APASL clinical practice guidelines on the management of acute kidney injury in acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

Incidence and causes of early hospital readmissions after living donor renal transplant - A single centre study.

Background: Kidney transplantation in spite of being the best modality for the treatment of ESRD remains a complex therapeutic option as it has its own set of problems due to associated morbidity especially in the first month after transplantation. Aim: The primary aim of this study was to find the incidence, causes, and factors responsible for early hospital readmissions (EHRs) and secondary aim was to find the effect of EHR on morbidity, mortality, and graft loss. Patients and Methods: A retrospective analysis of the records of the chronic kidney disease (CKD) patients who underwent living donor renal transplantation. 202 patients were included in the study. Inpatient records and charts were assessed for the medical status of the patients, cause of CKD, comorbidities, admissions 3 months prior to transplant, vintage dialysis, and modality of dialysis. Results: Sixty-one (30.2%) patients were readmitted to the hospital once or more within 30 days of discharge after renal transplantation. Thirty-four (55.7%) patients in the EHR group were admitted once or more in the 90 days prior to transplant as compared to 48 (34%) patients in the no readmission group. Thirty-four (55.7%) patients in the EHR group were hospitalised again within 1 year of EHR and 50 (35.5%) in the no EHR group got admitted within 1 year of discharge. Conclusions: Renal transplant recipients with hospital admissions 90 days before transplant and readmissions within 30 days of discharge after transplantation are at high risk of morbidity and should be treated as high-risk category and should have more stringent follow-up protocols.

Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study.

Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07-2.33), episodes of previous AKI (SHR, 1.26; 1.02-1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30-8.25] vs. stage 2 [SHR, 4.33; 1.76-10.66] vs. stage 3 [SHR, 4.5; 1.59-12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR, 1.01; 1.00-1.03), number of AKI episodes (SHR, 1.25; 1.15-1.37), and CysC (SHR, 1.38; 1.01-1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one-third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.

AKI in patients with acute on chronic liver failure is different from acute decompensation of cirrhosis.

BACKGROUND AND AIMS: The current definitions of acute kidney injury (AKI) including HRS have been derived from patients with decompensated cirrhosis. No studies have carefully addressed AKI in patients with acute on chronic liver failure (ACLF). We evaluated the prevalence, spectrum, natural history and mortality of AKI at admission and new-onset AKI in hospitalized patients with ACLF and compared the results with patients with acute decompensation of cirrhosis (ADC). PATIENTS AND METHODS: Consecutive patients with ACLF (n = 382) and ADC (n = 451) were prospectively studied. Serial renal and liver functions were recorded and correlated with the disease course and outcome. RESULTS: AKI at admission and new onset AKI in the hospital were not different in patients with ACLF and ADC (p > 0.05). However, a significant difference in the spectrum of AKI was noted; functional volume-responsive AKI was more common (p < 0.05) in ADC, while patients with ACLF more frequently had the structural form of AKI (p < 0.05). Moreover, patients with ADC had significantly less AKI progression (p < 0.05) and prolonged duration (p < 0.05), a lower requirement of RRT (p < 0.05) and also less AKI resolution (p < 0.05) compared to ACLF patients. Patients with ACLF (versus ADC) had a significantly higher mortality on multivariate analysis. CONCLUSIONS: The kidneys are differentially affected in patients with cirrhosis with or without liver failure. Patients with ACLF with AKI have more structural AKI, greater potential for reversibility despite higher progression as well as higher mortality compared to patients with ADC. Prevention and early detection of AKI should be considered in patients with ACLF.

Observational study to evaluate the safety and efficacy of saroglitazar in Indian diabetic dyslipidemia patients.

UNLABELLED: Saroglitazar is a dual PPAR α/γ agonist approved in India for the management of diabetic dyslipidemia. AIMS: The objective of this study was to evaluate the safety and efficacy of saroglitazar 4 mg once daily in clinical practice. METHODS: This was an observational, multicenter, single-arm study. Patients with type 2 diabetes (with on-going antidiabetic medication), age above 18 years, and triglycerides ≥200 mg/dL were included. RESULTS: A total 2804 patients with a mean duration of diabetes 6.29 yrs were included in this analysis. The baseline demographic profile was: mean age of 53 yrs, mean body weight 72.3 kg and mean BMI of 27 kg/m(2). 62.5% patients were male and 57.8% were reported to be on statin therapy at baseline. All 2804 patients were on antidiabetic medications with 15.4% patients on monotherapy and rest were on two or more than two antidiabetic medications at baseline. The baseline triglycerides and HbA1C values were 312.3 mg/dL and 8.3% respectively. At 3 months follow-up, use of saroglitazar 4 mg led to significant reduction in TG (35.8%), LDL-C (16.4%), total cholesterol (19%) and non-HDL-C (23.4%). Addition of saroglitazar to baseline antidiabetic medications showed a significant 0.9% absolute reduction in HbA1c with significant improvement in fasting and post prandial plasma glucose. No serious adverse events, alteration in liver or renal enzymes and edema or weight gain were reported. CONCLUSION: Saroglitazar is a potential therapeutic option in type 2 diabetic patients with high TG levels, not controlled by statins, for comprehensive control of lipid and glycemic parameters with acceptable safety profile.

Role of Alpha Blockers in Hypertension with Benign Prostatic Hyperplasia.

Hypertension and benign prostatic hyperplasia (BPH) are common disorders of aging men. As the world population is aging these two diseases are becoming a significant public health problem worldwide. Approximately 30% of men treated for BPH have coexisting hypertension. The α-Adrenergic Blockers: Prazosin, Terazosin and Doxazosin are established agents in the therapy of hypertension, and are also effective drugs in the treatment of BPH. It is reasonable to use α-Adrenergic Blockers as the treatment of choice for men with hypertension and BPH.

Management of acute kidney injury in cirrhosis.

Acute kidney injury (AKI) is a relatively frequent problem, occurring in approximately 20 % of hospitalized patients with cirrhosis. Although serum creatinine (S Cr) is the most commonly used method to determine AKI because of easy availability and low cost, practically it underestimates the extent of kidney injury in patients with chronic liver disease. AKI is defined as an abrupt rise in S Cr of 0.3 mg/dl or more (>26.4 mmol/l) or an increase of 150 % or more (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can be subdivided into either functional or structural. The functional group includes volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome). Volume responsive is the most common type of AKI due to frequent use of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding in patients with liver disease. The structural causes include acute tubular necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated cirrhosis are in a vasodilatory state leading to a decrease in effective arterial blood volume, predisposing to AKI. Therefore, management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause. The outcome in cirrhosis when patients are on dialysis is very dismal. Every effort should be made to prevent AKI.

Bioaccumulation and localization of exogenous cadmium in a teleost by electron microscopy (TEM) and its specific quantitation by electron probe X-ray microanalysis (EPMA).

A cadmium bioconcentration study was carried out in a fresh water teleost, Colisa fasciatus, to study the bioaccumulation kinetics and fate of exogenous cadmium (Cd) in biological tissues. Study shows that on exposure of the fish to a sublethal concentration of cadmium in test water, Cd uptake results in its bioconcentration in gills, liver and muscle tissues. To explore whether the accumulated Cd reaches the membranes or inside the cells, transmission electron microscopy (TEM) of the thin sections of tissues was done after histochemical localization of Cd in cells by modified SST method. TEM studies of sections of gills, liver and muscle tissues showed the deposits of exogenous Cd (visualized as dense clouds) in biological cells. This suggests the presence of free or loosely bound Cd on the membranes and inside the cells, which in the presence of Na2S is converted into insoluble metal sulfides. Electron probe X-ray microanalysis (EPMA) studies confirmed the presence of Cd on the membrane surface as well as inside the cells of bioindicator organs suggesting involvement of membrane transport of exogenous Cd inside the cells and its deposition as loosely bound insoluble metal complexes.

Identification of metabolites of malathion in plant, water and soil by GC-MS.

Metabolism of malathion (O,O,-dimethyl S-[1,2-bis(ethoxy carbonyl)-ethyl]phosphorodithioate) has been studied in plants, water and soil. A number of products identified by gas chromatography-mass spectrometry (GC-MS), have been formed by de-esterification, oxidation and hydrolysis of malathion. Hydrolysis of the P-S and C-S bonds occur in alkaline pH 8.0 and acidic pH 5.5, respectively.

Accumulation pattern of pesticides in tropical fresh waters.

High-performance liquid chromatography has been used to study the persistence of commonly used organophosphorus and carbamate pesticides-carbaryl, carbendazim, carbofuran, dimethoate, malathion and methyl parathion in river water in the presence of bottom sediment in laboratory aquaria. The fate of pesticides in water and sediment in pre- and post-monsoon water from three sources has been compared. It has been established that rapid degradation occurs once the pesticide leaches into sediment from water. Degradation was at a much faster rate in post-monsoon water and sediment. It was found that pH and organic matter content affect rate of decay.

Parameters affecting the decay of some organophosphorus pesticides: a study by high-performance liquid chromatography.

An HPLC procedure has been developed to follow the decay of malathion and methylparathion under control conditions using an mu-Bondapak C18 column with a mixture of acetonitrile and water to mobile phase and an ultraviolet detector for detection. Studies have been conducted to monitor their degradation in water and soil at different temperatures, pH and organic content. The results show that the persistence of the pesticides decreases with increase in temperature, pH and organic content.

Comparative evaluation of cell proliferative indices and epidermal growth factor receptor expression in gastric carcinoma.

A total of 62 patients of gastric carcinoma were studied to find a correlation between newer prognostic indicators like cell proliferative indices including Nucleolar Organizer regions (AgNORs), Ki 67 Labelling Index and Epidermal Growth Factor Receptor (EGFR) expression with the various, histopathological criteria and compared with 30 controls of non neoplastic gastric diseases. EGFR expression was positive in 48(77.4%) cases. The Ki 67 labelling indices ranged from 0 to 50% with a mean of 21.35 +/- 17.88% among the cases. AgNOR counts ranged from 1.64 to 4.49 with a mean of 3.41 +/- 0.81 among the cases. Positive EGFR expression correlated strongly with differentiation of the tumour, poorly differentiated tumours showing a higher positivity. EGFR positivity also showed good correlation with metastasis as well as with the invasiveness of the tumour. Ki 67 labelling indices correlated significantly with metastatic status, microscopic types and degree of differentiation of the tumour. A strong correlation was observed between AgNOR counts and metastasis as well as the microscopic type of the tumour. EGFR expression correlated strongly with Ki 67 scores and weakly with AgNOR counts among the patients of gastric carcinoma.

Degradation of organophosphorus and carbamate pesticides in soils--HPLC determination.

Best conditions suited for the extraction and trace analysis of dimethoate, malathion, methyl-parathion, carbaryl, carbendazim and carbofuran in soils, using HPLC, were established. This was followed by studies related to persistence of residues in different soils. Half-life and time taken for 95% dissipation were determined in each case. Higher pH, moderate moisture and high calcium carbonate content aided degradation while organic matter increased persistence.

Ecosystem studies on upper region of Ganga River, India.

A multi-disciplinary research programme on the Ganga River Ecosystem was launched by the Government of India in 1983 to collect information on its attributes. Monitoring of the initial 509 km unpolluted and unmonitored region of the river falling in partly mountainous and partly upper plain stretches for two years revealed good water quality. The Song River (a tributary) catchment, a victim of extensive mining activity in the past, was found to add maximum mineral load. The Bhagirathi River was found to carry maximum suspended solid load. Organic pollution was low throughout, occasionally showing seasonal and local peaks. The river exhibited a high oxidative state with pH falling in a slightly alkaline range and nutrient levels being very low.Diatoms formed a major part of the encountered genera of phytoplankton. Zooplankton were mainly represented by protozoans. Saprophytic bacteria underwent large spatial and temporal fluctuations. Coliforms exhibited an increasing trend with downstream river distance. The source of pollution could not be specifically characterized from an FC/FS ratio. Only one sample tested positive for enteric virus. The forms of benthic macroinvertebrates indicated a clean stream environment. It was observed that diversity indices, together with evenness and community comparison, could provide a promising approach to determine the state of the community.Eight heavy metals investigated, Cu, Zn, Fe, Cd, Mn, Pb, Ni and Co, were found to be present in the river water and bed sediments. The prominent mode of metal transport was found to be via the suspended load. The concentration of dissolved metals was found within WHO permissible limits. The heavy metal status of the Ganga River was compared with other rivers of the world. Sorptive properties of sediments were found to be similar to the general sorptive behaviour of the clays. Laboratory studies exhibited reasonable short t 90 values for coliform survival in Ganga water. Faecal streptococcus survived longer.

Simultaneous determination of a mixture of organophosphorus and carbamate pesticides by high performance liquid chromatography.

A simple HPLC procedure has been developed for the simultaneous determination of a mixture of standard carbaryl, carbofuran, carbendazim, dimethoate, malathion and methyl parathion from a spiked agricultural soil sample. The pesticide mixture has been extracted using methanol-water. A concave gradient elution with acetonitrile-phosphate buffer for 15 min followed by linear elution for 5 min, using a wavelength of 224 nm for detection, has been found to resolve the mixture efficiently.