Safety of gadolinium contrast angiography in patients with chronic renal insufficiency

OBJECTIVE: To prevent iodinated contrast medium-induced nephrotoxicity, gadolinium has been used increasingly for magnetic resonance angiography (MRA) or conventional digital subtraction angiography (DSA) to visualize arterial anatomy in patients undergoing vascular surgery who are considered at high risk because of chronic renal insufficiency. We assessed the safety of gadolinium-based contrast medium as a substitute for iodinated contrast medium-enhanced examinations. We determined the incidence of gadolinium-induced nephrotoxicity in a clinical setting and searched for contributing risk factors.Patients and methods In a single-center retrospective study from December 1999 to January 2001, 218 inpatients underwent MRA and 42 inpatients underwent DSA, with gadolinium as the sole contrast agent. Patient comorbid conditions, indications for vascular imaging, contrast dose, urine output, baseline and post-procedure serum creatinine concentration (SCr), and outcome were recorded for all patients in whom gadolinium-induced renal failure developed. RESULTS: Of 260 patients who received gadolinium-based contrast agents, at a dose of 0.25 mmol/kg or more, 195 patients (75%) had pre-test baseline chronic renal insufficiency. In 7 of 195 patients (3.5%) acute renal failure developed after gadolinium-based contrast medium administration, for MRA (n = 153) in 3 patients (1.9%) and DSA (n = 42) in 4 patients (9.5%). Average baseline SCr in the 195 patients with chronic renal insufficiency was 38.2 +/- 1.6 mL/min/1.73 m(2), and in the 7 patients in whom acute renal failure developed, baseline SCr was 32.5 +/- 7.8 mL/min/1.73 m(2) (P =.33). Respective intravenous and intra-arterial gadolinium doses in these 7 patients ranged from 0.31 to 0.41 mmol/kg for MRA and 0.27 to 0.42 mmol/kg for DSA. Acute renal failure did not develop in any of 65 patients with normal baseline SCr. CONCLUSION: Despite reports of negligible nephrotoxicity, rarely gadolinium-based contrast agents can cause acute renal failure in patients with underlying chronic renal insufficiency. Estimation of creatinine clearance alone does not enable prediction of which patients are likely to have acute renal failure. Patients at high-risk should be identified, and prophylactic measures should be taken to reduce the risk for nephrotoxicity.     

Gadolinium and nephrogenic systemic fibrosis: association or causation

SUMMARY:   With widespread availability of magnetic resonance imaging (MRI), it has become standard practice for patients with severe renal impairment or previous severe reactions to iodine-containing contrast media to receive gadolinium-based MRI contrast agents instead of traditional radiographic contrast agents, particularly for magnetic resonance angiography. However, there is growing concern about the use of gadolinium contrast agents in the presence of severe renal insufficiency, because of increasing reports of nephrogenic fibrosing dermopathy (NFD)/nephrogenic systemic fibrosis (NSF), associated with the exposure to certain gadolinium-containing contrast agents. In this review we explore the causal link between gadolinium exposure and NSF, using an established system of epidemiological criteria proposed by Bradford Hill. Though the current evidence makes gadolinium a strong suspect as an aetiologic agent for NSF in the presence of severe renal failure, the die is not cast yet. At this stage there needs to be cautious approach to the use of gadolinium-containing contrast agents in the presence of severe renal failure (glomerular filtration rate <30 mL/min per 1.73 m²).     

Gadolinium and nephrogenic systemic fibrosis: an update

Nephrogenic systemic fibrosis (NSF) is a multisystem disease seen exclusively in patients with renal impairment. It can be severely debilitating and sometimes fatal. There is a strong association with gadolinium-based contrast agents used in magnetic resonance imaging (MRI). Risk factors include renal impairment and proinflammatory conditions, e.g. major surgery and vascular events. Although there is no single effective treatment for NSF, the most successful outcomes are seen following restoration of renal function, either following recovery from acute kidney injury or following renal transplantation. There have been ten biopsy-proved pediatric cases of NSF, with no convincing evidence that children have a significantly altered risk compared with the adult population. After implementation of guidelines restricting the use of gadolinium-based contrast agents in at-risk patients, there has been a sharp reduction in new cases and no new reports in children. Continued vigilance is recommended: screening for renal impairment, use of more stable gadolinium chelates, consideration of non-contrast-enhanced MRI or alternative imaging modalities where appropriate.     

IgA肾病合并急性肾衰竭的临床与病理分析

目的：探讨IgA肾病合并急性肾衰竭（ARF）的临床与病理特点。方法：1992年～2006年经肾活检确诊IgA肾病合并ARF 20例患者的临床与病理资料进行回顾性分析。根据不同病理选择治疗方案并进行随访。结果：本组20例IgA肾病合并ARF,占活检IgA肾病的3.8%（20/527）。其中急性肾炎综合征4例,急性肾炎综合征合并肾病综合征5例,以浮肿、少尿为主8例,以恶性高血压为主3例。病理改变上系膜增生性肾炎5例,新月体肾炎8例,增生硬化性肾炎伴新月体肾炎3例、轻度系膜增生性肾炎合并急性肾小管间质肾炎4例。14例肾功能恢复正常,4例部分缓解,2例无效性透析治疗后行肾移植。结论：IgA肾病合并急性肾衰竭发生率达3.8%,高于目前文献报道。临床表现多样化,病理表现为多种病理类型。病理轻则预后好,新月体肾炎诊断治疗及时预后好,多数患者肾功能可以恢复正常。因此早期及时肾活检对IgA肾病指导治疗、判断预后有非常重要的价值。     

Outcomes of stage 1–5 chronic kidney disease in Mainland China

Objective: This study aims to quantify and compare the risks of death and end stage renal disease (ESRD) in a prospective cohort of patients with chronic kidney disease (CKD) stages 1–5 under renal management clinic at Peking University Third Hospital and to evaluate the risk factors associated with these two outcomes. Method: This was a prospective cohort study. Finally, 1076 patients at CKD stage 1–5 short of dialysis were recruited from renal management clinic. Patients were monitored for up to Dec, 2011 or until ESRD and death. Glomerular filtration rate was estimated (eGFR) according to the using the CKD Epidemiology Collaboration (CKD-EPI) formula. Results: At the end of follow-up, 111 patients (10.1%) developed ESRD (initiated dialysis or kidney transplantation (ESRD)) and 24 patients (2.2%) had died. There were more ESRD occurrence rate in patients with baseline diabetic nephropathy, lower eGFR, hemoglobin <100?g/L and 24?h urinary protein excretion ≥3.0?g. By multivariate Cox regression model, having heavy proteinuria and CKD stage were the risk factors of ESRD. For all-cause mortality, the most common cause was cardiovascular disease, followed by infectious disease and cancer. But we failed to conclude any significant variable as risk factors for mortality in multivariate analysis. Conclusions: Our study indicated that baseline diabetic nephropathy, lower hemoglobin level, lower baseline GFR and heavy proteinuria were the risk factors of ESRD. In this CKD cohort, patients were more likely to develop ESRD than mortality, and cardiovascular mortality was the leading cause of death, and then followed by infectious diseases and cancer in this population.     

Hyperglycaemia and renal ischaemia-reperfusion injury.

Introduction Hyperglycaemia is most probably a contributing factor in thedevelopment of ischaemic acute renal failure (ARF) in many patients.Both clinical and experimental data suggest that hyperglycaemiaincreases the risk of ARF [1–3]. Hyperglycaemia also worsensthe outcome in renal transplantation [4,5]. Conversely, ischaemia–reperfusion(I/R) combined with hyperglycaemia could also be important inthe development of diabetic nephropathy. Studies in our laboratoryshow that a brief renal ischaemia results in a progressive injuryleading to end-stage renal failure in diabetic animals [6,7].The mechanisms behind this increased sensitivity to renal I/Rduring hyperglycaemia are still poorly understood. Experimental findings An increased susceptibility to renal I/R injury in diabeticrats has been shown in several studies [1,3,6–9]. Furthermore,non-diabetic rats and dogs are more vulnerable     

Acute Renal Failure in Hospitalized Patients in China: A Prospective Study

Acute renal failure (ARF) is a common complication in hospitalized patients, but little is known about the epidemiology of ARF in China. In this study, we performed a prospective examination of the cause, prognosis, and risk factors associated with ARF at a hospital in Shanghai, China. We considered all ARF patients who were admitted to our hospital from December 2003 to December 2006. Among the 320 ARF patients, 135 (42.2%) were over the age of 60. Sepsis, heart failure, and nephrotoxic drug use were the leading causes of ARF. The overall mortality rate was 31.9%, and mortality rate was significantly higher among the elderly. Logistic regression indicated that heart failure, respiratory failure, and malignant cancer were risk factors independently associated with poor prognosis. In this Shanghai hospital, there was a high incidence and mortality rate of patients hospitalized with ARF. The prognosis of patients who underwent renal replacement therapy was better than those who were treated more conservatively.     

Effect of Fenoldopam Mesylate in Critically Ill Patients at Risk for Acute Renal Failure is Dose Dependent

Background: Acute renal failure (ARF) is common and difficult to prevent, especially in intensive care unit (ICU) patients with cancer. Therapeutic trials with various agents have generally been ineffective in preventing ARF. We describe the effects of two different doses of the dopamine DA-1 receptor agonist fenoldopam mesylate on renal function in a series of critically ill cancer patients at risk of developing ARF. Methods: We performed a retrospective chart review of 100 consecutive patients who received fenoldopam mesylate for at least 72 h in the medical and surgical ICUs of The University of Texas M. D. Anderson Cancer Center who were at risk of developing ARF. Eighteen patients received low-dose fenoldopam mesylate (≤ 0.05 µg/kg/min). The remaining 82 patients received high-dose fenoldopam mesylate (0.07–0.1 µg/kg/min). Data were collected relating to drug dosage, patient demographics, severity of illness, and indices of renal function. Results: Patients were moderately ill, with a mean APACHE II score of 18 ± 6 at initiation of fenoldopam infusion. Eighty-five percent of patients had at least two risk factors for the development of ARF, and 20% had four. For the group overall, the incidence of ARF was 13%, and the hospital mortality rate was 37%. When compared with the low-dose group, patients who received high-dose fenoldopam had a significantly shorter ICU length of stay despite a significantly higher APACHE II score (p = 0.01). The high-dose group also had a highly significant decrease in serum creatinine levels at 72 h (p = 0.005). Conclusions: These data support the hypothesis that fenoldopam mesylate may provide a degree of dose-dependent renal protection in cancer patients with early acute renal failure.     

High incidence of renal failure in patients with aortic aneurysms.

BACKGROUND: Renal failure (RF) is a well-recognized complication of aortic aneurysms (AA) although its incidence has been poorly documented previously. The purpose of this study is to examine the incidence of RF in patients with AA and prognosis of AA patients with RF. METHODS: Renal function, complications and prognosis of AA patients with RF were retrospectively reviewed in 350 AA patients (median age 69.8+/-10.7 years) in the International Medical Center of Japan from 1989 to 1999. RESULTS: Among 350 patients with AA, 90 patients (25.7%) had chronic renal failure (CRF) at the initiation of follow-up. The number of CRF patients increased to 117 (33.4%) at 30 months of follow-up. Forty-four out of 160 patients (27.5%) who had aortic surgery developed postoperative acute renal failure (ARF). Stepwise logistic regression analysis revealed that age (>or=65 years), hypertension and multiple aneurysms were independent risk factors for CRF, whereas dissecting aneurysms, preoperative serum creatinine (sCr) levels and duration of surgery were independent risk factors for postoperative ARF in AA patients. In the 5-year follow-up of AA patients with CRF, the mean slopes of 1/serum-creatinine did not significantly differ between conservative treatment and surgical treatment. The survival rates were 49.5% in the conservative treatment group and 67.3% in the surgical treatment group. CONCLUSION: Our data suggest that the management of renal function including blood pressure from an early stage in AA patients is important since CRF is highly prevalent in AA patients and affects their prognosis and mortality.     

Acute Renal Failure as a Complication of Acute Pancreatitis

To assess the prevalence of acute renal failure (ARF) inpatients with acute pancreatitis, as well as the factors predictive of a lethal outcome, we retrospectively studied the data of all patients admitted to our hospital over a 5-year period. Between 1989 and 1993, 554 patients presented with acute pancreatitis, of which 24 (4.4%) subsequently developed ARF. Death occurred in 14/24 (58%) of patients with ARF, and was associated with an increased incidence of multiorgan failure. There was no statistically significant difference in the age, admission blood pressure, or admission pulse rate of the patients who survived and those who died. In contrast, death was associated with a higher Ranson score, and the increased prevalence of multiorgan failure. The length of hospitalization of the nonsurviving group was significantly shorter. Acute renal failure is not a common finding in patients with acute pancreatitis. However, when it occurs, it is associated with a poor prognosis, and is predicted by a higher Ranson score and the presence of multiorgan failure.     

Predictors of worsening renal function in adult patients with congestive heart failure receiving recombinant human B-type brain natriuretic peptide (nesiritide).

BACKGROUND: A recent meta-analysis suggested that the use of nesiritide (NES), a new agent for the treatment of congestive heart failure (CHF), is associated with an increased risk of acute renal failure (ARF). METHODS: We examined this issue among 219 consecutive CHF patients, and determined the risk factors for development of ARF [defined as a rise in serum creatinine (SCr) >0.3 mg/dl]. The sole primary outcome was the development of ARF. RESULTS: Seventy one of 219 patients received NES. There was no difference in ARF between patients receiving vs not receiving NES (29 vs 20%, P = 0.17). Evaluation of the entire cohort employing forward stepwise regression analysis revealed the following independent predictors of ARF: admission blood urea nitrogen (BUN) [P = 0.0004, odds ratio (OR) = 1.026], and admission brain natiuretic peptide (P = 0.04, OR = 1.0003). We repeated the same analysis for the subgroups of patients receiving or not receiving NES. For patients not receiving NES (n = 148), ARF developed in 30 (20%), with lower estimated glomerular filtration rate and older age being independent predictors. For patients receiving NES (n = 71), ARF developed in 21 (29%), with hypertension, elevated BUN/SCr ratio, and lack of use of angiotensin inhibitors being independent predictors. CONCLUSION: Among all patients with CHF, the use of NES was not an independent risk factor for the development of ARF. However, risk factors for developing ARF differed among patients receiving vs not receiving NES. Comparison of these differing factors suggests that administering NES in the setting of diminished renal perfusion and/or altered renal autoregulation may confer an increased risk of ARF.     

Risk for Contrast Nephropathy in Patients Undergoing Coronarography

Among the causes of in‐hospital acute renal failure, contrast‐induced nephropathy ranks third in prevalence. Although it represents a condition of renal impairment with spontaneous recovery, contrast nephropathy should always be considered, because it prolongs hospitalization and it may become a severe complication requiring dialysis. The purposes of this study are: (i) to determine if the application of the most effective contrast‐induced nephropathy prevention strategies in the Cardiology Intensive Care Unit can prove to be successful in reducing nephropathy risk; and (ii) to identify which of the involved risk factors persist after the preventive treatment. We examined the patients who had a coronarography at the Bentivoglio hospital from April 2007 to April 2008 who required at least 3 days of permanence in hospital due to the presence of potential risk factors; 136 out of 784 patients were included. Among the selected patients, 21 (15.44%) developed a renal impairment compatible with contrast‐induced nephropathy. The risk factors that seemed to display the best correlation with risk of contrast nephropathy were advanced age and an ventricular failure (ejection fraction <40%); however, the critical condition did not appear to be due to a single risk factor, but it resulted from the association of more contextual risk factors. Particularly, the concomitant presence of ventricular failure, anemia, diabetes, previous myocardial infarction and advanced age (>70 years) determined a threefold increased risk of contrast nephropathy. Our data suggest that the development of contrast nephropathy following coronarography is associated with worse renal function during hospitalization and at discharge.     

Acute reversible renal failure with macroscopic haematuria in IgA nephropathy

Macroscopic haematuria is common in IgA nephropathy, but itssignificance and influence on prognosis remains uncertain. Wecompared the clinical and pathological features of 11 adultpatients with primary IgA nephropathy who had had a renal biopsyduring or shortly after a bleeding episode. Six patients developedtransient acute renal failure (ARF) (group 1) and five did not(group 2). Patients of group 1 had a higher percentage of tubularred-blood-cell (RBC) casts (P<0.05) and of glomerular crescents(P<0.001). However, crescents were focal and involved lessthan 50% of glomeruli. Acute tubular necrosis was only presentin patients of group 1, and ARF was attributed to the acutetubular changes rather than to the glomerular lesions. Despitea prolonged duration of ARF (mean: 38 days), further outcomedid not differ in patients of both groups. We suggest that acutetubular damage and/or tubular obstruction by RBC casts shouldbe considered in any patient who develops ARF soon after a haematuricepisode.     

Acute renal failure in patients with pre-existing renal dysfunction following coronary artery bypass grafting

BACKGROUND: Pre-existing renal dysfunction predisposes to acute renal failure (ARF) in patients undergoing coronary artery bypass grafting. We assessed the incidence and impact of the development of ARF in this patient population in our unit. METHODS: One-hundred and six patients had a preoperative serum creatinine of >or=0.13 mmol/L and underwent coronary artery bypass grafting in the year 2000. The incidence of ARF (as defined by a >or=50% rise in postoperative serum creatinine), hospitalization days, dialysis requirement, in-hospital and 1-year mortality, and potential risk factors for ARF were recorded. RESULTS: Of the patients recorded, 43/104 (41.35%) developed ARF following coronary artery bypass grafting. Patients with ARF stayed in hospital longer (P < 0.02). Ten out of forty-three patients required some form of dialysis and the in-hospital mortality of the renal failure group was 23% compared to 3.1% in the other group (P < 0.002). One year postoperatively, the group with renal failure had significantly worse survival (71.8% vs 98%P < 0.0001). CONCLUSION: For patients undergoing coronary artery bypass grafting, pre-existing renal dysfunction predisposes to the development of ARF, this is associated with prolonged hospitalization and increased mortality.     

Low-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness and renal safety

Background: To observe effectiveness and renal safety of long-term low-dose cyclosporine in idiopathic membranous nephropathy (IMN).

Methods: Sixty-eight patients were enrolled in this prospective cohort study. Renal endpoint was defined as a decrease in eGFR?≥50% from baseline and a development of eGFR ≤60?ml/min/1.73m².

Results: A cyclosporine dose of 2.0?±?0.5?mg/kg/d and a prednisone of 0.3?±?0.2?mg/kg/d were prescribed. The duration of cyclosporine treatment was 27 (3–80) months. The overall remission rate was 91% with a relapse rate of 42%. Fourteen patients had cyclosporine-related acute renal injury (CsA-ARI) within the first three months, and 16 patients had cyclosporine related chronic renal injury (CsA-CRI) within the first year. At the end of follow-up (50?±?18?months), 16 patients (24%) reached renal endpoint. Presence of intimal fibrosis of small artery and higher time-averaged proteinuria were identified as independent risk factors for renal endpoint. RAS inhibition treatment decreased the risk of poor renal outcome. Patients in CsA-ARI group had the highest proteinuria at the third month, the highest time-average proteinuria and the highest proportion of cases reaching renal endpoint. Patients with CsA-CRI were of the oldest age and with the lowest baseline eGFR.

Conclusions: Low-dose cyclosporine is effective in treating IMN. CsA-ARI and no response in proteinuria during the first three months of cyclosporine treatment had the lowest benefit/risk ratio, and these patients should be switched to non-calcineurin-inhibitor based regimen. Patients of older age, with lower baseline eGFR, or having intimal sclerosis of small artery, are more likely to develop progressive renal dysfunction.     

A risk prediction model for contrast-induced nephropathy associated with gadolinium-based contrast agents

ObjectiveThis is the first study to explore the risk factors for nephropathy caused by gadolinium-based contrast agents and establish a prediction model to identify high-risk patients.MethodsA total of 1404 patients who received gadolinium-based contrast agents in our hospital were included. The participants were randomly assigned in a 7:3 ratio to the modeling and validation groups. The modeling group was divided into a contrast-induced nephropathy group and a non-contrast-induced nephropathy group. The clinical characteristics before the use of contrast agents were compared between the two groups. The risk factors for contrast-induced nephropathy were analyzed by logistic regression. A nomogram that could predict the incidence of contrast-induced nephropathy was plotted. The validation group was used to verify the predictive model.ResultsThe incidence of contrast-induced nephropathy caused by gadolinium-based contrast agents was 3.92% (55/1404). The logistic stepwise regression analysis showed that sex, systolic pressure (SBP), absolute neutrophil count, albumin, fasting blood glucose level, and furosemide use were significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. The above predictors were then included in the nomogram construction. The area under the receiver operating characteristic (ROC) curve was 0.82 (p < 0.001). The specificity and sensitivity corresponding to the optimal cutoff point (0.039) based on the area under the ROC curve were 71.9% and 80.5%, respectively.ConclusionSex, SBP, absolute neutrophil count, albumin, fasting blood glucose levels, and furosemide use are significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. Therefore, the incidence of contrast-induced nephropathy may be estimated by the prediction model established in this study before the use of contrast agents.     

Toxicité rénale des produits de contraste radiologiques

The nephrotoxicity of iodinated contrast agent/media is defined by acute renal failure occurring within 48 to 72 hours after injection of iodized contrast product, in the absence of other etiology. The risk factors for contrast agent renal injury must systematically be sought before the exam. The presence of risk factors, including the existence of a renal failure defined by a creatinine clearance (eGFR) of less than 60 mL/min/1.73 m², requires to take prevention measures including hydration. If eGFR is less than 30 mL/min/1.73 m², the advice of a nephrologist is necessary.     

Nephrogenic systemic fibrosis and the use of gadolinium-based contrast agents

Nephrogenic systemic fibrosis (NSF) is a disease seen exclusively in patients with decreased renal function. The use of gadolinium-based contrast agents (GBCAs) has a strong association with NSF. Linear non-ionic GBCAs that are more prone to release free gadolinium are the more likely to cause NSF. The number of reported cases has increased recently, and there are currently nine pediatric cases, the patients ranging in age from 8 years to 19 years, and the oldest adult patient is 87 years of age. The most successful treatment is improvement of renal function with renal transplantation or with recovery of acute kidney injury. NSF can be severely debilitating and even fatal. Avoidance of a GBCA in patients at risk, or limitation of the dose in the patients who need gadolinium enhancement, is recommended.     

Simultaneous Intestinal and Kidney Transplantation in Adults

Aim of the study: Intestinal transplantation (IT) is a life-saving procedure for carefully selected patients with intestinal failure. We evaluated patients who had undergone simultaneous intestinal and kidney transplantation (SIKT) to determine whether UK guidelines for inclusion of a renal allograft (dialysis dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m²) are justified. Methods: A single centre analysis was undertaken of adults undergoing IT at the Cambridge Transplant Centre between December 2007 and January 2016. A prospectively maintained database was used to identify SIKT recipients and determine outcomes. Results: Over this period, 63 intestinal transplants were performed. Seven (11.1%) recipients received a SIKT. Five were pre-dialysis (median eGFR 29 ml/min/1.73 m², range 16–36 ml/min/1.73 m²). One recipient was on dialysis, and one needed bilateral nephrectomy at transplant. There were no primary kidney allograft failures and at three months, the median eGFR (55 ml/min/1.73 m² range 39–124) was similar to recipients of IT alone (median eGFR 56 ml/min/1.73 m² range 17–143 ml/min/1.73 m²). Two recipients required dialysis due to sepsis related kidney injury and died from multi-organ failure (20 and 63 months). Two died with a functioning renal transplant (10 and 15 months). The remaining three patients are alive at follow up (12–96 months) with an eGFR of 20–45 ml/min/1.73 m². Conclusion: Patients with significant renal impairment (eGFR <45 ml/min/1.73 m²), and receiving dialysis may benefit from SIKT. Patient survival and renal function are broadly comparable to those undergoing IT alone. Further studies are required to justify allocation of a kidney to this complex high risk group.