BackgroundThe timing of initiation of renal replacement therapy (RRT) in severe acute kidney injury (AKI) remains controversial, with early initiation resulting in unnecessary therapy for some patients while expectant therapy may delay RRT for other patients. The furosemide stress test (FST) has been shown to predict the need for RRT and therefore could be used to exclude low-risk patients from enrollment in trials of RRT timing. We conducted this multicenter pilot study to determine whether FST could be used to screen patients at high risk for RRT and to determine the feasibility of incorporating FST into a trial of early initiation of RRT.MethodsFST was performed using intravenous furosemide (1 mg/kg in furosemide-naive patients or 1.5 mg/kg in previous furosemide users). FST-nonresponsive patients (urine output less than 200 mL in 2 h) were then randomized to early (initiation within 6 h) or standard (initiation by urgent indication) RRT.ResultsFST was completed in all patients (100%). Only 6/44 (13.6%) FST-responsive patients ultimately received RRT while 47/60 (78.3%) nonresponders randomized to standard RRT either received RRT or died (P <  0.001). Among 118 FST-nonresponsive patients, 98.3% in the early RRT arm and 75% in the standard RRT arm received RRT. The adherence to the protocol was 94.8% and 100% in the early and standard RRT group, respectively. We observed no differences in 28-day mortality (62.1 versus 58.3%, P = 0.68), 7-day fluid balance, or RRT dependence at day 28. However, hypophosphatemia occurred more frequently in the early RRT arm (P = 0.002).ConclusionThe furosemide stress test appears to be feasible and effective in identifying patients for randomization to different RRT initiation times. Our findings should guide implementation of large-scale randomized controlled trials for the timing of RRT initiation.Trial registrationclinicaltrials.gov, NCT02730117. Registered 6 April 2016.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2021-1) contains supplementary material, which is available to authorized users.

Noninvasive molecular tests of urine cells have been developed to monitor the activity of kidney diseases. We evaluate whether measurement of urinary messenger RNA (mRNA) levels of chemokine and growth factor genes could distinguish between diffuse proliferative lupus nephritis (class IV LN) and others and whether it is able to predict the response to therapy. Prebiopsy urine samples were collected from 26 LN patients. Urine specimens were serially collected over a period of 6 months from class IV LN patients who were receiving standard immunosuppressive treatments. Urinary interferon-producing protein 10 and its CXC chemokine receptor (CXCR)3, transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF) mRNA levels were analyzed by quantitative real-time polymerase chain reactions. Levels of chemokine or growth factor mRNAs in urine could distinguish class IV LN from others, with a sensitivity of 85% and a specificity of 94%. The receiver-operative characteristic curve demonstrated that urine mRNA levels of these genes could identify active class IV LN with an accuracy greater than the current available clinical markers, namely systemic lupus erythematosus (SLE) disease activity index, proteinuria, renal function, or urinalysis. A significant reduction of interferon-producing protein 10 (IP-10), CXCR3, TGF-beta, and VEGF mRNA levels from baselines was observed in patients who responded to therapy, whereas the levels tended to increase in those who resisted to treatment. Measurement of urinary chemokine and growth factor mRNAs can precisely distinguish class IV LN from others. Temporal association between these markers and therapeutic response is demonstrated. This noninvasive approach serves as a practical tool in diagnosis and management of LN.

Evidence-based cinical practice guidelines improve delivery of uniform care to patients with and at risk of developing kidney disease, thereby reducing disease burden and improving outcomes. These guidelines are not well-integrated into care delivery systems in most low- and middle-income countries (LMICs). The KDIGO Controversies Conference on Implementation Strategies in LMIC reviewed the current state of knowledge in order to define a road map to improve the implementation of guideline-based kidney care in LMICs. An international group of multidisciplinary experts in nephrology, epidemiology, health economics, implementation science, health systems, policy, and research identified key issues related to guideline implementation. The issues examined included the current kidney disease burden in the context of health systems in LMIC, arguments for developing policies to implement guideline-based care, innovations to improve kidney care, and the process of guideline adaptation to suit local needs. This executive summary serves as a resource to guide future work, including a pathway for adapting existing guidelines in different geographical regions.

Background When severe, COVID-19 shares many clinical features with bacterial sepsis. Yet, secondary bacterial infection is uncommon. However, as epithelium is injured and barrier function is lost, bacterial products entering the circulation might contribute to the pathophysiology of COVID-19. Methods We studied 19 adults, severely ill patients with COVID-19 infection, who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between 13th March and 17th April 2020. Blood samples on days 1, 3, and 7 of enrollment were analyzed for endotoxin activity assay (EAA), (1 → 3)-β-d-glucan (BG), and 16S rRNA gene sequencing to determine the circulating bacteriome. Results Of the 19 patients, 13 were in intensive care and 10 patients received mechanical ventilation. We found 8 patients with high EAA (≥ 0.6) and about half of the patients had high serum BG levels which tended to be higher in later in the illness. Although only 1 patient had a positive blood culture, 18 of 19 patients were positive for 16S rRNA gene amplification. Proteobacteria was the most abundant phylum. The diversity of bacterial genera was decreased overtime. Conclusions Bacterial DNA and toxins were discovered in virtually all severely ill COVID-19 pneumonia patients. This raises a previously unrecognized concern for significant contribution of bacterial products in the pathogenesis of this disease.

BackgroundCalciphylaxis is a life-threatening complication of chronic kidney disease (CKD). To inform clinical practice, we performed a systematic review of case reports, case series, and cohort studies to synthesize the available treatment modalities and outcomes of calciphylaxis in patients with CKD.MethodsElectronic databases were searched for studies that examined the uses of sodium thiosulfate, surgical parathyroidectomy, calcimimetics, hyperbaric oxygen therapy, and bisphosphonates for calciphylaxis in patients with CKD, including end-stage renal disease. For cohort studies, the results were synthesized quantitatively by performing random-effects model meta-analyses.ResultsA total of 147 articles met the inclusion criteria and were included in the systematic review. There were 90 case reports (90 patients), 20 case series (423 patients), and 37 cohort studies (343 patients). In the pooled cohorts, case series, and case reports, 50.3% of patients received sodium thiosulfate, 28.7% underwent surgical parathyroidectomy, 25.3% received cinacalcet, 15.3% underwent hyperbaric oxygen therapy, and 5.9% received bisphosphonates. For the subset of cohort studies, by meta-analysis, the pooled risk ratio for mortality was not significantly different among patients who received sodium thiosulfate (pooled risk ratio [RR] 0.89; 95% confidence interval [CI] 0.71–1.12), cinacalcet (pooled RR 1.04; 95% CI 0.75–1.42), hyperbaric oxygen therapy (pooled RR 0.89; 95% CI 0.71–1.12), and bisphosphonates (pooled RR 0.77; 95% CI 0.44–1.32), and those who underwent surgical parathyroidectomy (pooled RR 0.88; 95% CI 0.69–1.13).ConclusionThis systematic review found no significant clinical benefit of the 5 most frequently used treatment modalities for calciphylaxis in patients with CKD. Randomized controlled trials are needed to test the efficacy of these therapies.