Bartonella Endocarditis and Pauci-Immune Glomerulonephritis: A Case Report and Review of the Literature.

Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti-neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.

Cardiovascular Outcomes in Action to Control Cardiovascular Risk in Diabetes: Impact of Blood Pressure Level and Presence of Kidney Disease.

BACKGROUND: Persons with chronic kidney disease (CKD) represent a population prone to cardiovascular disease (CVD) but vulnerable to adverse medication effects. We assessed the impact of intensive antihypertensive therapy on the cerebrovascular and other CVD outcomes in high-risk patients with type 2 diabetes and baseline CKD. METHODS: Using current guideline criteria, 1,726 (36.9%) of 4,678 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure (BP) arm had mild to moderate CKD (CKD1-3B) at baseline. Participants of this study were randomized to intensive (systolic <120 mm Hg) or standard (systolic <140 mm Hg) BP goals. Fatal and non-fatal stroke were pre-specified secondary outcomes of the ACCORD study. RESULTS: Total cerebrovascular events were significantly higher in participants with baseline CKD (0.66%/year) compared with participants free of CKD (0.28%/year). A significantly higher rate of events was observed in CKD participants. Intensive antihypertensive therapy in participants without CKD at baseline resulted in a 55% significant reduction of any stroke (hazard ratio 0.447; 95% CI 0.227-0.880) and a 50% reduction of non-fatal stroke (hazard ratio 0.498; 95% CI 0.250-0.993). In participants with CKD at baseline, the occurrence of any stroke was reduced by 38% (hazard ratio 0.623; 95% CI 0.361-1.074) and non-fatal stroke by 36% (hazard ratio 0.642; 95% CI 0.361-1.142). Test for interaction was NS between the 2 groups. Changes in other CVD outcomes did not reach statistical significance. CONCLUSIONS: These findings suggest that intensive antihypertensive therapy offers significant cerebrovascular protection in diabetic participants without CKD at baseline, but significant benefit to patients with CKD cannot be excluded.

Pre-empting Antibody-Mediated Rejection: A Program of DSA Monitoring and Treatment Can Effectively Prevent Antibody Mediated Rejection.

Antibody-mediated rejection (AMR) remains a problem without a reliable treatment in the care of kidney transplant patients. We proposed and tested a program of screening for donor specific antibodies (DSA) to initiate treatment of patients before AMR was detected and to prevent its occurrence. Starting in April 2012, we stratified patients into high-, medium-, and low-risk groups for the development of DSA and instituted a program of screening for and treatment of these antibodies. We used a historic control group of patients transplanted at our center as a comparator and looked at rates of DSA testing and development as well as rates of development of AMR, cell-mediated rejection, and graft loss. 614 patients were transplanted under the protocol compared with 266 patients in the control group. Length of follow-up was similar in both groups. The group undergoing DSA screening had lower rates of DSA development (17.6% versus 24.8%, p=0.016) and that DSA was found at a significantly earlier time post-transplant (147 versus 248 days, p=0.02). Incidence of AMR was dramatically lower in the screened group (1.3% versus 8.6%, p<0.0001) with no grafts lost due to AMR. AMR was found to occur at an average of 181 days post-transplant. Rates of acute cellular rejection did not decrease in a manner similar to AMR rates. In conclusion, a program of universal risk-stratified DSA testing in kidney transplant patients can dramatically reduce rates of AMR and virtually eliminate graft loss due to AMR.

Lipoprotein-associated phospholipase A2 mass is significantly reduced in dyslipidemic patients treated with lifestyle modification and combination lipid-modifying drug therapy.

Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) mass is a novel inflammatory biomarker. In human blood, Lp-PLA(2) is predominately associated with low-density lipoprotein (LDL). This study examines the ability of lifestyle modification (diet and exercise) and combination lipid therapy to reduce Lp-PLA(2) levels while also determining the relationship between changes in LDL cholesterol and Lp-PLA(2). Thirty dyslipidemic patients who received lifestyle intervention and combination lipid therapy for an average of 6 months were included in these analyses (mean age, 60.9 years); 40% had stable angiographically established coronary artery disease, 40% had the metabolic syndrome, and 70% were men. Drug therapy included omega-3 fish oil, extended-release niacin, colesevelam hydrochloride, and a fixed combination of 10-mg ezetimibe and 40-mg simvastatin. The study revealed a 33% reduction in mean Lp-PLA(2) values (baseline 224.9+/-47.5 vs posttreatment 149.5+/-35.5 ng/mL; P<.001). Significant changes in mean LDL cholesterol from baseline (127.9+/-49.3 vs posttreatment 65.2+/-32.1 mg/dL; P<.001) were also observed. However, regression analysis revealed only a weak positive relationship between changes in LDL cholesterol and Lp-PLA(2) mass (R(2)=0.29; P<.01). Thus, Lp-PLA(2) mass is significantly reduced with lifestyle and combination lipid therapy. Changes in Lp-PLA(2) were only partially explained by the changes observed for LDL cholesterol.

Efficacy of combination drug pulse therapy in maintaining lipid levels in patients intolerant of daily statin use.

The objective of this study was to evaluate the efficacy of combination drug pulse therapy in maintaining lipid levels in patients intolerant of a daily dose of statins. Twenty-three patients, previously receiving aggressive statin therapy, were treated twice weekly with rosuvastatin or atorvastatin in different dosages along with ezetimibe as well as daily doses of bile acid sequestrant for a mean period of 4.5 months. The recommended National Cholesterol Education Program Adult Treatment Panel III goals had already been achieved in 78% of patients (n=18) before starting combination pulse therapy. This combination therapy significantly increased high-density lipoprotein cholesterol values by 5.82% (t=2.138, P=.044), while the increases in total cholesterol, low-density lipoprotein cholesterol, triglyceride, and apolipoprotein B levels compared with baseline were not statistically significant. Overall, 3 of 23 patients (13%) discontinued the combination therapy because of muscle-related symptoms over a mean course of 4.5 months of treatment.

Effects of lifestyle counseling and combination lipid-modifying therapy on lipoprotein-associated phospholipase A2 mass concentration.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA(2)) is a novel inflammatory biomarker that is associated with increased cardiovascular disease risk independent of and additive to traditional risk factors. Lp-PLA(2) activity is correlated with the degree of inflammation in the atherosclerotic plaque. In human blood, approximately 80% of Lp-PLA(2) is associated with low-density lipoproteins (LDL). Thus, it is hypothesized that changes in Lp-PLA(2) should imitate the changes in the LDL cholesterol. OBJECTIVE: In this present study, we examined the efficacy of lifestyle intervention and combination lipid-lowering therapy on reducing the Lp-PLA(2) levels and determined the relationship between changes in LDL-C and Lp-PLA(2). METHODS: This retrospective chart review study includes two hundred forty eight patients (58% men and 42% women) who completed the life style intervention in combination with pharmacologic therapy for an average period of 10.5 months. Life style modification included diet and exercise counseling. Combination therapy included omega 3 fish oil (2000mg/d), extended-release niacin (500-1000mg/d), ezetimibe (10mg/d), fenofibrate 160mg/d and colesevelam HCI (1850mg/d), as well as statins. The statins used were either simvastatin (20-40mg/d) or rosuvastatin (5-20mg/d). Sixty five percent (n=161) received low to medium doses of simvastatin, whereas 35% (n=87) received low to medium doses of rosuvastatin. RESULTS: The study revealed a 32.5% reduction in mean Lp-PLA(2) values (baseline 181.1±41.5 vs 122.1±28.1 ng/mL after treatment; P<.001). The change observed in LDL-C was 41%, (baseline 126.2±43 vs 73.9±37.7mg/dL after treatment), which also was significant (P < .001). However, a Pearson correlation test analysis revealed only a weak positive association between changes in Lp-PLA(2) and LDL-C (r(2)=0.052, P < .001). CONCLUSION: Lp-PLA(2) is reduced with the use of life style counseling and combination lipid lowering therapy. Results also revealed that changes in Lp-PLA(2) may be partially explained by the changes in LDL-C.