BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.
Colchicine/adverse effects* ; Gout/drug therapy* ; Humans ; Kidney ; Male ; Middle Aged ; Muscular Diseases/chemically induced* ; Renal Insufficiency, Chronic/complications*

OBJECTIVE: To investigate the incidence, risk factors and prognosis for contrast-induced acute kidney injury (CI-AKI) according to ESUR and KDIGO criteria in patients undergoing angiography.
 METHODS: We evaluated 260 patients undergoing angiography and/or intervention therapy from April 2011 to January 2012 in the Second Xiangya Hospital of Central South University. All patients received low-osmolality contrast agent (ioversol). Serum creatinine was measured before angiography or at 48 or 72 h after procedure. The multivariate logistic regression was used to analyze the risk factors of CI-AKI. The major adverse events were observed in a year of follow-up.
 RESULTS: Among the 260 patients, 23 experienced CI-AKI and the incidence was 8.8% according to ESUR criteria. Twelve patients experienced CI-AKI and the incidence was 4.6% according to KDIGO criteria. The multivariate logistic regression analysis showed that diabetes mellitus and dehydration were the independent risk factors for CI-AKI according to ESUR criteria; In another KDIGO criteria, chronic kidney disease (CKD), hypercholesterolemia and diabetes mellitus were the independent risk factors for CI-AKI. The prognosis study showed that the mortality of patients with CI-AKI were significantly higher than those without CI-AKI (P<0.05).
 CONCLUSION The incidence of CI-AKI is associated with diagnostic criteria. Diabetes mellitus, CKD, dehydration and hypercholesterolemia were the independent risk factors for CI-AKI. CI-AKI is a relevant factor for mortality in a year after angiography and/or intervention therapy.
Acute Kidney Injury ; chemically induced ; diagnosis ; mortality ; Angiography ; Contrast Media ; adverse effects ; Dehydration ; epidemiology ; Diabetes Mellitus ; epidemiology ; Humans ; Incidence ; Iodopyracet ; adverse effects ; Logistic Models ; Prognosis ; Renal Insufficiency, Chronic ; epidemiology ; Risk Factors

Lead (Pb), mercury (Hg), and cadmium (Cd) are common heavy metal toxins and cause toxicological renal effects at high levels, but the relevance of low-level environmental exposures in the general population is controversial. A total of 1,797 adults who participated in the KNHANES (a cross-sectional nationally representative survey in Korea) were examined, and 128 of them (7.1%) had chronic kidney disease (CKD). Our study assessed the association between Pb, Hg, Cd exposure, and CKD. Blood Pb and Cd levels were correlated with CKD in univariate logistic regression model. However, these environmental heavy metals were not associated with CKD after adjustment for age, sex, BMI, smoking, hyperlipidemia, hypertension, diabetes, and these metals in multivariate logistic regression models. We stratified the analysis according to hypertension or diabetes. In the adults with hypertension or diabetes, CKD had a significant association with elevated blood Cd after adjustment, but no association was present with blood Pb and Hg. The corresponding odds ratio [OR] of Cd for CKD were 1.52 (95% confidence interval [CI], 1.05-2.19, P=0.026) in adults with hypertension and 1.92 (95% CI, 1.14-3.25, P=0.014) in adults with diabetes. Environmental low level of Pb, Hg, Cd exposure in the general population was not associated with CKD. However, Cd exposure was associated with CKD, especially in adults with hypertension or diabetes. This finding suggests that environmental low Cd exposure may be a contributor to the risk of CKD in adults with hypertension or diabetes.
Adult ; Cadmium/blood/*toxicity ; Cross-Sectional Studies ; Diabetes Mellitus/chemically induced/epidemiology ; *Environmental Exposure ; Female ; Humans ; Hypertension/chemically induced/epidemiology ; Kidney/drug effects/pathology ; Lead/blood/*toxicity ; Male ; Mercury/blood/*toxicity ; Metals, Heavy/*poisoning ; Middle Aged ; Nutrition Surveys ; Poisoning/*epidemiology ; Renal Insufficiency, Chronic/*epidemiology ; Republic of Korea ; Surveys and Questionnaires ; Young Adult

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 +/- 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.
Aged ; Antineoplastic Agents/*adverse effects ; Carcinoma, Renal Cell/complications/drug therapy/mortality ; Female ; Humans ; Incidence ; Indoles/*adverse effects ; Kidney Neoplasms/complications/drug therapy/mortality ; Male ; Middle Aged ; Proteinuria/*chemically induced/epidemiology ; Pyrroles/*adverse effects ; Renal Insufficiency/*chemically induced/epidemiology ; Republic of Korea/epidemiology ; Retrospective Studies ; Risk Factors ; Treatment Outcome

No abstract available.
Antineoplastic Agents/*adverse effects ; Female ; Humans ; Indoles/*adverse effects ; Male ; Proteinuria/*chemically induced ; Pyrroles/*adverse effects ; Renal Insufficiency/*chemically induced

Cerebellitis is a rarely encountered complication of isoniazid therapy. Its occurrence is usually associated with concomitant renal disease and haemodialysis. Herein, we report the case of a patient with this complication who presented with isolated bilateral symmetrical dentate nucleus T2 hyperintensities on magnetic resonance imaging. Isoniazid neurotoxicity has never been reported to cause bilateral dentate hyperintensities, for which the differentials are few and include metronidazole toxicity.
Adult ; Antitubercular Agents ; adverse effects ; Cerebellar Diseases ; chemically induced ; Cerebellar Nuclei ; pathology ; Diagnosis, Differential ; Female ; Humans ; Isoniazid ; adverse effects ; Magnetic Resonance Imaging ; Renal Dialysis ; Renal Insufficiency ; therapy ; Tuberculosis ; drug therapy

BACKGROUNDContrast induced acute kidney injury (CIAKI) is an important complication in the use of iodinated contrast media (CM). Our study was to evaluate the neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C for early diagnosis of CIAKI.

METHODSThe patients with established or suspected coronary artery disease (CAD) with the estimated glomerular filtration rate (eGFR) was more than 30 ml × min(-1) × 1.73 m(-2) and nor more than 90 ml × min(-1)× 1.73 m(-2) were continuously enrolled. The blood samples of the first 50 patients were obtained before and at 2, 4, 8, 24 and 48 hours after procedure to identify the time points at which the biomarkers reached peaks and at which the blood samples of the rest of patients were obtained. The plasma NGAL and cystatin C measure used enzyme-linked immunosorbent assay (ELISA) kit. The diagnostic characteristics of absolute and relative increasing NGAL and cystatin C for CIAKI were evaluated.

RESULTSTotal 311 patients were enrolled, among whom 39 (12.5%) developed CIAKI. Plasma NGAL increased at 2 hours and reached peak at 4 hours after procedure, while plasma cystatin C increased at 2 hours and reached peak at 24 hours after procedure. Thus, we determine rational point of time at 4 hours for NGAL and at 24 hours after procedure for cystatin C, respectively. The plasma NGAL at 4 hours after CM exposure showed largest area under curve (AUC) of 0.662 (95% confidence interval (CI): 0.565 - 0.758, P = 0.002) with 51.5% sensitivity and 80.6% of specificity. The relative increasing 25% of NGAL showed the best sensitivity and specificity of 0.872 and 0.808, respectively, with maximum Youden index of 0.680, while cystatin C with relative increasing more than 25% had 76.9% of sensitivity and 81.2% of specificity. Combined two biomarkers might get more than 90% of specificity.

CONCLUSIONSSingle measurement of NGAL or cystatin C had poor sensitivity and specificity; however, the relative increasing 25% of NGAL at 4 hours after CM exposure demonstrated higher diagnostic values for CIAKI. Combining relative increasing plasma NGAL with relative increasing plasma cystatin C might perform better for early diagnosis of CIAKI.

Acute Kidney Injury ; blood ; chemically induced ; diagnosis ; Acute-Phase Proteins ; Aged ; Angioplasty, Balloon, Coronary ; Biomarkers ; blood ; Contrast Media ; adverse effects ; Creatinine ; blood ; Cystatin C ; blood ; Female ; Humans ; Lipocalin-2 ; Lipocalins ; blood ; Male ; Middle Aged ; Proto-Oncogene Proteins ; blood ; Renal Insufficiency ; complications

OBJECTIVETo investigate the clinical and pathological characteristics of bevacizumab-induced renal impairment.

METHODThe clinical and pathological data of 4 patients with bevacizumab-induced renal impairment in Peking Union Medical College Hospital was retrospectively analyzed.

RESULTSThere were 2 men and 2 women aged (56.5±11.5) years. Before bevacizumab treatment, three non-small cell lung cancer patients (75%) had normal renal function and only one pancreatic cancer patient (25%) had mild renal impairment. After 2-14 cycles of bevacizumab treatment, the most common clinical manifestation of bevacizumab-induced renal injury was proteinuria (>3.5 g/d) (n=4, 100%). Other clinical symptoms included microscopic hematuria (n=2, 50%), malignant hypertension (n=1, 25%), elevated serum creatinine level as accompanied with acute renal failure (n=1, 25%), and anuria (n=1, 25%). Thrombotic microangiopathy was the main pathological type (n=2, 50%), whereas other pathological types included membranoproliferative glomerulonephritis (n=1, 25%) and benign arteriolar nephrosclerosis (n=1, 25%). After the detection of renal impairment, bevacizumab therapy was stopped in all 4 cases (100%). Hemodialysis was performed in the patient with acute renal failure. The prognosis was relatively good. The renal function and proteinuria was completely recovered in one patient (25%), whereas the other three patients (75%) presented with persistent alleviated proteinuria but normal renal function.

CONCLUSIONSBevacizumab may cause renal injury via complex mechanisms. Therefore, urine protein excretion and renal function should be closely monitored during bevacizumab treatment to identify any renal injury. The prognosis is relatively good after discontinuation of bevacizumab.

Adult ; Aged ; Antibodies, Monoclonal, Humanized ; adverse effects ; Bevacizumab ; Female ; Humans ; Kidney ; drug effects ; pathology ; Male ; Middle Aged ; Renal Insufficiency ; chemically induced ; pathology ; Retrospective Studies

BACKGROUNDAnisodamine is widely used in therapy for treating acute glomerulonephritis and diabetic nephropathy because it can improve renal microcirculation. We performed a study to evaluate the preventive effects of anisodamine against contrast-induced nephropathy (CIN) in type 2 diabetics with renal insufficiency undergoing coronary angiography or angioplasty.

METHODSA total of 260 patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) of 60 ml(-1)×min(-1)×1.73 m(-2) or less, who were undergoing coronary angiography or angioplasty, were randomly assigned to receive an infusion of either sodium chloride (control group, n = 128) or anisodamine (treatment group, n = 132). Patients in the treatment group received an infusion of anisodamine at a rate of 0.2 µg×kg(-1)×min(-1) from 12 hours before to 12 hours after coronary angiography or angioplasty, while patients in the control group received an infusion of sodium chloride with the same volume as the treatment group. All patients received intravenous sodium chloride hydration. CIN was defined as a 25% increase in serum creatinine from baseline or an absolute increase of > 0.5 mg/dl within three days after contrast exposure. The primary end point was the incidence of CIN. The secondary end point was a 25% or greater reduction in eGFR.

RESULTSThere were no significant differences between the two groups with regard to age, gender, risk factors, laboratory results, medications and interventions. The incidence of CIN was 9.8% (13/132) in the treatment group and 20.3% (26/128) in the control group (P < 0.05). The secondary end point was 6.0% (8/132) in the treatment group and 16.4% (21/128) in the control group (P < 0.05).

CONCLUSIONThese results indicate the preventive effects of anisodamine against CIN in type 2 diabetics with renal insufficiency who are undergoing coronary angiography or angioplasty.

Acute Kidney Injury ; chemically induced ; prevention & control ; Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Contrast Media ; adverse effects ; Coronary Angiography ; adverse effects ; Creatinine ; blood ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Glomerular Filtration Rate ; Humans ; Male ; Middle Aged ; Renal Insufficiency ; blood ; drug therapy ; Sodium Chloride ; administration & dosage ; Solanaceous Alkaloids ; therapeutic use