The Proximal Tubule as the Pathogenic and Therapeutic Target in Acute Kidney Injury.

BACKGROUND: In 2004, the term acute kidney injury (AKI) was introduced with the intention of broadening our understanding of rapid declines in renal function and to replace the historical terms of acute renal failure and acute tubular necrosis (ATN). Despite this evolution in terminology, the mechanisms of AKI have stayed largely elusive with the pathophysiological concepts of ATN remaining the mainstay in our understanding of AKI. SUMMARY: The proximal tubule (PT), having the highest mitochondrial content in the kidney and relying heavily on oxidative phosphorylation to generate ATP, is vulnerable to ischaemic insults and mitochondrial dysfunction. Histologically, pathological changes in the PT are more consistent than changes to the glomeruli or the loop of Henle in AKI. Physiologically, activation of tubuloglomerular feedback due to PT dysfunction leads to an increase in preglomerular afferent arteriole resistance and a reduction in glomerular filtration. Pharmacologically, frusemide - a drug commonly used in the setting of oliguric AKI - is actively secreted by the PT and its diuretic effect is compromised by its failure to be secreted into the urine and thus be delivered to its site of action at the loop of Henle in AKI. Increases in the urinary, but not plasma biomarkers, of PT injury within 1 h of shock suggest that the PT as the initiation pathogenic target of AKI. KEY MESSAGE: Therapeutic agents targeting specifically the PT epithelial cells, in particular its mitochondria - including amino acid ergothioneine and superoxide scavenger MitoTEMPO - show great promises in ameliorating AKI.

The incidence and determinants of bariatric reoperations: a population-based cohort study.

BACKGROUND: Bariatric surgery is the strongest evidence-based treatment available for obesity, but the long-term morbidity and durability of these procedures is being increasingly scrutinized. OBJECTIVE: To report the incidence, timing, indications, and risk factors for bariatric reoperations. SETTING: A state-wide, multicenter, retrospective study. METHODS: Using the Western Australian Department of Health Data Linkage Unit, all patients undergoing an index bariatric procedure where identified across a 10-year period (2007-2016). RESULTS: Of 24,766 patients who underwent bariatric surgery, 5001 patients (20.2%) required at least 1 bariatric reoperation. The 5-yearly rates were 19.6% (95% confidence interval [CI], 19.0%-20.2%) for a first revision, 58.2% (95%CI, 56.6%-59.8%) for a subsequent second revision, 38.3% (95%CI, 35.4%-41.2%) for a subsequent third revision, and 45.2% (95%CI, 39.9%-50.5%) for a subsequent fourth revision. Surgical complications (67.4%) were the main indication for any bariatric reoperation ahead of weight-related causes (32.6%). In a Cox regression analysis, being younger, female, without private health insurance, and having a gastric band as the initial bariatric procedure were all significant risk factors for bariatric reoperations. Compared with bariatric patients needing only an index procedure, patients requiring bariatric reoperations also had higher postoperative incidence rate ratios of endoscopic (incidence rate ratio 2.4; 95%CI, 2.3-2.5) and body contouring (incidence rate ratio 3.8; 95%CI, 3.5-4.1) procedures. CONCLUSIONS: Patients undergoing bariatric surgery had a high incidence of bariatric reoperations, predominantly for surgical complications. Of those patients who required bariatric reoperations, there were additional high rates of recurrent bariatric surgery, postoperative endoscopy, and body contouring procedures.

Incidence and Determinants of Mental Health Service Use After Bariatric Surgery.

Importance: Obesity is associated with an increased prevalence of psychiatric disorders. The association of bariatric surgery with mental health outcomes is poorly understood. Objective: To investigate the association of bariatric surgery with the incidence of outpatient, emergency department (ED), and inpatient mental health service use. Design, Setting, and Participants: This statewide, mirror-image, longitudinal cohort study used data from Western Australian Department of Health Data Linkage Branch records from all patients undergoing index (ie, first) bariatric surgery in Western Australia over a 10-year period (January 2007-December 2016), with mean (SD) follow-up periods of 10.2 (2.9) years before and 5.2 (2.9) years after index bariatric surgery. The data analysis was performed between November 2018 and March 2019. Exposures: Index bariatric surgery. Main Outcomes and Measures: The incidence and predictors for mental health presentations, deliberate self-harm, and suicide in association with the timing of bariatric surgery. Results: A total of 24 766 patients underwent index bariatric surgery; of these, the mean (SD) age was 42.5 (11.7) years and 19 144 (77.3%) were women. Use of at least 1 mental health service occurred in 3976 patients (16.1%), with 1401 patients (35.2%) presenting only before surgery, 1025 (25.8%) presenting before and after surgery, and 1550 patients (39.0%) presenting only after surgery. There was an increase in psychiatric illness presentations after bariatric surgery (outpatient clinic attendance: incidence rate ratio [IRR], 2.3; 95% CI, 2.3-2.4; ED attendance: IRR, 3.0; 95% CI, 2.8-3.2; psychiatric hospitalization: IRR, 3.0; 95% CI, 2.8-3.1). There was also a 5-fold increase in deliberate self-harm presentations to an ED after surgery (IRR, 4.7; 95% CI, 3.8-5.7), with 25 of 261 postoperatives deaths (9.6%) due to suicide. Complications after bariatric surgery requiring further surgical intervention and a history of mental health service provision before surgery were the most important associations with subsequent mental health presentations after surgery. Deliberate self-harm and mental and behavioral disorders due to psychoactive substance use before bariatric surgery were the main associations with subsequent deliberate self-harm or suicide after surgery. Conclusions and Relevance: We observed an increase in mental health service presentations after bariatric surgery, particularly among those who had prior psychiatric illnesses or developed surgical complications requiring further surgery. These findings caution the hypothesis that weight reduction by bariatric surgery will improve mental health in patients with obesity.

Advance care planning documentation strategies; goals-of-care as an alternative to not-for-resuscitation in medical and oncology patients. A pre-post controlled study on quantifiable outcomes.

BACKGROUND: Health services in Tasmania, Victoria and now Western Australia are changing to goals-of-care (GOC) advance care planning (ACP) documentation strategies. AIM: To compare the clinical impact of two different health department-sanctioned ACP documentation strategies. METHODS: A non-blinded, pre-post, controlled study over two corresponding 6-month periods in 2016 and 2017 comparing the current discretional not-for-resuscitation (NFR) with a new, inclusive GOC strategy in two medical/oncology wards at a large private hospital. Main outcomes were the uptake of ACP forms per hospitalisation and the timing between hospital admission, ACP form completion and in-patient death. Secondary outcomes included utilisation of the rapid response team (RRT), palliative and critical care services. RESULTS: In total, 650 NFR and 653 GOC patients underwent 1885 admissions (mean Charlson Comorbidity Index = 3.7). GOC patients had a higher uptake of ACP documentation (346 vs 150 ACP forms per 1000 admissions, P < 0.0001) and a higher proportion of ACP forms completed within the first 48 h of admission (58 vs 39%, P = 0.0002) but a higher incidence of altering the initial ACP level of care (P = 0.003). All other measures, including ACP documentation within 48 h of death (P = 0.50), activation of RRT (P = 0.73) and admission to critical (P = 0.62) or palliative (P = 0.81) care services, remained similar. GOC documentation was often incomplete, with most sub-sections left blank between 74 and 87% of occasions. CONCLUSION: Despite an increased uptake of the GOC form, overall use remained low, written completion was poor, and most quantitative outcomes remained statistically unchanged. Further research is required before a wider GOC implementation can be supported in Australia's healthcare systems.

Out-of-office hours' elective surgical intensive care admissions and their associated complications.

BACKGROUND: The 'weekend' effect is a controversial theory that links reduced staffing levels, staffing seniority and supportive services at hospitals during 'out-of-office hours' time periods with worsening patient outcomes. It is uncertain whether admitting elective surgery patients to intensive care units (ICU) during 'out-of-office hours' time periods mitigates this affect through higher staffing ratios and seniority. METHODS: Over a 3-year period in Western Australia's largest private hospital, this retrospective nested-cohort study compared all elective surgical patients admitted to the ICU based on whether their admission occurred 'in-office hours' (Monday-Friday 08.00-18.00 hours) or 'out-of-office hours' (all other times). The main outcomes were surgical complications using the Dindo-Clavien classification and length-of-stay data. RESULTS: Of the total 4363 ICU admissions, 3584 ICU admissions were planned following elective surgery resulting in 2515 (70.2%) in-office hours and 1069 (29.8%) out-of-office hours elective ICU surgical admissions. Out-of-office hours ICU admissions following elective surgery were associated with an increased risk of infection (P = 0.029), blood transfusion (P = 0.020), total parental nutrition (P < 0.001) and unplanned re-operations (P = 0.027). Out-of-office hours ICU admissions were also associated with an increased hospital length-of-stay, with (1.74 days longer, P < 0.0001) and without (2.8 days longer, P < 0.001) adjusting for severity of acute and chronic illnesses and inter-hospital transfers (12.3 versus 9.8%, P = 0.024). Hospital mortality (1.2 versus 0.7%, P = 0.111) was low and similar between both groups. CONCLUSION: Out-of-office hours ICU admissions following elective surgery is common and associated with serious post-operative complications culminating in significantly longer hospital length-of-stays and greater transfers with important patient and health economic implications.

Incidence and outcomes after bariatric surgery in older patients: a state-wide data-linked cohort study.

BACKGROUND: The burgeoning problem of obesity is seen most profoundly in older populations. Despite the dramatic increase in bariatric surgery rates over the last 20 years, weight reduction surgery is largely restricted to younger patients. METHODS: This retrospective, longitudinal, self-matched, population-based cohort study assessed the incidence and outcomes of all patients undergoing bariatric surgery who were ≥55 years old in Western Australia between 2007 and 2011. The mean preoperative and post-operative follow-up periods were 2.5 years and 3.4 years, respectively. RESULTS: Of the 12 062 bariatric surgical operations recorded during the study period, 2179 (18.1%) were performed in patients aged ≥55 years old. Older bariatric patients were statistically more likely to require longer hospital admissions (2.85 versus 2.65 days, P < 0.001), have post-operative complications (12.0 versus 6.3%, P < 0.001) and require intensive care admissions (8.2 versus 4.3%, P = 0.001) compared to patients <55 years old. However, both 30-day (no deaths in the older cohort) and long-term mortality rates (1.07 versus 0.42 deaths per 1000 patient-years, P = 0.10) remained relatively low. All-cause long-term hospitalization rates were also significantly reduced (P < 0.001) after bariatric surgery for patients who were older than 55 years compared to before surgery. CONCLUSION: Despite older age being associated with a higher risk of complications and longer hospital stays, there was a reduction in subsequent overall hospitalizations for older patients after bariatric surgery, suggesting that bariatric surgery may still confer health benefits to carefully selected obese older patients who cannot achieve weight loss by other means.

Incidence and Risk Factors for Deliberate Self-harm, Mental Illness, and Suicide Following Bariatric Surgery: A State-wide Population-based Linked-data Cohort Study.

OBJECTIVE: Assess the incidence and determinants of hospitalization for deliberate self-harm and mental health disorders, and suicide after bariatric surgery. BACKGROUND: Limited recent literature suggests an increase in deliberate self-harm following bariatric surgery. METHODS: A state-wide, population-based, self-matched, longitudinal cohort study over a 5-year period between 2007 and 2011. Utilizing the Western Australian Department of Health Data Linkage Unit records, all patients undergoing bariatric surgery (n = 12062) in Western Australia were followed for an average 30.4 months preoperatively and 40.6 months postoperatively. RESULTS: There were 110 patients (0.9%) hospitalized for deliberate self-harm, which was higher than the general population [incidence rate ratio (IRR) 1.47, 95% confidence interval (CI) 1.11-1.94, P = 0.005]. Compared with before surgery, there was no significant increase in deliberate self-harm hospitalizations (IRR 0.79, 95% CI 0.54-1.16; P = 0.206) and a reduction in overall mental illness related hospitalizations (IRR 0.76, 95% CI 0.63-0.91; P = 0.002) after surgery. Younger age, no private-health insurance cover, a history of hospitalizations due to depression before surgery, and gastrointestinal complications after surgery were predictors for deliberate self-harm hospitalizations after bariatric surgery. Three suicides occurred during the follow-up period, a rate comparable to the general population during the same time period (IRR 0.61, 95% CI 0.11-2.27, P = 0.444). CONCLUSIONS: Hospitalization for deliberate self-harm in bariatric patients was more common than the general population, but an increased incidence of deliberate self-harm after bariatric surgery was not observed. Hospitalization for depression before surgery and major postoperative gastrointestinal complications after bariatric surgery are potentially modifiable risk factors for deliberate self-harm after bariatric surgery.

A Comparison of Bariatric Surgery in Hospitals With and Without ICU: a Linked Data Cohort Study.

BACKGROUND: It is uncertain whether bariatric surgery can be safely performed in secondary hospitals without on-site intensive care unit (ICU) support. This study describes the outcomes of elective bariatric surgery patients who required inter-hospital transfers for unplanned ICU management, extrapolating this as a parameter for secondary hospital safety after bariatric surgery. METHODS: This was a retrospective, statewide, population-based, linked data cohort study capturing all adult bariatric surgery patients for an entire Australian state between 2007 and 2011 (n = 12,062) with minimum 12-month follow-up. RESULTS: In secondary hospitals, 2663 (22.1%) bariatric patients were operated on, with the majority (n = 2553) undergoing sleeve gastrectomies (SG) or adjustable gastric bands (LAGB). Forty-two patients (including 19 LAGB and 20 SG) required inter-hospital transfer to a tertiary hospital for unplanned ICU care (1.6%, 95% confidence interval 1.2-2.1), mainly due to surgical complications. Inter-hospital transfers incurred two deaths, both following sleeve gastrectomies. When compared to patients requiring unplanned ICU admissions after bariatric surgery in tertiary hospitals with an on-site ICU (n = 155), there was no difference in their demographic parameters, comorbid illnesses, or mortality (4.8 vs 3.9%, p = 0.68). The mortality following bariatric procedures both statewide (0.2%) and in secondary hospitals (0.2%) was both uncommon and comparable. CONCLUSIONS: Statewide inter-hospital transfers for unplanned ICU care from secondary hospitals were low. Inter-hospital transfer mortality was comparable to a similar bariatric cohort requiring unplanned ICU care after surgery in a tertiary hospital. This suggests that certain bariatric procedures can be safely done in most secondary hospitals where elective ICU admission is deemed unnecessary.

Acute kidney injury in bariatric surgery patients requiring intensive care admission: a state-wide, multicenter, cohort study.

BACKGROUND: A multidisciplinary bariatric surgical approach is currently the most effective treatment for obesity. However, little is known about how the physiologic impact of weight reduction surgery superimposed on premorbid obesity-related co-morbidities may adversely influence perioperative renal function. METHODS: This observational, multicenter study investigated all bariatric surgery patients (n = 590) admitted to any intensive care unit (ICU) in Western Australia between 2007 and 2011. Using Acute Kidney Injury Network (AKIN) criteria, we ascertained the incidence and contributing risk factors for acute kidney injury (AKI). RESULTS: Acute kidney injury (AKI) occurred in 103 patients, accounting for 17.5% of all ICU admissions after bariatric surgery with 76.8% of the AKI episodes limited to AKIN stage 1. In a multivariate analysis, male gender, premorbid hypertension, higher admission APACHE II scores, and blood transfusions were all associated with AKI, while preexisting chronic kidney disease and body mass index (BMI) appeared not to influence renal decline. Both ICU (6.7 versus 2.5 d, P<.001) and hospital (18.6 versus 6.8 d, P<.001) length of stays were significantly increased after AKI. Six patients required hemodialysis while both ICU mortality (2.9 versus 0%, P = .005) and long-term mortality (18.2 versus 4.7 deaths per 1000 bariatric patient-yr, P = .01) were greater in patients experiencing AKI. CONCLUSIONS: AKI is common in bariatric patients requiring critical care support leading to increased healthcare utilization, prolonged hospitalization, and is associated with a higher mortality. BMI, a previously described risk factor, was not predictive of AKI in this cohort.

Long-term Clinical Outcomes and Health Care Utilization After Bariatric Surgery: A Population-based Study.

OBJECTIVE: To determine the long-term outcomes, health care utilization, and risk factors for complications after bariatric surgery. BACKGROUND: With the burgeoning problem of obesity and the consequential rise in bariatric surgery, uncertainty remains as to whether this has been matched by a reduction in long-term health care utilization. METHODS: A population-based linked-data cohort study, utilizing a comprehensive set of data, including detailed comorbidity and complications, of each individual who had undergone bariatric surgery between 2007 and 2011 in Western Australia. Records were obtained via data linkage through the Western Australian Department of Health Data Linkage Unit. Every patient was followed for a minimum of 12-months after surgery or until death. RESULTS: A total of 12062 patients underwent bariatric surgery during the study period with a mean follow-up period of 41 months. Hospitalization rates after bariatric surgery were substantially reduced for all-cause (361 vs 501 per 1000 patient-years, P = 0.002) and diabetes mellitus-related (7 vs 31 per 1000 patient-years, P < 0.001) diagnoses when compared with hospitalization rates before bariatric surgery. Complications occurred in 2171 (18.0%) patients during the follow-up period. Patient age, sex, open surgical procedures, and Charlson Comorbidity Index were associated with an increased risk of complications, with age the most important and accounting for 77% of the variability in the risk of complications. Long-term all-cause mortality rate after surgery was extremely low (0.54 deaths per 1000 patient-years). CONCLUSIONS: When measured against long-term safety outcomes, bariatric surgery has low mortality and morbidity associated with a significant reduction in subsequent hospitalizations.

Life-threatening hypokalaemia associated with ibuprofen-induced renal tubular acidosis.

Renal tubular acidosis is an underreported complication of ibuprofen misuse, and can result in life-threatening hypokalaemia. We describe four patients who presented with profound hypokalaemia and muscle weakness associated with excessive ibuprofen ingestion. Ibuprofen cessation and supportive management resulted in complete biochemical resolution within a few days. These cases remind practitioners about potential complications of unmonitored use of over-the-counter analgesics, including those with potential for misuse due to their codeine content.

A comparison of nonoliguric and oliguric severe acute kidney injury according to the risk injury failure loss end-stage (RIFLE) criteria.

BACKGROUND: Risk, Injury, Failure, Loss, and End-Stage (RIFLE) criteria have been proposed as a standard definition of acute kidney injury (AKI). The most severe form of AKI, class F AKI, can be defined by either severe oliguria or a 3-fold increase in serum creatinine concentrations. We hypothesized that the outcomes of patients with these 2 alternative criteria of severe AKI were different. METHODS: A prospective cohort study was conducted of all patients attaining RIFLE class F AKI during a 12-month period in a tertiary critical care facility. RESULTS: Among a total of 2,379 critical care admissions, 129 (5.4%) fulfilled the serum creatinine criteria without oliguria (RIFLE class F) and 99 (4.2%) fulfilled oliguric (RIFLE class F) AKI criteria. Patients with oliguric AKI suffered a more severe disease process than nonoliguric AKI. Oliguric AKI was associated with a significantly higher risk of requiring acute dialysis (70.7 vs. 22.4%, p = 0.001), long-term dialysis >90 days (15 vs. 1.9%, p = 0.006), and hospital mortality (adjusted hazard ratio 3.33, 95% confidence interval, p = 0.001) than nonoliguric AKI. CONCLUSIONS: Oliguric RIFLE class F AKI is a more severe form of AKI than nonoliguric class F AKI. These 2 forms of AKI should be considered separately when AKI is evaluated in a clinical trial.

Meta-analysis of N-acetylcysteine to prevent acute renal failure after major surgery.

BACKGROUND: Acute renal failure after major surgery is associated with significant mortality and morbidity that theoretically may be attenuated by N-acetylcysteine. DESIGN: Meta-analysis of relevant studies sourced from the Cochrane Controlled Trial Register (2007 issue 4), EMBASE, and MEDLINE databases (1966 to February 1, 2008) without language restriction. SETTING & POPULATION: Adult patients undergoing major surgery without the use of radiocontrast. SELECTION CRITERIA FOR STUDIES: Randomized controlled studies comparing N-acetylcysteine with a placebo perioperatively. DATA ANALYSIS: Categorical variables are reported as odds ratio (OR) with 95% confidence interval (CI), and continuous variables are reported as weighted-mean-difference (WMD) with 95% CI. OUTCOME MEASURES: Effects of N-acetylcysteine on mortality and acute renal failure requiring dialysis were the main outcomes of interest. Additional outcome measures included an incremental increase in serum creatinine concentration greater than 25% above baseline, surgical reexploration for bleeding, amount of allogeneic blood transfusion, and length of intensive care unit stay. RESULTS: 10 studies involving a total of 1,193 adult patients undergoing major surgery were considered. N-Acetylcysteine use was not associated with a decrease in mortality (OR, 1.05; 95% CI, 0.58 to 1.92), acute renal failure requiring dialysis (OR, 1.04; 95% CI, 0.45 to 2.37), incremental increase in serum creatinine concentration greater than 25% above baseline (OR, 0.84; 95% CI, 0.64 to 1.11), or length of intensive care unit stay (WMD in days, 0.46; 95% CI, -0.43 to 1.36). N-acetylcysteine did not appear to increase the risk of surgical reexploration for bleeding (OR, 1.16; 95% CI, 0.57 to 2.38) or amount of allogeneic blood transfusion required (WMD in units, 0.31; 95% CI, -0.21 to 0.84). LIMITATIONS: Most studied patients had cardiac surgery and normal renal function preoperatively. CONCLUSIONS: There is no current evidence that N-acetylcysteine used perioperatively can alter mortality or renal outcomes when radiocontrast is not used.