Background and objectives: The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, which is a poor marker of early renal dysfunction. The discriminative and predictive abilities of serum and urinary cystatin C were examined for the prediction of AKI.Design, setting, participants, & measurements: In this prospective cohort study, serum and urinary cystatin C were serially measured in a heterogeneous group of patients (n ‫؍‬ 616) presenting to a tertiary care emergency department. The primary outcome was AKI, classified according to RIFLE and AKIN criteria. The secondary outcome was an adjudication based on clinical criteria to AKI, prerenal azotemia, chronic kidney disease (CKD), and normal kidney function.Results: Patients were adjudicated to have AKI in 21.1%, prerenal azotemia in 25.8%, CKD in 2.4%, and normal kidney function in 50.7%. For the diagnosis of AKI, the discriminatory ability of urinary creatinine and cystatin C was marginal. Both serum cystatin C and serum creatinine (at presentation and 6 hours later) showed high discriminatory ability for the diagnosis of AKI. However, only serum cystatin C attained a significant early predictive power (Hosmer-Lemeshow P value > 0.05). Serum cystatin C could differentiate between AKI and prerenal azotemia, but not between AKI and CKD.Conclusions: Serum cystatin C is an early, predictive biomarker of AKI, which outperforms serum creatinine in the heterogeneous emergency department setting. However, neither biomarker discriminated between AKI and CKD. Additional biomarkers continue to be needed for improved specificity in the diagnosis of community-acquired AKI.

SummaryBackground and objectives The purpose of this study was to determine the accuracy of plasma neutrophil gelatinase-associated lipocalin as a marker of AKI in patients admitted from the emergency department.Design, setting, participants, & measurements In this prospective cohort study, patients (n=616) admitted from the emergency department from March to November of 2008 were classified according to clinical criteria as AKI, transient azotemia, stable CKD, and normal function. Plasma neutrophil gelatinase-associated lipocalin was measured serially. A logistic regression model using clinical characteristics was fitted to the data, and a second model included discretized plasma neutrophil gelatinase-associated lipocalin. Performance of the models was evaluated by Hosmer-Lemeshow goodness-of-fit test, area under the receiver operating characteristic curve, net reclassification improvement, integrated discrimination improvement, and predictiveness curve.Results Twenty-one percent of patients were classified as AKI; the highest median levels of plasma neutrophil gelatinase-associated lipocalin were in the AKI group (146-174 ng/ml at various time points) and increased with AKI severity (207-244 ng/ml for Acute Kidney Injury Network classification stage.2). The discriminative ability of plasma neutrophil gelatinase-associated lipocalin for AKI diagnosis (area under the curve, 0.77-0.82 at various time points) improved with higher grades of severity (area under the curve, 0.85-0.89 for AKIN.2). Plasma neutrophil gelatinase-associated lipocalin discriminated AKI from normal function and transient azotemia (area under the curve, 0.85 and 0.73, respectively). Patients were classified into three grades of AKI risk according to plasma neutrophil gelatinase-associated lipocalin levels (low, moderate [i.e., the gray zone], and high). Patients with plasma neutrophil gelatinase-associated lipocalin in the high-risk category displayed a 10-fold greater risk of AKI (odds ratio, 9.8; 95% confidence interval, 5.6 to 16.9). The addition of plasma neutrophil gelatinase-associated lipocalin to the clinical model yielded a net reclassification improvement of 94.3% and an integrated discrimination improvement of 0.122.Conclusion Plasma neutrophil gelatinase-associated lipocalin is an accurate biomarker for prediction of AKI in patients admitted from the emergency department. This work proposes a three-grade classification of AKI risk based on plasma neutrophil gelatinase-associated lipocalin levels.

Kidney diseases in human immunodeficiency virus (HIV)-infected patients are often misdiagnosed. Despite reductions in morbidity and mortality owing to widespread use of highly effective combination antiretroviral therapy (cART), acute kidney injury (AKI) and chronic kidney disease (CKD) are still more common in these patients than in the general population, and are associated with poor health outcomes. HIV-associated nephropathy and HIV immune complex kidney diseases are the more recognizable HIV-related kidney diseases. However, a broad spectrum of kidney disorders related or not directly related with HIV infection can be observed, including cART-induced AKI, CKD, proximal tubular dysfunction, crystalluria and urolithiasis, among others. This review summarizes the major epidemiologic studies of kidney diseases in HIV-infected patients, discusses novel approaches that may potentially limit nephrotoxicity such as the use of tenofovir alafenamide, and outlines current screening measures for early diagnosis of kidney dysfunction or tubular damage, and for accurate detection of increased risk for acute or chronic kidney diseases.

Light chain cast nephropathy (LCCN) in multiple myeloma often leads to severe and poorly reversible acute kidney injury. Severe renal impairment influences the allocation of chemotherapy and its tolerability; it also affects patient survival. Whether renal biopsy findings add to the clinical assessment in predicting renal and patient outcomes in LCCN is uncertain. We retrospectively reviewed clinical presentation, chemotherapy regimens, hematologic response, and renal and patient outcomes in 178 patients with biopsy-proven LCCN from 10 centers in Europe and North America. A detailed pathology review, including assessment of the extent of cast formation, was performed to study correlations with initial presentation and outcomes. Patients presented with a mean estimated glomerular filtration rate (eGFR) of 13 ± 11 mL/min/1.73 m2, and 82% had stage 3 acute kidney injury. The mean number of casts was 3.2/mm2 in the cortex. Tubulointerstitial lesions were frequent: acute tubular injury (94%), tubulitis (82%), tubular rupture (62%), giant cell reaction (60%), and cortical and medullary inflammation (95% and 75%, respectively). Medullary inflammation, giant cell reaction, and the extent of cast formation correlated with eGFR value at LCCN diagnosis. During a median follow-up of 22 months, mean eGFR increased to 43 ± 30 mL/min/1.73 m2. Age, β2-microglobulin, best hematologic response, number of cortical casts per square millimeter, and degree of interstitial fibrosis/tubular atrophy (IFTA) were independently associated with a higher eGFR during follow-up. This eGFR value correlated with overall survival, independently of the hematologic response. This study shows that extent of cast formation and IFTA in LCCN predicts the quality of renal response, which, in turn, is associated with overall survival.

Familial renal glucosuria is an inherited renal tubular disorder. A homozygous nonsense mutation in the SLC5A2 gene, encoding the sodium/glucose co-transporter SGLT2, has recently been identified in an affected child of consanguineous parents. We now report novel compound heterozygous mutations in the son of non-consanguineous parents. One allele has a p.Q167fsX186 mutation, which is expected to produce a truncated protein, and the other a p.N654S mutation involving a highly conserved residue. These findings confirm that mutations in the SLC5A2 gene are responsible for recessive renal glucosuria.

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We investigated whether community-acquired acute kidney injury encountered in a tertiary hospital emergency department setting increases the risk of chronic kidney disease (CKD) and mortality, and whether plasma biomarkers could improve the prediction of those adverse outcomes. In a prospective cohort study, we enrolled 616 patients at admission to the emergency department and followed them for a median of 62.1 months. Within this cohort 130 patients were adjudicated as having acute kidney injury, 159 transient azotemia, 15 stable CKD and 312 normal renal function. Serum cystatin C and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at index admission. After adjusting for clinical variables, the risk of developing CKD stage 3, as well as the risk of death, were increased in the acute kidney injury group (hazard ratio (HR) 5.7 (95% confidence interval, 3.8–8.7) and HR 1.9 (95% confidence interval, 1.3–2.8), respectively). The addition of serum cystatin C increased the ability to predict the risk of developing CKD stage 3, and death (HR 1.5 (1.1–2.0) and 1.6 (1.1–2.3) respectively). The addition of plasma NGAL resulted in no improvement in predicting CKD stage 3 or mortality (HR 1.0 (0.7–1.5) and 1.2 (0.8–1.8), respectively). The risk of developing CKD stage 3 was also significantly increased in the transient azotemia group (HR 2.4 (1.5–3.6). Thus, an episode of community acquired acute kidney injury markedly increases the risk of CKD, and moderately increases the risk of death. Our findings highlight the importance of follow up of patients with community acquired acute kidney injury, for potential early initiation of renal protective strategies.

<b><i>Background:</i></b> The recent growing evidence that the proximal tubule underlies the early pathogenesis of diabetic kidney disease (DKD) is unveiling novel and promising perspectives. This pathophysiological concept links tubulointerstitial oxidative stress, inflammation, hypoxia, and fibrosis with the progression of DKD. In this new angle for DKD, the prevailing molecular mechanisms on proximal tubular cells emerge as an innovative opportunity for prevention and management of DKD as well as to improve diabetic dysmetabolism. <b><i>Summary:</i></b> The mercapturate pathway (MAP) is a classical metabolic detoxification route for xenobiotics that is emerging as an integrative circuitry detrimental to resolve tubular inflammation caused by endogenous electrophilic species. Herein we review why and how it might underlie DKD. <b><i>Key Messages:</i></b> MAP is a hallmark of proximal tubular cell function, and cysteine-<i>S</i>-conjugates might represent targets for early intervention in DKD. Moreover, the biomonitoring of urinary mercapturates from metabolic inflammation products might be relevant for the implementation of preventive/management strategies in DKD.