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.

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

Acute kidney injury is common and associated with negative renal and patient outcomes. The human kidney has a real but limited regeneration capacity. Understanding renal regeneration may allow us to manipulate this process and thus develop therapeutic weapons to improve patients' outcome. In the first part of this paper we discuss the clinical factors associated with renal recovery: baseline patient particularities, acute kidney injury characteristics and the medical approach taken in the short and long-term. In the second part, the cellular and molecular mechanisms underlying renal regeneration are explored. The immune system seems to have an important role, first promoting inflammation and then tissue healing. Other players, such as cellular senescence, mitochondrial dysfunction, renal haemodynamics and metabolic reprogramming also have a role in renal regeneration. We aim to develop a short review of renal regeneration, offering a holistic view of this process.

Abstract:Almost half the patients on peritoneal dialysis are diabetic and glycemic control is essential to improve both patient and technique survival. Hemoglobin A1c (HbA1c) is widely used in the general population for diabetes diagnosis and monitoring as it highly correlates with blood glucose levels and outcomes. Its use has been extrapolated to the peritoneal dialysis population, despite HbA1c being commonly underestimated. In renal failure patients, HbA1c is influenced by variables affecting not only glycemia but also hemoglobin and the time of interaction between the two. Importantly, the impact of these variables differs in peritoneal dialysis compared to nondialysis chronic kidney disease and hemodialysis patients. Although HbA1c in peritoneal dialysis patients is less directly associated with blood glucose levels than in the general population, studies have confirmed its association with patient mortality. In this paper we review the variables that can influence HbA1c value emphasizing their impact in peritoneal dialysis patients. By providing clinicians with a comprehensive understanding of HbA1c results, we provide them with tools for a better patient management care and potential improved outcomes of peritoneal dialysis patients.

The definition of a good glycemic control in patients with diabetes mellitus on hemodialysis is far from settled. In the general population, hemoglobin A1c is highly correlated with the average glycemia of the last 8-12 weeks. However, in hemodialysis patients, the correlation of hbA1c with glycemia is weaker as it also reflects changes in hemoglobin characteristics and red blood cells half-life. As expected, studies show that the association between HbA1c and outcomes in these patients differ from the general population. Therefore, the value of HbA1c in the treatment of hemodialysis patients has been questioned. Guidelines are generally cautious in their recommendations about possible targets of HbA1c in this population. Indeed, the risk of not treating hyperglycemia should be weighed against the particularly high risk of precipitating hypoglycemia in dialysis patients. In this review, a critical analysis of the current role of HbA1c in the care of hemodialysis patients is presented.

As SARS-CoV-2 and its related clinical syndrome (COVID-19) became a pandemic worldwide, questions regarding its clinical presentation, infectivity, and immune response have been the subject of investigation. We present a case of a patient previously considered recovered from nosocomially transmitted asymptomatic COVID-19 illness, who presented with new respiratory, radiological, and RT-PCR findings consistent with COVID-19, while on high-dose prednisolone due to a suspected secondary demyelinating disease. Importantly, it led to three subsequent cases within patient's household after discharge from the hospital. After reviewing this case in light of current evidence and debates surrounding SARS-CoV-2 RT-PCR results, we hypothesize that patients on corticosteroids may have particular viral shedding dynamics and should prompt a more conservative approach in regard to isolation discontinuation and monitoring.

Purpose: The aim of this study is to characterize a Portuguese Intensive Care Unit experience in therapeutic plasma exchange in critically ill patients. Methods: We performed a retrospective analysis of the patients treated with therapeutic plasma exchange between 2000 and 2019. Data on patient characteristics, therapeutic plasma exchange prescription, adjuvant therapy used, adverse events and outcome under treatment were collected. Results: A total of 101 therapeutic plasma exchange procedures in 20 patients were studied. Mean number of therapeutic plasma exchange sessions per patient was 5.1±1.3. The most frequent indications to begin this treatment were myasthenia gravis (25.0%) and anti-neutrophil-cytoplasmic antibody-associated vasculitis (15.0%). There were 45.5% adverse events and the most frequent was hypotension (15.2%). 98% of the complications were mild-to-moderate. The outcome was favorable in 60.0% of patients. Conclusion: Therapeutic plasma exchange is an effective and safe therapy in many diseases that had high morbidity and mortality prior to the use of this technique.