variation, and deviations in the patient's height, weight or muscle mass may result in an imprecise estimate. If an accurate measurement of kidney function is essential, glomerular filtration rate can be measured using an exogenous substance.

Glomerulonephritis after contact with a horse. / Glomerulonefritt etter kontakt med hest.

BACKGROUND: Zoonoses are important to consider when humans become ill after being in contact with animals. In such cases thorough patient history is crucial, especially when infections have an unclear cause. We present a patient with infection-associated glomerulonephritis, where a horse was the probable source of infection. CASE PRESENTATION: A young woman was admitted to the district general hospital in Vestfold, Norway, with infection and acute kidney failure. Renal biopsy suggested glomerulonephritis, and nasopharyngeal culture taken at admission detected Streptococcus equi. It emerged that the patient had daily contact with horses. INTERPRETATION: As Streptococcus equi is not part of normal human flora and the clinical signs were compatible with infection-associated glomerulonephritis, it was considered a probable causal link between the microbial finding and diagnosis. The source of infection was one of the horses.

Neopterin is associated with cardiovascular events and all-cause mortality in renal transplant patients.

BACKGROUND: Inflammatory markers show significant associations with cardiovascular events and all-cause mortality after kidney transplantation. Neopterin, reflecting interferon-γ-release, may better reflect the proinflammatory state of recipients than less specific markers. METHODS: Kidney transplant recipients in the Assessment of LEscol in Renal Transplant (ALERT) trial were examined and investigated for an association between serum neopterin and subsequent clinical events: graft loss, major cardiovascular events (MACE) and all-cause mortality. RESULTS: After adjustment for established and emerging risk factors neopterin expressed as neopterin-to-creatinine ratio was significantly associated with MACE (p = 0.009) and all-cause mortality (p = 0.002). Endpoints were more frequent with increasing quartiles of neopterin-to-creatinine ratio. The incidence rates of MACE and all-cause mortality were significantly increased in the upper quartiles compared with the first. CONCLUSIONS: This long-term prospective analysis in stable kidney allograft recipients suggests that neopterin is associated with long-term risk of cardiovascular events and all-cause mortality, but not renal outcomes.

Anemia is a predictor of graft loss but not cardiovascular events and all-cause mortality in renal transplant recipients: follow-up data from the ALERT study.

BACKGROUND: It is well established that post-transplantation anemia (PTA) in renal transplant recipients (RTRs) is associated with reduced graft survival. However, there is an uncertainty of the effect of PTA on cardiovascular events and all-cause mortality. We examined prospectively in a large cohort of erythropoietin-naive patients the effects of PTA on cardiovascular morbidity, patient survival, and graft survival. METHODS: A prospective cohort study of RTRs (n = 2102) included in the ALERT study. Cox regression models were used to evaluate the impact of PTA on study endpoints: first occurrence of a major adverse cardiac event, all-cause death, and the incidence of death-censored graft loss. Mean follow-up was 6.7 yr. All endpoints were adjudicated by an independent endpoint committee. RESULTS: Twenty-nine percent of women and 30% of men were anemic. Hemoglobin levels were not associated with any effect on cardiovascular morbidity and mortality (HR 0.97 [0.90-1.05] per g/dL, p = 0.48) or all-cause death (HR 0.96 [0.90-1.03] per g/dL, p = 0.24) after extensive multivariate adjustments for clinical and demographic factors. Hemoglobin levels were negatively associated with graft loss (HR 0.86 [0.80-0.92] per g/dL, p < 0.001). CONCLUSIONS: PTA was not associated with an increased incidence of cardiovascular morbidity and mortality or all-cause mortality.

Hyperkalemia and the Use of New Potassium Binders a Single Center Experience from Vestfold Norway (The PotBind Study).

Purpose: Hyperkalemia is a common metabolic complication of chronic kidney disease (CKD) and is associated with several serious adverse events. We aimed to treat/prevent hyperkalemia using the new of potassium-binders, allowing maintained renin-angiotensin-aldosterone system inhibitors (RAASi) treatment in proteinuric CKD and/or congestive heart failure (CHF) patients. Patients and Methods: We conducted a retrospective cohort study in long-term users of potassium binders for chronic hyperkalemia. Patients aged 18 years and older, treated with potassium-binders and who met the reimbursement criteria and indication for RAASi treatment were included. Results: Fifty-seven percent of the patients were males and mean age was 65 years. During the study period, no patients were admitted to hospital due to hyperkalemia after initiation of potassium binders. Potassium maximum values were significantly lower after treatment. Few patients reported major side effects, and discontinuation was mostly due to normokalemia. We found no significant changes in bicarbonate, serum creatinine or GFR stage after starting potassium binder treatment. All patients on RAASi treatment before initiating potassium-binders were retained on RAASi treatment. Conclusion: New potassium binders in clinical practice are an easy and safe treatment with few side effects and good tolerance, that significantly lowers the risk of hyperkalemia. Furthermore, and most importantly, patients can be maintained on RAASi treatment.

Inflammation-associated graft loss in renal transplant recipients.

BACKGROUND: Although short-term graft survival has improved substantially in renal transplant recipients, long-term graft survival has not improved over the last decades. The lack of knowledge of specific causes and risk factors has hampered improvements in long-term allograft survival. There is an uncertainty if inflammation is associated with late graft loss. METHODS: We examined, in a large prospective trial, the inflammation markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) and their association with chronic graft dysfunction. We collected data from the Assessment of Lescol in Renal Transplant trial, which recruited 2102 maintenance renal transplant recipients. RESULTS: Baseline values were hsCRP 3.8 ± 6.7 mg/L and IL-6 2.9 ± 1.9 pg/mL. Adjusted for traditional risk factors, hsCRP and IL-6 were independently associated with death-censored graft loss, the composite end points graft loss or death and doubling of serum creatinine, graft loss or death. CONCLUSION: The inflammation markers hsCRP and IL-6 are associated with long-term graft outcomes in renal transplant recipients.

Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients.

Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.

Metabolic syndrome and cardiovascular risk in renal transplant recipients: effects of statin treatment.

BACKGROUND: Renal transplant recipients (RTR) have high risk for cardiovascular disease (CVD). They also have high prevalence of insulin resistance and metabolic syndrome (MS). Statin treatment reduces CVD risk in RTR. The aim was to study MS as CVD risk factor in RTR, and to investigate the effect of statin treatment in RTR with MS. METHODS: In total, 1706 non-diabetic RTR from the Assessment of Lescol in Renal Transplantation trial were followed for 7-8 yr. The captured endpoints included major adverse cardiac events [MACE, defined as cardiac death (CD), non-fatal myocardial infarction or coronary revascularization procedure], and CD. MS was defined at baseline according to Adult Treatment Panel III definition with waist girth replaced by body mass index > or =30 kg/m2. RESULTS: MS was diagnosed in 32% of the patients. During the follow-up, MACE incidence was 16% in those with MS and 11% in those without MS (p < 0.001). Statin treatment reduced MACE risk by 53% in the group with MS. CD risk was 74% higher in RTR with MS (p = 0.012), and statin treatment reduced CD risk in those with MS (p = 0.03). CONCLUSIONS: RTR with MS have increased risk for CVD. RTR with MS are an easily identifiable group of patients who benefit from statin treatment.

Hospital-based comprehensive cardiac rehabilitation versus usual care among patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease: 12-month results of a randomized clinical trial.

BACKGROUND: Current guidelines broadly recommend comprehensive cardiac rehabilitation (CCR), although evidence for this is still limited. We investigated the 12-month effect of hospital-based CCR versus usual care (UC) for a broadly defined group of cardiac patients within the modern therapeutic era of cardiology. METHODS: We conducted a centrally randomized single-center clinical trial with blinded assessment of the primary outcome: registry-based composite of total mortality, myocardial infarction, or acute first-time readmission due to heart disease. Other outcomes were hospitalization, risk profile, and quality of life. The trial included 770 participants (20-94 years) with congestive heart failure (12%), ischemic heart disease (58%), or high risk of ischemic heart disease (30%). Comprehensive cardiac rehabilitation is composed of 6 weeks of intensive intervention and systematic follow-up for 10.5 months. RESULTS: We randomized 380 patients to CCR versus 390 to UC. Randomization was well balanced. The primary outcome occurred in 31% of both groups (relative risk 0.96, 95% confidence interval 0.78-1.26). Compared with the UC group, CCR significantly reduced length of stay by 15% (95% confidence interval 1.1%-27.1%, P = .04), mean number of cardiac risk factors above target (4.5 vs 4.1, P = .01), patients with systolic blood pressure below target (P = .003), physically inactivity (P = .01), and unhealthy dietary habits (P = .0003). Short-Form-36 and Hospital Anxiety and Depression Scale did not differ significantly. CONCLUSION: At 12 months, the CCR and UC groups did not differ regarding the primary composite outcome. Comprehensive cardiac rehabilitation significantly reduced length of hospital stay and improved cardiac risk factors.

Immunosuppression Adherence in Stable Kidney Transplant Patients Converted From Immediate- to Prolonged-Release Tacrolimus in Clinical Practice: A Norwegian Study.

BACKGROUND: This study investigated medication adherence in kidney transplant patients (KTPs) converted from immediate-release tacrolimus (IR-T) to prolonged-release tacrolimus (PR-T)-based immunosuppression in routine practice. METHODS: Noninterventional, observational, multicenter study in Norway. Included adult KTPs with stable graft function, converted from IR-T (baseline) to PR-T (1 mg:1 mg) in routine practice. Data were collected at baseline, and months 1, 3, 6, and 12 postconversion. Primary endpoint: adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale. Secondary assessments: tacrolimus dose and trough levels (target, 3-7 ng/mL), clinical laboratory parameters (eg, estimated glomerular filtration rate [Modified Diet in Renal Disease]), and adverse events. RESULTS: Ninety-one KTPs (mean ± SD age 47.7 ± 14.3 years) were analyzed. Mean ± SD change in PR-T dose from baseline (4.4 ± 2.4 mg/d) to month 12 was -0.1 ± 0.9 mg/d; mean tacrolimus trough levels remained within target. Overall medication adherence increased from 45.6% at baseline to 58.1% at month 1, but was similar to baseline thereafter; taking and timing adherence followed a similar pattern. Odds ratio (OR) for adherence at month 1 (but not at other time points) was greater versus baseline for overall (OR, 1.71; P = 0.0205), taking (OR, 3.38; P = 0.0004), and timing (OR, 1.77, P = 0.0252) dimensions. Mean ± SD Basel Assessment of Adherence to Immunosuppressive Medication Scale visual analogue scale score at baseline was 96.4 ± 5.5%, and increased postconversion. Estimated glomerular filtration rate remained stable (month 12, 61.6 ± 17.7 mL/min per 1.73 m2), as did other laboratory parameters. Two (2.2%) patients had adverse events considered probably/possibly treatment-related. CONCLUSIONS: There was disparity between high, patient-perceived and low, actual adherence. Converting stable KTPs from IR-T to PR-T in routine practice did not impact long-term adherence to immunosuppression; renal function remained stable.

Cuff extrusion in peritoneal dialysis: single-centre experience with the cuff-shaving procedure in five patients over a 4-year period.

Catheter-related infections in peritoneal dialysis (PD) remain a significant complication, and some patients with recurrent exit-site (ESI) and/or tunnel infections may experience external cuff extrusion. In these cases, cuff-shaving has been described as a possible course of treatment. During a 4-year period, there were 44 patients with PD at our department; all received double-cuffed Tenckhoff catheters. Six (13%) never started on PD. Five (13%) of the 38 active PD patients experienced cuff extrusion. Causes of end-stage renal disease (ESRD) were diabetic nephropathy (n = 1), toxic nephropathy (n = 1), hypertensive nephrosclerosis (n = 1), systemic disease (n = 1) and one with unknown cause. PD catheters were inserted by the Department of Surgery and our patients waited a mean of 3.71 weeks (0.57-7.86) from catheter insertion to PD start. Patients were followed up by monthly and even fortnightly during infections. Our cohort experienced two (1-5) ESIs per patient prior to cuff extrusion. Cultures showed growth of Staphylococcus aureus and the patients received dicloxacillin orally 500 mg qid for 3-4 weeks. Of the 38 active PD patients, 5 (13%) developed cuff extrusion with an incidence of 0.20 episodes/patient/year, manifesting on average at 32 weeks (17.3-40.6), due to repeated ESI in four patients and substantial weight loss in one patient. All five underwent cuff-shaving and the ESIs resolved completely in 80% of the cases assisted by supplemental treatment with mupirocin and/or dicloxacillin. There were no complications to the cuff-shaving procedure itself. None of the five patients experienced new ESIs after cuff-shaving had been performed. Cuff-shaving reduces the rate of recurring ESIs. The procedure is safe, if performed correctly, and poses no risk to the patient or the catheter.

Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results From the Assessment of Lescol in Renal Transplantation Study.

BACKGROUND: Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study. METHODS: Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107). RESULTS: Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 µmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 µmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 µmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13-5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36-4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63-10.69) and 2.50 (95% CI, 1.38-4.55), respectively. CONCLUSIONS: Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.

Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism.

BACKGROUND: Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. METHODS: We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. RESULTS: Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P=0.004), and with graft loss (6% increased risk per 10 units; P<0.001), but not with major cardiovascular events. Parathyroid hormone above the upper limit of normal (65 pg/mL) indicated a 46% (P=0.006) higher risk of death and an 85% higher risk of graft loss (P<0.001) compared with low/normal values. CONCLUSIONS: Hyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.

Symmetric dimethylarginine as predictor of graft loss and all-cause mortality in renal transplant recipients.

BACKGROUND: Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated. METHODS: We analyzed SDMA in the placebo arm of the Assessment of Lescol in Renal Transplantation study, a randomized controlled trial of fluvastatin in RTR. Mean follow-up was 5.1 years. Patients were grouped into quartiles based on SDMA levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analyzed in 925 RTR using univariate and multivariate survival analyses. RESULTS: In univariate analysis, SDMA was significantly associated with renal graft loss, all-cause death, and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA-level (4th quartile, >1.38 µmol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95-15.57; P=0.001, compared to the 1st quartile. Similarly, SDMA in the 4th quartile was independently associated with all-cause mortality (HR, 4.56; 95% CI, 2.15-9.71; P<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99-8.21; P=0.051). CONCLUSION: In stable RTR, an elevated SDMA level is independently associated with increased risk of all-cause mortality and renal graft loss.

Graft loss risk in renal transplant recipients with metabolic syndrome: subgroup analyses of the ALERT trial.

BACKGROUND: Several nonimmunologic risk factors for late renal graft loss (RGL) are also known components of metabolic syndrome (MS). We aimed to study MS as a risk factor for RGL. Also, the effect of statin treatment in reducing renal risk in renal transplant recipients (RTRs) with MS was studied. METHODS: Nondiabetic RTRs (n=1,706) from the ALERT trial were followed for 7-8 years. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III definition with waist girth replaced by BMI ≥30 (calculated as kg/m(2)). Renal end points included death-censored RGL and graft loss or doubling of serum creatinine. RESULTS: During the follow-up, 284 patients experienced RGL, and there were 343 cases of graft loss or doubling of serum creatinine. Those with MS had increased risk for RGL (relative risk = 1.28, 95% confidence interval, 1.00-1.63; p=0.047), but not for the combined end point. After adjustment for other known and potential risk factors, MS was no longer associated with increased risk for RGL. The association between MS and RGL risk was attenuated once adjustment for creatinine was made. Statin treatment did not reduce the risk for renal end points in RTRs with or without MS. CONCLUSION: MS had no independent association with RGL risk. Adjustment for renal function attenuated the association between MS and RGL.

Cerebrovascular events in renal transplant recipients.

BACKGROUND: The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. METHODS: The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. RESULTS: The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. INTERPRETATION: Risk factors for CBV events in renal transplant recipients differ according to subtype.

Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: a randomized placebo-controlled study.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. METHODS: Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5-6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7-8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. RESULTS: Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3-40%), from a mean +/- SD of 4.0 +/- 0.9 mmoles/liter to 2.8 +/- 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7-27.5%), from 6.4 +/- 0.9 mmoles/liter to 5.1 +/- 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9-119.4], P = 0.064). CONCLUSION: Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.

Inflammation in renal transplantation.

BACKGROUND AND OBJECTIVES: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated. RESULTS: The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049). CONCLUSIONS: The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.

Effects of pharmacological modulation of the ATP-sensitive potassium channels on the development of warm-up angina pectoris.

The aim of this study was to examine the effect of pharmacological modulation of the ATP-sensitive potassium channels in the development of warm-up angina pectoris. Thirty-one patients with stable angina pectoris, a positive exercise test and angiographically documented coronary artery disease underwent three exercise tests 90 min after receiving either glibenclamide 10.5 mg (an ATP-sensitive potassium channel blocker), pinacidil 25 mg (an ATP-sensitive potassium channel opener) or placebo in a blinded fashion. There was a 30-min recovery period between the first and the second test and 60 min between the second and the third test. The rate-pressure product at 1-mm ST-segment depression (ischemic threshold) and the maximum ST-segment depression (STD) adjusted to the highest rate-pressure product common to the three tests were analyzed. In the placebo group, there was a significant increase in the ischemic threshold during the second and third test and a significant decrease in the maximum adjusted STD during the second test which was lost during the third test. This apparent adaptation to exercise-induced ischemia was not seen in the glibenclamide-treated patients. In the pinacidil-treated patients, there was a paradoxical decrease in ischemic threshold during the second test with no change in maximum adjusted STD which tended to be lower than in the placebo-treated patients on each exercise test. This study confirms that the warm-up phenomenon can be induced during repeated exercise testing. The blockade of this phenomenon by glibenclamide suggests that the ATP-sensitive potassium channels may be involved in this potential protective mechanism. At the same time, the paradoxical response in the pinacidil-treated patients flags a warning that drugs acting on the sarcolemmal ATP-sensitive potassium channels may have a direct effect on the ST-segment that may interfere with the interpretation of the electrocardiogram.

No detrimental effect on renal function during long-term use of fluvastatin in renal transplant recipients in the Assessment of Lescol in Renal Transplantation (ALERT) study.

BACKGROUND: Concerns have recently been raised regarding a potential harmful effect of statins on renal function. This study investigated the effect of fluvastatin treatment on renal function in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) trial. METHODS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40-80 mg daily (n = 1050) or placebo (n = 1052) on cardiac and renal outcomes in renal transplant recipients over a follow-up period of five to six years. The incidence of graft loss, changes in serum creatinine, calculated creatinine clearance and proteinuria, and the incidence of renal adverse events (AEs) were assessed in both treatment groups. RESULTS: Fluvastatin treatment in ALERT had no significant effect compared with placebo on renal function, assessed by serum creatinine (overall adjusted mean +/- SEM: fluvastatin, 175.4 +/- 2.20 micromol/L; placebo, 172.7 +/- 2.20 micromol/L; p = 0.39), creatinine clearance (fluvastatin, 55.3 +/- 0.30 mL/min; placebo, 55.8 +/- 0.30 mL/min; p = 0.26) or proteinuria (fluvastatin, 0.58 +/- 0.03 g/24 h; placebo, 0.53 +/- 0.03 g/24 h; p = 0.31). There were no significant differences between treatment groups when the 283 patients suffering graft loss were excluded from the analysis. Fluvastatin also had no detrimental effect on creatinine clearance or proteinuria in the subgroup of 340 diabetic patients without graft loss in ALERT. No notable differences in the rate of renal or musculoskeletal AEs were observed between fluvastatin and placebo groups. CONCLUSIONS: Fluvastatin had no detrimental effect on renal function, or the risk of renal AEs, in renal transplant recipients with or without diabetes enrolled in ALERT. Fluvastatin treatment for the prevention of cardiac events may therefore be used without fear of jeopardizing renal function.