Clinical review: Timing of renal replacement therapy

Acute kidney injury is common in intensive care patients and continuous renal replacement therapy is the preferred treatment for this in most centres. Although these techniques have been adopted internationally, there remains significant variation with regard to their clinical application. This is particularly pertinent when one considers that the fundamental questions regarding any treatment, such as initiation, dose and length of treatment, remain a source of debate and have not as yet all been fully answered. In this narrative review we consider the timing of renal replacement therapy, highlighting the relative paucity of high quality data regarding this fundamental question. We examine the role of the usual biochemical criteria as well as conventional clinical indications for commencing renal replacement therapy together with the application of recent classification systems, namely RIFLE and AKIN. We discuss the potential role of biomarkers for acute kidney injury as predictors for the need for renal support and discuss commencing therapy for indications other than acute kidney injury

Developing and validating a new comprehensive glucose-insulin pharmacokinetics and pharmacodynamics model

Type 2 diabetes has reached epidemic proportions worldwide. The resulting increase in chronic and costly diabetes related complications has potentially catastrophic implications for healthcare systems, and economics and societies as a whole. One of the key pathological factors leading to type 2 diabetes is insulin resistance (IR), which is the reduced or impaired ability of the body to make use of available insulin to maintain safe glucose concentrations in the bloodstream. It is essential to understand the physiology of glucose and insulin when investigating the underlying factors contributing to chronic diseases such as diabetes and cardiovascular disease. For many years, clinicians and researchers have been working to develop and use model-based methods to increase understanding and aid therapeutic decision support. However, the majority of practicable tests cannot yield more than basic metrics that allow only a threshold-based assessment of the underlying disorder. This thesis gives an overview on several dynamic model-based methodologies with different clinical applications in assessing glycaemia via measuring effects of treatment or medication on insulin sensitivity. Other tests are clinically focused, designed to screen populations and diagnose or detect the risk of developing diabetes. Thus, it is very important to observe sensitivity metrics in various clinical and research settings

Renal Failure

The book "Renal Failure - The Facts" consists of some facts about diagnosis, etiopathogenis and treatment of acute and chronic renal failure. Acute, as well as chronic renal failure is great medical problems and their treatment is a burden for the budget of each government. The purpose of the chapters is to present some important issues of diagnosis and causes of AKI, as well as caused by snakes and arthropods, after cardiac surgery, as well as some therapeutic achievements in AKI. Well presented are the psychological condition in patients on haemodialysis, as well as the treatment of diabetic uremics. The book is aimed at clinicians with a special interest in nephrology, but it should also prove to be a valuable resource for any generalists who encounter a nephrological problems in their day-to-day practice

A retrospective review of the profile and clinical course of patients requiring acute dialysis at Chris Hani Baragwanath Academic Hospital over a 2 year period

A Research Report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfillment of the requirements for the degree Of Master of Medicine Johannesburg, 2014Acute kidney injury (AKI) is a condition with high rates of mortality and morbidity in the hospital setting. Various factors, such as social, political and ethical dilemmas are closely associated with scarce resources in the management of AKI in Africa. We therefore reviewed the demography, causes and outcomes of AKI at Chris Hani Baragwanath Academic Hospital (CHBAH). Methods A retrospective review of 324 patients with renal failure who were initiated on acute dialysis at the CHBAH over the periods of 1 July 2009 to 30 June 2011 was done. Results The mean age at presentation with AKI was 40±13 years. Males accounted for 57% whist 92% of the total cohort were Black. HIV positivity occurred in 26% of patients, whilst 4% and 2% of the cohort had Hepatitis B and C infection respectively. The leading causes for initiation of acute dialysis included decompensated chronic kidney disease (38.9%), acute tubular necrosis (ATN) (38.3%), HIV related kidney disease (13.6%), pregnancy-related kidney disease (7.4%), glomerulonephritis (7.4%) and malaria (5.7%). Acute tubular necrosis due to sepsis was the predominant cause of AKI in HIV positive patients. Decompensated chronic kidney disease was present in a large proportion of patients, suggesting that chronic co-morbid diseases such as hypertension and diabetes mellitus occurred in a large proportion of the general population. Medical referrals accounted for 78% of the patients presenting with AKI. Renal recovery occurred in patients presenting with a lower average pre-dialysis blood urea level of 34±19 mmol/l, compared to higher levels seen in patients with poorer outcomes (p <0.0001). Pregnancy- related kidney injury had the lowest average pre-dialysis blood urea levels of 20±6 mmol/l. The average pre-dialysis serum creatinine in patients with renal recovery was 804±467 μmol/l compared to those with poorer outcomes, that had average serum creatinine levels of greater than 1000 μmol/l at initiation of dialysis (p <0.0001). The overall renal recovery rate was 31%, with a mortality rate of 23%. Failure to regain renal function with subsequent chronic consequences occurred in 44.6% of patients, of which 23% were transferred to chronic renal replacement therapy and the remaining 21.6% of patients were transferred to Renal out patients department with cessation of acute dialysis. HIV positive patients had a greater renal recovery rate (36% vs 26%); however they had a higher mortality rate compared to their HIV negative counterparts (34% vs 19%); (p <0.0001). HIV positive patients with CD4 counts greater than 200 cells/μl had a 46% renal recovery rate compared to 30% in patients with CD4 counts less than 200 cells/μl (p=0.1894). Mortality with CD4 counts less than 200 cells/μl was 38% compared to 26% in patients with CD4 counts greater than 200 cells/μl (p=0.1894). Mortality rates were similar in HIV positive patients treated with antiretrovirals (ARVs) compared to those that were ARV-naive (p =0.5857). Pregnancy-related kidney injury and malaria both had high rates of renal recovery, 92% and 79% respectively. Discussion The mean age of presentation of AKI were consistent with other studies in developing countries but was substantially lower than in developed countries such as the United Kingdom and Spain. The underlying aetiology of AKI at CHBAH resembles that of other developing nations with ATN, malaria and pregnancy-induced kidney injury being amongst the leading causes. Acute tubular necrosis still remains a common cause of AKI in South Africa as previously documented by Seedat et al. Malignancy and obstructive uropathy occurs at a much lower frequency compared to developed nations. The leading cause in HIV positive patients is ATN secondary to sepsis. Mortality occurred in 23% of the cohort, with HIV positive patients having a much higher mortality of 34%, concurring with a Johannesburg-based study by Vachiat et al. Initiating dialysis at lower blood urea and serum creatinine levels in all patent groups had a much better outcome, including in HIV positive patients. Conclusion AKI remains a common presentation that frequently requires dialysis, a scarce resource in an already overburdened health system, with a high mortality rate. HIV positive patients had a higher mortality rate compared to HIV negative patients; however a higher renal recovery rate was observed in this group. CD4 count and ARV status had no statistical significant effect on outcomes, probably due to the small sample size

Year in review in Intensive Care Medicine 2009: I. Pneumonia and infections, sepsis, outcome, acute renal failure and acid base, nutrition and glycaemic control

Journal ArticleReviewSCOPUS: re.jinfo:eu-repo/semantics/publishe

Exploring metabolic dysfunction in chronic kidney disease

Abstract Impaired kidney function and chronic kidney disease (CKD) leading to kidney failure and end-stage renal disease (ESRD) is a serious medical condition associated with increased morbidity, mortality, and in particular cardiovascular disease (CVD) risk. CKD is associated with multiple physiological and metabolic disturbances, including hypertension, dyslipidemia and the anorexia-cachexia syndrome which are linked to poor outcomes. Specific hormonal, inflammatory, and nutritional-metabolic factors may play key roles in CKD development and pathogenesis. These include raised proinflammatory cytokines, such as interleukin-1 and −6, tumor necrosis factor, altered hepatic acute phase proteins, including reduced albumin, increased C-reactive protein, and perturbations in normal anabolic hormone responses with reduced growth hormone-insulin-like growth factor-1 axis activity. Others include hyperactivation of the renin-angiotensin aldosterone system (RAAS), with angiotensin II and aldosterone implicated in hypertension and the promotion of insulin resistance, and subsequent pharmacological blockade shown to improve blood pressure, metabolic control and offer reno-protective effects. Abnormal adipocytokine levels including leptin and adiponectin may further promote the insulin resistant, and proinflammatory state in CKD. Ghrelin may be also implicated and controversial studies suggest activities may be reduced in human CKD, and may provide a rationale for administration of acyl-ghrelin. Poor vitamin D status has also been associated with patient outcome and CVD risk and may indicate a role for supplementation. Glucocorticoid activities traditionally known for their involvement in the pathogenesis of a number of disease states are increased and may be implicated in CKD-associated hypertension, insulin resistance, diabetes risk and cachexia, both directly and indirectly through effects on other systems including activation of the mineralcorticoid receptor. Insight into the multiple factors altered in CKD may provide useful information on disease pathogenesis, clinical assessment and treatment rationale such as potential pharmacological, nutritional and exercise therapies

Acute lung injury in paediatric intensive care: course and outcome

Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) carry a high morbidity and mortality (10-90%). ALI is characterised by non-cardiogenic pulmonary oedema and refractory hypoxaemia of multifactorial aetiology [1]. There is limited data about outcome particularly in children. Methods This retrospective cohort study of 85 randomly selected patients with respiratory failure recruited from a prospectively collected database represents 7.1% of 1187 admissions. They include those treated with High Frequency Oscillation Ventilation (HFOV). The patients were admitted between 1 November 1998 and 31 October 2000. Results: Of the 85, 49 developed acute lung injury and 47 had ARDS. There were 26 males and 23 females with a median age and weight of 7.7 months (range 1 day-12.8 years) and 8 kg (range 0.8-40 kg). There were 7 deaths giving a crude mortality of 14.3%, all of which fulfilled the Consensus I [1] criteria for ARDS. Pulmonary occlusion pressures were not routinely measured. The A-a gradient and PaO2/FiO2 ratio (median + [95% CI]) were 37.46 [31.82-43.1] kPa and 19.12 [15.26-22.98] kPa respectively. The non-survivors had a significantly lower PaO2/FiO2 ratio (13 [6.07-19.93] kPa) compared to survivors (23.85 [19.57-28.13] kPa) (P = 0.03) and had a higher A-a gradient (51.05 [35.68-66.42] kPa) compared to survivors (36.07 [30.2-41.94]) kPa though not significant (P = 0.06). Twenty-nine patients (59.2%) were oscillated (Sensormedics 3100A) including all 7 non-survivors. There was no difference in ventilation requirements for CMV prior to oscillation. Seventeen of the 49 (34.7%) were treated with Nitric Oxide including 5 out of 7 non-survivors (71.4%). The median (95% CI) number of failed organs was 3 (1.96-4.04) for non-survivors compared to 1 (0.62-1.62) for survivors (P = 0.03). There were 27 patients with isolated respiratory failure all of whom survived. Six (85.7%) of the non-survivors also required cardiovascular support.Conclusion: A crude mortality of 14.3% compares favourably to published data. The A-a gradient and PaO2/FiO2 ratio may be of help in morbidity scoring in paediatric ARDS. Use of Nitric Oxide and HFOV is associated with increased mortality, which probably relates to the severity of disease. Multiple organ failure particularly respiratory and cardiac disease is associated with increased mortality. ARDS with isolated respiratory failure carries a good prognosis in children