Research progress on animal models of contrast-induced acute kidney injury / 中南大学学报(医学版)

Contrast-induced acute kidney injury (CI-AKI) refers to acute kidney injury that occurs after intravascular contrast media is applied. It is the third most common cause for acute renal failure in hospitalized patients and can cause severe renal impairment and adverse cardiovascular outcomes. In severe cases, it can even lead to the death of the patient. Due to its complicated pathogenesis, the pathogenesis of CI-AKI has not yet been elucidated. Therefore, it is of great significance to further study the pathogenesis for the prevention of CI-AKI. Moreover, a good animal model of CI-AKI is an important tool for in-depth research on the pathogenesis of acute kidney injury induced by contrast agents.

The Efficacy and Safety of Daratumumab-Based Regimen in Treatment of Multiple Myeloma Patients with Renal Impairment / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).@*METHODS@#The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.@*RESULTS@#The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.@*CONCLUSION@#Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.

Heavy metal exposure and renal impairment: A systematic review of observational studies

Background: Environmental exposure to toxins has been strongly implicated in its multi-faceted etiology of chronic kidney disease, a serious public health problem affecting individuals, families, and communities. There is a need to synthesize available studies on the effect of heavy metal exposure on renal function, considering the rising global burden of kidney disease. The objective of this study is to determine the association between exposure to heavy metals and renal disease. Methods: The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) were used to conduct the review. A comprehensive independent search, title, abstract, and full-text screening of available literature on Google Scholar, PubMed, and OAREScience was done between March 2021 and May 2021. The criteria for study inclusion were full-text articles published in English language in the last 20 years (2001-2020), and observational primary human studies reporting the association between heavy metal exposure and renal disease. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of the included studies. Results: A total of 552 studies were identified following the search from the different databases. A total of 13 studies were finally included in the review. Heavy metals implicated in the studies include cadmium, lead, mercury, and arsenic, with ten studies showing environmental exposure as the primary source. Ten (10) studies showed an association between heavy metal exposure and renal impairment (p<0.05) while only 3 studies reported no association. Conclusion: Environmental monitoring is needed to stem the tide of heavy metal exposure in view of the growing burden of chronic kidney disease.

Efficacy of alfacalcidol on liver and kidney function，inflammatory cytokines and RAS activity in hypertensive patients with renal impairment / 中国药房

OBJECTIVE To explore the efficacy of alfacalcidol combined with conventional antihypertensive and lipid- lowering drugs on liver and kidney function， serum inflammatory cytokines and renin-angiotensin system（RAS） in hypertensive patients with renal impairment. METHODS A total of 200 hypertensive patients with renal impairment who were treated in the department of nephrology in our hospital from December 2017 to December 2020 were selected and randomly divided into control group and observation group， with 100 cases in each group. Both groups of patients were treated with conventional antihypertensive and lipid-lowering drugs for a total of 14 weeks， patients in the observation group were additionally treated with oral alfacalcidol after 2 weeks of treatment （0.25 μg each time， once a day， for a total of 12 weeks）. The levels of liver function indexes [aspartate aminotransferase （AST）， alanine aminotransferase （ALT）]， renal function indexes [blood calcium， blood phosphorus， blood urea nitrogen （BUN）， cystatin C （Cys-C）， serum creatinine （Scr）， urine microalbumin （mAlb）， β2-microglobulin （β2-MG）， urinary N- acetyl β-D-glucosaminidase （NAG）， 24 h urinary protein]， inflammatory factors [serum interleukin 6 （IL-6）， tumor necrosis factor α （TNF-α）， hypersensitive C-reactive protein （hs-CRP）] and RAS activity indexes [renin， angiotensin Ⅰ（Ang Ⅰ）， Ang Ⅱ and aldosterone] were observed in 2 groups before and after treatment， and the occurrence of adverse drug reactions was recorded during treatment. RESULTS There was no statistical significance in the levels of detection indexes between 2 groups before treatment （P＞0.05）. After treatment， the level of blood calcium in the observation group was significantly higher than before treatment （P＜0.05）， but remained at clinically normal level. Compared with before treatment， the levels of Cys-C， Scr， BUN， urine mAlb， β2-MG， NAG and 24 h urinary protein， hs-CRP， IL-6， TNF-α， renin， Ang Ⅰ， Ang Ⅱ and aldosterone were significantly decreased in the observation group after treatment （P＜0.05）. After treatment， the level of blood calcium in observation group was significantly higher than control group （P＜0.05）. Additionally， the levels of Cys-C， Scr， BUN，urine mAlb， β2-MG， NAG， 24 h urinary protein， hs-CRP， IL-6， TNF-α， renin， Ang Ⅰ， Ang Ⅱ and aldosterone were significantly lower than control group （P＜0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups during treatment （P＞0.05）. CONCLUSIONS Alfacalcidol combined with routine therapy of antihypertensive and lipid-lowering drugs could effectively improve liver and renal functions， inhibit inflammation and RAS activity in hypertensive patients with renal impairment， with a favorable safety.

Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

Safety of a rapid outpatient hydration protocol for patients with renal impairment requiring intravenous iodinated contrast media for computed tomography

INTRODUCTION@#Patients receiving intravenous iodinated contrast media for computed tomography (CT) are predisposed to contrast-induced nephropathy. Chronic kidney disease is an important risk factor, and hydration is the mainstay of prevention. While inpatients can undergo intravenous hydration, limited knowledge exists regarding regimens for outpatients. We employed a rapid outpatient hydration protocol to reduce postponement of imaging appointments for patients with suboptimal estimated glomerular filtration rate (eGFR).@*METHODS@#From June 2015, we amended our CT preparation protocol to mandate rapid hydration (oral, intravenous or both) for patients with an eGFR of 30-60 mL/min/1.73 m@*RESULTS@#226 outpatients received the hydration protocol, which correlated with a 95% reduction in postponement of imaging appointments. No complications of fluid overload from hydration were encountered. A significant association was observed between age and decrease in eGFR, but this was not significant when stratified by drop in eGFR category. No statistical significance was found between decrease in eGFR and gender or race. Higher baseline eGFR was less likely to be associated with decrease in eGFR after imaging. Type of hydration was not related to a drop in eGFR category for patients with an eGFR of 45-59 mL/min/1.73 m@*CONCLUSION@#We defined a shorter hydration regimen that is safe to use in the outpatient setting.

Clinical characteristics and risk factors of multiple myeloma patients with renal impairment / 中华肾脏病杂志

Objective@#To explore the clinical and cytogenetic characteristics and risk factors of multiple myeloma (MM) patients with renal impairment (RI).@*Methods@#A total of 113 newly diagnosed patients with MM in the department of nephrology and hematology in Zhongnan Hospital of Wuhan University from January 2013 to December 2017 were enrolled. The patients were divided into RI group and non-renal impairment (NRI) group according to whether serum creatinine (Scr) at the time of diagnosis was higher than 177 μmol/L. The clinical and laboratory data of two groups were compared. The risk factors of RI in MM patients were analyzed by binary logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors.@*Results@#The incidence of RI in 113 MM patients was 34.5%. Compared with NRI group, levels of white blood cells, serum uric acid, blood urea nitrogen, neutrophil-to-lymphocyte ratio (NLR), cystatin C, β2-microglobulin (β2-MG), blood phosphorus, urine light chain, bone-marrow plasma cell percentage, International Staging System (ISS) stage III percentage, light chain type percentage, positive urinary Bence-Jones protein percentage and positive urinary protein percentage were higher in RI group, while levels of estimated glomerular filtration rate (eGFR), serum bicarbonate concentration and globulin were lower in RI group (all P<0.05). There were no significant differences in other clinical variables between the two groups (all P>0.05). Fluorescence in situ hybridization (FISH) was applied to 42 MM patients to detect the following five genetic abnormalities: IgH rearrangement, 1q21 amplification, RB1 deletion, D13S319 deletion and P53 deletion. Among them, 29 (69.0%) patients were abnormal. The incidence of RB1 deletion in RI group was higher than NRI group (P<0.05), and there were no significant differences in the incidences of other genetic abnormalities (all P>0.05). Further logistic regression analysis showed that increase of NLR (OR=1.589, 95%CI 1.115-2.266, P=0.010), bone-marrow plasma cell percentage (OR=1.053, 95%CI 1.008-1.101, P=0.021) and β2-MG (OR=22.166, 95%CI 2.146-228.927, P=0.009), light chain type (OR=15.399, 95%CI 1.002-236.880, P=0.049), and hyperuricemia (OR=11.707, 95%CI 1.580-86.717, P=0.016) were the independent risk factors for RI in MM patients. The comparison of area under the ROC (AUC) among these risk factors showed the AUC of β2-MG was larger than that of NLR or uric acid (both P<0.05), while there were no significant differences in the rest of pairwise comparison (all P>0.05). The AUC of β2-MG predicting RI was the largest (AUC=0.907, 95%CI 0.853-0.962, P<0.001).@*Conclusions@#MM patients have high morbidity of RI, and there are more RI patients with RB1 deletion in RI patients. Light chain type, hyperuricemia, high level of NLR, high bone-marrow plasma cell percentage and increased β2-MG are the independent risk factors for RI in MM patients. Among them, β2-MG is the best predictor for RI, and NLR plays an important role in predicting RI as a convenient and effective inflammatory marker.

Protective Effect of Modified Qiju Dihuang Pills on Renal Function of Patients with Early Renal Impairment / 中国实验方剂学杂志

Objective::To observe the efficacy of modified Qiju Dihuang pills in protecting renal function of patients with early renal impairment with syndrome of Yin deficiency and Yang hyperactivity caused by hypertension and its effect in resisting inflammation and oxidative stress, and improving endothelial function. Method::Randomly divided into control group (59 cases) and observation group (60 cases) by random number table. Patients in control got valsartan capsules, 80 mg/time, 1 time/day. And patients whose blood pressure can't be controlled were added with nifedipine tablets, 10 mg/time, 1 time/day. In addition to the therapy of control group, patients in observation group were added with modified Qiju Dihuang pills, 1 dose/day. The control group took Qiju Dihuang pills.The courses of treatment were 16 weeks. And levels of cystatin C (CysC), urinary N-acetyl-β-glucosaminidase (NAG), β2 microglobulin (β2-MG), urinary microalbumin to creatinine ratio (UACR) and emodynamics of kidney were detected. Blood pressure, systolic pressure (SBP), diastolic pressure (DBP) and blood pressure renal artery resistance index (RI) and pulsatility index (PI) were recorded, and Yin deficiency and Yang hyperactivity were scored. Levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), adiponectin (ADPN) and nuclear factor-kappa B (NF-κB) were detected. Result::The total effective rate in observation group was 91.67%(55/60), which was higher than 76.27%(45/59) in control group (χ2=5.255, P<0.05). Levels of SBP and DBP were lower than those in control group (P<0.05). At the 16th week during the treatment, the compliance rate of blood pressure was 90.66%, which was higher than 84.13% in control group (χ2=127.65, P<0.01). And levels of CysC, β2-MG, NAG, UACR, RI, PI, ET-1, SOD, GSH-Px, IL-6, NF-κB and TNF-α were lower than those in control group (P<0.01), while levels of NO, SOD and GSH-Px were higher than those in control group (P<0.01). Conclusion::In addition to the therapy for controlling blood pressure with routine western medicine, modified Qiju Dihuang pills can reduce level of the blood pressure, and control blood pressure with the standard, with anti-inflammatory and anti-oxidative stress effects. It can also improve the vasomotor function and the flow of kidney, protect the kidney function, and reduce the degree of injury, so as to delay the process of kidney damage and improve the prognosis.

Vasculitis en adultos mayores. A propósito de dos casos y revisión de la literatura / Vasculitis in elderly. About two clinical cases and literature review

Resumen Actualmente vivimos un proceso de transición en la pirámide poblacional. Por lo tanto, se hacen más frecuentes las enfermedades renales en los ancianos. Así, las vasculitis primarias en adultos mayores son enfermedades raras, causadas por la inflamación de los vasos sanguíneos y muy poco diagnosticadas. La literatura se limita a escasos casos clínicos. La vasculitis por anticuerpo citoplasmático anti neutrófilo (ANCA) positivo (VAA) es más frecuente en personas mayores de 50 años. La detección de ANCA es de peor pronóstico en esta población. También, es importante la alta sospecha y diagnóstico oportuno, ya que así se puede brindar un tratamiento óptimo y disminuir las complicaciones propias de la enfermedad y aquellas asociadas a la inmunosupresión. Los adultos mayores con VAA tienen mayor compromiso renal, hipertensión, dislipidemia y mortalidad incrementada. Por lo que a continuación se detallan dos casos clínicos desde la fecha del diagnóstico, edad, valores de laboratorio de la presentación inicial y la escala de actividad de vasculitis de Birmingham confirmados con biopsia renal (ANCA positivo) identificados en un hospital de especialidades de Ecuador.

Abstract Currently we live a process of transition in the population pyramid. Therefore, kidney diseases become more frequent in the elderly. Thus, primary vasculitis in older adults are rare diseases, caused by the inflammation of blood vessels and poorly diagnosed. The literature is limited to few clinical cases. Cytoplasmic anti-neutrophil antibody (ANCA) positive vasculitis (AAV) is more common in people older than 50 years. The detection of ANCA gives a very poor prognosis in this population. Also, high suspicion and timely diagnosis is important, as this can provide optimal treatment and reduce the complications of the disease and those associated with immunosuppression. Older adults with AAV have greater renal involvement, hypertension, dyslipidemia and increased mortality. Therefore, two clinical cases from the date of diagnosis, age, laboratory values of the initial presentation and the scale of activity of Birmingham vasculitis confirmed with renal biopsy (ANCA positive) identified in a specialty hospital of Ecuador are detailed below.

Development of a physiologically-based pharmacokinetic model for cyclosporine in Asian children with renal impairment

This study aimed to assess the pharmacokinetics of cyclosporine A (CsA) in Asian children with renal impairment (RI) by developing a physiologically-based pharmacokinetic (PBPK) model with Simcyp Simulator. The PBPK model of Asian children with RI was developed by modifying the physiological parameters of the built-in population libraries in Simcyp Simulator. The ratio of healthy and RI populations was obtained for each parameter showing a difference between the populations. Each ratio was multiplied by the corresponding parameter in healthy Asian children. The model verification was performed with published data of Korean children with kidney disease given multiple CsA administrations. Simulations were performed with different combinations of ethnicity, age, and renal function to identify the net impact of each factor. The simulated results suggested that the effect of RI was higher in children than adults for both Caucasian and Asian. In conclusion, the constructed model adequately characterized CsA pharmacokinetics in Korean children with RI. Simulations with populations categorized by ethnicity, age, and renal function enabled to assess the net impact of each factor on specific populations.

Drug usage pattern of antimicrobials in elderly hypertensive, diabetic in-patients with or without impaired renal function

Background: Hypertension (HTN) and diabetes mellitus (DM) are the primary contributors to renovascular mortality and morbidity including chronic kidney diseases. Additionally, these patients are in frequent need of an antimicrobial agent. Drug utilisation studies (DUS) are prospective tools in the assessment of health care systems. The objective of the present study was to analyse the prescription pattern of anti-microbials in elderly hypertensive diabetic in-patients with or without renal impairment in a tertiary hospitalMethods: The study population comprised of 165 hypertensive diabetic in-patients at Shri Dharmasthala Manjunatheshwara (SDM) Hospital. Questionnaire based evaluation was carried out and prescriptions of patient with HTN and DM at and above the age of 60 years irrespective of gender were included.Results: Among anti-microbial agents, other ? lactam antibacterial were the most commonly prescribed class of drugs (40.85%) which was similar in patients with impaired renal function (21.8%).Conclusions: There was a significant increase in the number of anti-microbial agents and other drugs in the patients with impaired renal function when compared to patients with normal renal function (p <0.05).

Ischemic cerebrovascular accident and its secondary renal impairment

Background: Renal impairment is one of the most frequent but anticipated potential complications. The objective of this meta-analysis was to evaluate the renal impairment following ischemic cerebrovascular accident (CVA) patients worldwide.Methods: Authors were using meta-analysis. Studies were obtained from several databases like Pubmed, Cochrane, Karger and JNS. Keywords were "renal" or "kidney" and "stroke" and "ischemic". Included studies were full-text observational study or randomized control trial (RCT). Subjects in study were newly diagnosed acute kidney disease (AKI) after ischemic CVA, with age range 18-100 years old. From 425 studies, total 5 studies were eligible for this study.Results: From those 5 studies, it is shown that the pooled risk ratio (RR) for mortality ischemic CVA with AKI was 2.56. AKI appeared insignificantly in both ischemic CVA and intracerebral haemorrhage (ICH) (RR 0.75; p=0.01). The pooled risk ratio had wide heterogeneity (I2 = 0.95) so random effect model was used.Conclusions: Renal impairment and its mortality appeared more frequent in ischemic CVA with AKI. It still needs more multicentre and long-term period researches in the future to get better understanding AKI in ischemic CVA.

Prognostic use of Prostate Specific Antigen, Some Renal Indices and Uric Acid in the Diagnosis of Prostate Cancer and Renal Impairment at Urology Clinic Federal Medical Centre Lokoja, Nigeria

Aims: Improved diagnosis of prostate cancer has led to increasing life expectancy in adult men. The use of PSA as the current practice for screening and treatment has become a key prognostic factor in the management of PCa. This study was designed to evaluate the prognostic use of serum PSA, creatinine, urea, protein and uric acid in PCa subjects with or without renal impairment. Study Design: The study was a prospective study conducted between March and September 2016 at federal Medical Centre Lokoja, Kogi State, Nigeria. Methods: One hundred and ten adult men aged 51 - 70 years were conveniently recruited for the study. Diagnosis was based on biopsy, PSA, Cr/U and UA results obtained, and grouped as (A) PCa subjects with RI (35), (B) PCa subjects without RI (35) and 40 apparently healthy men (Controls) which is regarded as group (C). Blood samples were collected and analyzed for PSA and renal indices using ELISA and colorimetric methods respectively. Results: The result showed that serum tPSA, fPSA, cPSA, %fPSA, creatinine, urea and uric acid were significantly higher while total protein was significantly lower in PCa subjects with RI compared with controls (P<.05). Similar results were obtained in PCa without RI compared with controls except for urea (P=.001respectively). However, tPSA, fPSA, cPSA were significantly lower while creatinine, urea and uric acid were significantly higher in Pca with RI compared with the corresponding values in PCa without RI (P<.05). The correlation between cPSA, creatinine and urea showed association between PCa and RI. ROC showed that tPSA and cPSA had significantly higher diagnostic performance than fPSA and % fPSA in the prediction of PCa associated with RI while Creatinine, urea and uric acid had significantly higher diagnostic accuracy in the prediction of RI associated with PCa within the age range of 50-61 than 61-70 years. Conclusions: Increased serum uric acid level observed in RI subjects suggests decreased excretion of uric acid by the kidney. ROC analysis shows significant evidence that tPSA and cPSA have higher predictive value for PCa with or without RI while creatinine, urea and uric acid have higher predictive efficacy for RI in PCa subjects. Adult men from 50 years are recommended for early screening for PDs to minimize progression to RI.

Factores de riesgo asociados al desarrollo de eventos cardiovasculares en pacientes postrasplante renal / Risk factors associated with cardiovascular events in kidney transplant patients

Resumen Objetivo: describir el comportamiento de los factores de riesgo cardiovascular en pacientes con trasplante renal y su relación con los desenlaces cardiovasculares a uno y cinco años luego del trasplante. Métodos: se realizó un estudio analítico de cohorte retrospectivo en los pacientes con trasplante renal del Hospital Universitario San Ignacio con seguimiento institucional por lo menos de un año. Se analizaron las variables demográficas, los factores de riesgo cardiovascular y los desenlaces cardiovasculares a uno y cinco años. Resultados: se incluyeron 166 pacientes con seguimiento a un año y 79 con seguimiento a cinco años postrasplante renal. En el primer año postrasplante hubo una reducción significativa del tabaquismo y la hipertensión arterial sin cambios en el control de la dislipidemia ni de la diabetes mellitus. Se presentaron 9 eventos en el primer año con 6 casos de angina inestable, 2 infartos de miocardio y un ataque cerebrovascular. En la evaluación al quinto año se mantuvo el cese del tabaquismo con aumento de los casos de hipertensión arterial. Se presentaron 8 casos de angina inestable, cifra que corresponde a un 10% de eventos cardiovasculares. Conclusiones: en el seguimiento a uno y cinco años postrasplante renal de los pacientes del Hospital Universitario San Ignacio se identificó una tasa baja de eventos cardiovasculares con una modificación en la prevalencia de algunos factores de riesgo cardiovascular.

Abstract Objective: To describe the behaviour of the cardiovascular risk factors in kidney transplant patients, and its relationship with the outcomes at 1 and 5 years after the transplant. Methods: A retrospective analytical cohort study was performed on patients with kidney transplant from the Hospital Universitario San Ignacio with a follow-up of at least 1 year. An analysis was carried out on the demographic variables, cardiovascular risk factors, and the cardiovascular outcomes at 1 and 5 years. Results: The study included 166 patients with a follow-up of 1 year, and 79 with a follow-up of 5 years post-kidney transplant. In the first year post-transplant there was a significant reduction in smoking, as well as in blood pressure, with no changes in the control of dyslipidaemia or in diabetes mellitus. There were 9 events in the first year, with 6 cases of unstable angina, 2 myocardial infarctions, and one stroke. In the evaluation at the fifth year the quitting smoking was maintained, with an increase in arterial hypertension. There were 8 cases of unstable angina, corresponding to 10% of the cardiovascular events. Conclusions: A low rate of cardiovascular events was identified in the one year and five year follow-up of post-kidney transplant patients from the Hospital Universitario San Ignacio, with a change in the prevalence of some of cardiovascular risk factors.

Assessment of Hepatic Cytochrome P450 3A Activity Using Metabolic Markers in Patients with Renal Impairment

BACKGROUND: The renal function of individuals is one of the reasons for the variations in therapeutic response to various drugs. Patients with renal impairment are often exposed to drug toxicity, even with drugs that are usually eliminated by hepatic metabolism. Previous study has reported an increased plasma concentration of indoxyl sulfate and decreased plasma concentration of 4β-hydroxy (OH)-cholesterol in stable kidney transplant recipients, implicating indoxyl sulfate as a cytochrome P450 (CYP) inhibiting factor. In this study, we aimed to evaluate the impact of renal impairment severity-dependent accumulation of indoxyl sulfate on hepatic CYP3A activity using metabolic markers. METHODS: Sixty-six subjects were enrolled in this study; based on estimated glomerular filtration rate (eGFR), they were classified as having mild, moderate, or severe renal impairment. The plasma concentration of indoxyl sulfate was quantified using liquid chromatography-mass spectrometry (LC-MS). Urinary and plasma markers (6β-OH-cortisol/cortisol, 6β-OH-cortisone/cortisone, 4β-OH-cholesterol) for hepatic CYP3A activity were quantified using gas chromatography-mass spectrometry (GC-MS). The total plasma concentration of cholesterol was measured using the enzymatic colorimetric assay to calculate the 4β-OH-cholesterol/cholesterol ratio. The correlation between variables was assessed using Pearson's correlation test. RESULTS: There was a significant negative correlation between MDRD eGFR and indoxyl sulfate levels. The levels of urinary 6β-OH-cortisol/cortisol and 6β-OH-cortisone/cortisone as well as plasma 4β-OH-cholesterol and 4β-OH-cholesterol/cholesterol were not correlated with MDRD eGFR and the plasma concentration of indoxyl sulfate. CONCLUSION: Hepatic CYP3A activity may not be affected by renal impairment-induced accumulation of plasma indoxyl sulfate.

Application of blood purification in renal impairment of multiple myeloma / 基础医学与临床

Renal impairment is common in multiple myeloma .Besides effective chemotherapy , direct removal of se-rum free light chain by plasmapheresis or high cut-off hemodialysis is also important in the treatment of renal im-pairment in multiple myeloma .Based on results of the randomized controlled trials , the role of plasmapheresis in treating renal disease of multiple myeloma is debated .On the other side , high cut-off hemodialysis is novel and re-cently developed .Many studies have shown its potential function to further increase renal response rate when com -bined with chemotherapy .

Renal compromise in a patient with Wegener's granulomatosis: clinical case and literature review / Compromiso renal en un paciente con granulomatosis de Wegener: caso clínico y revisión de la literatura

Absctrat Wegener's granulomatosis (WG) is characterized by small vessel vasculitis that affects the upper respiratory tract, lungs and kidneys. Renal involvement may occur between 40 and 100% of cases. The disease varies from asymptomatic to fulminant rapidly progressive glomerulonephritis forms, leading to terminal renal failure in days. Methodology We present a case of a patient diagnosed with WG in the Hospital de San José in Bogotá, Colombia, and a literature review focused on renal involvement. Literature search was conducted in the following databases: PubMEed, LILAC, SciELO and Cochrane. Articles in english and spanish were selected and no restriction date was made, but at least 70% of selected references were published after 2010. Conclusions Renal involvement in patients with WG is common and can be lethal. A high percent may even require renal replacement therapy, although patients can return to normal renal function. Factors associated with return to normal renal function are unclear, but it depends on early therapy and high doses of immunomodulators. Rituximab has shown greater effectiveness and fewer side effects than conventional treatments, so it's a valid therapeutic option for the management of patients with WG and renal involvement.

Resumen El presente manuscrito se hace con el fin de reportar un caso del tema en mención y realizar una revisión de la literatura disponible más reciente con respecto al diagnóstico y tratamiento. Antecedentes La granulomatosis de Wegener (GW) se caracteriza por ser una vasculitis de pequeños vasos que afecta generalmente la vía respiratoria alta, pulmones y riñones. La afección renal puede presentarse entre el 40 % y el 100 % de los casos. La enfermedad varía en su presentación clínica, desde formas asintomáticas hasta glomerulonefritis rápidamente progresiva, llevando a la insuficiencia renal terminal en pocos días. Metodología Se realiza la presentación del caso de una paciente diagnosticada con granulomatosis de Wegener (GW) en el Hospital San José (Bogotá, Colombia), y se muestra una revisión de la literatura enfocada en el compromiso renal de la patología. La revisión bibliográfica se realizó en las bases de datos: PubMEed, LILAC, SciELO y Cochrane, seleccionando para revisión artículos en inglés y español, sin restricción de fecha, pero asegurándose de que el 70 % de las referencias seleccionadas se hubieran publicado después del año 2010. Conclusiones El compromiso renal en pacientes con GW es frecuente y puede llegar a ser letal. Una proporción de pacientes considerable puede llegar a requerir terapia de reemplazo renal, con potencial recuperación de la función renal. No están claros los factores que se asocian al retorno de la función renal normal, pero sí se ha descrito que se asocia a tratamiento temprano con altas dosis de inmunomoduladores. El rituximab es un medicamento con uso frecuente en estos pacientes, que ha demostrado efectividad y menores efectos secundarios que los tratamientos convencionales, constituyendo una opción válida para el manejo de pacientes con GW y compromiso renal asociado.

Monitoring of early renal injury in chronic hepatitis B patients with long-term adefovir dipivoxil treatment / 中华临床感染病杂志

Objective To evaluate urinary β2-microglobulin (β2-MG) and retinoid binging protein (RBP) in monitoring of early renal impairment in chronic hepatitis B (CHB) patients with long-term adefovir dipivoxil (ADV) treatment. Methods Three hundred and fifty five with CHB admitted in Shaoxing Municipal Hospital from June 2009 to June 2011 were enrolled in the study, among whom 180 cases study group) were treated with ADV monotherapy (n=100) or ADV + lamivudine (LAM) combination therapy (n=80); and 175 cases (control group) were treated with entecavir (ETV). Serum creatinine, urinary β2-MG, RBP and creatinine were measured and glomerular tration rate (eGFR) was estimated regularly during 5-year follow up. Kaplan-Meier method was used to calculate the cumulative incidence of changes in urinary β2-MG and RBP. Results Five-year follow-up results showed that in study group 2, 6, 10, 14 and 24 cases developed urinary β2-MG abnormality in year 1, 2, 3, 4 and 5 of treatment, respectively; and 2, 7, 11, 16 and 20 cases developed urinary RBP abnormality in year 1, 2, 3, 4 and 5 of treatment, respectively; eGFR decreased 20%-30% from baseline in 20 cases, 30%-50% in 13 cases and >50% in 2 cases. The decrease of eGFR ≥30% in 5 years was significantly correlated with urinary RBP and β2-GM abnormality. However, both serum creatinine and eGFR remained stable during the 5 years of follow-up in control group; only 2 cases developed urinary β2-MG abnormality and 3 cases developed urinary RBP abnormality. Conclusions Urinary RBP and β2-MG are sensitive biomarkers of early renal injury during long-term ADV treatment in CHB patients, and ADV should not be used as first-line treatment for CHB.

Clinical analysis of the microangiopathic hemolytic anemia and renal impairment secondary to methylmalonic ;academia in children / 临床儿科杂志

Objectives To review the clinical features in children with methylmalonic academia (MMA) having the primary clinical manifestations of microangiopathic hemolytic anemia and renal impairment. Methods The clinical data of 4 children diagnosed of MMA with the primary clinical manifestations of microangiopathic hemolytic anemia and renal impairment were retrospectively analyzed from August 2013 to present. Results In the four children (two boys and two girls) with the age from nine months to three years seven mouths, two children were diagnosed with MMA combined with homocysteine, and 2 children were diagnosed with MMA, but there was no homocysteine testing. All four children showed moderate to severe anemia, proteinuria, hematuria, and hypertension. One child had abnormal renal function and thrombocytopenia, and manifested as hemolytic uremic syndrome. Renal biopsy was performed in 2 children and they had glomerular sclerosis lesions with renal tubular necrosis and mesangial proliferative glomerulonephritis respectively. All children were treated with vitamin B12, and the indexes of microangiopathic hemolytic anemia and renal impairment were improved signiifcantly. Conclusions MMA may be combined with microangiopathic hemolytic anemia, renal impairment and even hemolytic uremic syndrome, and the early diagnosis and treatment is required.

Correlation between the levels of serum Klotho with renal impairment in chronic kidney disease patients / 实用医学杂志

Objective To explore the relationship between the level of serum Klotho with renal impairment in chronic kidney disease (CKD) patients. Methods 100 patients with CKD 1-5 stages (CKD group) and 30 non-CKD patients (control group) were enrolled. The serum of Klotho was detected by ELISA (enzyme-linked immunosorbent assay ) to investigate the correlation between the level of serum Klotho to progression of CKD. Results The levels of serum Klotho in CKD group 9.81 (7.45,12.2) ng/mL and control group 2.97 (1.75,5.23) ng/mL were significantly different (P < 0.01); The Klotho level declined as renal insufficiency progressed. Pearson correlation analysis showed that serum Klotho in CKD patients was positively correlated with eGFR (estimated glomerular filtration rate), blood calcium and hemoglobin,while was negatively correlated with phosphate, age, logserum creatinine, and logFGF-23. Multiple regression analysis showed age, logScr and logFGF-23 were independent factors for expression of serum Klotho in CKD patients. Conclusion Serum Klotho level in CKD patients decreased with the deterioration in renal function and serum Klotho maybe one of indicators to predict the progression of renal function in CKD patients.