Maximum Serum Creatinine Level Research Articles

Early predictive factors for progression to kidney failure in infants with severe congenital anomalies of the kidney and urinary tract.

Severe congenital anomalies of the kidney and urinary tract (CAKUT) progress to infantile kidney failure with replacement therapy (KFRT). Although prompt and precise prediction of kidney outcomes is important, early predictive factors for its progression remain incompletely defined. This retrospective cohort study included patients with CAKUT treated at 12 centers between 2009 and 2020. Patients with a maximum serum creatinine level ≤ 1.0mg/dL during the first 3days, patients who died of respiratory failure during the neonatal period, patients who progressed to KFRT within the first 3days, and patients lacking sufficient data were excluded. Of 2187 patients with CAKUT, 92 were finally analyzed. Twenty-five patients (27%) progressed to KFRT and 24 (26%) had stage 3-5 chronic kidney disease without replacement therapy during the median observation period of 52.0 (interquartile range, 22.0-87.8) months. Among these, 22 (24%) progressed to infantile KFRT. The kidney survival rate during the infantile period was significantly lower in patients with a maximum serum creatinine level during the first 3days (Cr-day3-max) ≥ 2.5mg/dL (21.8%) compared with those with a Cr-day3-max < 2.5mg/dL (95.2%) (log-rank, P < 0.001). Multivariate analysis demonstrated Cr-day3-max (P < 0.001) and oligohydramnios (P = 0.025) were associated with higher risk of infantile KFRT. Eighty-two patients (89%) were alive at the last follow-up. Neonatal kidney function, including Cr-day3-max, was associated with kidney outcomes in patients with severe CAKUT. Aggressive therapy for severe CAKUT may have good long-term life outcomes through infantile dialysis and kidney transplantation. A higher resolution version of the Graphical abstract is available as Supplementary information.

Disease severity and renal outcomes of patients with chronic kidney disease infected with COVID-19

IntroductionWhile there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking.MethodsThis retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization (“baseline serum creatinine”) and at admission, as well as minimum and maximum serum creatinine levels during hospitalization.ResultsAmong 658 patients, 152 had eGFR < 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8–8.7; p < 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1–10.8) for renal replacement therapy (p < 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p < 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p < 0.001).ConclusionDespite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.

Association between diffuse renal uptake of 18F-FDG and acute kidney injury.

The aim of this study was to investigate the clinical characteristics of patients with diffuse renal uptake (DRU) of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG), with particular focus on renal function. We retrospectively analyzed 40 patients who showed DRU on FDG PET/CT and the same number of matched controls. The clinical features, imaging parameters (the mean SUVmax of the kidneys and the kidney size), and laboratory data including renal function parameters (Cr, the serum creatinine level; estimated glomerular filtration ratio (eGFR); Cr-ratio, Cr divided by the baseline; max-Cr-ratio, the maximum serum creatinine level within 30days divided by the baseline) and C-reactive protein (CRP) were compared between the two groups. In the DRU group, follow-up FDG PET/CT scans were additionally evaluated to determine the presence of DRU. No significant differences were observed in the clinical features except for antibiotic administration, Cr, and eGFR. Significantly more patients underwent antibiotic administration within 30days in the DRU group (p = 0.002). The mean SUVmax of the kidneys was significantly higher (p < 0.001) and the kidney size was significantly larger in the DRU group (p = 0.003). Cr-ratio and max-Cr-ratio were significantly higher in the DRU group (p = 0.005 and p < 0.001, respectively). CRP was significantly higher in the DRU group (p < 0.001). Eighteen of the 40 patients in the DRU group underwent a second FDG PET/CT scan, and 16 of them did not show DRU. Six of the 18 patients showed acute kidney injury (AKI, i.e., Cr-ratio ≥ 1.5) at the time of the initial scan and recovered before the second scan. None of the six patients showed DRU on the second scan. DRU indicates the presence of AKI, could be a reversible finding, and may disappear as renal function improves.

Association between Ureteral Clamping Time and Acute Kidney Injury during Robot-Assisted Radical Cystectomy.

Robot-assisted radical cystectomy (RARC) is replacing open radical cystectomy (ORC) and requires clamping of the ureters, resulting in a predisposition to postrenal acute kidney injury (AKI). We investigated the association between ureteral clamping or its duration and acute/chronic postoperative kidney function. Patients who underwent radical cystectomy (robotic or open) at two tertiary institutions during 2002–2021 were retrospectively enrolled. In those who underwent RARC, the maximum postoperative percentage serum creatinine level (%sCre) change was plotted against ureteral clamping duration. They were divided into two groups using the median clamping time (210 min), and the maximum %sCre change and percentage estimated glomerular filtration rate (%eGFR) change at 3–6 months (chronic) were compared between the ORC (no clamp), RARC < 210, and RARC ≥ 210 groups. In 44 RARC patients, a weak correlation was observed between the duration of ureteral clamping and %Cre change (R2 = 0.22, p = 0.001). Baseline serum creatinine levels were comparable between the groups. However, %sCre change was significantly larger in the RARC ≥ 210 group (N = 17, +32.1%) than those in the RARC < 210 (N = 27, +6.1%) and ORC (N = 76, +9.5%) groups (both, p < 0.001). Chronic %eGFR change was comparable between the groups. Longer clamping of the ureter during RARC may precipitate AKI; therefore, the clamping duration should be minimized.

Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients.

BackgroundAcute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25–29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known.MethodsWe retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients.ResultsIn non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597).ConclusionTriple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents.

The Invisible Threat of Non-steroidal Anti-inflammatory Drugs for Kidneys.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) are often used as analgesic and antipyretic drugs. Nephrotoxicity is a common side effect and leads in 1–5% of pediatric cases to acute kidney injury (AKI). The nephrotoxic effects of NSAIDs arise mainly from two pathological mechanisms: (1) acute tubulo-interstitial nephritis (ATIN) following immune reaction and (2) prerenal failure because of reduced renal plasma flow. Histological examinations are required to confirm the pathomechanism of AKI after NSAID exposure. The aim of this study was to illustrate the risk of ATIN in children with AKI after NSAID exposure.Results: The medical records of all 100 pediatric patients with biopsy-proven AKI treated between January 2006 and 2016 at La Timone Hospital, Marseille, France, were analyzed retrospectively. Twenty-five of these patients had ATIN, four of which were healthy children who had been treated with NSAIDs. In other words, NSAID side effects accounted for 4% of all cases of biopsy-proven AKI and 16% of all cases of ATIN. None of the patients had hypovolemia when they received NSAIDs. Clinical symptoms were non-specific. All patients had abdominal pain and vomiting but normal urine volume output. Maximum serum creatinine levels ranged from 300 to 512 μmol/l, with estimated minimum creatinine clearances of 12–26 ml/min/1.73 m2. None of the patients had significant proteinuria. One child had hyperechogenic enlarged kidneys. Three patients were treated with steroids, one of whom also received intravenous methylprednisolone. Renal function improved gradually in all patients, but the patient who received methylprednisolone developed moderate chronic kidney disease (CKD).Conclusions: Biopsy proven-AKI secondary to NSAID use can be severe and be associated with ATIN. Since NSAID-induced ATIN can lead to CKD, clinicians using NSAIDs should focus on preventing AKI.

Predictors of Organ Donation Among Patients With Brain Death in the Intensive Care Unit

IntroductionDespite the improved care of potential organ donors with probable brain death (BD) in the intensive care unit (ICU), few epidemiologic and clinical data are available in developing countries. ObjectivesTo evaluate ICU patients with suspected BD aiming to identify factors possibly related to success (organ donation) or failure (nondonation). MethodsRetrospective cohort study, from the patient records of an adult ICU of a Brazilian teaching hospital for 12 months. Data were tabulated, and descriptive statistics and univariate and multivariate analyses were performed. ResultsDuring the study period, 85 patients with acute neurologic diseases and suspected BD were admitted to the ICU and included for analysis. Of these, there were 9 organ donors (7 liver and 9 kidney donors); 77.7% were men, with a mean age of 39.6 years and admission Acute Physiology and Chronic Health Evaluation II of 25.5. Two-thirds of the patients were victims of trauma. The mean time between acute neurologic event and organ withdrawal was 269 hours. The main prognostic factors related to the success of organ donation were the maximum serum lactate and creatinine levels during ICU admission. ConclusionsThe main clinical factors correlated with nonevolution for organ donation among ICU patients with clinical suspicion of BD were related to patient severity and organic dysfunction: serum lactate and creatinine level. Clinical care and monitoring are emphasized to improve the efficiency of the donation process.

Lp25 membrane protein from pathogenic Leptospira spp. is associated with rhabdomyolysis and oliguric acute kidney injury in a guinea pig model of leptospirosis.

Acute kidney injury (AKI) from leptospirosis is frequently nonoliguric with hypo- or normokalemia. Higher serum potassium levels are observed in non-survivor patients and may have been caused by more severe AKI, metabolic disarrangement, or rhabdomyolysis. An association between the creatine phosphokinase (CPK) level and maximum serum creatinine level has been observed in these patients, which suggests that rhabdomyolysis contributes to severe AKI and hyperkalemia. LipL32 and Lp25 are conserved proteins in pathogenic strains of Leptospira spp., but these proteins have no known function. This study evaluated the effect of these proteins on renal function in guinea pigs. Lp25 is an outer membrane protein that appears responsible for the development of oliguric AKI associated with hyperkalemia induced by rhabdomyolysis (e.g., elevated CPK, uric acid and serum phosphate). This study is the first characterization of a leptospiral outer membrane protein that is associated with severe manifestations of leptospirosis. Therapeutic methods to attenuate this protein and inhibit rhabdomyolysis-induced AKI could protect animals and patients from severe forms of this disease and decrease mortality.

Fluid Overload Is Associated With Higher Mortality and Morbidity in Pediatric Patients Undergoing Cardiac Surgery.

Fluid overload after pediatric cardiac surgery is common and has been shown to increase both mortality and morbidity. This study explores the risk factors of early postoperative fluid overload and its relationship with adverse outcomes. Secondary analysis of the prospectively collected data of children undergoing open-heart surgery between 2004 and 2008. Tertiary national cardiac center. One thousand five hundred twenty consecutive pediatric patients (<18 years old) were included in the analyses. None. In the first 72 hours of the postoperative period, the daily fluid balance was calculated as milliliter per kilogram and the daily fluid overload was calculated as fluid balance (L)/weight (kg) × 100. The primary endpoint was in-hospital mortality; the secondary outcomes were low cardiac output syndrome and prolonged mechanical ventilation. One thousand three hundred and sixty-seven patients (89.9%) had a cumulative fluid overload below 5%; 120 patients (7.8%), between 5% and 10%; and 33 patients (2.1%), above 10%. After multivariable analysis, higher fluid overload on the day of the surgery was independently associated with mortality (adjusted odds ratio, 1.14; 95% CI, 1.008-1.303; p = 0.041) and low cardiac output syndrome (adjusted odds ratio, 1.21; 95% CI, 1.12-1.30; p = 0.001). Higher maximum serum creatinine levels (adjusted odds ratio, 1.01; 95% CI, 1.003-1.021; p = 0.009), maximum vasoactive-inotropic scores (adjusted odds ratio, 1.01; 95% CI, 1.005-1.029; p = 0.042), and higher blood loss on the day of the surgery (adjusted odds ratio, 1.01; 95% CI, 1.004-1.025; p = 0.015) were associated with a higher risk of fluid overload that was greater than 5%. Fluid overload in the early postoperative period was associated with higher mortality and morbidity. Risk factors for fluid overload include underlying kidney dysfunction, hemodynamic instability, and higher blood loss on the day of the surgery.

Combined predictive value of the expanded donor criteria for long-term graft survival of kidneys from donors after cardiac death: A single-center experience over three decades.

Kidneys procured from the deceased hold great potential for expanding the donor pool. The aims of the present study were to investigate the post-transplant outcomes of renal allografts recovered from donors after cardiac death, to identify risk factors affecting the renal prognosis and to compare the long-term survival from donors after cardiac death according to the number of risk factors shown by expanded criteria donors. A total of 443 grafts recovered using an in situ regional cooling technique from 1983 to 2011 were assessed. To assess the combined predictive value of the significant expanded criteria donor risk criteria, the patients were divided into three groups: those with no expanded criteria donor risk factors (no risk), one expanded criteria donor risk factor (single-risk) and two or more expanded criteria donor risk factors (multiple-risk). Among the donor factors, age ≥50 years, hypertension, maximum serum creatinine level ≥1.5 mg/dL and a warm ischemia time ≥30 min were identified as independent predictors of long-term graft failure on multivariate analysis. Regarding the expanded criteria donors criteria for marginal donors, cerebrovascular disease, hypertension and maximum serum creatinine level ≥1.5 mg/dL were identified as significant predictors on univariate analysis. The single- and multiple-risk groups showed 2.01- and 2.40-fold higher risks of graft loss, respectively. Renal grafts recovered from donors after cardiac death donors have a good renal function with an excellent long-term graft survival. However, an increased number of expanded criteria donors risk factors increase the risk of graft loss.

Russells Viper Envenomation-associated Acute Kidney Injury in Children in Southern India.

To determine the frequency and risk factors of acute kidney injury in children with Russells viper envenomation using Acute Kidney Injury Network definition and classification system. A prospective observational study recruiting 61 subjects managed as per the National Snakebite Protocol. 45.9% of envenomed children had acute kidney injury. The median (IQR) of the maximum serum creatinine level during hospitalization was 2 (1.3-4.8) mg/dL. The distribution of stages 1, 2 and 3 of acute kidney injury was 32.1%, 17.9% and 50% respectively. Dialysis was required in 35.7% of the children with acute kidney injury. Acute kidney injury is common with Russells viper envenomation. Native treatments and bleeding manifestations were associated with acute kidney injury in our patient population.

Relationship between acute kidney injury before thoracic endovascular aneurysm repair and in-hospital outcomes in patients with type B acute aortic dissection.

ObjectiveAcute kidney injury (AKI) frequently occurs after catheter-based interventional procedures and increases mortality. However, the implications of AKI before thoracic endovascular aneurysm repair (TEVAR) of type B acute aortic dissection (AAD) remain unclear. This study evaluated the incidence, predictors, and in-hospital outcomes of AKI before TEVAR in patients with type B AAD.MethodsBetween 2009 and 2013, 76 patients were retrospectively evaluated who received TEVAR for type B AAD within 36 h from symptom onset. The patients were classified into no-AKI vs. AKI groups, and the severity of AKI was further staged according to kidney disease: improving global outcomes criteria before TEVAR.ResultsThe incidence of preoperative AKI was 36.8%. In-hospital complications was significantly higher in patients with preoperative AKI compared with no-AKI (50.0% vs. 4.2%, respectively; P < 0.001), including acute renal failure (21.4% vs. 0, respectively; P < 0.001), and they increased with severity of AKI (P < 0.001). The maximum levels of body temperature and white blood cell count were significantly related to maximum serum creatinine level before TEVAR. Multivariate analysis showed that systolic blood pressure on admission (OR: 1.023; 95% CI: 1.003–1.044; P = 0.0238) and bilateral renal artery involvement (OR: 19.076; 95% CI: 1.914–190.164; P = 0.0120) were strong predictors of preoperative AKI.ConclusionsPreoperative AKI frequently occurred in patients with type B AAD, and correlated with higher in-hospital complications and enhanced inflammatory reaction. Systolic blood pressure on admission and bilateral renal artery involvement were major risk factors for AKI before TEVAR.

Spleen enlargement is a common finding in acute Puumala hantavirus infection and it does not associate with thrombocytopenia.

The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5-8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury.

Association of ethnicity and acute kidney injury after cardiac surgery in a South East Asian population

Postoperative acute kidney injury (AKI) is a frequent and serious complication after cardiac surgery. Clinical factors alone have failed to accurately predict the incidence of AKI after cardiac surgery. Ethnicity has been shown to be a predictor of AKI in the Western population. We tested the hypothesis that ethnicity is an independent predictor of AKI in patients undergoing cardiac surgery in a South East Asian population. A total of 1756 consecutive patients undergoing cardiac surgery were prospectively recruited. Among them, data of 1639 patients met the criteria for analysis. There were 1182 Chinese, 195 Indian, and 262 Malay patients. The main outcome was postoperative AKI, defined as a 25% or greater increase in preoperative to a maximum postoperative serum creatinine level within 3 days after surgery. Five hundred and seventy-nine patients (35.3%) developed AKI after cardiac surgery. Ethnicity was shown to be an independent predictor of AKI after cardiac surgery with Indians and Malays having a higher risk of developing AKI when compared with Chinese patients (odds ratio: Indian vs Chinese 1.44, Malay vs Chinese 1.51). Indians and Malays have a higher risk of developing AKI after cardiac surgery than Chinese in a South East Asian population. Ethnicity was shown to be an independent predictor of AKI after cardiac surgery.

Renal Toxicity Caused by Brand-name Versus Generic Cisplatin: A Comparative Analysis

A generic cisplatin formulation has replaced the brand-name formulation since November 2003 in our hospital. We retrospectively assessed the renal toxicity caused by the brand-name and generic cisplatin formulations. The medical records of patients with thoracic malignancy who were treated at our hospital between November 2000 and April 2008 were reviewed. In total, 1296 eligible patients received 80 mg/m(2) of cisplatin: 499 patients were treated with the brand-name cisplatin formulation before November 2003 (Group 1) and 797 patients were treated with the generic formulation after November 2003 (Group 2). We compared the maximum serum creatinine level after chemotherapy in the two groups. The patient characteristics, including age, sex and performance status, and pretreatment serum creatinine levels were well balanced between the two groups. More patients received four cycles of chemotherapy in Group 2 (P < 0.0001). The median (range) of the maximum serum creatinine levels during all the chemotherapy cycles were 1.1 (0.5-4.1) mg/dl and 1.1 (0.5-4.4) mg/dl in Groups 1 and 2, respectively (P = 0.0237). The incidence of grade 0 serum creatinine elevations decreased from 47% to 39%, while that of grade 1 serum creatinine elevations increased from 32% to 41% (P = 0.0094). The incidence rates of grade 2 or 3 serum creatinine elevations were similar (21 vs. 20%). The time to serum creatinine elevation was also similar in Groups 1 and 2 (P = 0.161). Although grade 1 maximum serum creatinine level was more common in the generic cisplatin formulation group, this was attributed to the larger number of patients receiving four cycles of chemotherapy in this group.

Moderate renal dysfunction may not require a cisplatin dose reduction: a retrospective study of cancer patients with renal impairment

The aim of this study was to assess the tolerability of cisplatin (CDDP) in patients with moderate renal dysfunction. To investigate the relationship between CDDP dose and nephrotoxicity, a retrospective chart review was conducted of patients with a creatinine clearance (Ccr) of 30-60mL/min. Subjects were classified into three groups according to the CDDP dose, as determined by the physician, and the nephrotoxicity among these groups was compared. Additionally, we investigated the correlation coefficients between maximum serum creatinine (Scr) level or minimum estimated glomerular filtration rate (eGFR) and baseline Ccr. Fifty-six patients were included in this study. Among these patients, 13 patients received 30-40mg/m(2) CDDP (group I), 18 patients received 40-70mg/m(2) (group II), and 25 patients received 70-80mg/m(2) (group III). No significant difference in nephrotoxicity was observed (median Scr 1.53, 1.61, and 1.53mg/dL, respectively), and no correlation was observed between baseline Ccr and maximum Scr (r=0.004, p=0.979) or minimum eGFR (r=0.21, p=0.119). Only two patients (3.5%) experienced grade 3 or 4 Scr elevation-one patient with a Ccr of 52.6mL/min received 60mg/m(2) CDDP, and the other patient with a Ccr of 52.1mL/min received 70mg/m(2) of CDDP. Hemodialysis was not observed. CDDP was tolerated at doses of 35-80mg/m(2) among patients with moderate renal impairment. Empiric dose reduction might create a risk of under-treatment.

Authors' Reply: Urinary Cytokines in BK Viruria

We are writing in response to the letter by Dr. Vanchiere, commenting on our article “Urinary Proinflammatory Cytokine Response in Renal Transplant Recipients With Polyomavirus BK Viruria.” Urine cytokine levels of 65 renal transplant outpatients with (BK positive) or without BK viruria (BK negative, n=33), low- (n=16) or high-level (n=16) BK viral load (VL), and 24 healthy controls (HCs) were analyzed. Dr. Vanchiere questioned the normalized urine cytokine levels, the presence of JC virus and cytomegalovirus (CMV) in the urine samples, the cytokine levels in serial urine specimens, and the ethnicity of the transplant recipients and HCs in our study. He asked for additional or confirmatory data. Our data were obtained in transplant recipients with only low retention. Maximum urine and serum creatinine levels in the 65 transplant recipients were 220 and 2.4 mg/dL, respectively. A retrospective normalization of the urine cytokine levels, calculating urine cytokine/ urine creatinine ratios, confirmed the published results. BK-positive patients (n=32), and particularly BK-positive patients with high VL (n=16), showed higher sIL-1RA (P=0.08 and P=0.041, respectively), interleukin (IL)-3 (P=0.002 and P=0.016, respectively), IL-6 (P=0.02 and P=0.003, respectively), and sIL-6R (P=0.006 and P=0.001, respectively) urine cytokine/urine creatinine ratios than BK-negative patients (n=33). A second urine specimen, obtained 99±128 days (mean±SD) after the first sample, was available from 13 patients. BK VL remained high in four and decreased in three patients with initially high VL, four patients showed low BK VL in both urine samples, and two initially BK-negative patients developed a low BK VL subsequently. Normalized and not normalized sIL-1RA, IL-3, IL-6, and sIL-6R levels were similar in the 2 urine samples of the 11 consistently BK-positive patients (P>0.05), indicating the stability of increased urine cytokine levels in BK-positive patients. Unfortunately, stability of low cytokine levels in the urine of BK-negative patients could not be tested, because the necessary samples were not available. We tested 42 available urine samples of the first series retrospectively for the presence of JC virus and CMV. Four of the 42 samples contained JC virus, and two samples contained CMV. Of the four JC virus-positive samples, one was BK positive and three were BK negative; of the two CMV-positive specimens, one was BK positive and one was BK negative. Because of the low frequency of CMV and JC virus in BK-positive urine samples, we would not expect that the high urine cytokine levels in BK-positive patients were associated with active CMV or JC virus infection. Ethnicity did not affect our data, because all patients and HCs were whites. In summary, additional analyses confirmed the previous finding that strong BK virus replication was associated with the strong increases of particular cytokines and soluble cytokine receptors in the urine. The increase of cytokine and cytokine receptor levels in the urine of consistently BK-positive patients was stable and may be helpful for disease monitoring. Mahmoud Sadeghi1 Volker Daniel1 Paul Schnitzler2 Imad Lahdou1 Cord Naujokat1 Martin Zeier3 Gerhard Opelz1 1 Department of Transplantation Immunology University of Heidelberg Heidelberg, Germany 2 Department of Virology University of Heidelberg Heidelberg, Germany 3 Department of Nephrology University of Heidelberg Heidelberg, Germany

Risk factors for deterioration of renal function after coronary artery bypass grafting

Various definitions of impairment of renal function after coronary artery bypass grafting (CABG) are used in the literature. Depending on the definition, several risk factors are identified. We analysed our data to determine the risk factors for postoperative deterioration of the creatinine clearance of 10% or more. All patients undergoing isolated coronary surgery in a single centre between January 1998 and December 2007 are included. Clinical data, including demographics and renal risk factors, were prospectively collected in our database. The most recent preoperative serum creatinine level and the maximum serum creatinine level within the first week postoperatively were used to calculate the creatinine clearance. A deterioration of 10% or more was considered to be an endpoint for this study. In 10098 out of a total of 10626 patients, the preoperative as well as the postoperative creatinine clearance could be calculated. In 1053 patients, the deterioration of the creatinine clearance was 10% or more. We could identify the following risk factors: advanced age, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, emergency operation, previous cardiac surgery, low preoperative haemoglobin level, high preoperative C-reactive protein level, perioperative myocardial infarction, re-exploration and the number of blood transfusions. Risk factors for the deterioration of renal function after revascularisation have been confirmed in this study. In addition, we found peripheral vascular disease, previous cardiac surgery, low preoperative haemoglobin, increased preoperative C-reactive protein level, perioperative myocardial infarction and the number of blood transfusions to be risk factors that have not been described earlier.

Cellular immune response to Hantaan virus nucleocapsid protein during the acute phase of hemorrhagic fever with renal syndrome: negative correlation with disease severity (128.13)

Abstract The cellular immune response to Hantaan virus (HTNV) is incompletely understood, especially in humans. To investigate the cellular immunity during acute HTNV infection, the magnitude of T cell response to HTNV nucleocapsid protein was quantitated by direct ex vivo IFN-γ ELISPOT using overlapping peptides. We found that the combined frequencies of HTNV-specific T cells at early time point were significantly higher in patients with mild or moderate hemorrhagic fever with renal syndrome (HFRS) than in those with severe or critical HFRS (P = .006). Moreover, these frequencies were higher in patients with subsequent mild renal failure (maximum serum creatinine level, =707 μmol/L) than in those with subsequent severe renal failure (maximum serum creatinine level, &amp;gt;707 μmol/L) (P = .006). Kinetic analysis showed that a decrease in the serum creatinine level during the acute phase of illness was often accompanied by an increase in the magnitude of IFN-γ-producing T cells. These data suggest that IFN-γ-producing T cells may help reduce the risk of progression to acute renal failure caused by HTNV infection. This work was supported by grants from the National Natural Science Foundation of China (No.30471625).

Cellular Immune Response to Hantaan Virus Nucleocapsid Protein in the Acute Phase of Hemorrhagic Fever with Renal Syndrome: Correlation with Disease Severity

The cellular immune response to Hantaan virus (HTNV) is incompletely understood, especially in humans. To investigate the cellular immunity during acute HTNV infection, the magnitude of the CD4(+) and CD8(+) T cell responses to HTNV nucleocapsid protein was quantitated by direct ex vivo interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot analysis, using an array of overlapping peptides. We found that the combined frequencies of HTNV-specific T cells at the earliest available time point (5-8 days after fever onset) were significantly higher in patients who had mild or moderate hemorrhagic fever with renal syndrome (HFRS) than in those who had severe or critical HFRS (P= .006). Moreover, these frequencies were higher in patients with subsequent mild renal failure (maximum serum creatinine level, <or=707 micromol/L) than in those with subsequent severe renal failure (maximum serum creatinine level, >707 micromol/L) (P= .006). Kinetic analysis showed that a decrease in the serum creatinine level during the acute phase of illness was often accompanied by an increase in the magnitude of IFN-gamma-producing T cells. Taken together with published data on the similar associations with neutralizing antibody, these data suggest that IFN-gamma-producing T cells may help reduce the risk of progression to acute renal failure caused by HTNV infection.