Patients with Diabetic Nephropathy in Established Renal Failure: Demographics, Survival and Biochemical Variables (Chapter 16)

Diabetic nephropathy is now the most common renal disease leading to renal replacement therapy in developed countries1,2,3,4. Within the UK, the number of DN patients accepted for RRT rose steadily in the 1990s5 especially in the African–Caribbean and South Asian populations3,4,5,6. This may be related to the increased prevalence of Type 2 diabetes in the general population, the ageing population and the liberalisation of attitudes to acceptance for RRT5,7. The overall rise has slowed in the last 4 years8 . DN patients starting RRT are likely to have more co-morbidity than other patients, in particular cardiovascular disease, and consequently worse survival on RRT9,10,11. In recent years there has been some reduction in the high mortality of such patients, so the prevalence of diabetic nephropathy patients on RRT (currently lower than the percentage of incident patients, see Chapter 3) might increase12,13. The National Service Frameworks for Diabetes14 and for Renal Services15 have highlighted the importance of the primary prevention of DN in diabetic patients by early detection and aggressive management of hypertension, glucose control and cardiovascular risk factors and of the timely referral (recommendation >1 yr before RRT) of those with progressive renal disease in order to plan for RRT. 251 There is a key policy drive to reduce health inequalities in England16. In the UK there is evidence that diabetic patients in more socially deprived areas have higher all cause mortality even after adjustment for smoking and blood pressure9 , and lower rates of attendance at GP and hospital clinics17. The UK Renal Registry 2003 Report highlighted the possible role of social deprivation in the context of DN. This chapter examines the characteristics of patients developing established renal failure from DN, their access to modalities of treatment and their survival on RRT relative to other incident patients. It also includes data on quality of care (HbA1c, cholesterol and blood pressure). These analyses were undertaken before individual patient data from the Scottish Registry became available and therefore only includes England and Wales

Polymorphisms in ARMS2/HTRA1 and complement genes and age-related macular degeneration in India: findings from the INDEYE study.

PURPOSE: Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. METHODS: Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1-3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. RESULTS: Of 3569 participants, 53.2% had no signs of amd, 45.6% had features of early amd, and 1.2% had late amd. CFH (RS1061170), C2 (RS547154), OR CFB (RS438999) was not associated with early or late AMD. In the ARMS2 locus, RS10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13-1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15-2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02-1.23; P = 0.02); rs10490923 was not associated with early or late AMD. CONCLUSIONS: Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India

Feasibility of evaluation of the natural history of kidney disease in the general population using electronic healthcare records

Background: Knowledge about the nature of long-term changes in kidney function in the general population is sparse. We aim to identify whether primary care electronic healthcare records capture sufficient information to study the natural history of kidney disease. / Methods: The National Chronic Kidney Disease Audit database covers ∼14% of the population of England and Wales. Availability of repeat serum creatinine tests was evaluated by risk factors for chronic kidney disease (CKD) and individual changes over time in estimated glomerular filtration rate (eGFR) were estimated using linear regression. Sensitivity of estimation to method of evaluation of eGFR compared laboratory-reported eGFR and recalculated eGFR (using laboratory-reported creatinine), to uncover any impact of historical creatinine calibration issues on slope estimation. / Results: Twenty-five per cent of all adults, 92% of diabetics and 96% of those with confirmed CKD had at least three creatinine tests, spanning a median of 5.7 years, 6.2 years and 6.1 years, respectively. Median changes in laboratory-reported eGFR (mL/min/1.73 m2/year) were −1.32 (CKD) and −0.60 (diabetes). Median changes in recalculated eGFR were −0.98 (CKD) and −0.11 (diabetes), underestimating decline. Magnitude of underestimation (and between-patient variation in magnitude) decreased with deteriorating eGFR. For CKD Stages 3, 4 and 5 (at latest eGFR), median slopes were −1.27, −2.49 and -3.87 for laboratory-reported eGFR and −0.89, −2.26 and −3.75 for recalculated eGFR. / Conclusions: Evaluation of long-term changes in renal function will be possible in those at greatest risk if methods are identified to overcome creatinine calibration problems. Bias will be reduced by focussing on patients with confirmed CKD

Do influenza and pneumococcal vaccines prevent community-acquired respiratory infections among older people with diabetes and does this vary by chronic kidney disease? A cohort study using electronic health records

Objective: We aimed to estimate the effectiveness of influenza and 23-valent pneumococcal polysaccharide vaccination on reducing the burden of community-acquired lower respiratory tract infection (LRTI) among older people with diabetes, and whether this varied by chronic kidney disease status. Research design and methods: We used linked UK electronic health records for a retrospective cohort study of 190,492 patients ≥65 years with diabetes mellitus and no history of renal replacement therapy, 1997–2011. We included community-acquired LRTIs managed in primary or secondary care. Infection incidence rate ratios were estimated using Poisson regression. Pneumococcal vaccine effectiveness (VE) was calculated as (1 – effect measure). To estimate influenza VE a ratio-of-ratios analysis (winter effectiveness/summer effectiveness) was used to address confounding by indication. Final VE estimates were stratified according to estimated glomerular filtration rate and proteinuria status. Results: Neither influenza nor pneumococcal vaccine uptake varied according to CKD status. Pneumococcal VE was 22% (95%CI: 11–31) against community-acquired pneumonia for the first year after vaccination, but was negligible after five years. In the ratio-of-ratios analysis, current influenza vaccination had 7% effectiveness for preventing community-acquired LRTI (95%CI: 3–12). Pneumococcal vaccine effectiveness was lower among patients with a history of proteinuria than among patients without proteinuria (p=0.04), but otherwise this study did not identify variation in pneumococcal or influenza VE by markers of CKD. Conclusions: The public health benefits of influenza vaccine may be modest among older people with diabetes. Pneumococcal vaccination protection against community-acquired pneumonia declines swiftly: alternative vaccination schedules should be investigated

Acute kidney injury in stable COPD and at exacerbation.

BACKGROUND: While acute kidney injury (AKI) alone is associated with increased mortality, the incidence of hospital admission with AKI among stable and exacerbating COPD patients and the effect of concurrent AKI at COPD exacerbation on mortality is not known. METHODS: A total of 189,561 individuals with COPD were identified from the Clinical Practice Research Datalink. Using Poisson and logistic regressions, we explored which factors predicted admission for AKI (identified in Hospital Episode Statistics) in this COPD cohort and concomitant AKI at a hospitalization for COPD exacerbation. Using survival analysis, we investigated the effect of concurrent AKI at exacerbation on mortality (n=36,107) and identified confounding factors. RESULTS: The incidence of AKI in the total COPD cohort was 128/100,000 person-years. The prevalence of concomitant AKI at exacerbation was 1.9%, and the mortality rate in patients with AKI at exacerbation was 521/1,000 person-years. Male sex, older age, and lower glomerular filtration rate predicted higher risk of AKI or death. There was a 1.80 fold (95% confidence interval: 1.61, 2.03) increase in adjusted mortality within the first 6 months post COPD exacerbation in patients suffering from AKI and COPD exacerbation compared to those who were AKI free. CONCLUSION: In comparison to previous studies on general populations and hospitalizations, the incidence and prevalence of AKI is relatively high in COPD patients. Coexisting AKI at exacerbation is prognostic of poor outcome

Urinary biomarkers of tubular injury in chronic kidney disease

It has been suggested that urinary biomarkers of tubular injury might help predict progression to end-stage renal disease. In this issue, Hsu et al. report that in those with established chronic kidney disease, this information does not add to what we know by quantifying creatinine and albuminuria. Here we discuss the evidence for urinary tubular injury markers in predicting renal outcomes in chronic kidney disease and the areas where measurement of these molecules might be useful in the future

Incomplete reversibility of estimated glomerular filtration rate decline following tenofovir disoproxil fumarate exposure.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI,.1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided