sCr Rise Research Articles

Urinary L-type fatty acid-binding protein is a predictor of cisplatin-induced acute kidney injury

BackgroundAlthough cisplatin-based chemotherapy is a standard treatment for urothelial carcinoma, it often causes acute kidney injury (AKI). AKI and dysfunction are observed in 25–35% of cisplatin-based chemotherapy patients, who may require treatment down-titration or withdrawal. In this study, we evaluated whether urinary L-FABP is a marker for early diagnosis of cisplatin-caused AKI.MethodsWe included 42 adult patients who underwent cisplatin-based chemotherapy for bladder cancer or upper tract urothelial carcinoma from January 2018 to March 2019. Urinary L-FABP and serum creatinine were measured at 2 and 6 h, and 1, 2, 3, 7 and 28 days after taking cisplatin.ResultsIn the first week after receiving cisplatin, 10 patients (23.8%) were diagnosed with AKI (AKI+ group). Pre-treatment (baseline) measurements did not significantly differ between the AKI+ and AKI− groups. However, urinary L-FABP concentrations rapidly increased in the AKI+ group and were significantly greater than in the AKI− group at Hour 2, Hour 6, Day 1 and Day 2. Serum creatinine also significantly differed between the AKI+ group and the AKI− group on Days 3 and 7. ROC analysis was performed to evaluate the superiority of urinary L-FABP magnification which had the highest at the hour 6. The urinary L-FABP magnification and levels of aria under curve was 0.977. Based on ROC analysis, the best cut-off value of urinary L-FABP magnification was 10.28 times urinary L-FABP levels at the hour 0 (base line urinary L-FABP).ConclusionsAcute renal function deterioration was predicted by increased urinary L-FABP excretion within 6 h after receiving CIS-CT and, in those with AKI, the increase in urinary L-FABP excretion preceded the rise in sCr by over 2 days. In contrast, no appreciable changes in urinary L-FABP levels were observed in patients with stable renal function throughout the whole observation period. So early increase in urinary L-FABP may identify patients at risk of cisplatin-induced AKI, who might benefit from treatment to prevent nephrotoxicity.Trial registrationThis study was retrospectively registered.

Improvement in Kidney Function after Discontinuation of Fenofibrate in Outpatient Nephrology Consultation for Chronic Kidney Disease

Background: It has been noted in observational and interventional studies that individuals exposed to fenofibrate can exhibit a rise in serum creatinine (sCr) concentration. However, it is not known to what extent this phenomenon impacts kidney function in patients who are referred to a nephrology clinic for consultation for chronic kidney disease (CKD). Methods: We conducted a prospective observational study of patients referred to our nephrology clinic for a new evaluation of a rise in sCr or worsening CKD and who were on fenofibrate therapy. We examined the effect of discontinuation of fenofibrate on kidney function, change in sCr, and estimated glomerular filtration (eGFR) at 3, 6, and 12 months. Results: A total of 22 patients (59% women, 86% White, 59% with type 2 diabetes, and 18% with peripheral arterial disease) were captured over 2.5 years. Median sCr at the time of fenofibrate discontinuation was 1.9 (1.1–3.3) mg/dL and eGFR, 32 (17–57) mL/min; proteinuria was absent in 17 (77%). Upon discontinuation of fenofibrate, median sCr decreased to 1.5 (0.9–2.4), 1.4 (1.0–2.5), and 1.4 (1.0–2.3) mg/dL at 3, 6, and 12 months, respectively (p < 0.05); whereas median eGFR increased to 44 (27–71), 45 (23–71), and 42 (21–71) mL/min, respectively (p < 0.05). A ≥30% rise in eGFR was observed in 59% of the patients at 3 months, and it persisted in 45% and 50% of patients at 6 and 12 months, respectively. Conclusion: Discontinuation of fenofibrate in patients referred for CKD evaluation can result in sustained reduction in sCr in about half of the patients and for up to 1 year. There is a need to raise awareness among primary practitioners about this phenomenon. Recognition of fenofibrate as a cause of rise in sCr could reduce unnecessary nephrology consultation and resource utilization.

P053 Interstitial Nephritis from IBD: Complicated Conclusions.

BACKGROUND: Kidney injury in IBD is challenging. Tubulointerstitial nephritis (TIN) is linked to aminosalicylates, but also described in drug-naïve patients, suggesting that TIN may be a direct manifestation of IBD. We describe three cases of TIN in IBD to illustrate the challenges in determining the etiology of the injury. Case #1: 58-year-old male with a horseshoe kidney deformity, uncontrolled hypertension, GERD and small bowel stricturing Crohn's disease (CD), previously on mercaptopurine and allopurinol, subsequently transitioned to adalimumab, maintaining clinical and radiologic remission. Two years later, he developed acute kidney injury in setting of high fevers and sweats, with negative infectious evaluation. Medications included adalimumab, PPI, valacyclovir and torsemide. Renal biopsy revealed TIN with dense, zonal and focal granulomatous features suggestive of drug-induced hypersensitivity, chronic infection, sarcoidosis or an extra-intestinal manifestation of CD. Case #2: 45-year-old female with SLE, nephrolithiasis, GERD, hypertension and ulcerative colitis (UC), initially on mesalamine, then vedolizumab, with clinical and endoscopic remission. Her SCr increased at the time of her UC diagnosis, and worsened over 6 months while on mesalamine, vedolizumab, PPI and losartan. Renal biopsy demonstrated acute and chronic TIN with eosinophils raising concern for an allergic/drug-induced injury. Nephrology concluded that her TIN was secondary to either UC or one of her medications. Case #3: 33-year-old male with UC transitioned to vedolizumab, having failed budesonide and mesalamine. He had latent TB and received 9 months of isoniazid. While on mesalamine, vedolizumab and PPI, he developed fever, chills and night sweats, with an acute rise in SCr, prompting discontinuation of meds. Three months later, still in remission and with improved SCr, he restarted vedolizumab. A year later he developed low-grade fever with elevated SCr, prompting discontinuation. Renal biopsy revealed acute and chronic TIN with severe interstitial fibrosis, tubular atrophy and focal global glomerulosclerosis. He started prednisone and remained off other IBD therapy for 6 months, but repeat colonoscopy revealed mild colitis. He restarted mesalamine, but again developed elevated SCr 2 months later. Repeat renal biopsy revealed TIN with less interstitial fibrosis and focal global glomerulosclerosis, and nephrology suggested his interstitial nephritis was likely secondary to UC over his medications. He started azathioprine with significant improvement in SCr and clinical remission of UC. In all three cases, neither nephrology consultation nor renal biopsy helped distinguish the etiology of renal injury, defaulting to either the IBD meds or an extra-intestinal manifestation of IBD, and not accounting for the acute inflammatory symptoms in two of the cases. While literature review reveals several cases that allege kidney injury as an extra-intestinal target of IBD serious doubts remain. TIN secondary to aminosalicylates is well-documented, but there are few reports of adalimumab-induced granulomatous TIN and only one report of vedolizumab-induced TIN. Each of our patients had well-controlled IBD and multiple confounding variables that could impact kidney function or cause TIN, including hypertension and multiple potential culprit medications, illustrating the dilemma of determining the etiology of renal injury in IBD patients.

MO345LIFESAVING BIOMARKERS IN CONTRAST-INDUCED ACUTE KIDNEY INJURY IN ADULT CRITICAL ICU PATIENTS

Abstract Background : - Intravenous administration of radiocontrast media is referred to as contrast-induced kidney injury (CI-AKI).CI-AKI is described as the third most common cause of new AKI in hospitalized patients. The occurrence of CI-AKI is reported up to 55% in these high-risk patients.: NGAL (Neutrophil gelatinase-associated Lipocalin)and Cystatin C have been found an early and sensitive marker of acute kidney injury (AKI). Aims To evaluate biomarkers in plasma (P) and urine (U) after intravenous contrast in adult ICU patients. Method Total of 36 patients recruited as per inclusion criteria. ICU patients who were &amp;gt;18 years with radiographic contrast for diagnostic or interventional computed tomography (CT scan), were included. After ethical approval, samples of 5 ml blood and 5 ml urine were collected before contrast exposure and at 4 h, 24 h, and 48 h after contrast exposure. NGAL and Cystatin C assay was done by ELISA, and urinary levels were normalized as per urine creatinine (UCr) values for each sample. In the present study, CI-AKI is defined as a rise in SCr of ≥0.3 mg/dl within 48 hrs. Data presented in a mean or median analysis performed. Results In this study, 30 CT scan episodes requiring intravenous contrast in 25 ICU patients were included. Median age was 36 yrs and 13 (43%) were male. On day of inclusion, median SOFA score was 3; 16% In patients having CI-AKI, mean values changes from pre-contrast to at 4 h, 24 h and 48 h after contrast are presented..Kinetics of plasma (P) and urine (U) NGAL and Cystatin C levels (Mean±SD) with p value among patients having CI-AKI P NGAL (ng/ml), Before Contrast(BC)( 708.5±201.76) , 04hrC(851.5±332.05, p=0.07), 24hrC(1093.25±225.03, p=0.02), 48hrC(788±323.4, p=0.21), UNGAL (ng/mg of U Cr)BC(67.63±48.09) , 04hrC(39.69±19.79, p=0.07) , 24hrC(101.97±90, p=0.12) , 48hrC(59.87±56.85, p=0.73) , P Cystatin C (ng/ml) BC(4698.85±574.71), 04hrC(4704.57±1144.87) , p=0.02) , 24hrC(4428.85±1135.73, p=0.03), 48hrC(4288.85±435.8, p=0.17), U Cystatin C (ng/mg of UCr) BC(3 46.06±224.7), 04hrC(219.66±72.18, p=0.91), 24hrC (470.21±536.28, p=0.99), 48hrC(633.61±811.77, p=0.23). Conclusion ROC curve analysis during pre-contrast exposure: NGAL, and Cystatin C), both plasma and urine level AUC was significantly higher in patients who develop CI-AKI and Post-contrast exposure Plasma levels AUC significantly higher than Urine levels.

Duration of pemetrexed maintenance therapy with or without pembrolizumab is associated with risk of renal toxicity in patients with metastatic nonsquamous NSCLC.

e21205 Background: Use of maintenance pemetrexed with pembrolizumab is the standard of care among patients with metastatic nonsquamous NSCLC without EGFR or ALK alterations treated with the KEYNOTE-189 regimen. Whether the addition of pembrolizumab to pemetrexed maintenance alters the risk of renal toxicity is not well characterized. Methods: A single center retrospective study was performed. The frequency of acute kidney injury as well as the rates of discontinuation due to renal injury was assessed. Acute renal injury was defined as ≥ 0.3 increase in serum creatinine (sCr) above the upper limit of normal or a rise in sCr ≥ 1.5 times baseline per KDIGO criteria. A Fisher exact test was conducted to compare the rate of renal injury between the two groups. Logistic regression adjusting for performance status, prior lines of treatment, and number of maintenance cycles was performed. Results: We identified 114 patients who received either maintenance pemetrexed or pemetrexed + pembrolizumab. The median number of cycles for the maintenance pemetrexed and pemetrexed + pembrolizumab groups was 5 and 7 cycles respectively. Of these, 41% (47/114) patients developed acute renal injury during their treatment course. Renal injury was seen in 14.3% (5/35) patients who received single agent pemetrexed maintenance and 25% (3/12) who received maintenance pemetrexed + pembrolizumab with no significant difference in the rates of renal injury between both arms (p = 0.403). Among patients who developed acute renal injury, 9% (4/47) permanently discontinued maintenance due to nephrotoxicity. All patients who permanently discontinued therapy received maintenance pemetrexed alone. When adjusting for covariates, ECOG performance status and number of prior lines of therapy did not increase the risk of renal toxicity. Logistic regression analysis identified that the rate of renal injury was significantly associated with the number of maintenance cycles received (p-value = 0.017, OR = 1.14, 95% CI 1.03 - 1.29). The odds of developing renal injury were 1.14 times higher with each additional cycle of maintenance therapy received. Conclusions: Renal injury is common among patients treated with patients receiving maintenance therapy. The addition of pembrolizumab to maintenance pemetrexed did not significantly increase the rate of renal injury. The risk of renal injury appears to correlate with the total number of maintenance cycles received suggesting a cumulative risk of nephrotoxicity over time.

Worsening Renal Function during Index Hospitalization Does Not Predict Prognosis in Heart Failure with Preserved Ejection Fraction Patients

Introduction: Worsening renal function (WRF) predicts poor prognosis in patients with left ventricular systolic dysfunction. The effect of WRF in heart failure with preserved ejection fraction (HFpEF) is unclear. Objective: The objective of this study was to determine whether WRF during index hospitalization for HFpEF is associated with increased death or readmission for heart failure. Methods: National Veterans Affairs electronic medical data recorded between January 1, 2002, and December 31, 2014, were screened to identify index hospitalizations for HFpEF using an iterative algorithm. Patients were divided into 3 groups based on changes in serum Cr (sCr) during this admission. WRF was defined as a rise in sCr ≥0.3 mg/dL. Group 1 had no evidence of WRF, group 2 had transient WRF, and group 3 had persistent WRF at the time of discharge. Results: A total of 10,902 patients with index hospitalizations for HFpEF were identified (mean age 72, 97% male). Twenty-nine percent had WRF during this hospital admission, with 48% showing recovery of sCr and 52% with no recovery at discharge. The mortality rate over a mean follow-up duration of 3.26 years was 72%. Compared to group 1, groups 2 and 3 showed no significant difference in risk of death from any cause (hazard ratio [HR] = 0.95 [95% confidence interval [CI]: 0.87, 1.03] and 1.02 [95% CI: 0.93, 1.11], respectively), days hospitalized for any cause (incidence density ratio [IDR] = 1.01 [95% CI: 0.92, 1.11] and 1.01 [95% CI: 0.93, 1.11], respectively), or days hospitalized for heart failure (IDR = 0.94 [95% CI: 0.80, 1.10] and 0.94 [95% CI: 0.81, 1.09], respectively) in analyses adjusted for covariates affecting renal function and outcomes. Conclusions: While there is a high incidence of WRF during index hospitalizations for HFpEF, WRF is not associated with an increased risk of death or hospitalization. This suggests that WRF alone should not influence decisions regarding heart failure management.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Electronic health records accurately predict renal replacement therapy in acute kidney injury

BackgroundElectronic health records (EHR) detect the onset of acute kidney injury (AKI) in hospitalized patients, and may identify those at highest risk of mortality and renal replacement therapy (RRT), for earlier targeted intervention.MethodsProspective observational study to derive prediction models for hospital mortality and RRT, in inpatients aged ≥18 years with AKI detected by EHR over 1 year in a tertiary institution, fulfilling modified KDIGO criterion based on serial serum creatinine (sCr) measures.ResultsWe studied 3333 patients with AKI, of 77,873 unique patient admissions, giving an AKI incidence of 4%. KDIGO AKI stages at detection were 1(74%), 2(15%), 3(10%); corresponding peak AKI staging in hospital were 61, 20, 19%. 392 patients (12%) died, and 174 (5%) received RRT. Multivariate logistic regression identified AKI onset in ICU, haematological malignancy, higher delta sCr (sCr rise from AKI detection till peak), higher serum potassium and baseline eGFR, as independent predictors of both mortality and RRT. Additionally, older age, higher serum urea, pneumonia and intraabdominal infections, acute cardiac diseases, solid organ malignancy, cerebrovascular disease, current need for RRT and admission under a medical specialty predicted mortality. The AUROC for RRT prediction was 0.94, averaging 0.93 after 10-fold cross-validation. Corresponding AUROC for mortality prediction was 0.9 and 0.9 after validation. Decision tree analysis for RRT prediction achieved a balanced accuracy of 70.4%, and identified delta-sCr ≥ 148 μmol/L as the key factor that predicted RRT.ConclusionCase fatality was high with significant renal deterioration following hospital-wide AKI. EHR clinical model was highly accurate for both RRT prediction and for mortality; allowing excellent risk-stratification with potential for real-time deployment.

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine

Background: Vancomycin-associated (VA) acute kidney injury (AKI) is being increasingly recognized. A distinct pattern of rapid rise in serum creatinine (sCr) during VA-AKI has occasionally been observed. However, such scenarios remain underreported. Methods: We conducted an online survey at the American Society of Nephrology Communities forum and reviewed publications of VA-AKI via PubMed or Google searching for cases of precipitous AKI (those with rise in sCr ≥1.5 mg/dL/day) attributable to vancomycin. Results: We identified 12 original cases compiled from 6 different hospitals and 4 published cases (n = 16; 38% women, age 43.5 ± 16 years, weight 108 ± 23 kg, body mass index 35 ± 7 kg/m²) of precipitous AKI observed shortly after large cumulative doses of VA (8.8 ± 5 g). The median steepest 24-h rise in sCr was 2.6 mg/dL (range 1.5–3.5 mg/dL) and the slope of the initial 48-h sCr rise was greater than that of a control AKI (non-VA, n = 48) group (2.03 ± 0.1 vs. 0.62 ± 0.0 mg/dL/day; p < 0.0001). The steep rise in sCr in the VA-AKI was not accompanied by anuria. Overt rhabdomyolysis was absent in all cases. Further, in 3 precipitous VA-AKI cases, simultaneous serum cystatin C values did not rise precipitously, suggesting that the reductions in glomerular filtration rate were overestimated by the sCr increase. Conclusions: VA-AKI can manifest with a precipitous rise in sCr shortly after a high cumulative dose of vancomycin. True toxic tubular injury overrepresented by the sCr rise is postulated.

Stroke volume variation and serum creatinine changes during abdominal aortic aneurysm surgery: a time-integrated analysis.

Patients undergoing abdominal aortic aneurysm (AAA) surgery with suprarenal clamping are at high risk for acute kidney injury (AKI) and major cardiac and cerebrovascular events (MACCE). We aimed to assess whether the stroke volume variation (SVV), a measure of hemodynamic instability, is associated with AKI in hypertensive patients undergoing elective AAA surgery with suprarenal clamping. In a cohort of 51 hypertensive patients, we performed serial measurements of SVV (n = 459) and serum creatinine (sCr) (n = 255). AKI was defined according to the KDIGO clinical practice guidelines. Data were analyzed by repeated-measures ANOVA and regression analysis of time-integrated changes of both SVV and sCr. AKI developed in 45% of patients (stage 1: 31%; stage 2: 10%; stage 3: 2%). The diuresis during surgery (beta - 0.29 Z-score 95% [CI -0.54, -0.05]; p = 0.02), clamp time (beta 0.29 Z-score [0.05-0.52]; p = 0.02), and time-integrated changes in SVV from baseline to 12h after surgery (beta 0.31 Z-score [0.03-0.60]; p = 0.03) were independent predictors of the time-integrated changes in sCr from baseline to 48h after the end of surgery. In a model adjusted for age and sex, patients with AKI had an increased risk for MACCE during a mean follow-up of 3.5 ± 1.1years (HR 5.53 [1.52-20.06]; p = 0.004). SVV increases progressively during and after AAA surgery in subjects who will develop AKI. The increase of SVV precedes and predicts the rise in sCr and is a good discriminator of the development of AKI. AKI is associated with an increased long-term risk for MACCE.

The Occurrence of Nephrotoxicity in Hepatitis C Patients Undergoing Sofosbuvir-Based Therapy

Introduction: Sofosbuvir along with other NS5A inhibitors such as ledipasvir is drug of choice for the treatment of hepatitis C virus (HCV) infection. While highly effective in achieving sustained virologic response, interstitial nephritis has been reported with sofosbuvir and ledipasvir treatment. However, the occurrence of acute kidney injury (AKI) associated with sofosbuvir based treatment is unknown. Methods: A retrospective chart review of chronic HCV patients treated with sofosbuvir based therapy at our institution from 10/2014 to 11/2016 was performed. Patients over age 18 with at least 2 serum creatinine (sCr) measurements during sofosbuvir based treatment were included. Demographics, duration of therapy, and any available renal testing such as urinalysis, renal ultrasound, or biopsy were reviewed. AKI was defined as a rise in sCr of more than 0.3mg/dL. Individuals with a documented cause for AKI were excluded. Glomerular filtration rate (GFR) was estimated via the Modification of Diet in Renal Disease (MDRD) formula, and Pearson correlation analysis was performed. Results: A total of 435 patient records were reviewed. Thirty-four cases with no sCr measurements were excluded. Of the remaining 401 subjects, age was 64.5 ± 10.2 years, with 56.4% male and 88% infected with genotypes 1a/b. The mean treatment duration was 13.4 ± 4.3 weeks. Eighty-five (21.2%) had F4 fibrosis. The mean baseline sCr prior to treatment was 0.95 ± 0.22mg/dL, and mean eGFR 79.5mL/min per 1.73 m2. AKI was noted in 22 (5.5%) out of 401 patients during therapy, with an average sCr rise of 0.5 ± 0.2mg/dL. All but 2 of the 22 patients with AKI had their sCr return to baseline levels after treatment, and none required intervention or renal replacement therapy. The AKI group had an average of 1.9 weeks longer treatment duration. The magnitude of sCr increment in the group with AKI correlated with duration of treatment (r=0.45, p=0.03) but not with age, fibrosis stage or baseline sCr. Conclusion: We studied the occurrence of nephrotoxicity in HCV patients undergoing sofosbuvir based therapy. A small fraction of patients treated with this regimen developed AKI. Interestingly, a modest but statistically significant correlation between treatment duration and sCr increment suggests that sofosbuvir may be potentially causative. Monitoring of sCr in this clinical setting is recommended. Further investigations regarding the association between nephrotoxicity and sofosbuvir based therapy is needed.

Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury

To study the outcome of extremely low birth weight (ELBW) infants with a history of acute kidney injury (AKI). In a retrospective, case control study, medical records of all ELBW infants admitted to the neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Medical records were reviewed for infants' demographics, blood pressure (BP) at NICU discharge and at ≥3years, and estimated glomerular filtration rate (eGFR) at ≥2years. During the study period, 222 patients met the inclusion criteria, of whom 10% (23 out of 222) had AKI stage 2 and 3, 39% (87 out of 222) had AKI stage 1, and the rest did not have AKI. At NICU discharge, there was a difference in diastolic BP (DBP) among infants who had AKI stages 2 and 3, those who had stage 1, and those who did not have AKI (53 ± 12 vs 46 ± 9 vs 46 ± 11mmHg respectively; p = 0.007), and 11% (23 out of 209) had hypertension (HTN). Although there was a significant correlation between the rise in SCr and DBP at NICU discharge in infants with AKI (R = 0.304; p = 0.004), there was no difference in HTN between infants with and those without AKI. At ≥2years of age, 4% (5 out of 120) across all groups had an eGFR < 90ml/min/1.73m2 or chronic kidney disease (CKD). At ≥3years of age, 5% (11 out of 222) had HTN. At NICU discharge, infants with AKI stages 2 and 3 have a higher DBP than infants with stage 1 AKI and those who did not have AKI. However, there is no difference in the rate of HTN between the two groups. At ≥2years ELBW infants are at risk for CKD independently of whether or not they develop neonatal AKI.

Acute kidney injury: a problem of definition

Individuals with acute kidney impairment can have defects in the excretion of water, salts, and metabolic products, including creatinine. Classical nephrology taught that defective kidney excretion should be described on the basis of aetiology and anatomy. We learned to approach the patient with a pathophysiological focus: was the cause of defective excretion due to extrarenal volume deficiency, impaired blood perfusion, intrinsic kidney causes, or post-renal causes? If intrinsic damage was found, was the cause primarily related to sepsis, ischaemia, drugs or toxins, interstitial or glomerular causes, or a combination of the above? These categories were useful because they provided prospective insights into the clinical course and suggested appropriate therapeutic interventions. Hence, excretory defects, which can result from various challenges to the kidney, must be understood in their pathophysiological context. The definition of acute kidney injury – Authors' replyWe thank John A Kellum and Norbert Lameire for their letter in response to our Comment.1 An acute increase in serum creatinine (sCr) is caused by direct injury to kidney cells (ie, pathophysiological processes resulting from ischaemia, sepsis, medications, metals, or enzymes) or a compromise in cardiovascular homoeostasis (ie, substantial volume depletion,2 congestive heart failure,3 or portal hypertension4). Hence, we appreciate that an acute rise in sCr can indicate several pathophysiological processes with worsened patient population outcomes. Full-Text PDF The definition of acute kidney injuryWe read with interest the Comment in The Lancet by Jon Barasch and colleagues (Feb 25, 2017, p 779)1 with its controversial title “Acute kidney injury: a problem of definition”. We appreciate the opportunity to clarify what is written in the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline on acute kidney injury (AKI),2 in the hope that clinicians will read beyond the headlines. The guideline clearly states that AKI is a clinical diagnosis and stresses the importance of clinical judgment: “While the definitions and classification system discussed in Chapter 2.1 provide a framework for the clinical diagnosis of AKI, they should not be interpreted to replace or to exclude clinical judgment”. Full-Text PDF

Diagnostic accuracy of serum cystatin C for early recognition of contrast induced nephropathy in Western Indians undergoing cardiac catheterization

AimsWe aimed to compare the diagnostic efficacy of serum cystatin C (sCyC) for contrast induced nephropathy (CIN) in Western Indians undergoing cardiac catheterization. We also aimed to propose a clinically applicable cut-off of sCyC for early identification of CIN in this ethnic group. MethodsIn this prospective study, 253 patients undergoing coronary angiography and/or percutaneous coronary intervention were enrolled. The demographic and risk factor details, levels of sCr at baseline, 24 and 48h after the procedure, whereas baseline and 24h levels of sCyC were noted. Increase of 0.5mg/dl or ≥25% from baseline sCr was used to define CIN. Optimum cut off of sCyC for CIN diagnosis was obtained using Receiver Operating Characteristic (ROC) curve analysis. ResultsAfter 48h of contrast media (CM) exposure, the incidence of CIN was 12.25% (31 patients) according to sCr definition, where only 3.9% (10 patients) had sCr rise in 24h. Overall significant (p<0.0001) rise in mean levels of sCr (48h) and sCyC (24h) was observed in CIN patients. However, the mean sCr rise at 24h was non-significant. The optimum cut off of sCyC for diagnosing CIN was found to be a rise of ≥10% from baseline (AUC – 0.901; sensitivity – 100%, specificity – 77.89%). According to sCyC, 94 (37.15%) patients had CIN. ConclusionWe may conclude that a rise of ≥10% in sCyC at 24h could be used as a reliable marker for identification of CIN in western Indians undergoing cardiac catheterization.

DDRGK1 in urine indicative of tubular cell injury in intensive care patients with serious infections.

Background: Acute kidney injury (AKI) is a life threatening condition. Despite intensive care treatment the occurrence cannot be predicted as very little indicators exist for direct measurement when tubular epithelial cell injury takes place. We therefore searched for novel peptide indicators expressed at intracellular level at the proximal kidney tubule for its appearance in urine samples. Objectives: Establishing a test for urinary C20orf116 protein measurement. Patients and Methods: Generation of immunoreagents against C20orf116 also named DDRGK1. These were used to measure its presence in urine collected at 8-24 hours interval in a prospective study from 99 ICU patients at 4-6 time points. These patients received therapy because of serious infection and were categorized into 4 groups. Results: 1) Ten tested highly for C20orf116 undergoing AKI graded Failure or Loss (3210 ± 4268 ng/mL) according to RIFLE criteria, all requiring renal replacement therapy (RRT) out of them 9 died. 2) Six patients with pre-existing kidney disease developed AKI and required RRT but had much lower C20orf116 levels of (33 ± 19), two of them died. 3) In contrast, out of 11 patients undergoing AKI grade Risk or Injury, four tested positive for C20orf116 but to much lower extent (66 ± 43) who recovered fully. 4) Out of 72 patients 25 tested positive (18 ± 12 ng/mL) not fulfilling criteria of AKI but with serum creatinine (sCr) rises of 1.2-1.4 (n = 52). Healthy donors (n = 48) showed no detectable C20orf116 at any time point. Conclusions: C20orf116 excretion was detectable more than 24 hours before sCr rise could be measured; high level seemed to indicate severity of organ failure.

Urine cystatin C (uCyC) as a predictor for acute kidney injury (AKI) in urothelial cancer (UC) patients (pts) treated with cisplatin (CDDP).

317 Background: CDDP-based treatment is limited by AKI. We aimed to test whether a novel AKI biomarker, uCyC, measured before and immediately after CDDP administration could permit earlier identification of UC pts at risk for AKI. Methods: In a nested case-control study, pts treated with CDDP were prospectively enrolled. uCyC was measured 2 hours pre- and 3 hours post-CDDP doses, with values normalized to urine creatinine. AKI was defined as an increase in serum creatinine (sCr) by ≥50% (severe cases) or ≥0.3 mg/dL above pre-CDDP baseline. Controls were pts with no significant sCr rise (sCr change &lt;25% and &lt;0.3 mg/dL). A sample size of 98 patients provided 80% power to detect a true difference in biomarker change pre- and post-CDDP between cases and controls. Results: 102 pts were enrolled: 47 had UC, and 55 had other cancers; 76 were male; 82 Caucasians/15 African Americans. 4 pts not providing urine samples were excluded from analysis. For the entire cohort, average pre-CDDP sCr was 0.98 mg/dL and mean cumulative CDDP dose was 220 mg/m2. Controls were younger (mean 59.2 vs 65.9 yrs, p=0.01). 25 pts (26%) developed AKI; 15 (15%) were severe cases. UC pts had a significantly increased risk of AKI compared with non-UC pts (UC n=17 [37%] vs non-UC n=8 [16%], Relative Risk 2.2, 95% CI 1.08-4.73; p=0.03). AKI risk did not correlate with total CDDP dose received. In AKI pts, uCyC increased temporally in accordance with sCr and did not increase in controls, but immediate uCyC changes (3 hrs post-CDDP) were not detectable in cases or controls. However, in UC severe cases, pre-CDDP uCyC was consistently higher than in UC controls (183 ng/mg vs 109 ng/mg, p=0.04). Additionally, in UC AKI pts compared to UC controls, average maximum (peak) uCyC was higher (1812 ng/mg vs 244 ng/mg, p=0.04). Baseline uCyC did not correlate with age, and there were no significant differences in age or baseline sCr between UC cases and controls. Conclusions: UC pts are over two times more likely to develop AKI with CDDP chemotherapy than pts with other cancers, even when pre-CDDP sCr is normal. Pre-treatment uCyC levels may have value in predicting which UC pts are at highest risk of developing CDDP-induced renal injury.

Is Nebivolol Really Effective in Preventing Contrast Induced Nephropathy?

Background/Aims: Contrast induced nephropathy (CIN) has multifactorial etiopatogenesis including oxidative stress and vasoconstriction. Nebivolol is an antioxidant and has vasodilatatory effect via NO release and may prevent CIN development. We have noticed that a few number of studies that have evaluated the effectiveness of nebivolol for the prevention of CIN used serum creatinine (sCr) levels for CIN detection. However, sCr is an insensitive marker for renal damage. Therefore in this study we used serum neutrophil-gelatinase associated lipocalin (NGAL), a more sensitive marker of renal damage, to evaluate preventive role of nebivolol in CIN. Methods: 159 patients undergoing coronary angiography (CAG) who had at least one risk factor for CIN were divided into nebivolol (+) and (-) groups. CIN was defined as a rise in sCr of 0.5mg/dl or a 25% increase from the baseline value. Serum Cr, glomerular filtration rate (eGFR) and NGAL levels were assessed before and 48 h after CAG. Mehran risk scores were calculated for both groups. Results: Both groups were similar in terms of baseline characteristics, Mehran risk scores, and current medications. Clinically, CIN developed at similar rates in both groups. Serum Cr, eGFR and NGAL values were similar in both groups before and after CAG. Serum Cr and NGAL levels increased and eGFR decreased significantly compared to the levels before CAG. Patients who developed CIN were significantly older (p=0.003), and were more likely to have DM (p=0.012), a higher mean contrast agent volume (p<0.001), and a higher Mehran score (p <0.001). We did not observe any favorable effect of Nebivolol in the prevention of CIN in patients undergoing CAG. Conclusion: According to the results of our study Nebivolol does not seem to prevent CIN in patients undergoing CAG. However, further randomised controlled trials with more sensitive renal damage markers are obviously needed to understand the actual effect of nebivolol on CIN especially through oxidative pathways and in high risk patients.

Effects Of Static Subnormothermic Preservation Following Warm Ischemia on Ischemia-Reperfusion Injury and Long-Term Outcome of the Renal Allograft in CLAWN Miniature Swine

Objective: Normothermic organ machine perfusion has been suggested in place of hypothermic preservation for kidneys from donors after cardiac death and other marginal donors. Here we attempted to evaluate the efficacy of static subnormothermic preservation on renal grafts exposed to periods of warm ischemia time (WIT) in a preclinical large animal model using MHC inbred miniature swine. Methods: Nine MHC-inbred CLAWN miniature swine received MHC-matched renal allografts with 12 days of FK506 (days 0-11). In Group 1, two animals received kidneys without WIT. In Groups 2 and 3, the grafts were subjected to 60-min of WIT, and then preserved at 4°C (Group 2; n=3) or 22°C (Group 3; n=4) for 60-min in ET-Kyoto solution. In 2 additional groups (4 and 5), WIT was extended to 2 hours. Renal function was monitored by serum creatinine (sCr) and biopsies. Serum levels of TNF-α and IL-6 were measured to characterize inflammatory responses. Results: In Group 1, both animals survived over 60 days with stable renal function and minimal rise in sCr (2.4 ± 0.8mg/dl around day 2). In Group 2, all animals showed moderate elevations of sCr (4.1 ± 0.8mg/dl), peaking at a median of 2 days; renal function recovered by day 7 in all three animals and remained stable for over 60 days in 2 animals. sCr in the remaining animal gradually increased after 30 days and the animal was sacrificed at day 60 (sCr=20.5 mg/dl). In Group 3, sCr increased to 3.6±1.0mg/dl, peaking at day 2 and recovered by day 6. One animal died from infection at day 24, but the other 3 recipients survived 60 days. Systemic early pro-inflammatory cytokine levels (TNF-α, IL-6) increased in both Group 2 and Group 3, peaking 6 hours after reperfusion (Group 2 vs. 3; TNF-α: 152 ± 9 vs. 122 ± 6 pg/ml; IL-6: 2357 ± 367 vs. 1823 ± 487 pg/ml). Although there was no statistical difference in peak levels of sCr, renal function as well as the peak cytokine concentration for animals receiving 22°C (vs 4°C) preservation was better across all three parameters. One animal underwent 2-hr of WIT plus 1-hr 4°C preservation (Group 4) and died of irreversible graft non-function on day 5. In contrast, 2 animals, underwent 2-hr of WIT plus 1-hr of 22°C preservation (Group 5) and maintained graft function >45 days (ongoing) although both had transient rise in sCr around day 3. Conclusion: We demonstrated that subnormothermic (22°C) organ preservation of kidney grafts exposed to 60-min of WIT was as effective as hypothermic (4°C) preservation, in miniature swine. These data also suggest a possible benefit of subnormothermic preservation for organs which experience of up to 2-hr of WIT. To our knowledge, this is the first demonstration of the applicability of static subnormothermic storage in preclinical large animals. Although further optimization is required, this preservation method may contribute to an expansion of the donor pool through improvement of extended criteria organs.

Lack of Concordance between Worsening Renal Function Defined by Rise in Creatinine Versus Rise in Cystatin C

Worsening renal function (WRF) is often defined as a 0.3 mg/dl rise in serum creatinine (sCr) in acute heart failure studies. Cystatin C (CysC) has been proposed as a better marker of glomerular filtration rate (GFR). This study investigates the concordance between WRF defined by either a rise in sCr or a rise in CysC. We determined sCr and CysC levels on day 1 and day 3 in 121 patients, admitted with acute decompensated heart failure. WRF was defined as a 0.3 mg/dl rise in sCr (WRFsCr) or a 0.3 mg/L rise in CysC (WRFCysC) in agreement with previously proposed definitions. In our patient cohort (age 60±14 year, 74% male, EF 31±17%), sCr levels were 1.39 [0.98-2.12] and 1.4 [0.98-1.96] mg/dl and CysC levels were 1.95 [1.42-2.69] and 1.97 [1.42-2.60] mg/L on day1 and day3, respectively. The correlation (Spearman) between sCr and CysC was good at day1 (r=0.81) and day3 (r=0.79) (both p<0.0001). However, the correlation between the change in sCr and CysC from day1 to day3 was less robust (r=0.47). WRFsCr and WRFCysC occured in 14/121 (12%) and 15/121 (12%) patients respectively. However, only 4 patients experienced WRF by both definitions.View Large Image Figure ViewerDownload Hi-res image Download (PPT) There is a poor agreement between WRF defined by a sCr rise or a CysC rise. This observation raises questions regarding the reliability of current definitions of WRF as it may vary by the renal indices to which the changes were determined.

Stable Plasma Myeloperoxidase Levels during Treatment of Acute Decompensated Heart Failure Despite Decongestion and a Decrease in B-Type Natriuretic Peptide

day1 (r50.81) and day3 (r50.79) (both p!0.0001). However, the correlation between the change in sCr and CysC from day1 to day3 was less robust (r50.47). WRFsCr and WRFCysC occured in 14/121 (12%) and 15/121 (12%) patients respectively. However, only 4 patients experienced WRF by both definitions.Conclusions: There is a poor agreement between WRF defined by a sCr rise or a CysC rise. This observation raises questions regarding the reliability of current definitions of WRF as it may vary by the renal indices to which the changes were determined.