Samira Bell

Risk of AKI with Gentamicin as Surgical Prophylaxis

In 2009, the Scottish government issued a target to reduce Clostridium difficile infection by 30% in 2 years. Consequently, Scottish hospitals changed from cephalosporins to gentamicin for surgical antibiotic prophylaxis. This study examined rates of postoperative AKI before and after this policy change. The study population comprised 12,482 adults undergoing surgery (orthopedic, urology, vascular, gastrointestinal, and gynecology) with antibiotic prophylaxis between October 1, 2006, and September 30, 2010 in the Tayside region of Scotland. Postoperative AKI was defined by the Kidney Disease Improving Global Outcomes criteria. The study design was an interrupted time series with segmented regression analysis. In orthopedic patients, change in policy from cefuroxime to flucloxacillin (two doses of 1 g) and single-dose gentamicin (4 mg/kg) was associated with a 94% increase in AKI (P=0.04; 95% confidence interval, 93.8% to 94.3%). Most patients who developed AKI after prophylactic gentamicin had stage 1 AKI, but some patients developed persistent stage 2 or stage 3 AKI. The antibiotic policy change was not associated with a significant increase in AKI in the other groups. Regardless of antibiotic regimen, however, rates of AKI were high (24%) after vascular surgery, and increased steadily after gastrointestinal surgery. Rates could only be ascertained in 52% of urology patients and 47% of gynecology patients because of a lack of creatinine testing. These results suggest that gentamicin should be avoided in orthopedic patients in the perioperative period. Our findings also raise concerns about the increasing prevalence of postoperative AKI and failures to consistently measure postoperative renal function.

Combined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin–angiotensin system inhibitors in the community increases the risk of acute kidney injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

Clinical InvestigationCombined use of nonsteroidal anti-inflammatory drugs with diuretics and/or renin–angiotensin system inhibitors in the community increases the risk of acute kidney injury

Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diuretics alone were not. However, earlier studies relied on hospital coding to define AKI, which may underestimate true risk. This nested case-control study characterized the risk of community-acquired AKI associated with NSAID use among 78,379 users of renin-angiotensin system inhibitors and/or diuretics, where AKI was defined as a 50% or greater increase in creatinine from baseline. The AKI incidence was 68/10,000 person-years. The relative increase in AKI risk was similar for NSAID use in both triple (adjusted rate ratio 1.64 (95% CI 1.25-2.14)) and dual combinations with either renin-angiotensin system inhibitors (1.60 (1.18-2.17)) or diuretics (1.64 (1.17-2.29)). However, the absolute increase in AKI risk was higher for NSAIDs used in triple versus dual combinations with renin-angiotensin system inhibitors or diuretics alone (numbers needed to harm for 1 year treatment with NSAID of 158 vs. over 300). AKI risk was highest among users of loop diuretic/aldosterone antagonist combinations, in those over 75 years of age, and in those with renal impairment. Thus, the nephrotoxic potential of both dual and triple combinations of NSAIDs with renin-angiotensin system inhibitors and/or diuretics yields a higher incidence of AKI than previously thought.

Risk of postoperative acute kidney injury in patients undergoing orthopaedic surgery--development and validation of a risk score and effect of acute kidney injury on survival: observational cohort study.

Study question What is the predicted risk of acute kidney injury after orthopaedic surgery and does it affect short term and long term survival? Methods The cohort comprised adults resident in the National Health Service Tayside region of Scotland who underwent orthopaedic surgery from 1 January 2005 to 31 December 2011. The model was developed in 6220 patients (two hospitals) and externally validated in 4395 patients from a third hospital. Several preoperative variables were selected for candidate predictors, based on literature, clinical expertise, and availability in the orthopaedic surgery setting. The main outcomes were the development of any severity of acute kidney injury (stages 1-3) within the first postoperative week, and 90 day, one year, and longer term survival. Study answer and limitations Using logistic regression analysis, independent predictors of acute kidney injury were older age, male sex, diabetes, number of prescribed drugs, lower estimated glomerular filtration rate, use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers, and American Society of Anesthesiologists grade. The model’s predictive performance for discrimination was good (C statistic 0.74 in development cohort, 0.70 in validation cohort). Calibration was good in the development cohort and after recalibration in the validation cohort. Only the highest risks were over-predicted. Survival was worse in patients with acute kidney injury compared with those without (adjusted hazard ratio 1.53, 95% confidence interval 1.38 to 1.70). This was most noticeable in the short term (adjusted hazard ratio: 90 day 2.36, 1.94 to 2.87) and diminished over time (90 day-one year 1.40, 1.10 to 1.79; >1 year 1.28, 1.10 to 1.48). The model used routinely collected data in the orthopaedic surgery setting therefore some variables that could potentially improve predictive performance were not available. However, the readily available predictors make the model easily applicable. What this study adds A preoperative risk prediction model consisting of seven predictors for acute kidney injury was developed, with good predictive performance in patients undergoing orthopaedic surgery. Survival was significantly poorer in patients even with mild (stage 1) postoperative acute kidney injury. Funding, competing interests, data sharing SB received grants from Tenovus Tayside, Chief Scientist Office, and the Royal College of Physicians and Surgeons of Glasgow; PT receives grants from Novo Nordisk, GlaxoSmithKline, and the New Drugs Committee of the Scottish Medicines Consortium. No additional data are available.

End stage renal disease and survival in people with diabetes: a national database linkage study

Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of chronic kidney disease (CKD)5 in 2008 was 1.63% of 19 414 people with type 1 diabetes (T1DM) compared with 0.58% of 167 871 people with type 2 diabetes (T2DM) (odds ratio for DM type 0.97, P = 0.77, on adjustment for duration. Although 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (odds ratio for DM type 0.83, P = 0.432). Diabetic nephropathy was the primary renal diagnosis in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI: 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.

Renal Artery Stenosis—When To Screen, What To Stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed.

Acute tubulointerstitial nephritis in Scotland

BACKGROUND AND AIMS Acute tubulointerstitial nephritis (ATIN) is a potentially reversible cause of acute kidney injury with the majority of cases drug related. Our aims were to examine the incidence profile of patients with ATIN in Scotland and to assess the impact of corticosteroid treatment. DESIGN AND METHODS All adult patients with biopsy-proven ATIN, diagnosed between 2000 and 2012, presenting to renal units serving 1.9 of Scotlands 5 million population were included. Patient demographics, presenting, aetiologic and pathologic features, treatment given and outcome were extracted from patient records. RESULTS In total, 171 cases representing 4.7% of native renal biopsies were identified. Median serum creatinine (sCr) was 327 μmol/l at biopsy (106 μmol/l at baseline). Eosinophilia, fever or rash was present in 57% with all 3 in only 1.1%. Active urinary sediment was found in 68%. Aetiology appeared drug induced in 73%. Proton pump inhibitors (PPIs) were likely causative in almost as many cases as antibiotics (35% each) and were more frequently implicated than non-steroidal anti-inflammatory drugs (20%). Number of PPI-related cases paralleled the rising prescription of these drugs. Corticosteroids were prescribed in 59% of drug-induced ATIN (median sCr at biopsy: 356 μmol/l vs. 280 μmol/l in those managed conservatively). There was no difference in sCr at 1, 6 and 12 months, with similar proportions of both groups experiencing complete renal recovery (48% vs. 41%) and becoming dialysis dependent (10% in both). CONCLUSIONS Incidence of biopsy-proven ATIN in Scotland has been rising over the past decade with the majority of cases drug induced. Evidence supporting corticosteroid treatment is lacking.

Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: systematic review and meta-analysis

BackgroundNon-steroidal anti-inflammatory drugs (NSAIDs) are a common cause of adverse drug events (ADEs), but renal risks of NSAIDs are less well quantified than gastrointestinal and cardiac risks. This paper reports a systematic review of published population-based observational studies examining the risk of acute kidney injury (AKI) associated with NSAIDs in community-dwelling adults and those with pre-existing chronic kidney disease (CKD).MethodsMEDLINE and EMBASE databases were searched until June 2016, and 3789 papers screened. Ten studies reporting NSAID risk of AKI in the general population were included in random effects meta-analysis, of which five additionally reported NSAID risk in people with CKD.ResultsIn the general population, the pooled odds ratio (OR) of AKI for current NSAID exposure was 1.73 (95%CI 1.44 to 2.07), with somewhat higher risk observed in older people (OR 2.51, 95%CI 1.52 to 2.68). In people with CKD, individual study OR of AKI due to current NSAID exposure ranged from 1.12 to 5.25, with pooled estimate OR 1.63 (95% CI 1.22 to 2.19).ConclusionsNo study reported baseline risk of AKI in different populations meaning absolute risks could not be estimated, but baseline risk and therefore the absolute risk of NSAID exposure is likely to be higher in people with CKD and older people. Large population based studies measuring AKI using current definitions and estimating the absolute risk of harm are needed in order to better inform clinical decision making.

Omega-3 fatty acids improve postprandial lipaemia in patients with nephrotic range proteinuria

BACKGROUND Patients with nephrotic range proteinuria have a marked increase in the risk of cardiovascular disease. Qualitative and quantitative changes in lipids and lipoproteins contribute to this increased risk with an abundance of atherogenic triglyceride (TG) rich apolipoprotein B containing lipoproteins. TG rich lipoproteins predominate postprandially and are associated with increased risk of coronary heart disease (CHD). Omega-3 fatty acids derived from fish oils have been shown to have beneficial effects on lipids and lipoproteins in patients without proteinuria. METHODS 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied. Postprandial lipaemia was assessed in patients and controls, before and after 8 weeks treatment with 4 g daily of omega-3 fatty acids (Omacor). A standard fat load (90 g) was administered and blood sampling was performed in the fasting state and at 2, 4, 6 and 8h after the fat load. Chylomicrons and VLDL(1) density fraction was isolated from plasma by density ultracentrifugation. Postprandial chylomicron and VLDL(1) triglyceride concentrations were measured and quantified using the incremental area under the curve (AUC) method. RESULTS Baseline postprandial chylomicron TG AUC was greater in patients compared with controls: median 18.5 mmol/lh (interquartile range 8.9-32.6) vs 9.3 mmol/lh (4.8-14.4) p=0.05. Following treatment patient chylomicron AUC fell [mean reduction 6.8 mmol/lh (95% CI 0.1-13.6) p=0.05]. No significant reduction in chylomicron AUC was observed in the controls [mean reduction 3.9 mmol/lh (95% CI -3.6 to 11.5)]. As a result, following 8 weeks treatment with omega-3 fatty acids, patient and control chylomicron AUC were no longer significantly different [patients 13.5 mmol/lh (7.4-22.9), controls 7.2 mmol/lh (4.6-14.5) both median and IQR, p=nsd]. VLDL(1) TG AUC did not differ at baseline between patients and controls. Furthermore, there was no significant effect on VLDL(1) AUC following treatment in either group. CONCLUSIONS We have shown that there is an excess of postprandial chylomicron density fraction in patients with nephrotic range proteinuria, which is reduced by treatment with omega-3 fatty acids. We suggest that this would be an ideal therapy in combination with statins for this high risk group of patients.

Reduction in post-operative acute kidney injury following a change in antibiotic prophylaxis policy for orthopaedic surgery: an observational study

OBJECTIVES Evidence has shown that a prophylactic antibiotic regimen of flucloxacillin and gentamicin for orthopaedic surgery was associated with increased rates of post-operative acute kidney injury (AKI). This resulted in changes in the national antibiotic policy recommendation for orthopaedic surgical prophylaxis. This study aimed to assess whether this change from flucloxacillin and gentamicin to co-amoxiclav was associated with changes in the rates of AKI and Clostridium difficile infection (CDI). METHODS An observational study and interrupted time series analyses were used to assess rates of post-operative AKI separately in patients undergoing neck of femur (NOF) repair and other orthopaedic operations that required antibiotic prophylaxis. Incidence rate ratios were used to evaluate changes in CDI rates. RESULTS Following the change in policy, from flucloxacillin and gentamicin to co-amoxiclav, there was a relative change in rates of post-operative AKI of -63% (95% CI -77% to -49%) at 18 months in the other orthopaedic operations group. In the NOF repair group, there was no change in the rate of post-operative AKI [-10% (95% CI -35%-15%)] at 18 months. The incident rate ratio for CDI in the other orthopaedic operations group was 0.29 (95% CI 0.09-0.96) and in the NOF repair group was 0.76 (95% CI 0.28-2.08). CONCLUSIONS The use of co-amoxiclav for antibiotic prophylaxis in orthopaedic surgery was associated with a decreased rate of post-operative AKI compared with flucloxacillin and gentamicin and was not associated with increased rates of CDI.