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

Background and objectives: Serum creatinine (Scr) does not allow for early diagnosis of acute kidney injury (AKI). The diagnostic utility of urinary kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and neutrophil gelatinase associated lipocalin (NGAL) was evaluated for the early detection of postoperative AKI in a prospective study of 90 adults undergoing cardiac surgery.Designs, setting, participants, & measurements: Urinary KIM-1, NAG, and NGAL were measured at 5 time points for the first 24 h after operation and normalized to the urinary creatinine concentration after cardiac surgery. Receiver-operating characteristic curves were generated and the areas under the curve (AUCs) compared for performance of biomarkers in detection of postoperative AKI.Results: Thirty-six patients developed AKI, defined as an increase in Scr of ≥0.3 mg/dl within 72 h after surgery. The AUCs for KIM-1 to predict AKI immediately and 3 h after operation were 0.68 and 0.65; 0.61 and 0.63 for NAG; and 0.59 and 0.65 for NGAL, respectively. Combining the three biomarkers enhanced the sensitivity of early detection of postoperative AKI compared with individual biomarkers: the AUCs for the three biomarkers combined were 0.75 and 0.78. The performance of combining biomarkers was even better among 16 early postoperative AKI patients with AUCs of 0.80 and 0.84, respectively.Conclusions: The results of this study support that a combination of urinary biomarkers may allow for early detection of postoperative AKI after cardiac surgery before a rise in Scr.Acute kidney injury (AKI) is an important cause of morbidity and mortality in hospitalized patients (1). The incidence of hospital-acquired AKI varies from 5% in patients with normal preoperative renal function to 25% in intensive care unit (ICU) patients (2–4). Mortality rates of patients with postoperative AKI range from 40 to 60% among ICU patients who require a renal replacement therapy (5–7). Dialysis remains the only U.S. Food and Drug Administration approved treatment option for established AKI.Recently, two new definitions of AKI have been developed: RIFLE (risk, injury, failure, loss, and ESRD) and AKIN (acute kidney injury network) criteria (8,9). It is, however, a challenge to detect AKI in a timely fashion with current RIFLE and AKIN criteria because these definitions are entirely based on increases of serum creatinine (Scr) or decreases of urine output. Scr is insensitive for the early detection of AKI because the change in Scr does not discriminate the time and type of renal insult or the site and extent of glomerular or tubular injury (8,10).Several proteins and biochemical markers emerged as sensitive and specific biomarkers capable of detecting acute tubular injury early and proved to be promising biomarkers as indicators of AKI in recent human studies (11,12). These include N-acetyl-β-D-glucosaminidase (NAG), neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, and IL-18 (13–25). However, there are no previously reported data for the temporal expression pattern of urinary KIM-1 and NAG before the development of AKI in adult patients. In addition, there is a large discrepancy in the performance of NGAL as an early AKI marker between adult and pediatric AKI patients (15,17,19,20). Furthermore, there are few data on the influence of prolonged duration of storage at −80°C and the number of freeze-thaw cycles on stability of urinary biomarkers at the present time, which will be critical to ongoing validation studies of potential tandem AKI biomarkers (26).In this study, we studied the diagnostic utility of urinary KIM-1, NAG, and NGAL as biomarkers separately and in combination for the early detection of postoperative AKI and the temporal expression patterns of urinary biomarkers before the development of postoperative AKI in patients undergoing cardiac surgery. In addition, the stability of urinary KIM-1, NAG, and NGAL were tested with various handling and storing conditions to evaluate the accuracy of the biomarker measurement because our prospective collected urine samples were frozen at −80°C for 1 yr and were subjected to at least two freeze-thaw cycles before measurement for KIM-1 and NAG.     

Novel Urinary Biomarkers in Early Diabetic Kidney Disease

In diabetic kidney disease, detection of urinary albumin is recommended to aid in diagnosis, evaluate disease severity, and determine effects of therapy. However, because typical histopathologic changes in diabetic kidney disease or early progressive renal decline may occur in patients with normoalbuminuria, urinary albumin may not be sufficient to identify patients with early-stage diabetic kidney disease or to predict its progression. Therefore, intensive efforts have been made to identify novel noninvasive urinary biomarkers to discriminate patients with a higher risk of end-stage renal failure. Because diabetic kidney disease progression is associated with the extent of histologic changes in the glomeruli and the degree of tubulointerstitial changes, urinary biomarkers that accurately reflect the degree of histopathologic damage may be excellent biomarkers. This review article summarizes the clinical significance of new urinary biomarkers in the early detection of diabetic kidney disease.     

Urinary Netrin-1 Is an Early Predictive Biomarker of Acute Kidney Injury after Cardiac Surgery

Background and objectives: Netrin-1, a laminin-related axon guidance molecule, is highly induced and excreted in the urine after acute kidney injury (AKI) in animals. Here, we determined the utility of urinary netrin-1 levels to predict AKI in humans undergoing cardiopulmonary bypass (CPB).Design, setting, participants, & measurements: Serial urine samples were analyzed by enzyme-linked immunosorbent assay for netrin-1 in 26 patients who developed AKI (defined as a 50% or greater increase in serum creatinine after CPB) and 34 controls (patients who did not develop AKI after CPB).Results: Using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine netrin-1 increased at 2 hours after CPB, peaked at 6 hours (2462 ± 370 pg/mg creatinine), and remained elevated up to 48 hours after CPB. The predictive power of netrin-1 as demonstrated by area under the receiver-operating characteristics curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.74, 0.86, and 0.89, respectively. The 6-hour urine netrin-1 measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay (all P < 0.05). Adjusting for CPB time, the 6-hour netrin-1 remained a powerful independent predictor of AKI, with an odds ratio of 1.20 (95% confidence interval: 1.08 to 1.41; P = 0.006).Conclusion: Our results suggest that netrin-1 is an early, predictive biomarker of AKI after CPB and may allow for the reliable early diagnosis and prognosis of AKI after CPB, before the rise in serum creatinine.The incidence of acute kidney injury (AKI) is increasing worldwide, affecting about 6% of all hospitalized patients in whom it is an independent predictor of mortality and morbidity (1–3). In the critical care setting, the prevalence of AKI requiring dialysis is about 6%, with a mortality rate exceeding 60% (4). Once established, the treatment is largely supportive, at an annual cost surpassing $10 billion in the United States alone (5). The diagnosis currently depends on detection of reduced kidney function by the rise in serum creatinine concentration, which is a delayed and unreliable measure in the acute setting (5). Ironically, experimental studies have identified interventions that may prevent or treat AKI if instituted early in the disease process, well before the serum creatinine rises (6). The lack of early predictive biomarkers has impaired our ability to translate these promising findings to human AKI.Cardiopulmonary bypass (CPB) surgery is the most frequent major surgical procedure performed in hospitals worldwide, with well over a million operations undertaken each year. AKI is a frequent and serious complication encountered in 30% to 40% of adults and children after CPB (7–14). AKI requiring dialysis occurs in up to 5% of these patients, in whom the mortality rate approaches 80%, and is indeed the strongest independent risk factor for death (15). However, even a minor degree of postoperative AKI as manifested by only a 0.2 to 0.3 mg/dl rise in serum creatinine from baseline is also associated with a significant increase in mortality (16,17). Additionally, AKI after cardiac surgery is associated with adverse outcomes, such as prolonged intensive care and hospital stay, dialysis dependency, and increased long-term mortality (18). Infants and children with congenital heart diseases may be especially vulnerable to developing AKI, because many require multiple surgeries for step-by-step repair of complex congenital anomalies (8–14). These patients comprise an important population for the initial validation of AKI biomarkers because they do not exhibit common comorbid variables that complicate similar studies in adults, such as diabetes, hypertension, atherosclerosis, and nephrotoxin use (19).Experimental studies aimed at a better understanding of the early adaptive response of the stressed kidney have recently yielded several candidate genes and proteins that are serendipitously emerging as noninvasive candidate biomarkers of AKI (20,21). One example of such a protein is netrin. The netrins were discovered more than a decade ago as neuronal guidance cues (22). Netrins are molecules with a distinctive domain organization that belong to the laminin-related family of axon-guidance molecules (23). Recent studies indicate various other roles for netrins beyond axonal guidance, including development of mammary gland, lung, pancreas, and blood vessels; inhibition of leukocyte migration during sepsis; mitogenesis; and chemoattraction of endothelial cells (23,24). The kidney has one of the highest levels of netrin-1 expression, and administration of recombinant netrin-1 before ischemia reperfusion reduces kidney injury and inflammation (25). Preclinical studies also indicate that netrin-1 protein is markedly induced in kidney tubule cells and appears in the urine early (within 1 to 3 hours) after murine renal ischemic injury as well as other forms of AKI (26). Therefore, the objective of this study was to determine whether urinary netrin-1 levels predict the development of AKI in pediatric patients undergoing CPB.     

Calprotectin and Neutrophil Gelatinase-Associated Lipocalin As Biomarkers of Acute Kidney Injury in Acute Coronary Syndrome

BackgroundAcute kidney injury (AKI) is increasingly being seen in patients with acute coronary syndromes (ACS) and it is associated with higher short-term and long-term morbidity and mortality. Therefore, it is of paramount importance to identify those ACS patients at risk for the development of AKI. The objective of this study was to evaluate two different plasma biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) in early detecting the development of AKI in ACS patients.Methods172 ACS patients admitted to the Coronary Care Unit in Yantai Yuhuangding Hospital were prospectively enrolled. Their blood samples were obtained on admission and subjected to enzyme-linked immunosorbent assay to determine the levels of novel biomarkers. The clinical data and biomarkers were recorded and analyzed.ResultsIn this study, 23 (13.4%) patients had a diagnosis of AKI. Statistical analysis demonstrated that in ACS patients with AKI, the following two biomarkers were significantly higher than these without AKI: plasma calprotectin (5942.26 ± 1955.88 ng/mL vs. 3210.29 ± 1833.60 ng/mL, p < 0.001) and plasma NGAL (164.91 ± 43.63 ng/mL vs. 122.48 ± 27.33 ng/mL, p < 0.001). Plasma calprotectin and NGAL could discriminate the development of AKI respectively with an area under the ROC curve (AUC) of 0.864 and 0.850. A combination of the two plasma biomarkers calprotectin and NGAL could early discriminate AKI in ACS patients with an AUC of 0.898.ConclusionsThis study demonstrated a promising panel of plasma calprotectin and NGAL as early diagnostic biomarkers for AKI in ACS patients.     

Novel Urinary Biomarkers in Detecting Acute Kidney Injury,Persistent Renal Impairment,and All-Cause Mortality Following Decongestive Therapy in Acute Decompensated Heart Failure

BackgroundNew urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18), are proposed to allow a more reliable early diagnosis and prognosis of acute kidney injury (AKI) in acute decompensated heart failure (ADHF). Our aim was to compare the predictive value of urinary NGAL, KIM-1, and IL-18 for the occurrence of AKI, persistent renal impairment, and mortality in ADHF.Methods and ResultsEighty-three patients admitted for ADHF were analyzed. Urinary creatinine (Cr), NGAL, KIM-1, and IL-18 were measured at baseline. Serum Cr was measured daily during the next 4 days and again at outpatient follow-up after 6 months. Mortality data were prospectively collected. Urinary NGAL, KIM-1, and IL-18 were modestly correlated with each other (Spearman ρ ≤0.61) and poorly correlated with estimated glomerular filtration rate (eGFR; Spearman ρ ≤0.28). None predicted AKI, defined as a 25% decrease in eGFR, during the index hospitalization, but urinary IL-18/Cr was the strongest predictor of persistently elevated serum Cr ≥0.3 mg/dL after 6 months compared with baseline (area under the receiver operating characteristic curve 0.674; P = .013). Urinary IL-18 was also significantly associated with all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.16–1.87; P = .001).ConclusionsLike urinary NGAL, urinary KIM-1 and IL-18 are relatively modest predictors of AKI in ADHF. Among these novel renal biomarkers examined, further investigations regarding the prognostic value of urinary IL-18 are warranted.     

老年急性脑梗死早期肾功能损害临床探讨

目的:探讨老年急性脑梗死患者微量蛋白尿与早期肾功能损害的关系。方法:用免疫散射比浊法对本院收治的480例老年急性脑梗死患者进行2次尿微量蛋白检测。结果:老年急性脑梗死微量蛋白尿组患者2周后出现严重肾功能损害发生率明显高于对照组。结论:提示微量蛋白尿是预测老年急性脑梗死患者早期肾功能损害的敏感指标,应引起重视。     

Urinary Neutrophil Gelatinase-Associated Lipocalin in Cirrhotic Patients with Acute Kidney Injury

Introduction and aim. It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. The aim of the current work is to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis and to assess it as a prognostic marker.Material and meth-ods. Out of 83 cirrhotic patients with AKI admitted between October 2015 and June 2016; 70 patients were included in this prospective study. Routine laboratory tests, uNGAL and fractional excretion of Na were obtained on admission. End points were death or improvement of kidney function and discharge.Results. The patients included in our study were 41 males and 29 females with mean age 54.27 ± 6.08 years. HCV was the etiology of cirrhosis in 69 cases while one had combined HBV and HCV infection. More than 50% of patients were classified as Child C. Causes of kidney injury were prerenal, hepatorenal syndrome (HRS) and intrinsic tubular injury (iAKI) in 39 patients (55.7%), 17 patients (24.3%) and 14 patients (20%) respectively. mean value of uNGAL in prerenal, HRS and iAKI was 21.70 ± 7.31, 115.53 ± 68.19 and 240.83 ± 116.94 ng/mg creatinine respectively. MELD above 20 and uNGL above 32 were predictors of mortality.Conclusion. A single baseline measurement of uNGAL level has the ability to determine type of kidney dysfunction in cirrhotic patients, perhaps accelerating management decisions and improving outcomes.     

老年糖尿病患者急性心衰时急性肾损伤发生及预后分析

【】　目的　分析老年糖尿病(DM)合并急性心衰(acute heart failure,AHF)患者急性肾损伤(acute kidney injury,AKI)发生情况及短期预后。方法 107例老年糖尿病合并急性心衰患者作为观察组, 老年非糖尿病合并急性心衰患者79例作为对照组,采集两组患者一般情况、病史、尿素氮、肌酐、左室射血分数(LVEF)、血浆NT-proBNP等指标,观察随访两组患者住院期间AKI发生情况,院内死亡情况和住院时间。6个月时随访心血管事件发生率及死亡情况。按院内是否发生AKI进行组内对比,了解亚组间死亡率的差异。结果　观察组患者的AKI发生率、平均住院时间及院内死亡率高于对照组 (P<0.05);观察组患者60天心血管事件发生率高于对照组差异(P<0.05);发生院内AKI的患者死亡率明显升高(P<0.05)。结论　合并糖尿病的老年急性心衰患者AKI发生率高,院内死亡率高,院外心血管事件发生率高,并且发生AKI的患者死亡率更高。     

对比剂所致早期肾损伤时尿中性粒细胞明胶酶脂质运载蛋白的变化

目的：观察冠心病患者经皮冠状动脉腔内介入治疗术（PCI）后对比剂所致肾损伤时尿中性粒细胞明胶酶脂质运载蛋白（NGAL）的变化。方法：选择105例术前肾功能正常的行PCI术的冠心病患者,检测其手术前后不同时间点血肌酐（Scr）、尿NGAL水平和肾小球滤过率（GFR）。结果：术后有11例患者诊断为对比剂肾损伤,其尿NGAL水平异常较Scr提前至少24h。术后12h尿NGALROC曲线得出ROC曲线下的面积为0.824,AUC95%的可信区间为（0.735,0.913）。单变量分析示术前NGAL水平与GFR呈负相关,与年龄、血Scr浓度、血糖水平及糖尿病患病时间、血压水平及高血压患病时间呈正相关;术后尿NGAL水平与GFR呈负相关,与血Scr、手术时间呈正相关;多元Logistic回归分析显示血Scr及GFR是NGAL水平的独立影响因子。结论：尿NGAL对于冠心病患者PCI术后发生早期肾损伤具有良好的预测作用。     

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Mortality and Identifies Acute Kidney Injury in Cirrhosis

Background

Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge.

Aims

We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis.

Methods

Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements.

Results

One hundred eighteen patients were enrolled. Fifty-two (44?%) patients had normal kidney function, 14 (12?%) stable chronic kidney disease, 17 (14?%) prerenal azotemia, 20 (17?%) HRS, and 15 (13?%) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5–387.5) vs. 20 (15–45) ng/mL, p?=?0.004] and iAKI [325 (100–700), p??110?ng/mL (OR 6.05, 95?% CI 1.35–27.2) and HRS (OR 6.71, 95?% CI 1.76–25.5) independently predicted mortality, adjusting for age and serum creatinine?>1.5?mg/dL.

Conclusions

uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.     

Renal Biomarkers of Kidney Injury in Cardiorenal Syndrome

The cardiorenal syndromes comprise a group of disorders in which impairment of either the heart or the kidney results in injury to the other. Although the pathophysiology is not yet well understood, the clinical consequences are increasingly recognized. In congestive heart failure, the development of worsening renal function is associated with increased hospitalizations and death. Urinary biomarkers offer a rapid and noninvasive method for detecting kidney injury. The role of urinary biomarkers such as neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, N-acetyl-β-D-glucosaminidase, interleukin-18, and cystatin C are being investigated to provide diagnostic, prognostic, and, eventually, therapeutic information. This article reviews the utility of urinary biomarkers in congestive heart failure and explores directions for future research.     

体外循环下冠状动脉旁路移植术后急性肾损伤发生与早期临床结果

目的明确体外循环下冠状动脉旁路移植术(on-pump coronary artery bypass surgery,ONCABG)患者术后心脏手术相关急性肾损伤(acute kidney injury associated with cardiac surgery,CSA-AKI)发生的危险因素及肾损伤对患者早期临床结果的影响。方法回顾性分析阜外医院2011年9月至2013年11月接受体外循环下单纯ONCABG的779例患者的临床资料。根据2012年KDIGO肾损伤诊断标准明确患者术后肾损伤情况并分为CSA-AKI组与无CSA-AKI组。应用Logistic二元回归分析方法,明确ONCABG患者术后CSA-AKI的发生相关的危险因素并评估CSA-AKI发生对ONCABG患者早期临床结果的影响。结果患者平均年龄为(59.8±8.5)岁,女性占18.9%,术中平均体外循环时间为(102.1±33.8)min。术后总的CSA-AKI发生率为74.1%。CSA-AKI组患者术后感染发生率(12.8%vs 7.4%,P=0.038)、呼吸机通气时间(22.8 mins vs 17.2 mins,P=0.003)、ICU停留时间(63.0 vs 44.5h,P<0.001)、术后住院天数(8.8 d vs 8.0 d,P=0.011)均显著高于无CSA-AKI组。CSA-AKI组与无CSA-AKI组术中应用体外循环时间(103.3 min vs 98.8 min,P=0.101)无统计学差异。Logistic回归分析显示:年龄是ONCABG患者术后CSA-AKI的独立影响因素(OR:1.02,95%CI:1.00~1.04,P=0.040),患者年龄越大愈加容易发生术后CSA-AKI。同时术前最后一次肌酐水平越低患者容易达到急性肾损伤的诊断标准。结论ONCABG患者术后心脏手术相关急性肾损伤的发生显著影响患者早期预后,高龄是ONCABG患者术后发生心脏手术相关急性肾损伤的独立危险因素。术前肌酐水平较低患者更容易达到急性肾损伤的诊断标准。     

458例ICU急性肾损伤患者预后影响因素的Logistic回归分析

［摘要］ 目的 探讨影响重症加强治疗病房（ICU）急性肾损伤（AKI）患者预后的相关因素,指导临床医师采取有效控制措施。方法 回顾性分析2005年1月至2017年12月期间入住我院ICU458例AKI患者的临床资料,其中死亡患者279例,存活患者179例,存活组、死亡组分别作为因变量,性别、年龄、入ICU原因、急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分、机械通气原因、机械通气时间、是否成功撤机、是否发生ICU院感、是否行连续性血液净化(CBP)、是否有脓毒性休克、是否行有创血流动力学监测、是否输血、住ICU时间分别作为自变量,先分别对计量及计数资料作单因素分析,通过单因素分析得到影响因变量的自变量,对该自变量对因变量做Logistic回归分析。结果 通过单因素分析,得到影响死亡与否的自变量有：成功撤机、ICU院感、脓毒性休克、血流动力学监测、输血、机械通气原因、APACHEⅡ评分。将相关因素进行Logistic回归分析得出,成功撤机、脓毒性休克2个自变量对死亡或存活的因变量有影响,其中自变量是否成功撤机回归系数为-3.369,Wald值为105.169,P =0.000,Exp（B）为0.034;自变量是否脓毒性休克回归系数为1.181,Wald值为12.305,P =0.000,Exp（B）为3.257。结论 影响ICU急性肾损伤患者预后的相关因素较多,是否成功撤机、是否发生脓毒性休克是影响ICUAKI患者预后的独立危险因素。     

Urinary Elafin and Kidney Injury in Hematopoietic Cell Transplant Recipients

Background and objectives

Graft-versus-host disease (GVHD) is associated with kidney injury after hematopoietic cell transplantation (HCT). Because plasma elafin levels correlate with skin GVHD, this study examined urinary elafin as a potential marker of renal inflammation and injury.

Design, setting, participants, & measurements

Urine was collected prospectively on 205 patients undergoing their first HCT from 2003 to 2010. Collections were done at baseline, weekly through day 100, and monthly through year 1 to measure elafin and urine albumin-to-creatinine ratio (ACR). Associations between urinary elafin levels and microalbuminuria, macroalbuminuria, AKI and CKD, and mortality were examined using Cox proportional hazards or linear regression models. Available kidney biopsy specimens were processed for immunohistochemistry.

Results

Mean urinary elafin levels to day 100 were higher in patients with micro- or macroalbuminuria (adjusted mean difference, 529 pg/ml; P=0.03) at day 100 than in those with a normal ACR (adjusted mean difference, 1295 pg/ml; P<0.001). Mean urinary elafin levels were higher in patients with AKI compared with patients without AKI (adjusted mean difference, 558 pg/ml; P<0.01). The average urinary elafin levels within the first 100 days after HCT were higher in patients who developed CKD at 1 year than in patients without CKD (adjusted mean difference, 894 pg/ml; P=0.002). Among allogeneic recipients, a higher proportion of patients with micro- or macroalbuminuria at day 100 also had grade II-IV acute GVHD (80% and 86%, respectively) compared with patients with a normal ACR (58%; global P<0.01). Each increase in elafin of 500 pg/ml resulted in a 10% increase in risk of persistent macroalbuminuria (hazard ratio, 1.10; 95% confidence interval [95% CI], 1.06 to 1.13; P<0.001) and a 7% increase in the risk of overall mortality (95% CI, 1.02 to 1.13, P<0.01). Renal biopsy specimens from a separate cohort of HCT survivors demonstrated elafin staining in distal and collecting duct tubules.

Conclusion

Higher urinary elafin levels are associated with an increased risk of micro- and macroalbuminuria, AKI and CKD, and death after HCT.