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Fulltext Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury

Barber BE, Grigg MJ, Piera KA, William T, Cooper DJ, Plewes K, et al.

Emerg Microbes Infect, 2018 Jun 06;7(1):106.
PMID: 29872039 DOI: 10.1038/s41426-018-0105-2

Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel-Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.

Matched MeSH terms: Acute Kidney Injury/etiology*
Fulltext Extensive crescent formation in idiopathic membranous glomerulonephritis. A case report

Cheong IK, Chong SM, Singh N, Suleiman AB

Med J Malaysia, 1981 Mar;36(1):8-10.
PMID: 7321940

We report this 21 years old Indian male with the nephrotic syndrome due to membranous nephropathy who later developed numerous epithelial crescents leading to a rapid loss of renal function. The pathogenesis of the crescentic transformation in this type of glomerulopathy is discussed.

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext Acute renal failure in the same hospital ten years apart

Chow YW, Lim BB, Hooi LS

Med J Malaysia, 2007 Mar;62(1):27-32.
PMID: 17682566 MyJurnal

A three month prospective study was carried out in 1994 (8/3/94 - 7/6/94) and late 2004/early 2005 (24/11/2004 - 15/2/2005) among patients with acute renal failure (ARF) (serum creatinine > 0.200 mmol/1). Incidence of ARF had increased from 0.48% (78/16,418) to 1.1% (211/18,697) of admissions between 1994 and 2004. Two thirds of patients were male. Mean age was 57.7 +/- 20.1 years in 1994 and 55.6 +/- 17.8 years in 2004. No difference was noted in causative factors, rate of oliguric ARF (about 10%) and mean peak urea and creatinine. The cause was pre-renal failure in 43.6% in 1994 and 53.5% in 2004. The second commonest cause was sepsis with 41% in 1994 and 37.9% in 2004. One in six patients needed dialysis and peritoneal dialysis was the main dialysis modality (69.2% and 74.3%). Mortality was 56.4% in 1994 and 44.5% in 2004. A quarter of deaths occurred within two days of admission due to severe underlying illness. Mortality among non-oliguric patients decreased from 52.9% in 1994 to 37.0% in 2004 (p = 0.04); for patients from intensive care units it was 78.3% in 1994 and 68.5% in 2004.

Matched MeSH terms: Acute Kidney Injury/etiology
Acute renal failure after a holiday in the tropics

Guron G, Holmdahl J, Dotevall L

Clin. Nephrol., 2006 Dec;66(6):468-71.
PMID: 17176921 DOI: 10.5414/cnp66468

A 20-year-old, previously healthy woman, presented with high fever, headache and myalgia 3 days after her return from a holiday in Southeast Asia. Laboratory data on admission demonstrated a pronounced increase in plasma creatinine, marked thrombocytopenia and moderately elevated liver aminotransferases. After having ruled out malaria, dengue fever was primarily suspected and supportive intravenous fluid therapy was initiated. Still, 1 day after admission, platelet counts dropped even further and she became anuric although she did not appear hypovolemic. On day 2 after admission, urine production commenced spontaneously and the patient slowly recovered. All laboratory test results had returned to normal approximately 2 months later. Serological analysis for dengue fever was negative. It turned out that the patient had been trekking in the jungle while in Thailand and we, therefore, analyzed serology for Leptospira spirochetes which was clearly positive. The patient was diagnosed with leptospirosis which is a serious condition associated with a high mortality when complicated by acute renal failure. Differential diagnoses in patients with acute renal failure and tropical infections are reviewed. The importance of early recognition of leptospirosis, and prompt treatment with antibiotics in suspected cases, is emphasized.

Matched MeSH terms: Acute Kidney Injury/etiology*
Fulltext Acute renal failure following jering ingestion

H'ng PK, Nayar SK, Lau WM, Segasothy M

Singapore Med J, 1991 Apr;32(2):148-9.
PMID: 2042077

We report two cases of acute renal failure that followed the ingestion of jering. Features of jering poisoning included clinical presentation of bilateral loin pain, fever, nausea, vomiting, oligo-anuria, haematuria and passage of sandy particles in the urine. Blood urea (40.8 mmol/l; 21.9 mmol/l) and serum creatinine (1249 mumols/l; 693 mumols/l) were markedly elevated. With conservative therapy which included rehydration with normal saline and alkalinisation of the urine with sodium bicarbonate, the acute renal failure resolved.

Matched MeSH terms: Acute Kidney Injury/etiology*
Fulltext Acute renal failure requiring dialysis--a 5 year series

Hooi LS

Med J Malaysia, 1997 Sep;52(3):251-6.
PMID: 10968094

A retrospective review of 246 patients with established acute renal failure (ARF) needing dialysis from 1990-1994 is reported from Hospital Sultanah Aminah, Johor Bahru. Peritoneal dialysis was more commonly used than haemodialysis or haemofiltration. Patients on mechanical ventilation in Intensive Care Unit (ICU) who were hypercatabolic and fluid overloaded were treated with haemofiltration. Males outnumbered females by a ratio of 1.5:1. The majority were Malays (61.4%). Most patients were from the district of Johor Bahru, but 41.5% were from other districts in the Johor state. The mean age was 47.1 years (SD 18.2). The ARF was caused by acute tubular necrosis in 55.3%, post-renal obstruction in 22.8%, nephrotoxins in 5.7% and other causes in 16.2%. The proportions of patients referred from the medical, surgical and obstetric and gynaecology units were 50.8%, 45.5% and 3.7% respectively. The mortality rate was 48%. Patients with established ARF should be dialysed early as they tolerate uraemia poorly. Prevention is by prompt treatment of patients with sepsis, avoidance of hypovolaemia and nephrotoxic drugs.

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext Associated factors of dialysis-dependence among acute kidney injury patients in intensive care unit

Kamaruddin M, Hamid SA, Adnan AS, Naing NN, Wan Adnan WN

Saudi J Kidney Dis Transpl, 2019 11 8;30(5):1131-1136.
PMID: 31696852 DOI: 10.4103/1319-2442.270269

Acute kidney injury (AKI) is a common problem in hospitals and many end up requiring dialysis. The aim was to identify the associated factors of dialysis-dependent of AKI patients admitted to the intensive care units (ICUs). A retrospective cohort study was conducted where a list of 121 AKI patients admitted to ICU in Hospital Universiti Sains Malaysia was retrospectively reviewed. AKI patients aged below 18 years old, had kidney transplantation or chronic dialysis before ICU admission and had incomplete medical record were excluded from the study. Simple and multiple logistic regression analysis were used. The mean [standard deviation (SD)] age of patients was 56 (17.15) years. Majority of patients were males (63.2%) and Malay ethnic (54.1%). 49.3% of patients were in stage I, 48.3% in stage II and 76.2% in stage III. The mean (SD) duration of patients stayed in ICU was 7 days (6.92) for non-dialysis dependent and 12 days (8.37) for dialysis-dependent. The associated factors were male gender [adjusted odds ratio (OR): 3.68; 95% confidence interval [CI]: 1.53, 8.86; P = 0.004], AKI Stage III (adjusted OR: 4.51; 95% CI: 1.28, 15.91; P = 0.019), admitted in ICU (adjusted OR: 3.05; 95% CI: 1.28, 7.29; P = 0.012), and longer length of stay (adjusted OR: 1.10; 95% CI: 1.03, 1.18; P = 0.003). The factors influence of dialysis-requiring AKI were observed to be dependent on the male male gender, suffer from the advanced stage (Stage III), admitted to the ICU and had a longer length of stay in ICU. Therefore, it is important for physicians to identify patients who are at high risk of developing AKI and implement preventive strategies.

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network

Kario K, Morisawa Y, Sukonthasarn A, Turana Y, Chia YC, Park S, et al.

J Clin Hypertens (Greenwich), 2020 Jul;22(7):1109-1119.
PMID: 32643874 DOI: 10.1111/jch.13917

There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext Acute respiratory distress syndrome and acute renal failure from Plasmodium ovale infection with fatal outcome

Lau YL, Lee WC, Tan LH, Kamarulzaman A, Syed Omar SF, Fong MY, et al.

Malar J, 2013;12:389.
PMID: 24180319 DOI: 10.1186/1475-2875-12-389

Plasmodium ovale is one of the causative agents of human malaria. Plasmodium ovale infection has long been thought to be non-fatal. Due to its lower morbidity, P. ovale receives little attention in malaria research.

Matched MeSH terms: Acute Kidney Injury/etiology*
Cefepime-associated thrombocytopenia in a critically ill patient

Lim PP, Chong CP, Aziz NA

Int J Clin Pharm, 2011 Dec;33(6):902-4.
PMID: 21986835 DOI: 10.1007/s11096-011-9571-5

CASE: Cefepime-induced thrombocytopenia is a rare adverse event (incidence <1.0%), based on data from clinical trials. However, there is limited post-marketing surveillance documentation on thrombocytopenia associated with cefepime. We describe a 45-year-old male who was admitted to the intensive care unit after allegedly being hit by a large metal bar in the right upper chest and shoulder. Rhabdomyolysis secondary to the trauma, pneumothorax, acute renal failure, and nosocomial sepsis were subsequently diagnosed. Four days after intravenous cefepime initiation, the patient developed thrombocytopenia with platelet count dropping from 102 × 10(3)/μL to 15 × 10(3)/μL. Cefepime was discontinued and the platelet count normalized to 140 × 10(3)/μL after 6 days. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between the patient's thrombocytopenia and cefepime therapy.
CONCLUSION: Although cefepime-induced thrombocytopenia is rare, clinicians should be alert to this potential adverse effect among critically ill patients.

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext Acute renal failure and posterior reversible encephalopathy syndrome following multiple wasp stings: a case report

Loh HH, Tan CHH

Med J Malaysia, 2012 Feb;67(1):133-5.
PMID: 22582570 MyJurnal

Wasp stings can present in various ways, ranging from mild self-limiting illness to severe multi organ failure with a potentially fatal outcome. We report a case of multiple wasp stings leading to acute renal failure needing prolonged dialysis support and posterior reversible encephalopathy syndrome.

Matched MeSH terms: Acute Kidney Injury/etiology*
Development of predisposition, injury, response, organ failure model for predicting acute kidney injury in acute on chronic liver failure

Maiwall R, Sarin SK, Kumar S, Jain P, Kumar G, Bhadoria AS, et al.

Liver Int, 2017 Oct;37(10):1497-1507.
PMID: 28393476 DOI: 10.1111/liv.13443

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients.
PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997).
RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P

Matched MeSH terms: Acute Kidney Injury/etiology*
Dengue-induced Acute Kidney Injury (DAKI): A Neglected and Fatal Complication of Dengue Viral Infection--A Systematic Review

Mallhi TH, Sarriff A, Adnan AS, Khan YH, Hamzah AA, Jummaat F, et al.

J Coll Physicians Surg Pak, 2015 Nov;25(11):828-34.
PMID: 26577971 DOI: 11.2015/JCPSP.828834

Dengue Viral Infection (DVI) imperils an estimated 2.5 billion people living in tropical and subtropical regions. World Health Organization (2011) guidelines also classified dengue as 'Expanded Dengue Syndrome' to incorporate wide spectrum of unusual manifestations of dengue infection affecting various organ systems - including liver, kidney, heart and brain. Renal involvements are least appreciated area of dengue infection, therefore, we systematically reviewed studies describing renal disorders in dengue infection, with emphasis on Acute Kidney Injury (AKI). The purpose of current review is to underscore clinicians’attention to this neglected intricacy of DVI. It suggests that dengue induced renal involvements vary from glomerulonephritis, nephrotic range proteinuria and AKI. We observed great disparity in incidence of AKI among dengue patients, based upon criteria used to define AKI. AKI among dengue patients was found to be associated with significant morbidity, mortality and longer hospitalization, adding financial burden to patients and healthcare system. Additionally, we identified several predictors of AKI in dengue patients including old age, obesity, severe dengue infection and concurrent bacterial or viral infection. Direct viral injury and deposition of antigen-antibody complex in glomerulus were found to be possible causes of renal disorders in dengue infection. Prior knowledge of clinico-laboratory characteristics and risk factors with early detection of AKI by using appropriate criteria would not only reduce morbidity and mortality but also decrease burden to patients and healthcare system.

Matched MeSH terms: Acute Kidney Injury/etiology*
Fulltext Determinants of mortality and prolonged hospital stay among dengue patients attending tertiary care hospital: a cross-sectional retrospective analysis

Mallhi TH, Khan AH, Sarriff A, Adnan AS, Khan YH

BMJ Open, 2017 Jul 10;7(7):e016805.
PMID: 28698348 DOI: 10.1136/bmjopen-2017-016805

OBJECTIVES: Dengue imposes substantial economic, societal and personal burden in terms of hospital stay, morbidity and mortality. Early identification of dengue cases with high propensity of increased hospital stay and death could be of value in isolating patients in need of early interventions. The current study was aimed to determine the significant factors associated with dengue-related prolonged hospitalisation and death.

DESIGN: Cross-sectional retrospective study.

SETTING: Tertiary care teaching hospital.

PARTICIPANTS: Patients with confirmed dengue diagnosis were stratified into two categories on the basis of prolonged hospitalisation (≤3 days and >3 days) and mortality (fatal cases and non-fatal cases). Clinico-laboratory characteristics between these categories were compared by using appropriate statistical methods.

RESULTS: Of 667 patients enrolled, 328 (49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88±2.74 days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3), elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR 1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ dysfunctions (OR 2.1) were independently associated with prolonged hospitalisation. Overall case fatality rate was 1.1%. Factors associated with dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040), comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022), multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis (p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal cases in our study had prolonged hospital stay of greater than three days.

CONCLUSIONS: The results underscore the high proportion of dengue patients with prolonged hospital stay. Early identification of factors relating to prolonged hospitalisation and death will have obvious advantages in terms of appropriate decisions about treatment and management in high dependency units.

Study site: Hospital Universiti Sains Malaysia (HUSM), Kelantan

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext Incidence, Characteristics and Risk Factors of Acute Kidney Injury among Dengue Patients: A Retrospective Analysis

Mallhi TH, Khan AH, Adnan AS, Sarriff A, Khan YH, Jummaat F

PLoS One, 2015;10(9):e0138465.
PMID: 26421839 DOI: 10.1371/journal.pone.0138465

BACKGROUND: Dengue induced acute kidney injury (AKI) imposes heavy burden of illness in terms of morbidity and mortality. A retrospective study was conducted to investigate incidence, characteristics, risk factors and clinical outcomes of AKI among dengue patients.
METHODOLOGY: A total 667 dengue patients (2008-2013) were retrospectively evaluated and were stratified into AKI and non-AKI groups by using AKIN criteria. Two groups were compared by using appropriate statistical methods.
RESULTS: There were 95 patients (14.2%) who had AKI, with AKIN-I, AKIN-II and AKIN-III in 76.8%, 16.8% and 6.4% patients, respectively. Significant differences (P<0.05) in demographics and clinico-laboratory characteristics were observed between patients with and without AKI. Presence of dengue hemorrhagic fever [OR (95% CI): 8.0 (3.64–17.59), P<0.001],rhabdomyolysis [OR (95% CI): 7.9 (3.04–20.49)], multiple organ dysfunction OR (95% CI):17.9 (9.14–35.12), P<0.001], diabetes mellitus [OR (95% CI): 4.7 (1.12–19.86), P = 0.034], late hospitalization [OR (95% CI): 2.1 (1.12–19.86), P = 0.033] and use of nephrotoxic drugs [OR(95% CI): 2.9 (1.12–19.86), P = 0.006] were associated with AKI. Longer hospital stay (>3days) was also observed among AKI patients (OR = 1.3, P = 0.044) [corrected].Additionally, 48.4% AKI patients had renal insufficiencies at discharge that were signicantly associated with severe dengue, secondary infection and diabetes mellitus. Overall mortality was 1.2% and all fatal cases had AKI.
CONCLUSIONS: The incidence of AKI is high at 14.2% among dengue patients, and those with AKI portended significant morbidity, mortality, longer hospital stay and poor renal outcomes. Our findings suggest that AKI in dengue is likely to increase healthcare burden that underscores the need of clinicians' alertness to this highly morbid and potentially fatal complication for optimal prevention and management.

Matched MeSH terms: Acute Kidney Injury/etiology*
Plasma Neutrophil Gelatinase-Associated Lipocalin diagnosed acute kidney injury in patients with systemic inflammatory disease and sepsis

Md Ralib A, Mat Nor MB, Pickering JW

Nephrology (Carlton), 2017 May;22(5):412-419.
PMID: 27062515 DOI: 10.1111/nep.12796

AIM: Sepsis is the leading cause of intensive care unit (ICU) admission. Plasma Neutrophil Gelatinase Associated-Lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI) detection; however, it is also increased with inflammation and few studies have been conducted in non-Caucasian populations and/or in developing economies. Therefore, we evaluated plasma NGAL's diagnostic performance in the presence of sepsis and systemic inflammatory response syndrome (SIRS) in a Malaysian ICU cohort.
METHODS: This is a prospective observational study on patients with SIRS. Plasma creatinine (pCr) and NGAL were measured on ICU admission. Patients were classified according to the occurrence of AKI and sepsis.
RESULTS: Of 225 patients recruited, 129 (57%) had sepsis of whom 67 (52%) also had AKI. 96 patients (43%) had non-infectious SIRS, of whom 20 (21%) also had AKI. NGAL concentrations were higher in AKI patients within both the sepsis and non-infectious SIRS cohorts (both P

Matched MeSH terms: Acute Kidney Injury/etiology
Fulltext Acute renal failure due to multiple bee stings--case reports

Ramanathan M, Lam HS

Med J Malaysia, 1990 Dec;45(4):344-6.
PMID: 2152058

This report deals with a father and his son who developed acute renal failure following multiple bee stings. The renal lesion in these patients appears to be due to rhabdomyolysis caused by the bee venom. The other mechanisms are also discussed. The need for clinicians to be aware of acute renal failure as a complication of bee stings is stressed.

Matched MeSH terms: Acute Kidney Injury/etiology*
Role of the renal sympathetic nervous system in mediating renal ischaemic injury-induced reductions in renal haemodynamic and excretory functions

Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Najim HS, et al.

Pathology, 2010 Apr;42(3):259-66.
PMID: 20350220 DOI: 10.3109/00313021003631304

We investigated the role of renal sympathetic innervation in the deterioration of renal haemodynamic and excretory functions during the early post-ischaemic phase of renal ischaemia/reperfusion injury.

Matched MeSH terms: Acute Kidney Injury/etiology
Effect of kidney ischemia/reperfusion injury on proliferation, apoptosis, and cellular senescence in acute kidney injury in mice

Sari FT, Sari FT, Sari FT, Arfian N, Sari DCR

Med J Malaysia, 2020 05;75(Suppl 1):20-23.
PMID: 32471965

INTRODUCTION: Kidney ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI). Kidney IRI demonstrated apoptosis of epithelial cells in acute phase followed by proliferation of interstitial cells in chronic episode, and cellular senescence may contribute to development of AKI, however, its occurrence within acute or chronic episodes is still not completely understood.
METHODS: Kidney IRI was performed with bilateral pediculus clamping in Swiss Background mice (3 months, 30-40g). Mice were euthanised on day one (I/R1, n=6), day eight (I/R8, n=6), and day twelve (I/R12, n=6) to exam acute and chronic episodes. Sham operation procedure was performed in the control. Tubular injury was assessed based on periodic acid- Schift (PAS) staining. Reverse transcriptase PCR (RT-PCR) was done to quantify mRNA expression of Bax, Bcl-2, and p16. Immunohistostaining (IHC) was performed to examine localisation of apoptosis (p53) and proliferation (Bcl-2).
RESULTS: RT-PCR analysis showed upregulation of mRNA expression of Bcl-2, Bax, and p16 (p<0.05). The data showed that ischemia/reperfusion induces upregulation of Bax (p=0.20), Bcl-2 (p=0.45), p16 (p=0.18). Apoptosis and proliferation occurred in the epithelial cells in acute episodes, but occurred in interstitial areas in chronic episodes.
CONCLUSIONS: Ischemia/reperfusion injury induces upregulation proliferation, apoptosis, and cellular senescence in acute kidney injury. Apoptosis reached its peak on day 1, proliferation on day 8, and cellular senescence on day 12.

Matched MeSH terms: Acute Kidney Injury/etiology*
Fulltext Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update

Sarin SK, Choudhury A, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.

Hepatol Int, 2019 Jul;13(4):353-390.
PMID: 31172417 DOI: 10.1007/s12072-019-09946-3

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the "APASL ACLF Research Consortium (AARC)" was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the 'Golden Therapeutic Window', extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here.

Matched MeSH terms: Acute Kidney Injury/etiology

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