Loin pain haematuria syndrome 1967-2020: a review.

The purpose of this retrospective review is to question the validity of the condition 'loin pain haematuria syndrome' (LPHS). We highlight the possibility that most patients regarded as having LPHS have a psychiatric/psychological basis for their symptoms, particularly loin pain. Because of this, and because it recurs despite treatment, the review also questions the use of treatments that are invasive, expensive, and carry considerable morbidity.

The role of albumin and the extracellular matrix on the pathophysiology of oedema formation in severe malnutrition.

BACKGROUND: While fluid flows in a steady state from plasma, through interstitium, and into the lymph compartment, altered fluid distribution and oedema can result from abnormal Starling's forces, increased endothelial permeability or impaired lymphatic drainage. The mechanism of oedema formation, especially the primary role of hypoalbuminaemia, remains controversial. Here, we explored the roles of albumin and albumin-independent mechanisms in oedema formation among children with severe malnutrition (SM). METHODS: We performed secondary analysis of data obtained from two independent clinical trials in Malawi and Kenya (NCT02246296 and NCT00934492). We then used an unconventional strategy of comparing children with kwashiorkor and marasmus by matching (discovery cohort, n = 144) and normalising (validation cohort, n = 98, 2 time points) for serum albumin. Untargeted proteomics was used in the discovery cohort to determine plausible albumin-independent mechanisms associated with oedema, which was validated using enzyme-linked immunosorbent assay and multiplex assays in the validation cohort. FINDINGS: We demonstrated that low serum albumin is necessary but not sufficient to develop oedema in SM. We further found that markers of extracellular matrix (ECM) degradation rather than markers of EG degradation distinguished oedematous and non-oedematous children with SM. INTERPRETATION: Our results show that oedema formation has both albumin-dependent and independent mechanisms. ECM integrity appears to have a greater role in oedema formation than EG shedding in SM. FUNDING: Research Foundation Flanders (FWO), Thrasher Foundation (15122 and 9403), VLIR-UOS-Ghent University Global Minds Fund, Bill & Melinda Gates Foundation (OPP1131320), MRC/DfID/Wellcome Trust Global Health Trials Scheme (MR/M007367/1), Canadian Institutes of Health Research (156307), Wellcome Trust (WT083579MA).

Prediction of cardiac surgery associated - acute kidney injury (CSA-AKI) by healthcare professionals and urine cell cycle arrest AKI biomarkers [TIMP-2]*[IGFBP7]: A single center prospective study (the PREDICTAKI trial).

PURPOSE: Cardiac surgery associated acute kidney injury (CSA-AKI) is a contributor to adverse outcomes. Preventive measures reduce AKI incidence in high risk patients, identified by biomarkers [TIMP-2]*[IGFBP7] (Nephrocheck®). This study investigate clinical AKI risk assessment by healthcare professionals and the added value of the biomarker result. MATERIALS AND METHODS: Adult patients were prospectively included. Healthcare professionals predicted CSA-AKI, with and without biomarker result knowledge. Predicted outcomes were AKI based on creatinine, AKI stage 3 on urine output, anuria and use of kidney replacement therapy (KRT). RESULTS: One-hundred patients were included. Consultant and ICU residents were best in AKI prediction, respectively AUROC 0.769 (95% CI, 0.672-0.850) and 0.702 (95% CI, 0.599-0.791). AUROC of NephroCheck® was 0.541 (95% CI, 0.438-0.642). AKI 3 occurred in only 4 patients; there was no anuria or use of KRT. ICU nurses and ICU residents had an AUROC for prediction of AKI 3 of respectively 0.867 (95% CI, 0.780-0.929) and 0.809 (95% CI, 0.716-0.883); for NephroCheck® this was 0.838 (95% CI, 0.750-0.904). CONCLUSIONS: Healthcare professionals performed poor or fair in predicting CSA-AKI and knowledge of Nephrocheck® result did not improved prediction. No conclusions could be made for prediction of severe AKI, due to limited number of events.

The importance of the urinary output criterion for the detection and prognostic meaning of AKI.

Most reports on AKI claim to use KDIGO guidelines but fail to include the urinary output (UO) criterion in their definition of AKI. We postulated that ignoring UO alters the incidence of AKI, may delay diagnosis of AKI, and leads to underestimation of the association between AKI and ICU mortality. Using routinely collected data of adult patients admitted to an intensive care unit (ICU), we retrospectively classified patients according to whether and when they would be diagnosed with KDIGO AKI stage ≥ 2 based on baseline serum creatinine (Screa) and/or urinary output (UO) criterion. As outcomes, we assessed incidence of AKI and association with ICU mortality. In 13,403 ICU admissions (62.2% male, 60.8 ± 16.8 years, SOFA 7.0 ± 4.1), incidence of KDIGO AKI stage ≥ 2 was 13.2% when based only the SCrea criterion, 34.3% when based only the UO criterion, and 38.7% when based on both criteria. By ignoring the UO criterion, 66% of AKI cases were missed and 13% had a delayed diagnosis. The cause-specific hazard ratios of ICU mortality associated with KDIGO AKI stage ≥ 2 diagnosis based on only the SCrea criterion, only the UO criterion and based on both criteria were 2.11 (95% CI 1.85-2.42), 3.21 (2.79-3.69) and 2.85 (95% CI 2.43-3.34), respectively. Ignoring UO in the diagnosis of KDIGO AKI stage ≥ 2 decreases sensitivity, may lead to delayed diagnosis and results in underestimation of KDIGO AKI stage ≥ 2 associated mortality.

Risk prediction models for acute kidney injury in adults: An overview of systematic reviews.

BACKGROUND: The incidence of Acute Kidney Injury (AKI) and its human and economic cost is increasing steadily. One way to reduce the burden associated with AKI is to prevent the event altogether. An important step in prevention lies in AKI risk prediction. Due to the increasing number of available risk prediction models (RPMs) clinicians need to be able to rely on systematic reviews (SRs) to provide an objective assessment on which RPM can be used in a specific setting. Our aim was to assess the quality of SRs of RPMs in AKI. METHODS: The protocol for this overview was registered in PROSPERO. MEDLINE and Embase were searched for SRs of RPMs of AKI in any setting from 2003 till August 2020. We used the ROBIS tool to assess the methodological quality of the retrieved SRs. RESULTS: Eight SRs were retrieved. All studies were assessed as being at high risk for bias using the ROBIS tool. Eight reviews had a high risk of bias in study eligibility criteria (domain 1), five for study identification and selection (domain 2), seven for data collection and appraisal (domain 3) and seven for synthesis and findings (domain 4). Five reviews were scored at high risk of bias across all four domains. Risk of bias assessment with a formal risk of bias tool was only performed in five reviews. Primary studies were heterogeneous and used a wide range of AKI definitions. Only 19 unique RPM were externally validated, of which 11 had only 1 external validation report. CONCLUSION: The methodological quality of SRs of RPMs of AKI is inconsistent. Most SRs lack a formal risk of bias assessment. SRs ought to adhere to certain standard quality criteria so that clinicians can rely on them to select a RPM for use in an individual patient. TRIAL REGISTRATION: PROSPERO registration number is CRD 42020204236, available at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=204236.

A rare presentation of kidney failure in a patient with giant cell arteritis: case report and review of literature.

Although giant cell arteritis, also called temporal arteritis, is the most common primary vasculitis in the elderly, an association with AA amyloidosis has rarely been reported. AA amyloidosis is a disorder that results from the extracellular deposition of proteolytic cleavage products of serum amyloid A, which occurs in the setting of long-standing inflammation. We present a case of a patient with giant cell arteritis who developed a rapidly deteriorating kidney function, due to AA amyloidosis. Early recognition of this rare phenomenon is crucial as prompt treatment may be beneficial in the salvage of renal function.

Mathematical model to predict B-type natriuretic peptide levels in haemodialysis patients.

AIM: Clinical interpretation of B-type natriuretic peptide (BNP) levels in haemodialysis (HD) patients for fluid management remains elusive. METHODS: We conducted a retrospective observational monocentric study. We built a mathematical model to predict BNP levels, using multiple linear regressions. Fifteen clinical/biological characteristics associated with BNP variation were selected. A first cohort of 150 prevalent HD (from September 2015 to March 2016) was used to build several models. The best model proposed was internally validated in an independent cohort of 75 incidents HD (from March 2016 to December 2017). RESULTS: In cohort 1, mean BNP level was 630 ± 717 ng/mL. Cardiac disease (CD - stable coronary artery disease and/or atrial fibrillation) was present in 45% of patients. The final model includes age, systolic blood pressure, albumin, CD, normo-hydrated weight (NHW) and the fluid overload (FO) assessed by bio-impedancemetry. The correlation between the measured and the predicted log-BNP was 0.567 and 0.543 in cohorts 1 and 2, respectively. Age (ß = 3.175e-2 , P < 0.001), CD (ß = 5.243e-1 , P < 0.001) and FO (ß = 1.227e-1 , P < 0.001) contribute most significantly to the BNP level, respectively, but within a certain range. We observed a logistic relationship between BNP and age between 30 and 60 years, after which this relationship was lost. BNP level was inversely correlated with NHW independently of CD. Finally, our model allows us to predict the BNP level according to the FO. CONCLUSION: We developed a mathematical model capable of predicting the BNP level in HD. Our results show the complex contribution of age, CD and FO on BNP level.

Evolution of protein-bound uremic toxins indoxyl sulphate and p-cresyl sulphate in acute kidney injury.

BACKGROUND: There is a gradual increase in serum concentrations of protein-bound colon-derived uremic toxins indoxyl sulphate (IxS) and p-cresyl sulphate (pCS) as chronic kidney disease (CKD) progresses. In acute kidney injury (AKI), up till now, the retention pattern has not been studied. METHODS: In this study, 194 adult patients admitted with sepsis to the intensive care unit were included. IxS, pCS and serum creatinine (sCrea) were quantified at inclusion (D0) and at day 4, unless follow-up ended earlier (Dend). RESULTS: Serum levels of sCrea (P < 0.001), IxS (P < 0.001) and pCS (P < 0.05) were higher in patients with AKI according to RIFLE classification at D0. In contrast with sCrea, IxS and pCS levels only increased from stage I (IxS) and F (pCS) on. When grouped according to evolution in RIFLE class from D0 to Dend, all solute concentrations were higher (P < 0.001) in the group with unfavourable evolution. In this group, there was a marked rise in sCrea (P < 0.001), a moderate one for pCS (P < 0.05), but no change for IxS (P = 0.112). There was a decrease (P < 0.001) of all solute concentrations in the group with favourable evolution. Comparing AKI with CKD patients matched for sCrea, total levels of both IxS and pCS were higher (P < 0.01) in patients with CKD. CONCLUSIONS: Although concentrations of IxS and pCS both tend to rise in sepsis patients with AKI, their evolution does not conform with that of sCrea. For the same level of sCrea, IxS and pCS concentrations are lower in AKI compared with CKD.

Subclinical AKI: ready for primetime in clinical practice?

There has been considerable progress over the last decade in the standardization of the acute kidney injury (AKI) definition with the publication of the RIFLE, AKIN, KDIGO and ERBP classification criteria. However, these classification criteria still rely on imperfect parameters such as serum creatinine and urinary output. The use of timed urine collections, kinetic eGFR (estimated glomerular filtration rate), real time measurement of GFR and direct measures of tubular damage can theoretically aid in a more timely diagnosis of AKI and improve patients' outcome. There has been an extensive search for new biomarkers indicative of structural tubular damage but it remains controversial whether these new markers should be included in the current classification criteria. The use of these markers has also led to the creation of a new concept called subclinical AKI, a condition where there is an increase in biomarkers but without clinical AKI, defined as an increase in serum creatinine and/or a decrease in urinary output. In this review we provide a framework on how to critical appraise biomarker research and on how to position the concept of subclinical AKI. The evaluation of biomarker performance and the usefulness of the concept 'subclinical AKI' requires careful consideration of the context these biomarkers are used in (clinical versus research setting) and the goal we want to achieve (risk assessment versus prediction versus early diagnosis versus prognostication). It remains currently unknown whether an increase in biomarkers levels without functional repercussion is clinically relevant and whether including biomarkers in classification criteria will improve patients' outcome.

Haste makes waste-Should current guideline recommendations for initiation of renal replacement therapy for acute kidney injury be changed?

There is broad consensus among guideline organizations that renal replacement therapy (RRT) should not be delayed in case of life-threatening conditions. However, in case of severe acute kidney injury (AKI) without these conditions, it is unclear whether immediate RRT has an advantage over delayed RRT. Two recently published randomized controlled trials (AKIKI and ELAIN) with seemingly opposite results have reignited the discussion whether guideline recommendations on initiation strategies in severe AKI should be adapted. This editorial discusses RRT initiation strategies in severe AKI, based on recent literature and highlights the potential advantages and disadvantages of immediate vs delayed start. Overall, evidence in favor of immediate compared to delayed strategies is sparse and there is wide heterogeneity across studies making it difficult to draw firm conclusions. RRT should not be delayed in case of refractory hyperkalemia, severe metabolic acidosis or pulmonary edema resistant to diuretics. In all other cases, a delayed strategy seems justified and might enhance renal recovery. RRT is not a "it doesn't hurt to try" technique and can expose the patient to a higher risk of bleeding, hemodynamic problems, under-dosing of antibiotics, loss of nutrients, catheter-related complications and the uncertain effects of blood-membrane interactions. There is no compelling reason to change current guideline recommendations and research focus should shift toward the development of algorithms as a decision aid tool for RRT initiation in severe AKI.

Points of Concern in Post Acute Kidney Injury Management.

The incidence of acute kidney injury (AKI) will in the future remain high, partly due to an increase in comorbidities and other AKI favoring factors such as the rise in high-risk diagnostic and therapeutic interventions. AKI has emerged as a major public health concern with high human and financial costs. It has recently been demonstrated that patients surviving an AKI episode show increased all-cause mortality, chronic kidney disease (CKD), ESRD, cardiovascular events, and reduced quality of life. Although it is important to acknowledge that, after an AKI episode, the risk of dying by far exceeds the risk of developing incident or progressive CKD and/or entering a maintenance renal replacement therapy (RRT) program, currently only a minority of patients are referred for renal follow-up, even after AKI-requiring RRT. On the other hand, renal follow-up for all AKI survivors might not be necessary and would represent an overwhelming work load for the health care system. There are at present no clear guidelines on which patients should be referred and on the elements of post AKI care that may improve non-renal and renal outcomes. In this review, we discuss several points of concern in post-AKI management and propose an algorithm on post-AKI care, mainly based on the renal recovery pattern at discharge from the hospital. Potential opportunities to improve care include appropriate risk stratification, close monitoring of kidney function, management of CKD complications, blood pressure control, medication reconciliation, and education of patients and non-nephrologists on AKI and its downstream complications.

Management of patients at risk of acute kidney injury.

Acute kidney injury (AKI) is a multifaceted syndrome that occurs in different settings. The course of AKI can be variable, from single hit and complete recovery, to multiple hits resulting in end-stage renal disease. No interventions to improve outcomes of established AKI have yet been developed, so prevention and early diagnosis are key. Awareness campaigns and education for health-care professionals on diagnosis and management of AKI-with attention to avoidance of volume depletion, hypotension, and nephrotoxic interventions-coupled with electronic early warning systems where available can improve outcomes. Biomarker-based strategies have not shown improvements in outcome. Fluid management should aim for early, rapid restoration of circulatory volume, but should be more limited after the first 24-48 h to avoid volume overload. Use of balanced crystalloid solutions versus normal saline remains controversial. Renal replacement therapy should only be started on the basis of hard criteria, but should not be delayed when criteria are met. On the basis of recent evidence, the risk of contrast-induced AKI might be overestimated for many conditions.

Epidemiology and outcome of acute kidney injury in children, a single center study.

BACKGROUND: Information on the epidemiology of Acute Kidney Injury (AKI) in children is scarce. We performed a single center retrospective cohort study to analyze the incidence of AKI, the male/female ratio, the underlying etiology, and age at presentation. We also aimed to assess outcome measured by mortality, duration of PICU stay, and development of Chronic Kidney Disease (CKD). METHODS: Records were searched for children presenting with or developing AKI between 1st January 2008 and 1st January 2015. AKI was classified according to the pediatric Rifle criteria while the cause of AKI was defined as the major underlying disease. RESULTS: Of the 28,295 children admitted, 167 episodes of AKI were identified, equaling 5.9 cases per 1000 children. Patients classified as Failure at presentation according to pRifle criteria where significantly more likely to need dialysis (27/50, 54%) compared to those presenting with Injury (12/57, 21.1%) or Risk (6/60, 10 %). Diarrhea-associated Hemolytic Uremic Syndrome (D+HUS) was the most frequent cause (20.3 %) peaking during the summer months, followed by cardiac surgery (13.7%), medication-related nephrotoxicity (13.2%), and acute Glomerulonephritis (12%). The median age of children admitted with AKI was 6.1 years (range 0.1-17) and 50.8% of cases were male. Twenty five (15%) children died while 27 (16.1%) developed CKD. CONCLUSIONS: Pediatric AKI poses a significant problem and strategies aimed at prevention, early detection, treatment, and adequate follow-up are needed. D+HUS is the most common underlying cause and effective surveillance of Enterohemorrhagic E. coli infections in association with additional measures is highly recommended.