Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.     

Dimethylarginines and inflammation markers in patients with chronic kidney disease undergoing dialysis

The aim of this study was to investigate the pro-oxidant and proinflammatory biomarkers and their relationship with dimethylarginines (DMAs) in patients at various stages of chronic kidney disease (CKD). We studied 114 CKD patients, 36 were hemodialyzed, 41 peritoneal dialyzed and 37 nondialyzed (early stage) CKD patients. The control group consisted of 31 healthy subjects. Plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), l-arginine, nitric oxide (NO) and proinflammatory cytokines (TNF-alpha and IL-6) were determined, and their relationships with the degree of disease were evaluated. Both DMAs were at high levels in all CKD patients, whereas arginine concentrations were low in patients undergoing dialysis. Elevated TNF-α and IL-6 in CKD patients were indicative of ongoing chronic inflammatory state. A significant positive correlation between SDMA and creatinine suggests that plasma SDMA level may be an index for renal function.     

Elevated levels of d-dimer are associated with inflammation and disease activity rather than risk of venous thromboembolism in patients with granulomatosis with polyangiitis in long term observation

PurposeGranulomatosis with polyangiitis (GPA) is one of antineutrophil cytoplasmic autoantibody (ANCA) - associated vasculitis. The disease is characterized by necrotizing inflammation of small vessels causing tissue ischemia in a variety of organs. The aim of the present study was an evaluation of inflammation, coagulation and fibrinolysis biomarkers, and their possible associations with various clinical and laboratory parameters in GPA patients.MethodsA group of 100 consecutive patients with GPA were prospectively followed in the study. In all patients, echocardiography and laboratory tests were performed.ResultsThe patients were followed-up for a median of 4.0 ± 1.9 years. Circulating d-dimer concentrations were elevated in a majority (56%) of GPA patients, and were significantly higher in GPA patients in the active stage compared to those in remission (median 652 vs. 405 ng/ml, p = 0.0002). In 23 patients (23%) venous thromboembolism (VTE) was diagnosed during observation. However, there were no differences in d-dimer concentrations between patients with and without VTE either in active stage or in remission. Correlation analysis showed that the levels of d-dimer correlated with hs-CRP (r = 0.42, p < 0.0001) and creatinine concentrations (r = 0.58; p < 0.0001), but not with ANCA levels.ConclusionsIn patients with GPA elevated levels of d-dimer are associated with disease activity and inflammation rather than with the risk of venous thromboembolism. The value of d-dimer as a biomarker of venous thromboembolism episodes in patients with small vessel vasculitis is low.     

Cyclooxygenase-2 -765G>C polymorphism is associated with C-reactive protein levels in resistant smokers but not in chronic obstructive pulmonary disease patients

We sought to investigate whether the serum concentrations of several inflammatory biomarkers are related to the cyclooxygenase-2 (COX2) −765G>C polymorphism in chronic obstructive pulmonary disease (COPD) and a control group of non-COPD smokers. Serum inflammatory markers (CRP, SAA, CXCL8, and sICAM-1) were measured by ELISA in 144 patients with COPD and in 55 control subjects. Genomic DNA was extracted from peripheral blood leukocytes, and the COX2 −765G>C (rs20417) polymorphism was genotyped. After adjustment for age and active smoking, CRP and SAA concentrations were associated with the COX2 polymorphism in controls (p = 0.041 and 0.014, respectively) but not in COPD patients. The CXCL8 and sICAM-1 concentrations were not associated with the COX2 polymorphism for either cases or controls. The results of the present study indicate that there is a relationship between the COX2 −765G>C polymorphism and the concentrations of CRP and SAA in non-COPD smokers and that this relationship does not exist in COPD patients.     

65例老年慢性肾脏病基础上急性肾损伤的临床观察

目的 分析老年慢性肾脏病基础上急性肾损伤(A/C)的基础疾病、发病诱因及影响预后的危险因素.方法 回顾性分析2005年12月至2009年12月于本院住院治疗的65例老年A/C患者的临床资料,分析A/C患者的基础疾病、发病诱因及影响预后的危险因素.根据治疗后肾功能恢复情况将患者分为2组:肾功能恢复患者和肾功能部分恢复患者合并为肾功能恢复组,肾功能未恢复患者与死亡患者合并为肾功能未恢复组,比较两组患者的少尿持续时间、入院时血清白蛋白水平和最高血清肌酐(Scr)水平.结果 糖尿病肾病是老年A/C患者的主要基础疾病(38.5％,25/65),药物因素(30.8％,20/65)和严重感染(27.7％,l8/65)是老年A/C患者的主要发病诱因.与肾功能恢复组比较,肾功能未恢复组患者少尿持续时间较长[(1 1.5±3.4)d比(4.2±1.8)d,P＜0.05]、入院时血清白蛋白水平较低[(23.6±3.1)g/L比(26.6± 4.5) g/L,P＜0.05],而最高Scr水平较高[(601.2± 142.7) μmol/L比(421.3±107.3) μmol/L,P＜0.05].结论 老年A/C患者应对其基础疾病进行有效治疗,积极消除发痫诱因和控制影响预后的危险因素.     

The reduction of serum aminotransferase levels is proportional to the decline of the glomerular filtration rate in patients with chronic kidney disease

OBJECTIVE:

This study sought to determine the serum aminotransferase levels of patients with predialysis chronic kidney disease and establish their relationships with serum creatinine levels and glomerular filtration rate.

METHODS:

Patients with chronic kidney disease were evaluated between September 2011 and May 2012. Aminotransferase and creatinine serum levels were measured using an automated kinetic method, and glomerular filtration rates were estimated using the Cockroft-Gault and Modification of Diet in Renal Disease formulas to classify patients into chronic kidney disease stages.

RESULTS:

Exactly 142 patients were evaluated (mean age: 64±16 years). The mean creatinine serum level and glomerular filtration rate were 3.3±1.2 mg/dL and 29.1±13 mL/min/1.73 m², respectively. Patients were distributed according to their chronic kidney disease stages as follows: 3 (2.1%) patients were Stage 2; 54 (38%) were Stage 3; 70 (49.3%) were Stage 4; and 15 (10.5%) were Stage 5. The mean aspartate aminotransferase and alanine aminotransferase serum levels showed a reduction in proportion to the increase in creatinine levels (p=0.001 and p=0.05, respectively) and the decrease in glomerular filtration rate (p=0.007 and p=0.028, respectively). Alanine aminotransferase and aspartate aminotransferase serum levels tended to be higher among patients classified as stage 2 or 3 compared with those classified as stage 4 or 5 (p=0.08 and p=0.06, respectively).

CONCLUSIONS:

The aspartate aminotransferase and alanine aminotransferase serum levels of patients with predialysis chronic kidney disease decreased in proportion to the progression of the disease; they were negatively correlated with creatinine levels and directly correlated with glomerular filtration rate.     

Anti-cytomegalovirus (CMV) IgG antibody titer in patients with risk factors to atherosclerosis

Abstract. Studies have demonstrated cytomegalovirus (CMV) DNA particles in restenotic lesions in atherosclerotic coronary arteries. We have shown that high (>1:800) anti-CMV IgG antibody titers in the serum are associated with active coronary disease and with post coronary angioplasty restenosis. In this study we assessed the anti-CMV antibody titer in patients with risk factors for atherosclerosis (but without documented clinical manifestations). One hundred and eighly-seven patients (men and women aged 40–80 years) that were admitted to the Department of Internal Medicine were recruited to this prospective study. All had at least one risk factor for atherosclerosis, and none had documented coronary artery disease. Fasting blood samples were drawn on admission. Risk factors included hypertension, diabetes mellitus, active smoking, hyperlipidemia, and a positive family history. Ninety-three age- and sex-matched individuals without atherosclerosis risk factors served as the control group. One Hundred and twentysix patients had high anti-CMV antibody titers (1:800) compared with none in the control group. Although 80 patients (90%) in the control group were seropositive, none had anti-CMV IgG antibody titers higher than 1:400. The statistical difference between the patients and the control group was highly significant (p<0.0001). An immunological response against CMV (expressed as an anti-CMV IgG antibody titer) could be a marker of a long-standing immunological reaction causing an inflammatory response that eventually would cause advanced clinical atherosclerosis. We suggest that anti-CMV antibody titer should be used as an early predictor of atherosclerosis. Our findings support the infectious theory and an association between CMV infection and atherosclerosis at an early stage, maybe even years before clinical events occur.     

Treatment of chronic periodontitis decreases serum prohepcidin levels in patients with chronic kidney disease

OBJECTIVE:

To determine the impact of periodontal treatment on serum levels of prohepcidin (the prohormone of hepcidin) and systemic inflammation markers, as well as correlations among these markers, in patients with chronic periodontitis and chronic kidney disease who were not undergoing dialysis.

METHODS:

We included 56 chronic periodontitis patients, 36 with chronic kidney disease and 20 without systemic diseases and with normal renal function (control group). Chronic kidney disease was defined as suggested by the clinical practice guidelines in the National Kidney Foundation. Chronic periodontitis was defined through clinical attachment level and by probing pocket depth, according to the American Association of Periodontology. The inflammatory markers ultrasensitive C-reactive protein, interleukin-6, and prohepcidin were evaluated before and 3 months after periodontal treatment.

RESULTS:

The efficacy of periodontal treatment was confirmed by the improvement in clinical parameters of chronic periodontitis in the control and chronic kidney disease groups. Periodontal treatment resulted in significant reductions in ultrasensitive C-reactive protein, interleukin-6 and serum prohepcidin levels in both groups. Moreover, in multivariate linear regression, the reduction in prohepcidin after periodontal treatment was significantly and independently associated with interleukin-6 levels in the control group.

CONCLUSIONS:

By inducing a decline in the systemic inflammatory response and a decrease in serum prohepcidin, successful periodontal treatment may represent an important means of ameliorating the inflammatory burden seen in patients with chronic kidney disease. Trial registration: ISRCTN59866656.     

Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1beta and tumor necrosis factor-alpha

Studies suggest that cytokines have a role in the biology of depression. In this study, we evaluated depression and cytokine levels in patients with and without chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines levels and may contribute to depressive symptomotology. Twenty-three adults with (n=16) and without (n=7) HCV were recruited through the Portland VA Medical Center. Research participants were excluded for current substance abuse, psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate plasma cytokine levels [i.e., interleukin (IL)-1beta, IL-10 and tumor necrosis factor (TNF)-alpha]. t-Tests were performed to compare cytokine levels in patients with or without HCV. HCV patients showed higher TNF-alpha values compared to patients without HCV (group means=7.94 vs. 3.41pg/mL, respectively, p=0.047). There were no significant differences between the groups for the other cytokines assessed. In patients with HCV, TNF-alpha and IL-1beta levels (but not IL-10) were correlated with BDI-II scores [r=0.594, p=0.020 and r=0.489, p=0.055 (trend), respectively]. Taken together, these results show an association between severity of depressive symptoms and expression of pro-inflammatory cytokines in patients with HCV. Future studies should investigate how inflammatory mediators play a role in the expression of specific depressive symptoms in patients with chronic infection. Patients with HCV represent an interesting model to examine this relationship.     

The relationship between Vaspin,Nesfatin-1 plasma levels and presence of fragmented QRS with the severity of coronary atherosclerosis

PurposeDespite continuous efforts to address classical risk factors for atherosclerosis, the battle to control the disease is far from over and atherosclerosis is still a major factor in all-cause mortality. To investigate the relations between early diagnosis and severity of coronary atherosclerosis we examined vaspin and nesfatin-1 levels, and the presence of fragmented QRS (fQRS) in admission electrocardiograms.Materials and methodsWe divided 168 patients into asymptomatic control (18%), <50% coronary artery stenosis (28%), >50% stenosis (31%) and myocardial infarction (MI) (23%) groups. Patients were also evaluated in anatomically significant (>50%stenosis ?+ ?MI) and non-significant atherosclerosis (control+<50%stenosis) groups. Vaspin and nesfatin-1 levels were measured using ELISA methods.ResultsVaspin in MI and >50% stenosis groups was lower than in other groups (p ?< ?0.001). Nesfatin-1 in MI and >50% stenosis groups was lower only than in <50%stenosis group (p0.007). The presence of fQRS was higher in MI and >50% stenosis groups than other groups (p ?< ?0.001). In the anatomically significant atherosclerosis group, vaspin, nesfatin-1 and left ventricular ejection fraction (LVEF) values were lower while Gensini score and the presence of fQRS were higher (for all p ?< ?0.001). Lower vaspin levels and fQRS were related to in-hospital mortality (p ?< ?0.001 and p ?= ?0.02,respectively). Logistic regression analysis showed that male gender, diabetes mellitus, smoking, family history, lower LVEF, lower vaspin and fQRS were defined as independent risk factors for anatomically significant atherosclerosis (p ?= ?0.001).ConclusionsOur results indicate that low vaspin and fQRS were found to be novel independent risk factors for anatomically significant atherosclerosis and were predictors of mortality.     

Elevated body mass index is associated with an increased risk of infectious disease admissions and mortality: a mendelian randomization study

ObjectiveThe effect of body mass index (BMI) on the risk of infectious diseases admissions and mortality is unclear and is difficult to study given the risks of confounding variables.MethodsWe used genome-wide association studies (GWASs) with mendelian randomization (MR) to obtain causal inference of BMI on the following infectious diseases outcomes: hospital admissions for pneumonia, sepsis, urinary tract infections, skin and soft tissue infections (SSTIs) or all-cause infections. For patients with pneumonia and sepsis, we also analysed their 28-day and 90-day mortalities. The UK Biobank (UKB) cohort (n > 500 000) provided data for GWASs on infectious diseases. The GIANT consortium (n = 681 265) GWAS was used to identify single-nucleotide polymorphisms (SNPs) associated with BMI.ResultsGenetically increased BMI, by one standard deviation, was associated with higher rates of admission due to all infectious disease. The effect was most important for SSTIs (OR: 1.11, 95%CI: 1.09, 1.12). Increasing BMI by one standard deviation was associated with higher pneumonia mortality, especially at 28 days (OR: 1.03, 95%CI: 1.01, 1.05). BMI was not clearly associated with sepsis mortality, although interpretation of the results was limited by a small sample size. There were consistent findings in sensitivity analysis performed by removing highly pleiotropic SNPs and multivariate MR including type-2 diabetes mellitus, estimated glomerular filtration rate, high-density lipoprotein, educational attainment, and a history of smoking.ConclusionsIncreased BMI was associated with increased risk of admission for infectious disease and mortality. While the pathophysiology behind this phenomenon remains unknown, increasing BMI may influence immune dysregulation.     

sTREM‐1 in patients with chronic kidney disease on hemodialysis

The triggering receptor expressed on myeloid cells‐1 (TREM‐1) is a member of the immunoglobulin superfamily. TREM‐1 has been implicated as an amplifier of inflammation. Soluble TREM‐1 (sTREM‐1) was investigated in different clinical conditions, but not in hemodialysis (HD) patients. We aimed to investigate sTREM‐1 as a marker of inflammation in HD patients. We investigated 40 CKD patients undergoing chronic HD treatment and 15 controls. Routine laboratory investigations in addition to CRP measured by immunoturbidimetry, TNF‐ α, and sTREM‐1 measured by ELISA were assayed in post–hemodialysis patients’ blood samples and in controls’ blood samples. CRP, TNF‐α, and sTREM‐1 levels were significantly higher in HD patients than in controls (p < 0.001 for all). sTREM‐1 was positively correlated with CRP and TNF‐α (r = +0.50, p < 0.001 and r = +0.53, p < 0.001 respectively). It was negatively correlated with hemoglobin concentration (r = ?0.69, p < 0.001). Hemoglobin concentration was the significant predictor of sTREM‐1 level (p < 0.001). In conclusion, sTREM‐1 level is significantly increased in HD patients as are other pro‐inflammatory markers.     

Reduced concentrations of the B cell cytokine interleukin 38 are associated with cardiovascular disease risk in overweight subjects

The IL-1 family member IL-38 (IL1F10) suppresses inflammatory and autoimmune conditions. Here, we report that plasma concentrations of IL-38 in 288 healthy Europeans correlate positively with circulating memory B cells and plasmablasts. IL-38 correlated negatively with age (p = 0.02) and was stable in 48 subjects for 1 year. In comparison with primary keratinocytes, IL1F10 expression in CD19⁺ B cells from PBMC was lower, whereas cell-associated IL-38 expression was comparable. In vitro, IL-38 is released from CD19⁺ B cells after stimulation with rituximab. Intravenous LPS in humans failed to induce circulating IL-38, compared to 100-fold induction of IL-6 and IL-1 receptor antagonist. In a cohort of 296 subjects with body mass index > 27 at high risk for cardiovascular disease, IL-38 plasma concentrations were significantly lower than in healthy subjects (p < 0.0001), and lowest in those with metabolic syndrome (p < 0.05). IL-38 also correlated inversely with high sensitivity C-reactive protein (p < 0.01), IL-6, IL-1Ra, and leptin (p < 0.05). We conclude that a relative deficiency of the B cell product IL-38 is associated with increased systemic inflammation in aging, cardiovascular and metabolic disease, and is consistent with IL-38 as an anti-inflammatory cytokine.     

Quality of life in patients with chronic kidney disease

AIM:

To compare the dimensions of quality of life in the stages of chronic kidney disease and the influence of sociodemographic, clinical and laboratory data.

INTRODUCTION:

The information available on the quality of life of patients on conservative treatment and the relationship between the quality of life and glomerular filtration rate is limited.

METHODS:

155 patients in stages 1–5 of chronic kidney disease and 36 in hemodialysis were studied. Quality of life was rated by the Medical Outcomes Study Short Form 36-Item (SF-36) and functional status by the Karnofsky Performance Scale. Clinical, laboratory and sociodemographic variables were investigated.

RESULTS:

Quality of life decreased in all stages of kidney disease. A reduction in physical functioning, physical role functioning and in the physical component summary was observed progressively in the different stages of kidney disease. Individuals with higher educational level who were professionally active displayed higher physical component summary values, whereas men and those with a higher income presented better mental component summary values. Older patients performed worse on the physical component summary and better on the mental component summary. Hemoglobin levels correlated with higher physical component summary values and the Karnofsky scale. Three or more comorbidities had an impact on the physical dimension.

CONCLUSION:

Quality of life is decreased in renal patients in the early stages of disease. No association was detected between the stages of the disease and the quality of life. It was possible to establish sociodemographic, clinical and laboratory risk factors for a worse quality of life in this population.     

Cardiac troponins in chronic kidney disease patients with special emphasis on their importance in acute coronary syndrome

Troponin measurement is one of crucial assessments facilitating diagnosis of acute coronary syndrome. Patients with chronic kidney disease are decimated by cardiovascular disease. Unfortunately, elevated concentration of serum troponin is commonly faced in clinical practice creating a challenge to rule out acute cardiac ischaemia in this vulnerable population. This review presents current knowlegde on analytical differences in troponin T and I measurements, their prognostic significance and their application in diagnosing acute coronary syndrome in chronic kidney disease patients. It also points out poorly known aspects and suggests directions for future research.     

Evaluation of serum osteoprotegerin and fetuin A levels in Egyptian patients with chronic kidney disease

Vascular calcifications are recognized as important risk factors for uremia-induced cardiovascular disease. Yet some patients with chronic kidney disease (CKD) do not develop calcification despite exposure to the same uremic conditions. Physiological inhibitors of calcification such as fetuin A, which is an extraosseous calcification inhibitor, and osteoprotegerin (OPG), which is a regulator of bone resorption, may prevent the development and progression of vascular calcification. The aim of this work is to study the serum levels of fetuin A and OPG to understand their role in vascular calcification in patients with chronic renal impairment. A total of 80 subjects (60 CKD patients and 20 age- and sex-matched healthy controls) were studied. Fetuin A and osteoprotegerin were measured by ELISA; in addition to standard biochemical analysis, ECG and echocardiography were done to evaluate cardiovascular calcification. Fetuin A levels were significantly lower; OPG levels were significantly higher in the patients group compared to the controls. There was an inverse association between fetuin A and vascular calcifications in the patients group (P = −0.498, r = −0.001), while OPG showed a positive association (P = 0.510, r = 0.003). Serum fetuin A and osteoprotegerin levels were related to vascular calcification in CKD stages III, IV, and V. Decreased serum fetuin A may have a role in enhancing the cardiovascular morbidity and mortality in those patients by promoting a process of accelerated vascular calcification; elevated serum OPG levels increase with the progression of CKD, so these can be used as markers in the follow-up of those patients.     

C5aR在慢性移植物抗宿主病中的表达及其作用机制

目的:探讨补体5a(C5a)及其受体(C5aR)在慢性移植物抗宿主病(cGVHD)中的表达及其作用机制。方法:用流式细胞术检测20例cGVHD患者及9例健康供者外周血淋巴细胞中C5aR的表达及CD4~+CD25~+Foxp3~+调节性T细胞(Tregs)在CD4~+T细胞中的比例,并分析两者的相关性;将体外分离培养小鼠脾细胞分为对照组及重组小鼠C5a蛋白(rmC 5a)刺激组,用流式细胞术检测2组Tregs在CD4~+T细胞中的表达比例;另外,提取患者外周血单个核细胞进行体外培养,分为空白对照组及C5aR拮抗剂(C5aRA)组,用流式细胞术检测2组Tregs在CD4~+T细胞中的表达比例。结果:cGVHD患者外周血淋巴细胞表面C5aR的表达明显增多,而Tregs在CD4~+T细胞中的比例明显减少,两者呈显著负性相关(P0.05);体外培养小鼠脾细胞结果显示C5a下调Tregs在CD4~+T细胞中的比例;而体外培养患者外周血单个核细胞显示阻断C5aR可上调Tregs在CD4~+T细胞中的比例。结论:C5a/C5aR可能通过抑制Tregs的分化来介导cGVHD的发生发展。