Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Understanding the impact of academic difficulties among medical students: A scoping review.

BACKGROUND: Many medical students may encounter a range of academic and personal challenges during their course of study, but very little is known about their experiences. Our aim was to review the literature to inform future scholarship and to inform policy change. METHODS: A scoping review was conducted searching PubMed, MEDLINE, EMBASE, PsycInfo, British Education Index, Web of Science and ERIC for English language primary research with no date limits. This retrieved 822 papers of which eight met the requirements for inclusion in the review. Data were independently reviewed by two researchers and underwent thematic analysis by the research team. RESULTS: Three major themes emerged. Theme 1: 'Identity preservation' addressed students' aim to preserve their sense of self in the face of academic difficulty and their tendency to seek support. This connected the apprehension many students expressed about their educational institutions to Theme 2: 'The dual role of the medical school'-medical schools are required to support struggling students but are predominantly seen as a punitive structure acting as the gatekeeper to a successful career in medicine. Students' apprehension and attempts to protect their identities within this complex landscape often resulted in 'maladaptive coping strategies' (Theme 3). CONCLUSION: Understanding and exploring the academic challenges faced by medical students through their own experiences highlight the need for the development of more individualised remediation strategies. Educators may need to do more to bridge the gap between students and institutions. There is a need to build trust and to work with students to enhance their sense of self and remediate approaches to engagement with learning, rather than focusing efforts on success in assessments and progression.

A Retrospective Study Assessing the Effect of Diabetes on Mortality in Patients With COVID-19 at a Teaching Hospital in the United Kingdom.

Aim The aim of the study was to compare the clinical characteristics and outcomes (mortality, intensive care admission, mechanical ventilation, and length of stay, LoS) of patients with and without diabetes with confirmed COVID-19.  Methods This retrospective study evaluated clinical and laboratory variables in adult inpatients from Brighton and Sussex University Hospitals NHS Trust with laboratory-confirmed COVID-19 between March 10, 2020, and June 30, 2020. Univariate and multivariate analyses were performed to compare the outcomes of patients with and without diabetes.  Results Over 457 patients were included in this study (140 with diabetes and 317 without diabetes), of which 143 (31.9%) died. The median age was 80 years and were predominantly males (59.1%). Baseline characteristics at the time of COVID-19 diagnosis demonstrated that the patients with diabetes were younger than those without diabetes (p=0.008). Mortality increased with age. There was no difference in adverse outcomes in those with and without diabetes. However, subgroup analysis of patients aged ≤60 years demonstrated a significantly increased mortality in those with diabetes (p=0.016). Patients with diabetes had an increased length-of-stay compared to those without diabetes, which was more evident in those aged ≤60 years. Conclusion Age is the most important predictor of mortality. Patients with diabetes did not have increased mortality from COVID-19, which is likely due to their younger age in our cohort. More patients with diabetes stayed in the hospital longer than seven days than those without diabetes.

Outcomes of immunosuppression in IgA nephropathy based on the oxford classification.

Numerous studies have addressed the predictive value of pathology findings from the Oxford Classification. Whether this influences treatment choice has not been determined. We evaluated patients with IgA nephropathy who were immunosuppressed and correlated our findings with both clinical and histological features as per the Oxford Classification. This was a retrospective observational study of 45 patients who had biopsy-proven IgA nephropathy with a mean follow-up of 2.6 years. Primary outcomes were time to end-stage renal disease (ESRD) or a 50% rise in serum creatinine. Immunosuppression was not associated with lower hazards for both ESRD and 50% rise in serum creatinine. From the Oxford Classification, only T0 was associated with significantly lower hazards for ESRD [hazard ratio (HR), 0.067; confidence interval (CI) 0.01-0.58]. Patients who had crescents and/or necrotizing lesions on biopsy were more likely to be immunosuppressed (odds ratio 9.99; 95% CI 1.99-50.06, P = 0.005) but demonstrated a statistically nonsignificant higher hazard for both renal end points (HR, 1.61; CI 0.19-13.89). Such lesions were also associated with a higher incidence of hypertension (149 vs. 135 mm Hg) and greater proteinuria (2.7 vs. 1.9 g/day) at presentation. The use of the Oxford Classification did not aid decision-making with regard to the use of immunosuppression. Crescents and/or necrosis identified on histology were associated with the use of immunosuppression. Hence, there is a need for these lesions to be evaluated further in large cohorts and incorporated into future disease classifications.

UK Renal Registry 18th Annual Report: Chapter 2 UK Renal Replacement Therapy Prevalence in 2014: National and Centre-specific Analyses.

There were 58,968 adult patients receiving renal replacement therapy (RRT) in the UK on 31st December 2014, an absolute increase of 4.0% from 2013.The actual number of patients increased 2.0% for haemodialysis (HD), 5.3% for those with a functioning transplant but decreased 0.7% for peritoneal dialysis (PD).The UK adult prevalence of RRT was 913 per million population (pmp). The reported prevalence in 2000 was 523 pmp.The number of patients receiving home HD increased by 6.7% from 1,113 patients in 2013 to 1,188 patients in 2014.The median age of prevalent patients was 59 years(HD 67 years, PD 64 years, transplant 53 years).In 2000, the median age was 55 years (HD 63 years, PD 58 years, transplant 48 years). In 2014,the percentage of RRT patients aged greater than 75 years was 16.0%.For all ages, the prevalence rate in men exceeded that in women, peaking in age group 75­79 years at 3,100 pmp in men and for women at 1,600 pmp in age group 70­74 years.The most common identifiable renal diagnosis was glomerulonephritis (19%), followed by diabetes(16%) and aetiology uncertain (16%).Transplantation continued as the most common treatment modality (53%), HD was used in 41%and PD in 6% of RRT patients.Prevalence rates in patients aged 585 years continued to increase between 2013 and 2014 (1,021 per million age related population (pmarp) to 1,060 pmarp).

Setting Priorities for Optimizing Vascular Access Decision Making--An International Survey of Patients and Clinicians.

BACKGROUND: Many decisions around vascular access for haemodialysis warrant a collaborative treatment decision-making process, involving both clinician and patient. Yet, patients' experiences in this regard have been suboptimal. Although clinical practice guidelines could facilitate collaborative decision making, they often focus on the clinicians' side of the process, while failing to address the patients' perspective. The objective of this study was to explore and compare kidney patients' and clinicians' views on what vascular access-related decisions deserved priority for developing guidelines that will contribute to optimizing collaborative decision making. METHODS: In the context of updating their vascular access guideline, European Renal Best Practice surveyed an international panel of 85 kidney patients, 687 nephrologists, 194 nurses, and 140 surgeons/radiologists. In an electronic questionnaire, respondents rated 42 vascular access-related topics on a 5-point Likert scale. Based on mean standardized ratings, we compared priority ratings between patients and each clinician group. RESULTS: Selection of access type and site, as well as prevention of access infections received top priority across all respondent groups. Patients generally assigned higher priority to decisions regarding managing adverse effects of arteriovenous access and patient involvement in care, while clinicians more often prioritized decisions around sustaining patients' access options, technical aspects of access creation, and optimizing fistula maturation and patency. CONCLUSION: Apart from identifying the most pressing knowledge gaps, our study provides pointers for developing guidelines that may improve healthcare professionals' understanding of when to involve patients along the vascular access pathway.

UK Renal Registry 17th Annual Report: Chapter 2 UK Renal Replacement Therapy Prevalence in 2013: National and Centre-specific Analyses.

INTRODUCTION: This chapter describes the characteristics of adult patients on renal replacement therapy (RRT) in the UK in 2013. METHODS: Data were electronically collected from all 71 renal centres within the UK. A series of cross sectional and longitudinal analyses were performed to describe the demographics of prevalent RRT patients in 2013 at centre and national level. RESULTS: There were 56,940 adult patients receiving RRT in the UK on 31st December 2013. The UK adult prevalence of RRT was 888 pmp which represented an annual increase of 4%,with transplantation the most common treatment modality(52%). There was variation between centres, Clinical Commissioning Groups and Health Boards. The number of patients increased by 1.2% for haemodialysis (HD) and 7.1% for functioning transplant but decreased 3.3% for peritoneal dialysis (PD). The number of patients receiving home HD has increased by 3% since 2012. Median RRT vintage for patients on HD was 3.4 years, PD 1.7 years and for transplant, 10.1 years. The median age of prevalent patients was 58 years (HD 67 years, PD 64 years, transplant 53 years)compared to 55 years in 2000. For all ages the prevalence rate in men exceeded that in women. The most common recorded renal diagnosis was glomerulonephritis (biopsy proven/not biopsy proven) (19%). CONCLUSIONS: The HD and transplant population continued to expand; but the prevalent PD population continues to decline. There were national, regional and centre level variations in prevalence rates. This has continued implications for service planning and ensuring equity of care for RRT patients.

Estimated GFR reporting influences recommendations for dialysis initiation.

Automated reporting of estimated GFR (eGFR) with serum creatinine measurement is now common. We surveyed nephrologists in four countries to determine whether eGFR reporting influences nephrologists' recommendations for dialysis initiation. Respondents were randomly allocated to receive a survey of four clinical vignettes that included either serum creatinine concentration only or serum creatinine and the corresponding eGFR. For each scenario, the respondent was asked to rank his or her likelihood of recommending dialysis initiation on a modified 8-point Likert scale, ranging from 1 ("definitely not") to 8 ("definitely would"). Analysis of the 822 eligible responses received showed that the predicted likelihood of recommending dialysis increased by 0.55 points when eGFR was reported (95% confidence interval, 0.33 to 0.76), and this effect was larger for eGFRs >5 ml/min per 1.73 m(2) (P<0.001). Subgroup analyses suggested that physicians who had been in practice ≥13 years were more affected by eGFR reporting (P=0.03). These results indicate that eGFR reporting modestly increases the likelihood that dialysis is recommended, and physicians should be aware of this effect when assessing patients with severe CKD.

Renal centre characteristics and physician practice patterns associated with home dialysis use.

BACKGROUND: There is a wide variation in home dialysis use (peritoneal dialysis and home haemodialysis) between renal centres. This study identifies which centre characteristics and practice patterns are associated with home dialysis use. METHODS: An observational study of all UK patients starting renal replacement therapy (RRT) in 2007-2008 using patient characteristics from the UK Renal Registry (UKRR) and renal centre characteristics ascertained from a national survey. Multilevel logistic regression was used to examine the association between patient and centre characteristics and home dialysis uptake. RESULTS: Twenty-six per cent of 11 913 patients used home dialysis and survey responses were available from every renal centre. After taking into account patient factors, several centre factors were associated with a higher probability of home dialysis: physicians aspiring to a higher 'ideal' peritoneal dialysis rate (odds ratio, OR 1.21, 95% CI 1.06-1.37, P = 0.003 per 10% increase in 'ideal' percentage), early use of peritoneal dialysis (PD, OR 1.52, 95% CI 1.18-1.95, P < 0.001), use of home visits to educate patients pre-dialysis (OR 1.39, 95% CI 1.05-1.83, P = 0.02) and to provide trouble-shooting advice for existing home dialysis patients (OR 1.63, 95% CI 1.11-2.42, P = 0.01). Using videos/DVDs as part of the pre-dialysis education programme was associated with a lower probability of home dialysis, but this was correlated with lower levels of physician enthusiasm (r = -0.48, P < 0.001). After adjustment for this, the association disappeared (OR 0.77, 95% CI 0.55-1.07, P = 0.1). CONCLUSIONS: Home dialysis use is associated with modifiable centre factors as well as individual patient characteristics.

Chapter 1 UK RRT incidence in 2010: national and centre-specific analyses.

INTRODUCTION: This chapter describes the characteristics of adult patients starting renal replacement therapy (RRT) in the UK in 2010 and the incidence rates for RRT in Primary Care Trusts and Health Boards (PCT/HBs) in the UK. METHODS: The basic demographics and clinical characteristics are reported on patients starting RRT from all UK renal centres. Presentation time, defined as time between first being seen by a nephrologist and start of RRT, was also studied. Age and gender standardised ratios for incidence rates in PCT/HBs were also calculated. RESULTS: In 2010, the incidence rates in the UK and England were similar to 2009 at 107 per million population (pmp). The incidence rate fell in Scotland (from 104 pmp to 95 pmp), increased in Northern Ireland (from 88 pmp to 101 pmp) and Wales (from 120 pmp to 128 pmp). There were wide variations between PCT/HBs in standardised incidence ratios. The median age of all incident patients was 64.9 years (IQR 51.0, 75.2). For transplant centres this was 63.1 years (IQR 49.7, 74.2) and for non-transplanting centres 66.5 years (IQR 52.9, 76.0). The median age for non-Whites was 57.1 years. Diabetic renal disease remained the single most common cause of renal failure (24%). By 90 days, 68.3% of patients were on haemodialysis, 18.1% on peritoneal dialysis, 7.7% had had a transplant and 5.9% had died or stopped treatment. The mean eGFR at the start of RRT was 8.7 ml/ min/1.73 m(2) which was similar to the previous three years. Late presentation (<90 days) fell from 28.2% in 2005 to 20.6% in 2010. There was no relationship between social deprivation and presentation pattern. CONCLUSIONS: Incidence rates have plateaued in England over the last five years. They have fallen in Scotland and fallen and then risen again in Northern Ireland and Wales. Wales continued to have the highest incidence rate of the countries making up the UK.

Chapter 6 Survival and causes of death of UK adult patients on renal replacement therapy in 2010: national and centre-specific analyses.

INTRODUCTION: These analyses examine a) survival from the start of renal replacement therapy (RRT), based on the total incident UK RRT population reported to the UK Renal Registry, including the 18% who started on PD and the 7% who received a pre-emptive transplant and b) survival of prevalent patients. Changes in survival between 1997 and 2009 are also reported. METHODS: Survival of incident patients (starting RRT during 2009) was calculated both from the start of RRT and from 90 days after starting RRT, both with and without censoring at transplantation. Survival of prevalent dialysis patients was calculated to exclude patients once they were transplanted. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. Relative risk of death was calculated compared with the general UK population. RESULTS: The 2009 unadjusted 1 year after 90 day survival for patients starting RRT was 86.6% (87.3% in 2008). In incident patients aged 18-64, the unadjusted 1 year survival had increased from 86.0% in 1997 to 91.3% in 2009. In incident patients aged ≥ 65, unadjusted 1 year survival had improved from 64.1% to 76.2%. There were no survival differences between genders. The relative risk of death compared to the general population decreased from 25 times at age 30-34 to 2.7 times at age 85+. Cause of death data completeness has improved 18% since last year. Cardiac disease is the most common cause of death in prevalent dialysis patients and malignancy most frequent in prevalent transplant patients. CONCLUSIONS: Survival of patients starting RRT has improved for all ages since 1997. The frequency of cardiac disease as the cause of death has decreased since 1997.

Chapter 2 UK RRT prevalence in 2010: national and centre-specific analyses.

INTRODUCTION: This chapter describes the characteristics of adult patients on renal replacement therapy (RRT) in the UK in 2010. METHODS: Data were electronically collected from all 72 renal centres within the UK. Cross-sectional and longitudinal analyses were performed to describe the demographics of prevalent RRT patients in 2010 at centre and national level. Age and gender standardised ratios for prevalence rates per million population per year were calculated. RESULTS: There were 50,965 adult patients receiving RRT in the UK on 31st December 2010. The UK prevalence of RRT (including paediatric patients) was 832 pmp. This represented an annual increase in prevalent numbers of approximately 4% although there was significant variation between centres and regions. From 2009 to 2010 there was a 1.5% increase in the number of patients on haemodialysis (HD), a 3.2% fall in peritoneal dialysis (PD) patients and a 5.4% increase in patients with a functioning transplant. The number of patients receiving home HD has increased 23% since 2009. Median RRT vintage was 5.6 years. The median age was 57.9 years (HD 66.3 years, PD 61.7 years and transplant 51.2 years) compared to 55 years in 2000. Prevalence rates in males exceeded those in females. The most common identifiable renal diagnosis was biopsyproven glomerulonephritis (16.0%), followed by diabetes (14.9%). Transplantation was the most common treatment modality (48%), HD in 44% and PD 8%. CONCLUSIONS: The HD and transplant population continued to expand whilst the PD population contracted. There were national, regional and dialysis centre level variations in prevalence rates. Prevalent patients were on average 4 years older than 10 years ago. This has implications for service planning and ensuring equity of care for RRT patients.

How much of the regional variation in RRT incidence rates within the UK is explained by the health needs of the general population?

BACKGROUND: Variation in end-stage renal disease treatment rates in the UK persist after adjustment for socio-demographic factors. METHODS: UK-wide ecological study using population socio-demographic factors, health status characteristics and access to health services factor in to explain the incidence of renal replacement therapy (RRT). RESULTS: There was a 6% higher incidence rate of RRT per standard deviation (SD) increase in area diabetes prevalence after adjustment for area level socio-economic deprivation status and the proportion of non-white residents [incidence rate ratio adjusted (IRR adjusted) 1.06 (95% confidence interval 1.03,1.09), P < 0.001]. A 3% lower-adjusted RRT incidence rate was seen with each SD higher proportion of diabetics achieving an HbA1c of <7.5% [IRR 0.97 (0.94, 1.00), P = 0.03]. Hypertension prevalence was independently associated with an 8% higher RRT incidence rate per SD increase [IRR adjusted 1.08 (1.04, 1.11), P < 0.001] and an SD increase in life expectancy in an area was independently associated with 7% lower RRT incidence rate [IRR adjusted 0.93 (0.91, 0.96), P < 0.001]. An SD increase in premature cardiovascular (CV) mortality rate in an area was also independently associated with RRT incidence rates [IRR adjusted 1.06 (1.03, 1.09), P < 0.001]. Rates of coronary artery bypass grafting (CABG)/angioplasty and knee replacement were positively associated with RRT incidence, but mammography uptake was not associated. In total, 31% of the regional variation in RRT incidence could be explained by these factors. CONCLUSIONS: Diabetes prevalence, the proportion of diabetics achieving good glycaemic control, hypertension prevalence, life expectancy, premature CV mortality, CABG/angioplasty and knee replacement rates were all associated with RRT incidence. A third of the regional variation in RRT incidence between areas can be explained by these demographic, health and access to health services factors.

UK Renal Registry 13th Annual Report (December 2010): Chapter 6: survival and causes of death of UK adult patients on renal replacement therapy in 2009: national and centre-specific analyses.

INTRODUCTION: These analyses examine (a) survival from the start of renal replacement therapy (RRT), based on the total incident UK RRT population reported to the UK Renal Registry, including the 18% who started on PD and the 6% who received a pre-emptive transplant and (b) survival of prevalent patients. Changes in survival between 1997 and 2008 are also reported. METHODS: Survival was calculated for both incident and prevalent patients on RRT and compared between the UK countries after adjustment for age. Survival of incident patients (starting RRT during 2008) was calculated both from the start of RRT and amongst the cohort who survived at least 90 days after RRT, both with and without censoring at transplantation. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. Relative risk of death was calculated compared with the general UK population. RESULTS: The 2008 unadjusted 1 year after 90 day survival for patients starting RRT was 87.3%. In incident patients aged 18-64, the unadjusted 1 year survival had risen from 85.9% in 1997 to 91.9% in 2008 and for those aged ≥ 65 it had risen from 64.2% to 75.8%. The age-adjusted one year survival (adjusted to age 60) of prevalent dialysis patients rose from 85% in 2000 to 89% in 2009. Diabetic prevalent patient one year survival rose from 76.6% in 2000 to 83.6% in 2009. The age-standardised mortality ratio for prevalent RRT patients compared with the general population was 19 at age 30 years and 2.4 at age 85 years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 24% of deaths, infection 19% and treatment withdrawal 14%; 22% were recorded as uncertain. Treatment withdrawal was a more frequent cause of death in patients aged ≥ 65 at start of RRT than in younger patients. The median life years remaining for a 25-29 year old on RRT was 20 years and 4 years for a 75+ year old. CONCLUSIONS: Survival of patients starting RRT, has improved in the 2008 incident cohort. The relative risk of death on RRT compared with the general population has fallen since 2001. Death rates on dialysis in the UK remained lower than when compared with a similar aged population on dialysis in the USA.

UK Renal Registry 13th Annual Report (December 2010): Chapter 1: UK RRT incidence in 2009: national and centre-specific analyses.

INTRODUCTION: This chapter describes the characteristics of adult patients starting renal replacement therapy (RRT) in the UK in 2009 and the acceptance rates for RRT in Primary Care Trusts and Health Boards (PCT/HBs) in the UK. METHODS: The basic demographics and clinical characteristics are reported on patients starting RRT from all UK renal centres. Late presentation, defined as time between first being seen by a nephrologist and start of RRT being <90 days was also studied. Age and gender standardised ratios for acceptance rates in PCT/HBs were calculated. RESULTS: In 2009, the incidence rate in the UK and England was 109 per million population (pmp). Acceptance rates in Scotland (104 pmp), Northern Ireland (88 pmp) and Wales (120 pmp) had all fallen although Wales still remained the country with the highest acceptance rate. There were wide variations between PCT/HBs with respect to the standardised ratios. The median age of all incident patients was 64.8 years (IQR 50.8, 75.1). For transplant centres this was 63.0 years (IQR 49.0, 74.2) and for non-transplanting centres 66.3 years (IQR 52.6, 75.9). The median age for non-Whites was 57.1 years. Diabetic renal disease remained the single most common cause of renal failure (25%). By 90 days, 69.1% of patients were on haemodialysis, 17.7% on peritoneal dialysis, 6.7% had had a transplant and 6.5% had died or stopped treatment. The mean eGFR at the start of RRT was 8.6 ml/min/1.73 m2 which was similar to the previous two years. Late presentation (<90 days) has fallen from 27% in 2004 to 19% in 2009. There was no relationship between social deprivation and presentation pattern. CONCLUSIONS: Acceptance rates have fallen in Northern Ireland, Scotland and Wales whilst they have plateaued in England over the last four years. Wales continued to have the highest acceptance rate of the countries making up the UK.