Acute Tubular Necrosis Patients Research Articles

Evaluation of Urinary Interleukin-18 Changes in Patients Treated with Vancomycin

Background: Vancomycin, used to treat severe gram-positive infections, can induce acute kidney injury. Some evidence introduced Interleukin-18 (IL-18) as an inflammatory mediator of ischemic damage to many organs and urinary IL-18 as a diagnostic biomarker of acute tubular necrosis. Objective: The current study aimed to evaluate the urinary level of IL-18 after vancomycin therapy. Methods: This cross-sectional study was conducted on patients under treatment with vancomycin selected from those referred to Dr. Sheikh Hospital, Mashhad, Iran, from 2018-2019. Urinary IL-18 was measured based on nanograms per milliliter using a human IL-18 enzyme-linked immunosorbent assay kit about this cytokine before vancomycin administration and then two days later. All the analyses were performed in SPSS software (version 25), and a P-value less than 0.05 was considered statistically significant. Results: A total of 36 patients with a mean age of 40.06±36.67 months were included in the study. The mean scores of IL-18 before and after taking vancomycin were 1453.00±555.01 and 1713.00±660.98, respectively. The IL-18 was significantly lower before vancomycin consumption than the level reported after 48 h (P<0.05). Conclusions: The present study highlighted a higher level of urinary IL-18 after vancomycin treatment, which may indicate kidney injuries. Therefore, it may be considered a potential biomarker of acute tubular necrosis in patients under vancomycin therapy.

Urinary proteomics identifies oxidative stress and inflammation pathways as key factors differentiating acute-kidney injury-hepatorenal syndrome from acute tubular necrosis in patients with cirrhosis

Urinary proteomics identifies oxidative stress and inflammation pathways as key factors differentiating acute-kidney injury-hepatorenal syndrome from acute tubular necrosis in patients with cirrhosis

Clinical and pathological characteristics of patients with acute kidney injury in Japan in whom kidney biopsy was performed: a cross-sectional analysis of the Japan Renal Biopsy Registry (J‑RBR).

Acute kidney injury (AKI) is a worldwide concern and it leads to a poor prognosis or end-stage kidney disease. The purpose of this study was to clarify the characteristics of patients with AKI in whom kidney biopsy was performed using data of the Japan Renal Biopsy Registry (J-RBR). We screened 38,351 cases that were registered in the J-RBR from 2007 to 2018. We obtained data for 383 patients with AKI based on clinical diagnosis for analysis 1 and data for 714 patients with acute interstitial nephritis (AIN) or acute tubular necrosis (ATN) based on pathological diagnosis for analysis 2. Of the cases screened, 383 patients with AKI (1.0%) were included in analysis 1. The main pathological diagnoses of AKI were AIN, ATN, chronic interstitial nephritis, nephro-sclerosis and crescentic glomerulonephritis. Of the cases screened, 589 patients with AIN (1.5%) and 110 patients with ATN (0.3%) were included in analysis 2. The main clinical diagnoses of AIN were AKI, rapidly progressive glomerulonephritis (RPGN), chronic nephritic syndrome (CNS) and drug-induced nephropathy (DIN), whereas those of ATN were AKI, RPGN, DIN and CNS. ATN patients had a higher serum creatinine level than that of AIN patients. Our results revealed that cases in the J-RBR included 1.0% of AKI cases based on clinical diagnosis and 1.5% and 0.3% of AIN and ATN cases, respectively, based on pathological diagnosis. In patients with suspected intrinsic AKI, kidney biopsy should be performed for diagnosis of the precise etiology and selection of appropriate treatment.

MO335URINARY CYTOKINES REFLECT THE ONGOING RENAL INFLAMMATION IN THE DIAGNOSTIC OF ACUTE TUBULOINTERSTITIAL NEPHRITIS: RESULTS OF A MULTIPLEX BEAD-BASED ASSAY ASSESSMENT

Abstract Background and Aims Acute tubulointerstitial nephritis (ATIN) diagnostic lays on the kidney biopsy given the absence of non-invasive biomarkers for disease demonstration and follow-up. The aim of this study was to evaluate the accuracy of ten urinary inflammatory-related cytokines in the diagnostic of ATIN and its clinical distinction from acute tubular necrosis (ATN). Method Observational prospective study including 21 ATIN and 12 ATN patients, and 6 healthy controls. We determined the urinary levels of 10 inflammation-related cytokines using a multiplex bead-based Luminex assay. We registered clinical, analytical and histological data from the medical records. Results Urinary levels of I-TAC/CXCL11, CXCL10, IL-6, TNFα and MCP-1 were higher in ATIN compared to healthy controls. In contrast, healthy controls exhibited higher EGF urinary levels compared to ATIN patients. Follow-up samples available from 11/21 ATIN patients showed a significant decrease in I-TAC/CXCL11, MIG/CXCL9 and CXCL10 levels. Urinary levels of I-TAC/CXCL11, IL-6 and MCP-1 were significantly higher in ATIN compared to ATN patients, with I-TAC/CXCL11 as the best discriminatory biomarker based on its higher AUC in the ROC curve and likelihood ratio. The combinatory model of the three cytokines increased the sensitivity of the individual biomarkers in the distinction of ATIN/ATN but the best results were obtained when blood eosinophil count and leukocyturia were added to the model. We found a positive correlation of the extent of the tubulointerstitial infiltrate in kidney biopsies with the urinary concentration of I-TAC/CXCL11, MIG/CXCL9, CXCL10, IL17, IFNα, MCP1 and EGF, indicating the potential renal source of the cytokines Conclusion the higher cytokine levels in ATIN compared to ATN patients and healthy controls, the significant decline after treatment and the positive correlation of the cytokines with the grade of the inflammatory infiltrate allows us to propose I-TAC/CXCL11, CXCL10, IL6 and MCP-1 as candidate biomarkers in this disease.

Clinical characteristics and related factors of acute tubular necrosis in patients with minimal change disease

Objective: To investigate the clinical characteristics and related factors of acute tubular necrosis (ATN) in patients with minimal change disease (MCD). Methods: Patients from Chinese PLA General Hospital who were pathologically diagnosed with MCD and had clinical manifestations of nephrotic syndrome from January 1, 2013 to December 31, 2019 were included. The clinical and pathological data of patients were retrospectively analyzed. Meanwhile, the incidence and clinical characteristics of ATN in different age groups were compared. The risk factors for ATN were assessed using binary logistic regression. Results: A total of 525 patients were included, with a gender ratio of 1.56∶1 (male: female), aged 33 (21, 48) years old. ATN occurred in 49 (9.3%) of 525 patients, of which 34 were male and 15 were female. The incidence of ATN increased with age in MCD patients of different age groups (χ(2)=31.442, P<0.001). The incidence of ATN in groups of age≤20 years, 21-40 years, 41-60 years, and >60 years was 2.4% (3/123), 5.2% (10/192), 13.2% (20/152) and 27.6% (16/58), respectively. Elevations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) and serum IgE occurred in 92 patients (17.5%), 53 patients (10.1%), 99 patients (18.9%), and 303 patients (57.7%), respectively. There were significant differences in age, ALT, serum creatinine, serum urea nitrogen, history of diabetes and history of hypertension between non-ATN group and ATN group (all P<0.05). The results of logistic regression analysis showed that>40 years old (OR=6.283, 95% CI: 2.695-14.649, P<0.001) and serum albumin (OR=0.924, 95% CI: 0.857-0.997, P=0.040) was independently associated with ATN in MCD patients. Conclusion: Age>40 years is an independent risk factor and serum albumin is a protective factor for ATN in MCD patients.

Renal Tubular TRPA1 as a Risk Factor for Recovery of Renal Function from Acute Tubular Necrosis.

Background: Transient receptor potential ankyrin 1 (TRPA1), a redox-sensing Ca2+-influx channel, serves as a gatekeeper for inflammation. However, the role of TRPA1 in kidney injury remains elusive. Methods: The retrospective cohort study recruited 46 adult patients with acute kidney injury (AKI) and biopsy-proven acute tubular necrosis (ATN) and followed them up for more than three months. The subjects were divided into high- and low-renal-tubular-TRPA1-expression groups for the comparison of the total recovery of renal function and mortality within three months. The significance of TRPA1 in patient prognosis was evaluated using Kaplan–Meier curves and logistic regression analysis. Results: Of the 46 adult AKI patients with ATN, 12 totally recovered renal function. The expression level of tubular TRPA1 was detected by quantitative analysis of the immunohistochemistry of biopsy specimens from ATN patients. The AKI patients with high tubular TRPA1 expression showed a high incidence of nontotal renal function recovery than those with low tubular TRPA1 expression (OR = 7.14; 95%CI 1.35–37.75; p = 0.02). High TRPA1 expression was independently associated with nontotal recovery of renal function (adjusted OR = 6.86; 95%CI 1.26–37.27; p = 0.03). Conclusion: High tubular TRPA1 expression was associated with the nontotal recovery of renal function. Further mechanistic studies are warranted.

Biomarkers for acute kidney injury in decompensated cirrhosis: A prospective study.

Acute kidney injury (AKI) is a frequent complication in cirrhotic patients. As serum creatinine is a poor marker of renal function in this population, we aimed to study the utility of several biomarkers in this context. A prospective study was conducted in hospitalized patients with decompensated cirrhosis. Serum creatinine (SCr), Cystatin C (CystC), NGAL and urinary NGAL, KIM-1, protein, albumin and sodium were measured on three separate occasions. Renal resistive index (RRI) was obtained. We analyzed the value of these biomarkers to determine the presence of AKI, its aetiology [prerenal, acute tubular necrosis (ATN), or hepatorenal (HRS)], its severity and a composite clinical outcome at 30 days (death, dialysis and intensive care admission). We included 105 patients, of which 55 had AKI. SCr, CystC, NGAL (plasma and urinary), urinary sodium and RRI at inclusion were independently associated with the presence of AKI. SCr, CystC and plasma NGAL were able to predict the subsequent development of AKI. Pre-renal state showed lower levels of SCr, NGAL (plasma and urinary) and RRI. ATN patients had high levels of NGAL (plasma and urinary) as well as urinary protein and sodium. HRS patients presented an intermediate pattern. All biomarkers paralleled the severity of AKI. SCr, CystC and plasma NGAL predicted the development of the composite clinical outcome with the same performance as the MELD score. In patients with decompensated cirrhosis, early measurement of renal biomarkers provides valuable information on AKI aetiology. It could also improve AKI diagnosis and prognosis.

Epidemiology and Outcomes of Dialysis-Requiring Acute Kidney Injury at Chris Hani Baragwanath Hospital

Abstract Background: Acute kidney injury (AKI) occurs commonly within the hospital setting and is associated with a high rate of morbidity and mortality. Factors such as social, economic and ethical dilemmas are closely associated with initiation of dialysis in the public health sector. Methods: A retrospective review of 324 patients presenting with kidney failure who were initiated on acute dialysis at the Chris Hani Baragwanath Hospital was carried out over a 2-year period from July 2009 to June 2011. Results: The mean age at presentation was 40 ± 13 years; 57% of patients were male and 92% were Black. HIV positivity occurred in 26% of patients. The leading indications for acute dialysis included decompensated chronic kidney disease (38.9%), acute tubular necrosis (ATN) (38.3%), HIV-related kidney disease (13.6%), malaria (5.7%), pregnancy-related kidney disease (7.4%) and glomerulonephritis (7.4%). ATN was the predominant cause of AKI in HIV-positive patients. The overall renal recovery rate was 31%, and the overall mortality rate was 23%. About 44.6% of patients had chronic consequences, with 23% being transferred to chronic renal replacement therapy (RRT) and 21.6% transferred to renal outpatients (ROPD) with cessation of dialysis; 1.4% were lost to follow-up. While HIV-positive patients had a better renal recovery rate compared to HIV-negative patients (36% versus 26%; p &lt; 0.0001), they had a higher mortality rate compared to their HIV-negative counterparts (34% versus 19%; p &lt; 0.0001). Conclusion: AKI remains a common presentation that often requires dialysis, a precious resource in an already overburdened health system, and occurs at similar rates in HIV-positive and HIV-negative patients. The underlying aetiology of AKI at Chris Hani Baragwanath resembles that of other developing countries with ATN, malaria, sepsis and pregnancy-induced kidney injury amongst the leading causes. High mortality rates were observed in patients with ATN, in both HIV-positive and HIV-negative patients.

Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease

Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13–71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

Urine Interleukin 18 and Lipocalin 2 Are Biomarkers of Acute Tubular Necrosis in Patients With Cirrhosis: A Systematic Review and Meta-analysis

Acute kidney injury (AKI) is a common complication in patients with cirrhosis that increases mortality. The most common causes of AKI in these patients are prerenal azotemia, acute tubular necrosis (ATN), and hepatorenal syndrome; it is important to determine the etiology of AKI to select the proper treatment and predict patient outcome. Urine biomarkers could be used to differentiate between patients with ATN and functional causes of AKI. We performed a systematic review and meta-analysis of published studies to determine whether urine levels of interleukin (IL)18 and lipocalin 2 or neutrophil gelatinase-associated lipocalin (NGAL) are associated with the development of ATN in patients with cirrhosis. We searched MEDLINE, Scopus, ISI Web of Knowledge, and conference abstracts through December 31, 2015, for studies that assessed urine biomarkers for detection of acute kidney injury in patients with cirrhosis or reported an association between urine biomarkers and all-cause mortality in these patients. We included only biomarkers assessed in 3 or more independent studies, searching for terms that included urine biomarkers, cirrhosis, NGAL, and IL18. We calculated the pooled sensitivities and specificities for detection and calculated the area under the receiver operating characteristic curve (AUC) values using a bivariate logistic mixed-effects model. We used the χ2 test to assess heterogeneity among studies. We analyzed data from 8 prospective studies, comprising 1129 patients with cirrhosis. We found urine levels of the markers discriminated between patients with ATN and other types of kidney impairments, with AUC values of 0.88 for IL18 (95% confidence interval [CI], 0.79-0.97) and 0.89 for NGAL (95% CI, 0.84-0.94). Urine levels of IL18 identified patients who would die in the hospital or within 90 days (short-term mortality) with an AUC value of 0.76 (95% CI, 0.68-0.85); NGAL identified these patients with the same AUC (0.76; 95% CI, 0.71-0.82). In a systematic review and meta-analysis, we found that urine levels of IL18 and NGAL from patients with cirrhosis discriminate between those with ATN and other types of kidney impairments, with AUC values of 0.88 and 0.89, respectively. Urine levels of IL18 and NGAL identified patients with short-term mortality with an AUC value of 0.76. These biomarkers might be used to determine prognosis and select treatments for patients with cirrhosis.

Urinary Albumin Excretion Patterns of Patients with Cast Nephropathy and Other Monoclonal Gammopathy–Related Kidney Diseases

Multiple myeloma is responsible for a wide variety of renal pathologies. Urinary protein and monoclonal spike cannot be used to diagnose cast nephropathy (CN). Because albuminuria is a hallmark of glomerular disease, this study evaluated the percentage of urinary albumin excretion (%UAE) as a tool to differentiate CN from Ig light chain amyloidosis (AL), light chain deposition disease (LCDD), and acute tubular necrosis (ATN). Patients were selected from the Renal Biopsy Database and the Dysproteinemia Database. Participants were excluded if laboratory data were missing within 1 week of the renal biopsy. The %UAE was obtained from urine protein electrophoresis. From 1992 to 2011, 260 patients were biopsied (177 with AL, 28 with LCDD, 43 with CN, and 12 with ATN). The %UAE for CN patients was significantly lower (7%) than for ATN (25%), LCDD (55%), and AL (70%) patients (P<0.001). Significant differences were also found in serum creatinine, serum albumin, free light chain ratio, total urine protein, and urine monoclonal spike; only the %UAE remained independently associated with CN in a logistic regression model (P<0.001). The area under the curve for the receiver operator characteristic curve for %UAE was 0.99. At <25%, the %UAE had a sensitivity of 0.98, specificity of 0.94, positive predictive value of 0.75, and negative predictive value of 0.99. This study showed that %UAE was significantly less in CN than the other three renal lesions and %UAE may thus be helpful in diagnosis of CN.

The meaning of the blood urea nitrogen/creatinine ratio in acute kidney injury.

Background.A blood urea nitrogen (BUN)/creatinine ratio (BCR) >20 (0.081 in international unit) is used to distinguish pre-renal azotemia (PRA) and acute tubular necrosis (ATN). However, there is little evidence that BCR can distinguish between these two conditions and/or is clinically useful.Methods.We conducted a retrospective study using a large hospital database. Patients were divided into three groups: ‘low BCR’ (if BCR when acute kidney injury (AKI) developed was ≤20), ‘high BCR’ (if BCR when AKI developed was >20) and ‘no AKI’ if patients did not satisfy any of the Risk, Injury, Failure, Loss and End-stage kidney disease criteria for AKI during hospitalization.Results.Among 20 126 study patients, 3641 (18.1%) had AKI. Among these patients, 1704 (46.8%) had a BCR <20 at AKI diagnosis (‘low BCR’) and 1937 (53.2%) had a BCR >20 (‘high BCR’). The average BCR for the two groups was 15.8 versus 26.1 (P < 0.001). Hospital mortality was significantly less in the ‘low-BCR’ group (18.4 versus 29.9%, P < 0.001). Multivariable logistic regression analysis for hospital mortality (‘no AKI’ as a reference) showed that the odds ratio of ‘high BCR’ (5.73) was higher than that of ‘low BCR’ (3.32).Conclusions.Approximately half of the patients with AKI have a BCR >20, the traditional threshold of diagnosing PRA. Unlike PRA patients who have a lower mortality than ATN patients, high BCR patients had higher hospital mortality compared with low BCR patients, which was confirmed with multivariable analysis. These findings do not support BCR as a marker of PRA.

Cytokine expression patterns in kidney transplant patients with acute tubular necrosis

Utilizing a custom antibody‐microarray we have identified unique expression patterns in the serum of kidney transplant patients with biopsy‐proven acute tubular necrosis (ATN) versus healthy transplant patients. Levels of Activin A, Fas Ligand, Fcγ RII, IL‐1α, IFN γ, MCP‐1, MCP‐2, MIP‐1α, MIP‐1βfz VEGF, BLC/BCA‐1, GM‐CSF, IP‐10 and IL‐1 RI were significantly increased (p&lt;0.05) in patients with ATN, relative to healthy transplants. A hallmark of ATN is regions of ischemia‐reperfusion (IRI) resulting in localized cellular injury within the tubules. Several current reports demonstrate the production of proinflammatory cytokines (MCP‐1, MCP‐2, MIP‐1α, MIP‐1β) by cells in the renal tubule of patients with ischemic renal failure. In addition, we have seen a significant decrease (p&lt;0.05) in Il‐5, Epo R, MIP‐3α, pro‐Cathepsin S, FGF‐6, TGFβ1, TIMP‐4, VEGF R2 and IL‐18 in ATN patients, relative to the stable transplant patients. These altered cytokine expression in patients with ATN associated renal graft dysfunction may occur at different stages of the disease, necessitating additional patients to confirm our findings. These patterns may eventually provide a biomarker signature of ATN, useful to differentiate patients with renal dysfunction, thus providing a sensitive, non‐invasive method to diagnose kidney injury. Work supported in part by NIH RO1 HL0709.

Expression of HLA-G and MICA mRNA in renal allograft

HLA-G is a nonclassical MHC class I antigen that displays tolerogenic functions; MICA is a stress-regulated molecule recognized by NKG2D cytotoxicity-activating receptor expressed by NK and T cells subsets. We evaluated HLA-G isoforms and MICA mRNA levels in peripheral blood mononuclear cells (PBMCs) and in biopsies from kidney allograft recipients with acute rejection (AR), chronic rejection (CR), and stable graft evolution (SE). HLA-G1 was the only transcript resulted from amplification, both in PBMCs as in biopsy samples. HLA-G1 mRNA levels in PBMCs from 9/10 patients with CR, 7/9 with AR and 8/10 healthy volunteers were below the median value of SE patients. The analysis of biopsies revealed that patients with AR ( n = 6), who overcame rejection had a tendency towards higher HLA-G1 levels than those with nephrotoxic acute tubular necrosis (ATN) ( n = 3). Similar levels of MICA expression were observed in PBMCs from AR, CR, SE and C groups; MICA expression levels were similar also in biopsy specimens from AR and nephrotoxic ATN patients. No correlation was found between MICA expression and the graft state. These preliminary results suggest that HLA-G1 isoforms, but not MICA mRNA levels, may provide a marker for measuring the state of kidney allograft, and be the basis for further studies that may establish the influence of these molecules in renal allograft rejection or acceptance.

Noninvasive Tim-3 Messenger RNA Evaluation in Renal Transplant Recipients With Graft Dysfunction

Renal biopsies are usually needed to elucidate graft dysfunction. In this study, T-cell immunoglobulin domain, mucin domain mRNA expression in the peripheral blood leukocytes (PBL) and urinary cells (UC) were studied as a noninvasive method for the diagnosis of acute rejection (AR) of kidney transplant patients with dysfunction. One hundred sixty biopsies were obtained from 115 patients. Blood and urine samples were collected immediately before the biopsies. Histopathologic diagnoses were acute tubular necrosis with superimposed AR or acute tubular necrosis in patients with delayed graft function (DGF), and (AR), or calcineurin inhibitor nephrotoxicity (CIN), or interstitial fibrosis and tubular atrophy in patients with acute graft dysfunction (AGD). Fifteen protocol biopsies of stable grafts were used as controls. mRNA relative quantification was performed by real-time polymerase chain reaction. Gene expression in tissue, PBL, and UC was always higher in patients with AR than in patients with the other causes of graft dysfunction (P<0.001). Significant correlations of gene expression in different compartments were observed (P<0.001). The obtained diagnostic parameters were 100% accurate in the DGF group and, respectively, for blood and urine: sensitivity (87% and 84%); specificity (95% and 96%); positive predictive value (87% and 89%); negative predictive value (93% and 94%); and accuracy (91% and 93%) for the group of patients with AGD. T-cell immunoglobulin domain, mucin domain mRNA quantification by real-time polymerase chain reaction in PBL and UC of renal transplant patients undergoing DGF or AGD may become a useful tool for an accurate noninvasive diagnosis of AR.

Diagnosis and treatment of acute renal failure in patients with cirrhosis

In patients with cirrhosis, acute renal failure is due to prerenal failure (a result of decreased renal perfusion) and tubular necrosis. There are 3 main causes of prerenal failure: 'true hypovolemia' (which complicates hemorrhage, gastrointestinal or renal fluid losses), sepsis, and type 1 hepatorenal syndrome (HRS). Prerenal failure may also be due to the administration of non-steroidal antiinflammatory drugs, or intravascular radiocontrast agents. Prerenal failure is reversible after restoration of renal blood flow. Treatments target the cause of hypoperfusion, and fluid replacement is used to treat 'non-HRS' prerenal failure. In patients with type 1 HRS with very low short-term survival rate, liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy with terlipressin (combined with intravenous human albumin), noradrenaline (combined with albumin and furosemide) or midodrine (combined with octreotide and albumin) may improve renal function in patients with type 1 HRS waiting for liver transplantation. MARS (for Molecular Adsorbent Recirculating System) and the transjugular intrahepatic portosystemic shunt may also improve renal function in these patients. In patients with cirrhosis, acute tubular necrosis is mainly due to an ischemic insult to the renal tubules. Studies are needed on the natural course and treatment (e.g., renal-replacement therapy) of acute tubular necrosis in patients with cirrhosis.

Enzymuria and low molecular weight protein excretion as the differentiating marker of complications in the early post kidney transplantation period

Renal function in the early post-transplantation period depends largely on factors affecting the kidney prior to implantation. Function of the graft may be also disturbed by the most common complications of the early post-operative period such as acute graft rejection (AGR), acute tubular necrosis (ATN) and may be modified by nephrotoxic action of cyclosporine A (CsA). Evaluation of excretion of enzymes and low molecular weight proteins (LMWP) may help in the differentiation of these complications. Aim Comparison of the urinary excretion of markers of tubular injury in patients with AGR, ATN, or patients with stable graft function (SGF) was made and differences between groups and correlations between markers and cold ischemia time (CIT), warm ischemia time (WIT) and blood trough level of cyclosporine A (CsA0) were determined. Material and methods In 60 cadaveric renal allograft recipients in the early post-transplantation period urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and B isoenzyme (NAG-B), alanylaminopeptidase (AAP), gamma-glutamyltransferase (GGT), alpha and pi isoenzymes of glutathione S-transferase (alpha-GST, pi-GST), retinol binding protein (RBP) and beta2- microglobulin (beta2M), were analyzed. Results NAG and NAB-B activities were higher in ATN (P<0.05, P<0.01) and in AGR (P<0.005, P<0.02) than in SGF. Excretion of pi-GST was higher in AGR than in SGF (P<0.0002) or ATN (P<0.007). CIT and WIT in patients with ATN were higher (P<0.05) than in SGF group. In ATN patients, correlations of CIT with RBP (P<0.05) and pi-GST (P<0.05), and WIT with RBP (P<0.05), and pi-GST (P<0.001) were found. Conclusions High urinary NAG and NAG B excretion characterizes ATN and AGR patients. Evaluating urinary excretion of pi-GST may be helpful in differentiating AGR from ATN. However, taking into account ischemia time is necessary in interpreting the pi-GST value in early post transplant period.

Association of High Pretransplant sIL-6R Plasma Levels with Acute Tubular Necrosis in Kidney Graft Recipients

Delayed graft function is primarily caused by acute tubular necrosis (ATN). We studied in renal transplant recipients with posttransplant graft biopsy whether an up-regulated immune system in the recipient immediately before transplantation affects the risk of developing ATN and might be relevant for the pathogenesis of ATN. In a retrospective study, we analyzed pretransplant and early posttransplant soluble interleukin (sIL)-1RA, interleukin (IL)-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-10, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta2, interferon (IFN)-gamma, and neopterin plasma levels in patients with ATN (n=26). Matched patients with acute rejection (AR) (n=26) or normal posttransplant biopsy (n=26) served as controls. Pretransplant sIL-6R was higher (P=0.0004) and pretransplant TGF-beta2 lower (P=0.002) in patients with ATN than in patients with normal biopsy. ROC curves showed that high pretransplant sIL-6R has a high sensitivity (77%) and high specificity (64%) for ATN (P=0.002). Posttransplant plasma sIL-6R continued to be higher in ATN patients than in patients with normal biopsy (P=0.001). Patients with acute rejection showed pre- and posttransplant sIL-6R and TGF-beta2 plasma levels similar to those of patients with normal biopsy (P=NS). High pretransplant sIL-6R plasma levels are associated with an increased risk of ATN and might contribute to the development of ATN early posttransplant. Our data suggest that preactivation of the recipient's immune system increases the risk of ATN.

Frequency of Vα24 +Vβ11 + NKT cells in peripheral blood of human kidney transplantation recipients

There are still lacking data supporting a role for natural killer T (NKT) cells in the maintenance of human tissue-specific tolerance. We are interested to study NKT cell frequency in kidney transplant recipients and its correlation with graft function. Peripheral blood T cell receptors (TCR) Vα24 +Vβ11 + NKT cells were phenotyped according to CD4 and CD8 expression in normal controls (NC), in 10 years rejection-free cadaver kidney allografts maintained with minimal immunosuppression (long-term rejection free [LTRF]), in patients with acute rejection (AR) and in patients with acute tubular necrosis (ATN). Results were expressed as percentages of CD4 +CD8 − (CD4 + NKT) or CD4 −CD8 − (double negative—DN NKT) Vα24 +Vβ11 + cells. The percentages of Vα24 +Vβ11 + cells were 0.09%, 0.14%, 0.02% and 0.09% on gated lymphocytes respectively in AR, ATN, LTRF and NC groups ( p=0.263). DN NKT cells were more frequent in NC patients (52.11%) and less present in ATN patients (11.04%). In contrast, CD4 + NKT (IL-4-producing NKT cells subset) was more frequent in AR (42.86%), and corresponded to almost 3 to 7 folds more what we obtained in the other groups. Although total Vα24 +Vβ11 + cells did not significantly differ among the groups, the lowest frequency was observed in the LTRF group. In conclusion, we observed that total number of NKT cells did not differ significantly among transplant patients when compared to normal controls, although specific-subsets seem to be more frequent in determined events.

Severe acute renal failure after exposure to sirolimus-tacrolimus in two livin donor kidney reciplents

We began a clinical trial in African Americans comparing sirolimus-tacrolimus to standard immunosuppression. We report two African American male living donor kidney recipients who developed acute renal failure after exposure to sirolimus-tacrolimus. Both patients received similar doses of sirolimus and tacrolimus to achieve target levels of 5 to 15 ng/mL and prednisone in tapering doses. Renal function and tacrolimus and sirolimus levels were systematically monitored. Although both kidneys functioned immediately, acute oliguric renal failure developed approximately 2 weeks after transplantation. Transplant kidney biopsy showed acute tubular necrosis in patient 2. Sirolimus-tacrolimus was then stopped in both patients. Both patients required temporary hemodialysis. Renal function returned 2 weeks later and was normal 2 months after transplantation on tacrolimus plus mycophenolate mofetil. Combination sirolimus-tacrolimus may cause nephrotoxicity in some patients by mechanisms that are presently unexplained.