Increase In sCr Research Articles

Contrast-induced Nephropathy after Percutaneous Coronary Intervention in Simple Lesions: Risk Factors and Incidence are Affected by the Definition Utilized

To compare the incidence, and risk factors, in-hospital and at the 18-month prognosis of contrast-induced nephropathy (CIN) according to the definition utilized: as an increase in serum creatinine (Scr) ≥ 0.5 mg/dL (CIN 1) or as an increase in Scr ≥ 25% above baseline values (CIN 2). We prospectively evaluated CIN according to two different definitions in 150 patients who underwent percutaneous coronary intervention (PCI) in simple lesions employing a low-medium dose of contrast media. Incidence of CIN was higher using the CIN 2 definition than CIN 1 (9.3% vs. 4%; p=0.0133). Patients with CIN 1 had a higher incidence of chronic kidney disease (CKD) (66.7% vs. 13.9%; p=0.006), higher mean serum creatinine levels (1.35±0.42 vs. 0.98±0.35; p=0.001) and lower mean eGFR levels (58.3±19.6 vs. 84±25.9; p=0.002). Patients with CIN 2 had a higher incidence of anemia (57.1% vs. 30.9%; p=0.049) and a higher mean contrast media volume was used (142.6±62.2 mL vs. 110.6±57.2 mL; p=0.05). In the multivariate analysis the only significant variable associated with CIN (CIN 2) was a higher volume of contrast media (OR=1.01; p=0.04). There were no differences in the major in-hospital events, but patients with CIN (both definitions) had a longer in-hospital stay. A persistent rise in serum creatinine at discharge occurred in only one patient. There were no differences between patients with and without CIN in events at the follow-up, with the exception of an increased risk of new hospitalization in patients with CIN 2. After PCI employing low-medium dose of contrast media the incidence of CIN varied according to the definition used. Neither of the two definitions offers additional information compared with the other. Chronic kidney disease and baseline parameters of renal function are the risk factors associated with CIN 1; anemia and higher volume of contrast media are associated with CIN 2.

Contrast-induced nephropathy after a second contrast exposure

Background: The risk of contrast-induced nephropathy (CIN) after repeated contrast exposure has not been evaluated. Methods: We prospectively evaluated the effects of two contrast exposures during an investigational study of a new computerized tomography (CT) scanner. Adult subjects who underwent a variety of contrast-enhanced imaging procedures with conventional apparatus, as part of routine care, were invited to undergo a second contrast-enhanced research scan. Subjects were required to have an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 and a serum creatinine (sCr) value measured immediately prior to the second contrast exposure that was <125% of that measured prior to the first imaging study. Results: Twenty-eight subjects underwent a second contrast exposure after a mean interval of 20 ± 13 days (75% males, 89% Caucasians, 21% diabetics, mean age 60.6 ± 6 years, mean contrast volume 130 ± 42 mL). There was a significant increase in mean sCr and decline in eGFR after the second contrast exposure (sCr 0.93 ± 0.14 vs. 0.86 ± 0.15 mg/dL prior, p = 0.027; eGFR 83.9 ± 13.5 vs. 89.8 ± 13 mL/min/1.73 m2 prior, p = 0.028). Four subjects (14.3% of the population) developed CIN. Conclusion: Even in subjects with relatively preserved renal function there is a notable risk of CIN after repeated contrast exposure. This conclusion was unaltered by several sensitivity analyses.

Incidence, Clinical Predictors, Genomics, and Outcome of Acute Kidney Injury Among Trauma Patients

To determine clinical and genomic characteristics and in-hospital mortality risk associated with acute kidney injury (AKI) in the multicenter prospective cohort of patients with blunt trauma. Less severe stages of AKI characterized by small changes in serum creatinine (sCr) are inadequately studied among trauma patients. We performed a secondary analysis of the "Inflammation and the Host Response to Injury" (Glue Grant) database to include adult blunt trauma patients without history of kidney disease. AKI was defined by the Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE) classification, which requires a 50% increase in sCr and stratifies patients into following 3 severity stages: risk, injury, and failure. Association between all stages of AKI and in-hospital mortality was analyzed using a multivariable logistic regression analysis. Genome-wide expression analysis was performed on whole blood leukocytes obtained within 12 hours of trauma. AKI occurred in 26% of 982 patients. The adjusted risk for hospital death was 3 times higher for patients with AKI compared with patients without AKI (odds ratio = 3.05) (95% confidence interval, 1.73-5.40). This risk was evident in a dose-response manner and even patients with mild AKI had odds ratio for dying of 2.57 (95% confidence interval, 1.19-5.50) compared with patients without AKI. Genome-wide expression analysis failed to show a significant number of genes whose expression could discriminate among patients with and without AKI. In a multicenter prospective cohort of blunt trauma patients, AKI characterized by small changes in sCr was associated with an independent risk of hospital death.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Cystatin C and Contrast-Induced Acute Kidney Injury

Cystatin C (CyC) is more sensitive than serum creatinine (sCr) to rapidly detect acute changes in renal function. We measured CyC together with sCr in 410 consecutive patients with chronic kidney disease undergoing either coronary and/or peripheral angiography and/or angioplasty. sCr was assessed at baseline and 24 and 48 hours after contrast media exposure. CyC was assessed at baseline and at 24 hours. Major adverse events (including death of any cause and dialysis) at 12 months were assessed. At 48 hours after contrast media exposure, contrast-induced acute kidney injury (defined as a sCr increase > or =0.3 mg/dL) occurred in 34 patients (8.2%). A CyC increase concentration > or =10% at 24 hours after contrast media exposure was detected in 87 patients (21.2%). This was the best CyC cutoff for the early identification of patients at risk for contrast-induced acute kidney injury (negative predictive value=100%; positive predictive value=39.1%). According to the defined cutoffs (that is, increase in CyC > or =10% and sCr > or =0.3 mg/dL), major adverse events occurred in 16 of 297 patients (5.4%) without any cutoffs satisfied (group 1), in 9 of 49 patients (18.4%) with only a CyC increase > or =10% (group 2), and in 9 of 31 patients (29%) with both cutoffs satisfied (group 3). By logistic regression analysis, the independent predictors of major adverse events at 1 year were group 2 (odds ratio=2.52; 95% confidence interval, 1.17 to 5.41; P=0.02), group 3 (odds ratio=4.45; 95% confidence interval, 1.72 to 11.54; P=0.002), and baseline glomerular filtration rate (odds ratio=0.91; 95% confidence interval, 0.88 to 0.95; P<0.001). In patients with chronic kidney disease, CyC seems to be a reliable marker for the early diagnosis and prognosis of contrast-induced acute kidney injury.

The contrast media and nephrotoxicity following coronary revascularization by primary angioplasty for acute myocardial infarction study: design and rationale of the CONTRAST-AMI study

Contrast-induced acute kidney injury (CI-AKI) is a complex syndrome of acute renal failure occurring after the administration of contrast media and contributing to prolonged hospital stay and mortality. The risk of CI-AKI is higher among patients undergoing primary percutaneous coronary interventions for acute myocardial infarction (AMI), but its clinical relevance in such setting has only been evaluated by small sample size single-center studies and retrospective or observational analyses. Furthermore, whereas high-osmolar contrast media was shown to have direct nephrotoxicity, the role of low-osmolar and iso-osmolar agents is still debated. The CONTRAST-AMI study is a prospective, multicenter, controlled, randomized, single-blind, parallel-group trial, designed to show the noninferiority of the effects of iopromide (low-osmolar) compared with iodixanol (iso-osmolar) contrast media on the incidence of CI-AKI and tissue-level perfusion in patients with AMI. All consecutive patients admitted to participating centers for ST-segment elevation AMI undergoing primary percutaneous coronary intervention will be enrolled. All patients will be treated with high-dose N-acetylcysteine (1200 mg intravenously during the procedure and 1200 mg orally two times daily for the next 48 h after percutaneous coronary intervention) and hydration according to a standardized protocol. The primary endpoint is the proportion of patients with a relative increase in serum creatinine (sCr) of at least 25% from baseline to 72 h after agent administration. The secondary endpoints are absolute and relative increases in sCr of at least 50%, thrombolysis in myocardial infarction (TIMI) perfusion grade, and major adverse cardiac events at 1, 6, and 12 months. The CONTRAST-AMI study will provide information on the effects of iodixanol and iopromide on the incidence of CI-AKI and tissue-level perfusion in patients with AMI.

Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients

IntroductionSerum creatinine concentration (sCr) is the marker used for diagnosing and staging acute kidney injury (AKI) in the RIFLE and AKIN classification systems, but is influenced by several factors including its volume of distribution. We evaluated the effect of fluid accumulation on sCr to estimate severity of AKI.MethodsIn 253 patients recruited from a prospective observational study of critically-ill patients with AKI, we calculated cumulative fluid balance and computed a fluid-adjusted sCr concentration reflecting the effect of volume of distribution during the development phase of AKI. The time to reach a relative 50% increase from the reference sCr using the crude and adjusted sCr was compared. We defined late recognition to estimate severity of AKI when this time interval to reach 50% relative increase between the crude and adjusted sCr exceeded 24 hours.ResultsThe median cumulative fluid balance increased from 2.7 liters on day 2 to 6.5 liters on day 7. The difference between adjusted and crude sCr was significantly higher at each time point and progressively increased from a median difference of 0.09 mg/dL to 0.65 mg/dL after six days. Sixty-four (25%) patients met criteria for a late recognition to estimate severity progression of AKI. This group of patients had a lower urine output and a higher daily and cumulative fluid balance during the development phase of AKI. They were more likely to need dialysis but showed no difference in mortality compared to patients who did not meet the criteria for late recognition of severity progression.ConclusionsIn critically-ill patients, the dilution of sCr by fluid accumulation may lead to underestimation of the severity of AKI and increases the time required to identify a 50% relative increase in sCr. A simple formula to correct sCr for fluid balance can improve staging of AKI and provide a better parameter for earlier recognition of severity progression.

Safety of Deferasirox (Exjade®) in Myelodysplastic Syndromes (MDS) and Non-MDS Patients with Transfusional Iron Overload: A Pooled Analysis Focusing On Renal Function.

Abstract 1768Poster Board I-794 BackgroundAssessment of the safety profile, in particular renal function, of the oral iron chelator deferasirox (Exjade®) is of particular relevance in MDS patients (pts), given their advanced age and associated decline in renal function. This 1-yr pooled analysis characterizes the safety profile of deferasirox in a large population of MDS and non-MDS pts (β-thalassemia [β-thal] and other anemias [sickle cell, Diamond-Blackfan, aplastic and other]), with emphasis on renal function. MethodsAnalysis is based on 1-yr pooled data from iron-overloaded pts who were enrolled in five open-label deferasirox studies: US02 and US03 (single-arm (SA), Low/Int 1 MDS pts, starting dose 20 mg/kg/day); 2409 (SA, pts with transfusional hemosiderosis, starting dose 20 mg/kg/day); 107 (randomized trial in β-thal pts, dosing 5–40 mg/kg/day) and 108 (SA, pts with chronic anemias, dosing 5–40 mg/kg/day). Datasets pooled: baseline (BL) characteristics, dosing, transfusion, adverse events (AEs) and laboratory data. Results1798 pts were assessed (951 β-thal; 584 MDS, 263 other). MDS pts were older (median age 71 yrs) compared with those with β-thal (25 yrs) and other anemias (38 yrs). Mean actual dose of deferasirox (mg/kg/day): β-thal pts 23.5; MDS pts 20.3; other 19.9. Mean transfusional iron intake (mg/kg/day): 0.34, 0.32 and 0.23 in β-thal, MDS and other anemias, respectively. At 1 yr, 88%, 53% and 69% of β-thal, MDS and other pts remained in the study, respectively. Most frequent reasons for discontinuation: AEs (n=42 [4%] β-thal; n=115 [20%] MDS; n=34 [13%] other anemias). Frequency of drug-related AEs was similar for MDS (68%) and other anemias (63%) compared with 49% for β-thal. Most common drug-related AEs in β-thal, MDS and others, respectively, were: diarrhea (11%; 37%; 23%), nausea (7%; 15%; 20%), vomiting (3%; 8%; 8%); rash (11%; 8%; 6%); abdominal pain (6%; 7%; 8%) and upper abdominal pain (4%; 5%; 8%). 64 deaths occurred (none assessed as related to deferasirox by the investigator); 4 (primarily cardiac), 47 (primarily infections, hemorrhages, progression to AML, cardiac events) and 13 (primarily infections) in the β-thal, MDS and other pts, respectively. BL versus last available creatinine clearance (CrCl) were analyzed graphically for MDS pts with/without investigator-reported renal dysfunction AEs (Figure). CrCl for the majority of β-thal and non-MDS pts was >60 mL/min at BL (not shown), while in the MDS group, as expected, there were more pts with CrCl <60 mL/min and reported renal dysfunction AEs (Fig. A). To evaluate pts with BL CrCl <60 mL/min, an expanded view was created (Fig. B). A greater proportion of MDS pts with renal AEs was reported in the 20–<30 mL/min (43%) and 30–<40 mL/min category (30%), versus the 40–<50 mL/min (13%) and 50–<60 mL/min categories (7%). Exploratory logistic regression modeling confirmed odds of reporting a renal dysfunction AE were 4 and 22 times for pts with CrCl 40–<60 mL/min and <40 mL/min, respectively, compared to pts with CrCl ≥60 mL/min. Pts with BL CrCl <40 mL/min (n=6) were >70 yrs with primarily pre-existing chronic renal insufficiency, diabetes, hypertension and congestive heart failure. Pts with BL CrCl 40–60 mL/min had fewer pre-existing conditions, but still had reported renal dysfunction AEs. In about half of cases with BL CrCl <60 mL/min, reported renal dysfunction AEs were not associated with a clinically significant increase in SCr and corresponding CrCl decline, consistent with investigators' discretion in reporting. [Display omitted] ConclusionsThis comprehensive assessment of MDS and non-MDS pts with transfusional iron overload confirmed the known safety profile of deferasirox; with the most frequent drug-related AEs reported as gastrointestinal events. The findings were also consistent with the clinical features of MDS such as advanced age and co-morbidities. Pts with BL CrCl <40 mL/min were more likely to report renal dysfunction AEs and less likely to be able to compensate for additional stresses on their existing decreased renal function, given their pre-existing co-morbidities and advanced age. Deferasirox may be used in pts with BL CrCl 40–<60 mL/min with close monitoring, and should not be used in pts with BL CrCl <40 mL/min. DisclosuresCappellini:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genzyme: Membership on an entity's Board of Directors or advisory committees. Porter:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Vifor International: Membership on an entity's Board of Directors or advisory committees. Greenberg:Amgen: Consultancy, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lawniczek:Novartis Pharma AG: Employment. Glaser:Novartis Pharma AG: Employment. Dong:Novartis Pharmaceuticals: Employment. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials.

A retrospective characterization of worsening renal function in patients with acute decompensated heart failure receiving nesiritide.

Nesiritide is approved by Food and Drug Administration (FDA) for the treatment of patients with acute decompensated heart failure (ADHF) due its ability to rapidly reduce cardiac filling pressures and improve dyspnea. Numerous studies have shown that renal dysfunction is associated with unfavorable outcomes in patients with heart failure. In addition, there have been reports suggesting that nesiritide may adversely affect renal function and mortality. The purpose of this retrospective analysis was to assess the effect of dose and duration of nesiritide use and the dose and duration of diuretic therapy on worsening renal function and increased in-hospital mortality in this patient population. Seventy-five patients who were hospitalized for ADHF and who were treated with nesiritide for at least 12 hours were reviewed retrospectively. The mean increase in SCr was 0.5 mg/dL (range 0 - 4.4 mg/dL). Thirty-six percent of patients (27/75) met the primary endpoint with an increase in SCr>0.5 mg/dL. Treatment dose and duration of nesiritide did not differ between those patients who had an increase in SCr>0.5 mg/dL and those who did not (p=0.44 and 0.61). Concomitant intravenous diuretics were used in 85% of patients with an increase in SCr >0.5 mg/dL compared to 90% of patients without an increase in SCr>0.5 mg/dL (p=0.57). The in-hospital mortality rate was also higher at 35% in those patients with an increase in creatinine >0.5 mg/dL compared to 11% in those without (p=0.01). Nesiritide was associated with an increase in SCr > 0.5 mg/dL in approximately one-third of patients. The increase occurred independently of dose, duration of nesiritide therapy, blood pressure changes, and concomitant intravenous diuretic use. However, the increase in SCr was associated with an increase in hospital stay and in hospital mortality consistent with previous reports in the literature.

A case of an acute kidney injury secondary to an implanted aminoglycoside

CASE PRESENTATION An 80-year-old African American woman with a past medical history of type II diabetes mellitus, hypertension, bilateral knee replacements and peripheral vascular disease presented to the nephrology clinic for evaluation of an elevated serum creatinine. Six weeks earlier she underwent removal of a total knee prosthesis due to septic arthritis with coagulase-negative staphylococci. A vancomycin and tobramycin-impregnated cement spacer block was mixed in the operating room and implanted. Her serum creatinine concentration (sCr) was 0.9 mg/dl upon hospital discharge. Periodic laboratory studies performed at the nursing facility showed a steady increase in sCr to 1.6 mg/dl at 2 weeks and then to 3.7 mg/dl by 6 weeks (Figure 1). One week before to presentation at the nephrology clinic, she began to develop uremic symptoms including nausea, vomiting, a metallic taste, and muscle cramps. Her furosemide and lisinopril had been held for 3 weeks due to her rising serum creatinine with no improvement. Her medications on presentation were insulin, omeprazole, synthroid, metoprolol, multivitamin, clopidogrel, atorvastatin, amlodipine, warfarin and minocycline. The minocycline had been initiated after she completed a 2-week course of intravenous vancomycin. Other than the warfarin, minocycline and intravenous vancomycin, she was on no new medications. There was no documented history of hypotension and she took no non-steroidal, herbal or over-the-counter medications. Physical examination revealed that she was afebrile, her blood pressure was 124/73 mmHg and pulse was 73 beats/min. She was alert and conversant. There was pitting edema of the lower extremities to the knee, but the lungs were clear to auscultation. No rashes or joint abnormalities were noted. She did not have asterixis. She had no auditory or vestibular symptoms although these were not formally tested. Laboratory studies are shown in Table 1. Her urinalysis revealed a specific gravity of 1.013, pH of 5.0, no protein or blood, and a positive spot leukocyte esterase with 2–5 white blood count per high powered field. Urine microscopic analysis by the nephrology consult team revealed few renal tubular epithelial cells and scant granular casts without red blood cells. She remained non-oliguric during her first few days of her admission. Based upon her clinical presentation, tobramycin toxicity from her knee cement spacer was suspected. Since this diagnosis would entail surgical treatment, a transjugular renal biopsy was performed for confirmation (Figures 2, 3).

Urinary Biomarkers in the Early Detection of Acute Kidney Injury after Cardiac Surgery

Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney injury molecule-1 (KIM-1), N-acetyl-beta-D-glucosaminidase (NAG), and neutrophil gelatinase associated lipocalin (NGAL) was evaluated for the early detection of postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery. Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were measured at 5 time points for the first 24 h after operation and normalized to the urinary creatinine concentration after cardiac surgery. Receiver-operating characteristic curves were generated and the areas under the curve (AUCs) compared for performance of biomarkers in detection of postoperative AKI. Thirty-six patients developed AKI, defined as an increase in Scr of > or =0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG; and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced the sensitivity of early detection of postoperative AKI compared with individual biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The performance of combining biomarkers was even better among 16 early postoperative AKI patients with AUCs of 0.80 and 0.84, respectively. The results of this study support that a combination of urinary biomarkers may allow for early detection of postoperative AKI after cardiac surgery before a rise in Scr.

RIFLE is not RIFLE: on the comparability of results

In the consensus RIFLE criteria [1] of acute kidney injury (AKI) the thresholds given for serum creatinine (sCr) increase and glomerular filtration rate (GFR) decrease (Table ​(Table1)1) do not correspond [2]. Direct measurement of GFR in clinical practice is difficult, and values are more often estimated (eGFR) by the Cockroft-Gault equation or the Modification of Diet in Renal Disease (MDRD) formula. In addition, there is controversy in the literature whether eGFR provides more clinical information regarding AKI than changes in sCr [3]. Table 1 RIFLE criteria for the definition of acute kidney injury (urinary output criteria not listed) As an example of the possible discrepancy, a 1.5-fold increase (50%) in sCr from a baseline of 1.0 mg/dL in a 60-year-old white male corresponds to only a 37% eGFR decrease using the MDRD formula. In this scenario the patient is classified in RIFLE class R by both methods. In the same patient an only 30% increase in sCr (1.0 mg/dL to 1.3 mg/dL), however, corresponds to a 26% decrease of eGFR. Therefore, the patient would consequently be classified as having AKI in RIFLE class R by the GFR threshold but not based on sCr changes. This theoretical disagreement in defining and staging AKI by RIFLE has been outlined previously [2], but data to estimate potential discrepancy in a 'real world' scenario are not available. Furthermore, the use of different versions of RIFLE criteria counteracts the original goal of a consensus definition and hinders comparability. To understand the differences better, we applied these two methods of calculating RIFLE to consecutive patients undergoing cardiac surgery with cardiopulmonary bypass between 2005 and 2007 at our institution. AKI was defined by using either largest sCr increase or eGFR decrease (MDRD formula) within the first postoperative week compared to baseline. In all patients a preoperative baseline sCr was available. We did not use urine output criteria to define AKI. Among the total cohort, 9.3% patients were diagnosed as having AKI by the sCr criteria versus 18.9% with eGFR criteria (Table ​(Table2).2). The largest disagreement was detected in class R. Overall, the diagnosis of AKI using eGFR thresholds was more sensitive than sCr changes, and this was also true for staging of patients in RIFLE classes R and I. However, for patients staged in the highest AKI class F, sensitivity was higher for sCr criteria. These discrepancies can be expected to be found in other patient populations when non-uniform methods of determining RIFLE criteria are utilized. Our findings may assist in interpretation of other clinical studies. Table 2 RIFLE classes by creatinine and estimated glomerular filtration rate thresholds Recently the RIFLE criteria have been modified by the Acute Kidney Injury Network (AKIN) [4], and the change in eGFR is no longer included in this consensus definition set. RIFLE criteria calculated by both methods remain widely used and the process of comparison between the two definition schemes (RIFLE and AKIN) in various patient populations is not yet complete. Further validation is required and modifications in the definition and staging of AKI can be expected [5].

Time for Reflection Predicts the Progression of Renal Dysfunction in Patients with Nondiabetic Chronic Kidney Disease

Our previous data indicated that both home blood pressure and arterial stiffness predicted the progression of renal dysfunction in the patients with chronic kidney diseases. In the present study, we examined both home blood pressure and the parameters of arterial stiffness as the indicator to the progression of chronic kidney diseases. Forty-two nondiabetic chronic kidney disease patients were enrolled and followed for 1 year. Anti-hypertensive therapy was adjusted to achieve office blood pressure below 130/80 mmHg. Home blood pressure was examined twice a day in the morning and evening. Pulse wave velocity (PWV) and augmentation index (AI) were measured as the index of arterial stiffness. The time for reflection (TR) was also determined. The relationship of annual changes in serum creatinine (Scr) with the above parameters was assessed. Multivariate regression analysis revealed that TR inversely correlated to annual increase in Scr (β = −0.03, p < 0.05). Home blood pressure did not correlate to annual changes in Scr in the present study. The present data indicated that arterial stiffness is elevated despite good blood pressure control in chronic kidney disease, especially among the dippings. In addition, our data suggest that PWV and AI correlated to each other, while they were influenced differently by hemodynamic factors. Finally, the present findings provide the evidence that the arterial stiffness parameter is more sensitive than home blood pressure as an indicator to the progression of chronic kidney disease.

Thrombotic Microangiopathy with Tacrolimus/Sirolimus-Based GVHD Prophylaxis Regimen in Patients Undergoing Hematopoietic Stem Cell Transplant from a Matched Unrelated Donor

Thrombotic microangiopathy (TMA) is a multifactorial complication of related and unrelated allogeneic hematopoietic stem cell transplant (allo-HSCT). The true incidence of TMA is difficult to estimate due to lack of agreement on a single definition. Diagnosis is often complicated by multiple potential etiologies for the clinical findings. Sirolimus (SIR), an inhibitor of mammalian target of Rapamycin (mTOR), is a novel immunosuppressive agent that works synergistically with calcineurin inhibitors (CNI) to prevent graft-versus-host disease (GVHD) in allo-HSCT. Recently, the addition of SIR to CNIs was reported to result in a higher than expected incidence (10.8%) of TMA (Cutler et al. BBMT 2005; 11:551–7). We evaluated the incidence and risk factors for TMA in a cohort of patients undergoing matched unrelated (MUD) HSCT using SIR combined with tacrolimus (TAC) and mini-methotrexate for GVHD prophylaxis at City of Hope. TMA was defined as SCr increase of ≥ 50% above baseline, LDH twice the institutional upper normal limit, presence of schistocytes or persistent presence of nucleated red blood cells, and prolonged or progressive thrombocytopenia (platelets <50 × 109/L or ≥ 50% decrease from previous count). A case series of 47 MUD-HSCT patients were included in this retrospective chart review study. The median age was 50 years (range: 19–67); (male/female: 28/19). Conditioning regimens consisted of fludarabine/melphalan (65%) and FTBI combined with cyclophosphamide or etoposide (35%). Diagnoses included ALL (32%), AML (25%), NHL (15%), MDS (15%), MPD (9%), CML (2%), CLL (2%). Twenty-six patients (55%) had a 10/10 matched (HLA-A, B, C, DRB1, and DQB1) donor by high-resolution on typing. The median follow up for the 30 surviving patients is 14.5 months (2.8–26). The one-year probabilities of overall survival and non-relapse mortality (NRM) were 61% and 19%, respectively. Grade II-IV acute GVHD (aGVHD) was reported in 60% of all patients (grade III-IV: 25%). Thirteen (28%) patients met the above diagnostic criteria for TMA. In addition, we included two patients who did not meet the criteria due to missing tests but were clinically diagnosed with TMA by independent attending physicians, resulting in the total incidence of 32% (15/47). Four of the 15 patients met the criteria for TMA as a result of ongoing multi-organ failure secondary to other causes. The median time to TMA onset was five weeks (2–20 weeks). Most cases (93%) occurred within the first 100 days post-HSCT. Thirteen patients developed both TMA and aGVHD, in which the majority of patients (70%) developed TMA after a diagnosis of aGVHD had been made. Initial treatments for TMA included holding TAC (33%), holding SIR (20%), holding or adjusting doses (27% and 20%, respectively) for both drugs. One patient underwent plasma exchange. Sixty percent of patients subsequently recovered from TMA as defined by normalization of laboratory values. Of the 17 expired patients, ten were diagnosed with TMA. Causes of death were as follows: for TMA cases, relapse mortality=3, NRM=7; for Non-TMA patients, relapse mortality=6, NRM=1. At the time of TMA diagnosis, the median TAC and SIR levels were 11.3 (0–18.8) and 7 (0–23.9) ng/ml, respectively, in contrast to the median TAC and SIR levels for non-TMA patients at 6.1 (p= 0.02) and 5.5 (p=0.13) ng/ml, respectively. To identify other possible risk factors for TMA, the following patient and treatment-related characteristics were examined: age, conditioning regimen, disease type, degree of HLA match, and exposure to triazole antifungals. Only higher tacrolimus levels (HR: 6.9, p<0.01) and aGVHD grades III-IV (HR: 3.5, p=0.02) were associated with an increased risk for TMA. In conclusion, TMA is common after MUD allo-HSCT using SIR-containing GVHD prophylaxis. The risk factors for TMA suggest that careful monitoring and adjustment of TAC/SIR dosages to avoid super-therapeutic levels is critical, particularly during ongoing GVHD.

SDF-1 Plays a Key Role in Chronic Allograft Nephropathy in Rats

Objectives Our previous study demonstrated that anti-stromal cell derived factor-1 (SDF-1) antibody delayed graft arteriosclerosis in rat abdominal aortic grafts. In this study, we investigated the mechanisms of SDF-1 on chronic allograft nephropathy (CAN), and whether SDF-1 antibody had protective effect on CAN. Methods Male Lewis rats that received left renal grafts from male Fisher 344 rats were randomly divided into three groups: group A only received cyclosporine (CsA; 10 mg · kg −1 · d −1) every day; group B received anti–SDF-1 antibody (8 μg · kg −1 · d −1) + CsA (10 mg · kg −1 · d −1); and group C, an isograft control (Fisher 344 to Fisher 344). All recipient animals were unilaterally right nephrectomized. Group A and B grafts were preserved in 4°C UW solution for 1 hour prolonged cold ischemia. Masson and hematoxylin and eosin staining were performed to evaluate glomerular sclerosis rate (GSR) and Banff score. Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined as well as histologic examinations of the kidneys with immunohistochemistry for SDF-1 and CXCR4, the only known receptor of SDF-1. Results Compared with group C, ischemia and rejection produced a nine-fold increase in GSR and Banff score, as well as significant increases in Scr and BUN levels in group A. Anti–SDF-1 antibody retarded the increase by downregulating the expression of SDF-1 and CXCR4. Furthermore, there was a significant relationship between the expression of SDF-1 and the mean Banff score. Conclusion Anti–SDF-1 antibody retarded the process of CAN.

The incidence of clinically significant contrast‐induced nephropathy following non‐emergent coronary angiography

The primary aim of this study was to assess the incidence of clinically significant contrast-induced nephropathy (CIN) among patients undergoing non-emergent coronary angiography. Although retrospective analyses have emphasized the association of CIN with adverse patient outcomes, the actual incidence of clinically significant CIN following non-emergent coronary angiography is not clear. We prospectively identified patients with baseline estimated glomerular filtration rates (eGFR) < 60 ml/min/1.73 m(2) undergoing non-emergent coronary angiography. We measured serum creatinine 48-96 hr following angiography and assessed the incidence of CIN using two definitions, a rise in Scr > or = 25% and > or = 0.5 mg/dl. We tracked the need for dialysis, hospitalization related to kidney injury, and 30-day mortality to examine the association of CIN with these outcomes. We enrolled 181 patients with a median eGFR of 52 ml/min/1.73 m(2). Of the 165 patients (91%) with post-procedure Scr data, the incidence of CIN was 6.1-8.5%. One patient required dialysis (0.55%) and one (0.55%) died within 30 days. Although 38 patients required hospital admission, CIN was not associated with the need for hospitalization. Patients with an increase in Scr > or = 25% demonstrated a trend toward increased risk for 30-day mortality (P = 0.09), whereas those with increments in Scr > or = 0.5 mg/dl had a marginally higher risk for dialysis (P = 0.06) and 30-day mortality (P = 0.06), although these associations failed to meet the level of statistical significance. Biochemically defined CIN occurs in a small, but notable proportion of patients undergoing non-emergent coronary angiography. However, clinically significant CIN is very uncommon.

Iso-Osmolality versus Low-Osmolality Iodinated Contrast Medium at Intravenous Contrast-enhanced CT: Effect on Kidney Function

To determine the effects of iso-osmolality contrast medium compared with a low-osmolality agent on renal function (serum creatinine [SCr] and glomerular filtration rate [GFR]) in high-risk patients undergoing intravenous contrast material-enhanced CT. This HIPAA-compliant study was IRB-approved; formal consent was obtained. One hundred seventeen patients (83 men, 34 women; mean age, 64.3 years; range, 18-86 years) with decreased renal function underwent contrast-enhanced CT with either iso-osmolality iodixanol (n = 61) or low-osmolality iopromide (n = 56). Outcome measures were of SCr increase or GFR decrease for 3 days after CT, a SCr increase (of >or=0.5 mg/dL [44.2 micromol/L, 25%] or >or=1.0 mg/dL [88.4 micromol/L, 50%]), a GFR reduction (of >or=5 mL/min), and patient outcome at 30- and 90-day follow-up. Iodixanol decreased SCr (mean +/- standard deviation) from 1.77 mg/dL +/- 0.24 (156.47 micromol/L +/- 21.22) at baseline to 1.65 mg/dL +/- 0.35 (145.86 micromol/L +/- 30.94, P = .046) at day 1, 1.73 mg/dL +/- 0.53 (152.93 micromol/L +/- 46.85, not significant) at day 2, and 1.73 mg/dL +/- 0.55 (152.93 micromol/L +/- 48.62, not significant) at day 3 (not significant). Iopromide increased SCr from 1.75 mg/dL +/- 0.32 (154.7 micromol/L +/- 28.29) at baseline to 1.8 mg/dL +/- 0.42 (159.12 micromol/L +/- 15.59) at day 1, 1.77 mg/dL +/- 0.49 (156.47 micromol/L +/- 43.32) at day 2, and 1.77 mg/dL +/- 0.62 (156.47 micromol/L +/- 54.81) at day 3 (not significant). Iodixanol increased and iopromide decreased GFR on all 3 days after CT (not significant). Fewer patients in the iodixanol group (8.5%) than in the iopromide group (27.8%) had SCr increase 0.5 mg/dL or higher (>or=25%, P = .012). Two patients in each group had SCr increase of 1.0 mg/dL or more (not significant). More patients in the iopromide group (42.3%) than in the iodoxanol group (24.1%) had a GFR reduction of 5 mL/min or higher (P = .0426). No patient had a contrast material-related adverse event at 30- or 90-day follow-up. Intravenous contrast material application in high-risk patients is unlikely to be associated with permanent adverse outcomes. SCr levels after contrast material administration are lower in iodixanol than iopromide groups.

Impact of Mild Acute Kidney Injury (AKI) on Outcome after Open Repair of Aortic Aneurysms

Recently, mild AKI has been considered as a risk factor for mortality in different scenarios. We conducted a retrospective analysis of the risk factors for two distinct definitions of AKI after elective repair of aortic aneurysms. Logistic regression was carried out to identify independent risk factors for AKI (defined as $25% or $50% increase in baseline SCr within 48 h after surgery, AKI 25% and AKI 50%, respectively) and for mortality. Of 77 patients studied (mean age 68 ± 10, 83% male), 57% developed AKI 25% and 33.7% AKI 50%. There were no differences between AKI and control groups regarding comorbidities and diameter of aneurysms. However, AKI patients needed a supra-renal aortic cross-clamping more frequently and were more severely ill. Overall in-hospital mortality was 27.3%, which was markedly higher in those requiring a supra-renal aortic cross-clamping. The risk factors for AKI 25% were supra-renal aortic cross-clamping (odds ratio 5.51, 95% CI 1.05–36.12, p = 0.04) and duration of operation for AKI 25% (OR 6.67, 95% CI 2.23–19.9, p < 0.001). For AKI 50%, in addition to those factors, post-operative use of vasoactive drugs remained as an independent factor (OR 6.13, 95% CI 1.64–22.8, p = 0.005). The risk factors associated with mortality were need of supra-renal aortic cross-clamping (OR 9.6, 95% CI 1.37–67.88, p = 0.02), development of AKI 50% (OR 8.84, 95% CI 1.31–59.39, p = 0.02), baseline GFR lower than 49 mL/min (OR 17.07, 95% CI 2.00–145.23, p = 0.009), and serum glucose > 118 mg/dL in the post-operative period (OR 19.99, 95% CI 2.32–172.28, p = 0.006). An increase of at least 50% in baseline SCr is a common event after surgical repair of aortic aneurysms, particularly when a supra-renal aortic cross-clamping is needed. Along with baseline moderate chronic renal failure, AKI is an independent factor contributing to the high mortality found in this scenario.

Abstract 3460: Liver-type Fatty Acid-binding Protein Is A Promising Predictive Marker Of Contrast-induced Nephropathy

Contrast-induced nephropathy (CIN), a well-known complication of contrast media exposure for the patients with chronic kidney disease (CKD), may results from acute tubular necrosis. Although 4 to 11 percent with mild to moderate renal insufficiency develop CIN, there were no biological markers to more accurately predict the occurrence of CIN than the existing makers such as serum creatinine (sCr). Liver-type fatty acid-binding protein (L-FABP) as a novel maker, is an intracellular carrier protein of free fatty acids that marked upregulated and expressed abundantly in proximal tubules after renal ischemia.We prospectively investigated whether urinary L-FABP is an alternative maker of predicting CIN. Methods: We enrolled sixty-five patients (46 male, 71.8 ± 8.2years) undergoing scheduled coronary angiography who had mild kidney disease with CKD stage3 (glomelurar filtration ratio (GFR) &lt;60 ml/1.73 m 2 or albuminuria (u-Alb)≥ 300 mg/gCRE), treated with one-half isotonic (0.45 percent) saline between 12 hours before and after the procedure. We measured urinary L-FABP, u-Alb,β 2 -microglobulin, α 1 -microglobulin, sCr and NAG( N -acetyl-β-d-glucosaminidase). CIN was defined as an increase of sCr of &gt;25% or 0.5 mg/dl (44.2micromol/l) within 2 days of contrast. The cohort was divided into two groups according to occurrence of CIN; CIN-G and nonCIN-G. Results: CIN occurred in 4 of 65 patients (6%). Demographics, the pre-procedural level of makers (β 2 -microglobulin, α 1 -microglobulin, sCr, NAG) and used contrast volume are no significant differences between the two groups. Pre-procedural urinary L-FABP levels were significantly greater in CIN-G than in nonCIN-G(112.5 ± 81.4μg/g Cr;19.7 ± 43μg/g Cr; P&lt; 0.01) as well as u-Alb (CIN-G;1711.3 31386.6 mg/gCRE nonCIN-G; 192.3 3482.3 mg/gCRE Cr; P &lt; 0.01). On the basis of ROC curve of urinary parameters , u-Alb and urinary L-FABP had the significantly high predictive value than other markers(p&lt;0.05). Conclusion: Urinary L-FABP combined with u-Alb can be more accurate markers to predict the risk of CIN than other existing urinary parameters.

Contrast-Induced Nephropathy in Patients With Chronic Kidney Disease Undergoing Computed Tomography

Based on a single clinical trial, it has been suggested that the contrast agent iodixanol, which is isotonic to human plasma, may be less nephrotoxic than other nonionic contrast agents in renally impaired patients after intra-arterial injection. We compared the effects on renal function of iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients with chronic kidney disease undergoing contrast-enhanced multidetector computed tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized, parallel-group design. A total of 166 patients with stable moderate-to-severe chronic kidney disease (screening and baseline serum creatinine, SCr, > or =1.5 mg/dL and/or creatinine clearance, CrCl, < or =60 mL/min) who were undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol-320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline, and at 48-72 +/- 6 hours after dose (mean, 57.4 hours). Contrast-induced nephropathy (CIN) was defined as an absolute increase > or =0.5 mg/dL (44.2 micromol/L) and/or a relative increase in SCr > or =25% from baseline. A total of 153 patients were included in the final analysis (13 patients excluded because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl variation >1% at screening). The 2 study groups were comparable with regard to age, gender distribution, the presence of diabetes, concomitant medications, hydration, and contrast dose. Mean predose SCr was 1.6 +/- 0.4 mg/dL in both groups (P = 0.9). An absolute increase > or =0.5 mg/dL (44.2 micromol/L) in SCr was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76) of patients receiving iodixanol-320 (95% confidence interval -6.2, 1.0, P = 0.2). A relative increase > or =25% in SCr occurred in 4% (3/77) of patients receiving iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95% confidence interval -6.2, 6.1, P = 1.0). The rate of CIN was similarly low in risk patients after intravenous administration of iopamidol-370 or iodixanol-320 for CE-MDCT.