Proteinuria and hematuria after remission induction are associated with outcome in ANCA-associated vasculitis.

In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), hematuria and proteinuria are biomarkers reflecting kidney involvement at diagnosis. Yet, the prognostic value of their persistence after immunosuppressive induction therapy, reflecting kidney damage or persistent disease, remains uncertain. To study this, our post hoc analysis included participants of five European randomized clinical trials on AAV (MAINRITSAN, MAINRITSAN2, RITUXVAS, MYCYC, IMPROVE). Urine protein-creatinine ratio (UPCR) and hematuria of spot urine samples collected at the end of induction therapy (four-six months after treatment initiation) were correlated with the occurrence of a combined end point of death and/or kidney failure, or relapses during follow-up. Among 571 patients (59% men, median age 60), 60% had anti-proteinase 3-ANCA and 35% had anti-myeloperoxidase-ANCA, while 77% had kidney involvement. After induction therapy, 157/526 (29.8%) had persistent hematuria and 165/481 (34.3%) had UPCR of 0.05 g/mmol or more. After a median follow-up of 28 months (interquartile range 18-42), and adjustment for age, ANCA type, maintenance therapy, serum creatinine and persistent hematuria after induction, a UPCR of 0.05 g/mmol or more after induction was associated with significant risk of death/kidney failure (adjusted Hazard Ratio [HR] 3.06, 95% confidence interval 1.09-8.59) and kidney relapse (adjusted subdistribution HR 2.22, 1.16-4.24). Persistent hematuria was associated with significant kidney relapse (adjusted subdistribution HR 2.16, 1.13-4.11) but not with relapse affecting any organ nor with death/kidney failure. Thus, in this large cohort of patients with AAV, persistent proteinuria after induction therapy was associated with death/kidney failure and kidney relapse, whereas persistent hematuria was an independent predictor of kidney relapse. Hence, these parameters must be considered to assess long-term kidney prognosis of patients with AAV.

Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials.

BACKGROUND: The timing of renal replacement therapy (RRT) for severe acute kidney injury is highly debated when no life-threatening complications are present. We assessed whether a strategy of delayed versus early RRT initiation affects 28-day survival in critically ill adults with severe acute kidney injury. METHODS: In this systematic review and individual patient data meta-analysis, we searched MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials for randomised trials published from April 1, 2008, to Dec 20, 2019, that compared delayed and early RRT initiation strategies in patients with severe acute kidney injury. Trials were eligible for inclusion if they included critically ill patients aged 18 years or older with acute kidney injury (defined as a Kidney Disease: Improving Global Outcomes [KDIGO] acute kidney injury stage 2 or 3, or, where KDIGO was unavailable, a renal Sequential Organ Failure Assessment score of 3 or higher). We contacted the principal investigator of each eligible trial to request individual patient data. From the included trials, any patients without acute kidney injury or who were not randomly allocated were not included in the individual patient data meta-analysis. The primary outcome was all-cause mortality at day 28 after randomisation. This study is registered with PROSPERO (CRD42019125025). FINDINGS: Among the 1031 studies identified, one study that met the eligibility criteria was excluded because the recruitment period was not recent enough, and ten (including 2143 patients) were included in the analysis. Individual patient data were available for nine studies (2083 patients), from which 1879 patients had severe acute kidney injury and were randomly allocated: 946 (50%) to the delayed RRT group and 933 (50%) to the early RRT group. 390 (42%) of 929 patients allocated to the delayed RRT group and who had available data did not receive RRT. The proportion of patients who died by day 28 did not significantly differ between the delayed RRT group (366 [44%] of 837) and the early RRT group (355 [43%] of 827; risk ratio 1·01 [95% CI 0·91 to 1·13], p=0·80), corresponding to an overall risk difference of 0·01 (95% CI -0·04 to 0·06). There was no heterogeneity across studies (I2=0%; τ2=0), and most studies had a low risk of bias. INTERPRETATION: The timing of RRT initiation does not affect survival in critically ill patients with severe acute kidney injury in the absence of urgent indications for RRT. Delaying RRT initiation, with close patient monitoring, might lead to a reduced use of RRT, thereby saving health resources. FUNDING: None.

Impact of renal replacement therapy strategy on beta-lactam plasma concentrations: the BETAKIKI study-an ancillary study of a randomized controlled trial.

BACKGROUND: Sepsis prognosis correlates with antibiotic adequacy at the early phase. This adequacy is dependent on antibacterial spectrum, bacterial resistance profile and antibiotic dosage. Optimal efficacy of beta-lactams mandates concentrations above the minimal inhibitory concentration (MIC) of the targeted bacteria for the longest time possible over the day. Septic acute kidney injury (AKI) is the most common AKI syndrome in ICU and often mandates renal replacement therapy (RRT) initiation. Both severe AKI and RRT may increase outside target antibiotic concentrations and ultimately alter patient's prognosis. PATIENTS AND METHODS: This is a secondary analysis of a randomized controlled trial that compared an early RRT initiation strategy with a delayed one in 620 critically ill patients undergoing severe AKI (defined by KDIGO 3). We compared beta-lactam trough concentrations between the two RRT initiation strategies. The primary outcome was the proportion of patients with sufficient trough plasma concentration of beta-lactams defined by trough concentration above 4 times the MIC. We hypothesized that early initiation of RRT could be associated with an insufficient antibiotic plasma trough concentration compared to patients allocated to the delayed strategy. RESULTS: One hundred and twelve patients were included: 53 in the early group and 59 in the delayed group. Eighty-three patients (74%) had septic shock on inclusion. Trough beta-lactam plasma concentration was above 4 times the MIC breakpoint in 80.4% (n = 90) of patients of the whole population, without differences between the early and the delayed groups (79.2% vs. 81.4%, respectively, p = 0.78). On multivariate analysis, the presence of septic shock and a higher mean arterial pressure were significantly associated with a greater probability of adequate antibiotic trough concentration [OR 3.95 (1.14;13.64), p = 0.029 and OR 1.05 (1.01;1.10), p = 0.013, respectively). Evolution of procalcitonin level and catecholamine-free days as well as mortality did not differ whether beta-lactam trough concentration was above 4 times the MIC or not. CONCLUSIONS: In this secondary analysis of a randomized controlled trial, renal replacement therapy initiation strategy did not significantly influence plasma trough concentrations of beta-lactams in ICU patients with severe AKI. Presence of septic shock on inclusion was the main variable associated with a sufficient beta-lactam concentration. TRIAL REGISTRATION: The AKIKI trial was registered on ClinicalTrials.gov (Identifier: NCT01932190) before the inclusion of the first patient.

Proteinuria and Clinical Outcomes in Hospitalized COVID-19 Patients: A Retrospective Single-Center Study.

BACKGROUND AND OBJECTIVES: Kidney involvement is frequent among patients with coronavirus disease 2019 (COVID-19), and occurrence of AKI is associated with higher mortality in this population. The objective of this study was to describe occurrence and significance of proteinuria in this setting. DESIGN , SETTING, PARTICIPANTS MEASUREMENTS: We conducted a single-center retrospective study to describe the characteristic features of proteinuria measured within 48 hours following admission among patients with COVID-19 admitted in a tertiary care hospital in France, and to evaluate its association with initiation of dialysis, intensive care unit admission, and death. RESULTS: Among 200 patients with available data, urine protein-creatinine ratio at admission was ≥1 g/g for 84 (42%), although kidney function was normal in most patients, with a median serum creatinine of 0.94 mg/dl (interquartile range, 0.75-1.21). Median urine albumin-creatinine ratio was 110 mg/g (interquartile range, 50-410), with a urine albumin-protein ratio <50% in 92% of patients. Urine retinol binding protein concentrations, available for 85 patients, were ≥0.03 mg/mmol in 62% of patients. Urine protein-creatinine ratio ≥1 g/g was associated with initiation of dialysis (odds ratio, 4.87; 95% confidence interval, 2.03 to 13.0; P <0.001), admission to the intensive care unit (odds ratio, 3.55; 95% confidence interval, 1.93 to 6.71; P <0.001), and death (odds ratio, 3.56; 95% confidence interval, 1.90 to 6.54; P <0.001). CONCLUSIONS: Proteinuria is very frequent among patients admitted for COVID-19 and may precede AKI. Low levels of albuminuria suggest a predominant tubular origin, confirmed by the elevated levels of urine retinol binding protein. Urine protein-creatinine ratio ≥1 g/g at admission is strongly associated with poor kidney and patient outcome.

Vascular access for renal replacement therapy among 459 critically ill patients: a pragmatic analysis of the randomized AKIKI trial.

BACKGROUND: Vascular access for renal replacement therapy (RRT) is routine question in the intensive care unit. Randomized trials comparing jugular and femoral sites have shown similar rate of nosocomial events and catheter dysfunction. However, recent prospective observational data on RRT catheters use are scarce. We aimed to assess the site of RRT catheter, the reasons for catheter replacement, and the complications according to site in a large population of critically ill patients with acute kidney injury. PATIENTS AND METHODS: We performed an ancillary study of the AKIKI study, a pragmatic randomized controlled trial, in which patients with severe acute kidney injury (KDIGO 3 classification) with invasive mechanical ventilation, catecholamine infusion or both were randomly assigned to either an early or a delayed RRT initiation strategy. The present study involved all patients who underwent at least one RRT session. Number of RRT catheters, insertion sites, factors potentially associated with the choice of insertion site, duration of catheter use, reason for catheter replacement, and complications were prospectively collected. RESULTS: Among the 619 patients included in AKIKI, 462 received RRT and 459 were finally included, with 598 RRT catheters. Femoral site was chosen preferentially (n = 319, 53%), followed by jugular (n = 256, 43%) and subclavian (n = 23, 4%). In multivariate analysis, continuous RRT modality was significantly associated with femoral site (OR = 2.33 (95% CI (1.34-4.07), p = 0.003) and higher weight with jugular site [88.9 vs 83.2 kg, OR = 0.99 (95% CI 0.98-1.00), p = 0.03]. Investigator site was also significantly associated with the choice of insertion site (p = 0.03). Cumulative incidence of catheter replacement did not differ between jugular and femoral site [sHR 0.90 (95% CI 0.64-1.25), p = 0.67]. Catheter dysfunction was the main reason for replacement (n = 47), followed by suspected infection (n = 29) which was actually seldom proven (n = 4). No mechanical complication (pneumothorax or hemothorax) occurred. CONCLUSION: Femoral site was preferentially used in this prospective study of RRT catheters in 31 French intensive care units. The choice of insertion site depended on investigating center habits, weight, RRT modality. A high incidence of catheter infection suspicion led to undue replacement.

[Renal replacement therapy for acute kidney injury in the intensive care unit]. / Épuration extrarénale et insuffisance rénale aiguë en soins intensifs.

Renal replacement therapy for acute kidney injury has been used for more than 60 years. Except when life-threatening metabolic complications such as severe hyperkalaemia are present, renal replacement therapy initiation criteria are the subject of intense debate. Significant progress has been made with the publication of the AKIKI multicenter trial, which showed that a delayed renal replacement therapy initiation strategy (in the absence of life-threatening metabolic complications) was not associated with a difference in mortality compared to an early renal replacement therapy initiation strategy. In addition, this delayed strategy obviated the need for renal replacement therapy in almost 50% of cases was associated with a more rapid renal function recovery and with a lower incidence of catheter-bloodstream related infections. Research on renal replacement therapy modalities (continuous vs. intermittent renal replacement therapy, citrate vs. heparin anticoagulation, jugular vs. femoral catheterization) did not show any obvious superiority of one modality over another. Thus, the choice depends mainly on local considerations (patient recruitment, availability of modalities, staff experience). The criteria for renal replacement therapy discontinuation are still unclear due to difficulties in assessing renal function recovery. Urine output remains the main criteria in the decision to wean from renal replacement therapy. Pending the confirmation of AKIKI trial by similar studies in progress, it seems reasonable to choose a delayed renal replacement therapy initiation strategy under watchful surveillance in case of severe acute kidney injury in the absence of life-threatening metabolic complications.