Prediction of contrast‐induced acute kidney injury by early post‐procedural analysis of urinary biomarkers and intra‐renal Doppler flow indices in patients undergoing coronary angiography

Background

The study was designed to evaluate the applicability of combined assessment of urinary biomarkers and intra‐renal Doppler flow indices for the prediction of contrast‐induced acute kidney injury (CI‐AKI) after coronary angiography/percutaneous coronary interventions (CA/PCI).

Methods

This prospective observational study covered 95 consecutive patients with coronary artery disease subject to elective or urgent CA/PCI. Doppler intra‐renal flow indices were assessed before and 1 h following CA/PCI. Urine samples were collected within 24 h before and 6 h after CA/PCI and assayed for urinary interleukin‐18 (IL‐18), liver‐fatty acid‐binding protein (L‐FABP), and kidney injury molecule‐1 (KIM‐1) using ELISA method. CI‐AKI was defined as ≥50% relative or ≥0.3 mg/dL absolute increase of serum creatinine concentration at 48 h post‐procedurally.

Results

CI‐AKI was confirmed in nine patients (9.5%). CI‐AKI onset was associated with significantly higher urinary KIM‐1 at 6 h (P = 0.003) and ΔKIM‐1 concentrations (P = 0.001), and urinary IL‐18 at 6 h (P = 0.014) and ΔIL‐18 concentrations (P = 0.012), however, L‐FABP and ΔL‐FABP levels were comparable in both groups. Receiver operating characteristic curve analysis denoted that post‐procedural IL‐18 levels at 6 h >89.8 pg/mg (AUC = 0.75, P = 0.007), KIM‐1 at 6 h >0.425 ng/mg (AUC = 0.81, P = 0.001), renal resistive index (RRI) at 1 h >0.73 (AUC 0.88; P < 0.0001), and renal pulsatility index (RPI) at 1 h >0.86 (AUC = 0.86; P < 0.0001) predicted CI‐AKI onset. Logistic regression analysis of postoperative predictors revealed that IL‐18 and RRI were independent predictors of CI‐AKI onset (AUC = 0.96; P < 0.0001).

Conclusions

Joint assessment of early post‐procedural urinary biomarkers and Doppler renovascular parameters aids early diagnosis of CI‐AKI in patients undergoing coronary interventions.

     

Mizoribine therapy for patients with lupus nephritis: the association between peak mizoribine concentration and clinical efficacy

The clinical efficacy of mizoribine (MZR; 4-carbamoyl-1-b-d-ribofuranosylimidazolium) in patients with lupus nephritis was investigated. Thirteen Japanese patients with biopsy-proved lupus nephritis were enrolled in this study. A change in global assessments score, total protein (TP) of serum, serum creatinine, creatinine clearance (Ccr), proteinuria, titers of serum anti-ds DNA antibody, C3, C4, and hemolytic complement activity (CH50) were examined. Following MZR treatment, the level of urinary protein decreased (P < 0.05), whereas the level of Ccr increased (P < 0.05). Moreover, the level of TP significantly increased from 5.5 g/dl to 6.3 g/dl (P < 0.01) and the level of C3 increased significantly (P < 0.01). However, there was no change in the levels of both C4 and CH50. The titer of anti-ds DNA antibody significantly decreased (P < 0.05). The dosage of prednisolone could be tapered from 24.8 mg to 14.9 mg daily during the period. The clinical effects associated with MZR concentration in the blood revealed that there was a significant correlation between the peak MZR blood concentration of more than 0.66 μg/ml and clinical improvement (P = 0.021). Our results suggest that an optimal MZR blood concentration was important for the treatment of lupus nephritis. The first two authors contributed equally to this work.     

Mizoribine therapy for patients with lupus nephritis: the association between peak mizoribine concentration and clinical efficacy

Abstract

The clinical efficacy of mizoribine (MZR; 4-carbamoyl-1-b-d-ribofuranosylimidazolium) in patients with lupus nephritis was investigated. Thirteen Japanese patients with biopsy-proved lupus nephritis were enrolled in this study. A change in global assessments score, total protein (TP) of serum, serum creatinine, creatinine clearance (Ccr), proteinuria, titers of serum anti-ds DNA antibody, C3, C4, and hemolytic complement activity (CH50) were examined. Following MZR treatment, the level of urinary protein decreased (P < 0.05), whereas the level of Ccr increased (P < 0.05). Moreover, the level of TP significantly increased from 5.5?g/dl to 6.3?g/dl (P < 0.01) and the level of C3 increased significantly (P < 0.01). However, there was no change in the levels of both C4 and CH50. The titer of anti-ds DNA antibody significantly decreased (P < 0.05). The dosage of prednisolone could be tapered from 24.8?mg to 14.9?mg daily during the period. The clinical effects associated with MZR concentration in the blood revealed that there was a significant correlation between the peak MZR blood concentration of more than 0.66?µg/ml and clinical improvement (P = 0.021). Our results suggest that an optimal MZR blood concentration was important for the treatment of lupus nephritis.     

Cyclophosphamide induction dose and outcomes in ANCA-associated vasculitis with renal involvement: A comparative cohort study

Treatment of ANCA-associated vasculitis (AAV) improved over the last decades but disease-unspecific agents such as cyclophosphamide are still associated with serious adverse events, including high rates of infectious complications and malignancy with increased mortality.In this comparative cohort study, we included 121 AAV patients with renal involvement from 2 German vasculitis centers. Patients were separated into subsequent groups: 2.5 to 3 g vs >3 g cumulative cyclophosphamide induction dose. We investigated if a cyclophosphamide induction dose of 2.5 to 3 g could maintain efficacy while minimizing adverse events in AAV patients with renal involvement.Patients with 2.5 to 3 g vs >3 g cumulative cyclophosphamide (median 3.0 g vs 5.5 g, P < .001) had a comparable time to remission (median 4.0 vs 3.8 months, log-rank P = .87) with 90.6% and 91.5% achieving remission after 12 months. Refractory disease was low in both groups (median 3.6% vs 6.2%, P = .68) and relapse rate did not differ (median 36% vs 42%, log-rank P = .51). Kidney function was comparable at disease onset in both groups (eGFR, mean ± SD 29 ± 20 mL/min/1.73 m² vs 35 ± 26 mL/min/1.73 m², P = .34) and improved after 2 years irrespective of the cyclophosphamide dose (ΔeGFR, mean ± SD +8.9 ± 1.4 mL/min/1.73 m² vs +6.0 ± 1.1 mL/min/1.73 m², P = .33). The 2.5–3 g group had a lower rate of leukopenia (HR = 2.73 [95% CI, 1.2−6.3], P = .014) and less infectious episodes per patient (median 1.2 vs 0.7, P = .012), especially urinary tract infections (HR = 2.15 [95% CI, 1.1–4.5], P = .032).A cyclophosphamide induction dose of 2.5 to 3 g was able to induce remission and prevent from relapses with fewer cases of leukopenia and less infectious episodes during follow-up. Especially elderly AAV patients who are particularly susceptible to infectious complications could benefit from minimizing dosing regimens with maintained efficacy to control disease activity.     

血清C1q抗体水平与系统性红斑狼疮活动性和狼疮肾炎的关系

目的分析探讨血清C1q抗体水平与系统性红斑狼疮（SLE）活动性以及狼疮肾炎之间的关系。方法采用ELISA方法检测92例SLE患者C1q抗体水平。并与其他SLE活动性指标进行相关分析。结果SLE患者C1q抗体阳性率为67.4%。活动性狼疮组的C1q抗体阳性率及C1q抗体水平显著高于非活动性狼疮组（P〈0.001）。活动性狼疮肾炎组C1q抗体阳性率（P〈0.05）和C1q抗体水平（P〈0.01）显著高于非活动性狼疮肾炎组。联合抗dsDNA抗体检测,没有1例活动性狼疮肾炎患者的C1q抗体和抗dsDNA抗体同时阴性。结论血清C1q抗体与狼疮活动以及活动性狼疮肾炎关系密切,C1q抗体的检测有助于活动性狼疮的诊断,联合抗dsDNA抗体的检测是活动性狼疮肾炎的特异性检测指标。     

血清肺炎衣原体IgA抗体水平与缺血性脑卒中关系的研究

目的探讨血清肺炎衣原体IgA抗体水平与缺血性脑卒中发生的关系。方法采用病例对照研究的方法,对2002年10月至2004年7月中国医科大学附属第一医院临床流行病学教研室从彰武县农村调查发现的符合入选标准的117例缺血性脑卒中患者中随机抽取76例作为病例组,同时从该调查人群中选取80例与病例组相匹配的无脑卒中史者作为对照组,每人采血5mL,采用EIA试剂盒进行血清肺炎衣原体IgA抗体的检测。结果(1)病例组与对照组肺炎衣原体IgA抗体EIU均值分别为45.56±40.95和48.75±40.72,差异无显著性(P>0.05)。(2)病例组与对照组肺炎衣原体IgA抗体阳性率分别为72.4%和75.0%,两组间差异无显著性(P>0.05),优势比OR=0.873(95%可信区间0.428～1.782)。(3)对缺血性脑卒中发生及其危险因素的多元Logistic回归分析,得到的调整IgA抗体阳性率与缺血性脑卒中的关系仍无显著性意义。结论肺炎衣原体抗体与缺血性脑卒中发生可能无关联。     

Urinary biomarkers of tubular injury to predict renal progression and end stage renal disease in type 2 diabetes mellitus with advanced nephropathy: A prospective cohort study

BackgroundNovel potential tubular biomarkers in diabetic nephropathy could improve risk stratification and prediction. The study aimed to evaluate the association of tubular damage markers with rapid renal progression and incidence of end stage renal disease (ESRD) in type 2 diabetes (T2DM).MethodsA prospective cohort study, involving a total of 257 patients with T2DM, was included. The baseline values of urine albumin, cystatin-C, angiotensinogen, kidney injury molecule-1 (KIM-1) and neutrophil-gelatinase associated lipocalin (NGAL) were measured. The composite outcomes included a rapid glomerular filtration rate (GFR) decline or incident of ESRD at 3-year follow-up.Main findingsThe composite outcomes were noted in 26.1%. Using univariate followed by multivariate COX proportional hazard regression analysis, the patients with highest quartiles of urine cystatin-C (HR 2.96, 95% CI, 1.38–6.35), urine angiotensinogen (HR 2.93, 95% CI, 1.40– 6.13) urine KIM-1 (HR 2.77, 95% CI, 1.27-6.05) and urine NGAL (HR 2.53, 95% CI, 1.11-5.76) were significantly associated with rapid renal progression when compared with the patients with the lowest quartiles of all tubular biomarkers.ConclusionsPatients with T2DM with high levels of baseline urine tubular biomarkers (cystatin-C, angiotensinogen, KIM-1 and NGAL) had a greater incidence of ESRD and rapid GFR decline.     

Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients with hyperthyroidism treated with antithyroid drugs: A long‐term followup study

Objective

To test whether antineutrophil cytoplasmic antibodies (ANCA) and ANCA‐associated vasculitis (AAV) are not only induced during treatment with antithyroid drugs, but can also become evident when medication has been ceased, possibly after years.

Methods

Patients who visited our hospital for the treatment of hyperthyroidism were included (n = 207). Treatment consisted of antithyroid medications, radioactive iodide, thyroidectomy, or a combination of these treatment options. Patients were retested 3–6 years later to evaluate long‐term effects of antithyroid drugs. Patients were tested for the presence of ANCA and, if positive, evaluated for the presence of AAV.

Results

Of 209 patients with hyperthyroidism, 12 patients (6%) were positive for myeloperoxidase‐ (MPO‐), proteinase 3‐, or human leukocyte elastase‐ANCA. Seventy‐seven of 209 patients were retested; 1 patient who had not been treated with antithyroid drugs had developed MPO‐ANCA. In 3 of 6 patients previously positive, ANCA could still be detected. The presence of ANCA was highly associated with treatment with antithyroid drugs (odds ratio 11.8 [95% confidence interval 1.5–93.3]). Of 13 patients with a positive ANCA result on enzyme‐linked immunosorbent assay, AAV with glomerulonephritis was diagnosed in 4 (31%).

Conclusion

The presence of ANCA with or without vasculitis is associated with previous treatment with antithyroid drugs, possibly after years.

     

Acute kidney injury and risk of cardiovascular outcomes: A nationwide cohort study

BackgroundAcute kidney injury (AKI) has been associated with cardiovascular disease, but this is sparsely studied in non-selected populations and with little attention to the effect in age and renal function. Using nationwide administrative data, we investigated the hypothesis of increased one-year risk of cardiovascular event or death associated with AKI.MethodsIn a cohort study, we identified all admissions in Denmark between 2008 and 2018. AKI was defined as ≥1.5 times increase from baseline to peak creatinine during admission, or dialysis. We excluded patients with age <50 years, estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m², renal transplantation, index-admission due to cardiovascular disease or death during index-admission. The primary outcome was cardiovascular risk within one year from discharge, which was a composite of the secondary outcomes ischemic heart disease, heart failure or stroke. To estimate risks, we applied multiple logistic regression fitted by inverse probability of censoring weighting and stratified estimations by eGFR and age. We adjusted for proteinuria in the subcohort with measurements available.ResultsAmong 565,056 hospital admissions, 39,569 (7.0%) cases of AKI were present. In total, 18,642 patients sustained a cardiovascular outcome. AKI was significantly associated with cardiovascular outcome with an adjusted OR [CI] of 1.33 [1.16–1.53], 1.43 [1.33–1.54], 1.23 [1.14–1.34], 1.38 [1.18–1.62] for eGFR ≥90, 60–89, 30–59 and 15–29 ml/min/1.73 m², respectively. When omitting the outcome heart failure, these results were 1.24 [1.06–1.45], 1.22 [1.11–1.33], 1.05 [0.95–1.16], 1.25 [1.02–1.54]. Results did not change substantially in strata of age groups, in AKI stages and in the subcohort adjusted for proteinuria.ConclusionNon-selected patients aged 50 years or above with AKI during admission had significantly higher one-year risk of cardiovascular event or death, especially, but not only due to heart failure, independent of age and eGFR.     

IgA肾病患者补体经典途径在血液及尿液中的活化及与肾损伤的关系

目的 研究循环系统中经典途径补体活化及调节方式在IgA肾病（IgAN）中的致病作用及与肾损伤的关系.方法 IgA肾病组30例,10例狼疮性肾炎（LN）患者作阳性对照,30例健康体检者作对照组.采用ELISA试剂盒检测IgA肾病患者和对照组血及尿液中经典途径补体激活标志物C1q、经典途径调节因子（sCR）1,分析补体浓度与肾组织病理结果及临床生化指标的相关性.将IgA肾病组患者按照病理Lee氏结果进行分组,Lee氏Ⅰ～Ⅲ级定为轻度损伤组,Lee氏Ⅳ～Ⅴ级定为重度损伤组,比较两组间的补体浓度差异.分析血C1q与sCR1间相关性.结果 IgA肾病组患者血清C1q及sCR1水平均高于对照组（P＜0.05）,而IgA肾病组与LN组间比较差异无统计学意义（P ＞0.05）;LN组患者尿液C1q浓度明显高于另外2组（P＜0.01）.当血清肌酐＞ 133μmol/L时,血C1q与肌酐水平呈显著负相关（P＜0.05）.尿C1q与肌酐水平呈显著正相关（P＜0.05）.Lee氏Ⅳ～Ⅴ级组患者血液及尿液C1q均明显低于Lee氏Ⅰ～Ⅲ级组（P＜0.05）.血sCR1与血C1q间呈显著正相关（P＜0.05）.结论 IgA肾病患者循环系统中可能存在补体经典途径激活通路,尤其是在肾损伤严重组,且与疾病的严重程度相关.IgA肾病中可溶型CR1对C1q存在介导调节作用.     

Incidence of acute kidney injury in cancer patients: A Danish population-based cohort study

Background

Cancer patients may be at increased risk of acute kidney injury, but evidence is limited.

Methods

We assembled a cohort of incident cancer patients diagnosed within a population-based hospital setting in Northern Denmark (population:~1.2 million) between 1999 and 2006. Patients were followed up to five years for acute kidney injury, identified using creatinine measurements recorded in a laboratory database covering the study area. Acute kidney injury was defined according to recent consensus criteria as a 50% increase in creatinine level. We computed incidence rate, 1-year, and 5-year risks of acute kidney injury, accounting for competing risk from death. Acute kidney injury incidence was compared between cancers using a Cox regression model adjusted for important confounders.

Results

Among 37,267 incident cancer patients with a creatinine measurement, 9613 (25.8%) developed acute kidney injury during 77,376 person-years. The incidence was 258 (95%CI: 252-264) per 1000 person-years the first year after cancer diagnosis decreasing to 43 (95%CI: 41-44) thereafter. The 1-year risk was 17.5% (95%CI: 17.1-17.9%), and the 5-year risk was 27.0% (95%CI: 26.5-27.5%). We observed the highest 1-year risk in patients with kidney cancer [44.0% (95%CI: 40.5-47.5)], liver cancer [33.0% (95%CI: 28.2-37.8%)], or multiple myeloma [31.8% (95%CI: 27.3-36.3%)]. Similar results were observed after adjustment for confounders. Both overall and for most specific cancer sites, risks were higher among patients with distant metastases at cancer diagnosis.

Conclusion

Acute kidney injury is a common complication in cancer patients, particularly in patients with kidney cancer, liver cancer, or multiple myeloma.     

Prevalence and clinical features of selective immunoglobulin A deficiency in coeliac disease: an Italian multicentre study

Background—Selective immunoglobulin A (IgA)deficiency (SIgAD) is associated with coeliac disease (CD).
Aim—To make a retrospective study of theassociation of SIgAD with CD in Italy.
Methods—Hospital medical records of 2098 patientsconsecutively diagnosed as having CD were reviewed.
Results—Of 2098 patients with CD, 54 (2.6%) hadSIgAD, representing a 10-16-fold increase over that in the populationin general. This increase was not influenced by age or geographicalfactors. Patients with SIgAD had a higher incidence of silent forms(7/54, 13%), recurrent infections (16/54, 29.6%), and atopic diseases (7/54, 13%) than those without. The association with autoimmune andmalignant diseases and the outcome after eating a gluten free diet weresimilar in patients with or without SIgAD. In all patients with SIgAD,antibodies for IgA gliadin and endomysium were absent, but serum levelsof IgG anti-gliadin antibodies were high in almost all of them (51/54).
Conclusions—Serum IgA should be measured in orderto be able to interpret negative results for IgA anti-gliadinantibodies and anti-endomysial antibodies in patients being screenedfor CD. Since some patients with CD and SIgAD may be negative for IgGanti-gliadin antibodies, an intestinal biopsy should be performed inall suspected cases.

Keywords:coeliac disease; IgA deficiency

     

Treatment response and progression to end stage renal disease in adolescents and young adults with lupus nephritis: A follow up study in an Egyptian cohort

BackgroundLupus nephritis (LN) badly affects the outcome in adolescents and young adults with systemic lupus erythematosus (SLE). Many have renal disease at onset and the significance of remission and relapse in adolescents and young adults is poorly evaluated.Aim of workTo outline the clinical and laboratory characteristics of treatment resistance, renal relapse and progression to end-stage renal disease (ESRD) in adolescents and young adults with LN.Patients and methodsEighty-five biopsy-proven LN patients were examined; SLE disease activity and renal damage were evaluated at baseline and followed up at 6 and 12 months. Laboratory and immunology profiles were assessed. Patients were evaluated for predictors of treatment response, renal flares, and renal survival.ResultsThe patients mean age was 15.12 ± 4.53 years. Female/male ratio was 10.5:1. 12.9% had treatment resistance, 87.1% achieved remission: complete (CR 31.8%) and partial (PR 55.2%) within 1st year. 27 (31.8%) developed a relapse within the 1st year (9 after CR and 18 after PR). Nephrotic range proteinuria persisted in 24 (28.2%) patients (13 PR and the 11 non-responders). Baseline hypertension (p = 0.034), persistent nephrotic range proteinuria (<0.001) and PR (p < 0.001) were predictive for renal flares. Treatment resistance (p = 0.021), disease relapse (p < 0.001), persistent nephrotic range proteinuria (p < 0.001) were predictors of ESRD, especially in males (p = 0.035). Autoimmune profile and histopathology class showed insignificant differences among groups.ConclusionPrevention and aggressive management of hypertension, proteinuria and renal flares is expected to prevent progression to ESRD in lupus nephritis in adolescent and young adult SLE patients.     

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants

Background and aimsAtherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification.Methods and resultsClinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (r_s = ?0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (r_s = ?0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (r_s = ?0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups.ConclusionCorrelations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.