• Takotsubo cardiomyopathy (Broken heart syndrome).

      Chitkara, Kamal (2015-11)
      Takotsubo cardiomyopathy is an acute reversible cardiomyopathy characterised by transient regional left ventricular (LV) motion abnormalities. It is diagnosed on a coronary angiography and left ventriculography. We report the case of a 50-year-old lady who presented with sudden onset of chest pain, with no history of cardiac disease and no risk factors. Remarkably though, she had lost her husband the previous night. Coronary and LV angiography was done which revealed findings typical of takotsubo cardiomyopathy. We report this case for its rarity. Informed consent was taken from the patient before undertaking and reporting this study.
    • Techniques to improve intradialytic haemodynamic stability.

      Selby, Nicholas (2018-08)
      PURPOSE OF REVIEW: Intra-dialytic hypotension (IDH) remains a significant problem for patients undergoing chronic haemodialysis. IDH causes symptoms that degrade patients' experience, compromises dialysis delivery and is strongly associated with adverse patient outcomes. Greater understanding of the link between IDH and dialysis-induced ischaemia in heart and brain has characterized mechanistic pathways, with repeated episodes of ischaemia resulting in organ dysfunction. This review provides updates from published evidence over the last 2 years across the range of potential interventions for IDH. RECENT FINDINGS: A literature search was undertaken to identify articles published in peer review journals between January 2016 and April 2018 using terms 'intradialytic hypotension,' 'haemodynamic instability,' 'ESRF,' 'renal replacement therapy,' 'dialysis' in Medline and EMBASE and identified 58 references from which 15 articles were included in this review. Interventions included: cooling the dialysate; sodium profiling; convective therapies; strategies to minimize inter-dialytic weight gain (IDWG) and improve accuracy of target weight assessment; prescribing of antihypertensive medications; and carnitine supplementation. SUMMARY: IDH remains a significant clinical problem. Recent evidence from the last 2 years does not support any major changes to current practice, with cooling of the dialysate and reduction of IDWG remaining cornerstones of management.
    • The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease.

      McIntyre, Christopher (2015-07)
      A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.
    • The burden of comorbidity in people with chronic kidney disease stage 3: a cohort study.

      Taal, Maarten; Fluck, Richard; Shardlow, Adam; McIntyre, Natasha; McIntyre, Christopher (2015-12)
      BACKGROUND: Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. Chronic kidney disease (CKD) is common but often considered in isolation. The extent and prognostic significance of its comorbidities is not well understood. This study aimed to assess the extent and prognostic significance of 11 comorbidities in people with CKD stage 3. METHODS: A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling. Comorbidity was defined by self-reported doctor-diagnosed condition, disease-specific medication or blood results (hemoglobin), and treatment burden as number of ongoing medications. Logistic regression was used to identify associations with greater treatment burden (taking >5 medications) and greater multimorbidity (3 or more comorbidities). Kaplan Meier plots and multivariate Cox proportional hazards models were used to investigate associations between multimorbidity and all-cause mortality. RESULTS: One thousand seven hundred forty-one people were recruited, mean age 72.9 +/-9 years. Mean baseline eGFR was 52 ml/min/1.73 m(2). Only 78/1741 (4 %) had no comorbidities, 453/1741 (26 %) had one, 508/1741 (29 %) had two and 702/1741 (40 %) had >2. Hypertension was common (88 %), 30 % had 'painful condition', 24 % anemia, 23 %, ischaemic heart disease, 17 % diabetes and 12 % thyroid disorders. Median medication use was 5 medications (interquartile range 3-8) and increased with degree of comorbidity. Greater treatment burden and multimorbidity were independently associated with age, smoking, increasing body mass index and decreasing eGFR. Treatment burden was also independently associated with lower education status. After median 3.6 years follow-up, 175/1741 (10 %) died. Greater multimorbidity was independently associated with mortality (hazard ratio 2.81 (95 % confidence intervals 1.72-4.58), p < 0.001) for 3 or more comorbidities vs 0 or 1). CONCLUSIONS: Isolated CKD was rare and multimorbidity the norm in this cohort of people with moderate CKD. Increasing multimorbidity was associated with greater medication burden and poorer survival. CKD management should include consideration of comorbidities.
    • The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study.

      Shardlow, Adam; McIntyre, Natasha; Fluck, Richard; Taal, Maarten (2017-10)
      BACKGROUND: To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45-59 ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed. METHODS AND FINDINGS: A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to 'no CKD' or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFRcys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFRcys to confirm the diagnosis in people classified as CKD G3aA1 by eGFRcreat. Mean eGFRcys was significantly lower than mean eGFRcreat (45.1 ml/min/1.73 m2, 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m2, 95% CI 53.0 to 54.1, P < 0.001). eGFRcys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFRcreat to eGFR ≥ 60 ml/min/1.73 m2. However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFRcreat-cys, but lower proportions were reclassified. Change in eGFRcreat and eGFRcys over 5 years were weakly correlated (r = 0.33, P < 0.001), but eGFRcys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFRcreat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFRcys. Use of eGFRcys or eGFRcreat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFRcreat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort. CONCLUSIONS: Implementation of current guidelines on eGFRcys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFRcreat. Use of eGFRcys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFRcys and eGFRcreat-cys.
    • The dietary management of patients with diabetes and renal disease: challenges and practicalities.

      Willingham, Fiona (2012-02)
      Diabetes mellitus is one of the major causes of chronic kidney disease and end-stage renal disease. Diet and lifestyle modification are vital components of optimal treatment for both conditions. This paper will address appropriate and often diverse treatment for each individual, understanding that advising changes which positively impact both conditions is a major challenge for health care professionals working within either speciality. It will also highlight where overlap can be contradictory rather than complementary, and offers practical guidance to support patients in making the necessary lifestyle changes to have maximal positive impact upon both conditions and their overall health.
    • The effects of acute kidney injury on long-term renal function and proteinuria in a general hospitalised population.

      Horne, Kerry; Packington, Rebecca; Monaghan, John; Reilly, Timothy; McIntyre, Christopher; Selby, Nicholas (2014-11)
      BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and is associated with adverse long-term consequences. There is an urgent need to understand these sequelae in general hospitalised patients utilising a prospective cohort-based approach. We aimed to test the feasibility of study methodology prior to commencing a large-scale study and investigate the effects of AKI on chronic kidney disease (CKD) progression and proteinuria. METHODS: Pilot study testing novel methodology for remote patient recruitment within a prospective case-control design. 300 cases (hospitalised patients with AKI) and controls (hospitalised patients without AKI) were matched 1:1 for age and baseline estimated glomerular filtration rate (eGFR). 70% of cases had AKI stage 1, 16% AKI stage 2 and 14% AKI stage 3. Renal function and proteinuria were measured 3 and 12 months after hospital admission. RESULTS: The study met pre-defined recruitment, withdrawal and matching criteria. Renal function was worse in the AKI group at 3 (eGFR 61 ± 20 vs. 74 ± 23 ml/min/1.73 m(2), p < 0.001) and 12 months (eGFR 64 ± 23 vs. 75 ± 25 ml/min/1.73 m(2), p < 0.001). More cases than controls had CKD progression at 3 months (14 vs. 0.7%, p < 0.001). This difference persisted to 12 months, but there was no significant change between 3 and 12 months. Proteinuria and albuminuria were more prevalent in the AKI group and associated with CKD progression. CONCLUSIONS: We describe a method of remote patient recruitment which could be employed more widely for prospective observational studies. Even mild AKI is associated with long-term renal dysfunction. Further investigation using this methodology is now underway.
    • The efficacy of unsupervised home-based exercise regimens in comparison to supervised laboratory-based exercise training upon cardio-respiratory health facets.

      Blackwell, James; Doleman, Brett; Williams, John P; Lund, Jonathan (2017-09)
      Supervised high-intensity interval training (HIIT) can rapidly improve cardiorespiratory fitness (CRF). However, the effectiveness of time-efficient unsupervised home-based interventions is unknown. Eighteen volunteers completed either: laboratory-HIIT (L-HIIT); home-HIIT (H-HIIT) or home-isometric hand-grip training (H-IHGT). CRF improved significantly in L-HIIT and H-HIIT groups, with blood pressure improvements in the H-IHGT group only. H-HIIT offers a practical, time-efficient exercise mode to improve CRF, away from the laboratory environment. H-IHGT potentially provides a viable alternative to modify blood pressure in those unable to participate in whole-body exercise.
    • The epidemiology of hospitalised acute kidney injury not requiring dialysis in England from 1998 to 2013: retrospective analysis of hospital episode statistics

      Kolhe, Nitin; Taal, Maarten (2016-04)
      Epidemiology studies of acute kidney injury (AKI) have focused on cases requiring dialysis but those not requiring dialysis represent the majority. To address this gap, we interrogated hospital episode statistics (HES) to investigate population trends in temporal epidemiology of AKI not requiring dialysis between 1998 and 2013. METHODOLOGY: In this retrospective observational study of HES data covering the entire English National Health Service, we identified 1,136,167 AKI events, not requiring dialysis, diagnosed between 1998 and 2013. We explored the effect of age, gender, ethnicity, Charlson's comorbidity score (CCS), method of admission, diagnosis period and AKI in diagnosis codes on temporal changes in the incidence and case-fatality of AKI with specific examination of its predictors. RESULT: The incidence of AKI increased from 15,463 cases (317 pmp) in 1998-1999 to 213,700 cases (3995 pmp) in 2012-2013. There was increase in proportion of people over 75 years from 51.1% in 1998-1999 to 63.4% in 2012-2013. Overall unadjusted case-fatality decreased from 42.3% in 1998-2003 to 27.1% in 2008-2013, p < 0.001. Compared with 1998-2003, the multivariable adjusted odds ratio for death was 0.64 in 2003-2008 (95% CI 0.63-0.65) and 0.35 in 2008-2013 (95% CI 0.34-0.35). Odds for death were higher for patients over 85 years (2.93; 95% CI 2.89-2.97), CCS of more than five (2.75; 95% CI 2.71-2.79), emergency admissions (2.14; 95% CI 2.09-2.18) and AKI in the secondary diagnosis code (1.35; 95% CI 1.33-1.36) and AKI in other diagnoses codes (2.17; 95% CI 2.15-2.20). CONCLUSIONS: In England, the incidence of AKI not requiring dialysis has increased and case-fatality has decreased over last 15 years. Efforts to reduce the incidence of AKI and improve survival should focus on elderly people, emergency admissions and those with multi-morbidity.
    • The impact of antihypertensive drug therapy on endotoxemia in elderly patients with chronic kidney disease

      John, Stephen; Owen, Paul; Harrison, Laura; McIntyre, Christopher (2011-10)
      BACKGROUND AND OBJECTIVES: Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We recruited 40 hypertensive nondiabetic patients (≥70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay. RESULTS: Mean age was 76 ± 5 years, estimated GFR (eGFR) (CKD group) was 40 ± 14 ml/min per 1.73 m(2), and achieved BP was 128/69 mmHg. Washout ET was 0.042 ± 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 ± 0.028 EU/ml; P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein. CONCLUSIONS: Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.
    • The impact of antihypertensive drug therapy on endotoxemia in elderly patients with chronic kidney disease.

      John, Stephen; Owen, Paul; Harrison, Laura; McIntyre, Christopher (2011-11)
      BACKGROUND AND OBJECTIVES: Endotoxin (ET) is recognized to cause adverse effects on cardiovascular (CV) structure. Circulatory translocation of gut bacterial ET is described in heart failure. Chronic kidney disease (CKD) is common in older people and aggressive BP control is the cornerstone of management. We therefore studied ET after improvement of the overall CV milieu with introduction of optimized antihypertensive therapy (AHT). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We recruited 40 hypertensive nondiabetic patients (≥70 years) with CKD stages 3 and 4 and hypertensive non-CKD matched controls. Assessment was performed after complete AHT washout and repeated after AHT reintroduction to target BP 130/80 mmHg. Pulse wave velocity (PWV) and analysis were assessed by applanation tonometry, central hemodynamics by continuous digital pulse wave analysis, vascular calcification (VC) by superficial femoral artery CT, and serum ET by Limulus Amebocyte assay. RESULTS: Mean age was 76 ± 5 years, estimated GFR (eGFR) (CKD group) was 40 ± 14 ml/min per 1.73 m(2), and achieved BP was 128/69 mmHg. Washout ET was 0.042 ± 0.011 EU/ml and was independent of renal function, gender, age, BP, VC, arterial stiffness, and high-sensitivity C-reactive protein. ET significantly decreased with AHT (to 0.020 ± 0.028 EU/ml; P < 0.001) and was associated with eGFR (R = -0.38; P = 0.02), arterial wave reflection (Augmentation Index R = -0.42; P = 0.01), and degree of tonic vasodilatation (total peripheral resistance R = -0.37; P = 0.03), but not VC, PWV, gender, age, BP, or high-sensitivity C-reactive protein. CONCLUSIONS: Elderly patients with hypertension have elevated serum ET. Improvement of their CV status with optimized AHT is associated with a significant reduction in endotoxemia. Further investigation of the potential pathophysiological mechanisms linking CV disease and CKD with this previously unappreciated effect of AHT appears warranted.
    • The impact of hemodialysis on segmental and global longitudinal myocardial strain.

      Huang, Shih-Han; Crowley, Lisa; Jefferies, Helen; Eldehni, Mohamed; Odudu, Aghogho; McIntyre, Christopher (2014-11)
      Strain analysis derived from the analysis of speckle tracked imaging echocardiography can be used to examine ventricular contractile functions. In this study, we examined the relationship of hemodialysis (HD)-induced circulatory stress with overall ventricular function assessed according to global longitudinal strain (GLS) and segmental distribution of strain. This prospective observational study included 104 conventional HD patients at Royal Derby Hospital. Averaged values of segmental and GLS were determined from the echocardiography of these patients before and at peak dialysis. These values were compared with the reference values of healthy individuals, correlated with their demographic characteristics, and the effect on survival was assessed. The global strain value was -11.5% ± 4.42, and the segmental strain values were significantly greater in HD patients than in healthy individuals by 2.7%-9.8% (P < 0.001). The strain values were not significantly different before dialysis and at peak dialysis (P > 0.05), except within the basal lateral segment (P = 0.01). The adjusted hazard ratio for mortality was 4.3 (95% confidence interval, 1.2-14.9; P = 0.021) when > 80% of the segments exhibited more than the mean of segmental strain values. For the 46 patients who died, there were statistically significant negative correlations between survival time and GLS (r = -0.30; P = 0.04). Global and segmental strain measured using speckle tracked imaging provides information relating to the effects of HD-induced cardiac injury. The segmental strain abnormalities in the watershed area of the left ventricle suggest a higher degree of vulnerability to HD-induced demand ischemia.
    • The impact of vitamin D status on the relative increase in fibroblast growth factor 23 and parathyroid hormone in chronic kidney disease.

      Taal, Maarten; Thurston, Victoria; McIntyre, Natasha; Fluck, Richard; McIntyre, Christopher (2014-08)
      Fibroblast growth factor (FGF) 23 is an important regulator of phosphaturia. Its serum level was found to increase before that of parathyroid hormone (PTH) in early chronic kidney disease (CKD) in some but not all previous studies. As vitamin D insufficiency is associated with elevated PTH, we determined the effect of vitamin D status on FGF23 and PTH levels in relation to glomerular filtration rate (GFR) in people with CKD stage 3. Serum intact FGF23, PTH, and 25(OH)vitamin D3 were measured in 1664 patients who were prospectively recruited from primary care. Mean or median values for key variables were an age of 73 years, estimated GFR (eGFR) of 53 ml/min per 1.73 m(2), PTH 46 pg/ml, FGF23 42 pg/ml, and 25(OH)vitamin D3 53 nmol/l. FGF23 and PTH concentrations were elevated in similar proportions of people with lower eGFR in the whole cohort. However, when 752 people with vitamin D insufficiency or deficiency were excluded, FGF23 was elevated in a greater proportion than PTH at all levels of eGFR. Conversely, among people with vitamin D insufficiency, PTH was elevated in a greater proportion than FGF23 at all GFR levels of ⩾40 ml/min per 1.73 m(2). In this cohort, we were able to triangulate the relationship between 25(OH)vitamin D3, PTH, and FGF23, showing that vitamin D status critically determines whether FGF23 or PTH becomes elevated first in the context of lower GFR. Future studies of FGF23 in people with CKD should routinely determine their vitamin D status.
    • The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

      Game, Frances (2017-10)
      BACKGROUND: Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. METHODS: People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. DISCUSSION: Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. TRIAL REGISTRATION: International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.
    • The management of gastric polyps.

      Goddard, Andrew (2010-09)
      BACKGROUND: Gastric polyps are important as some have malignant potential. If such polyps are left untreated, gastric cancer may result. The malignant potential depends on the histological type of the polyp. The literature base is relatively weak and any recommendations made must be viewed in light of this. DEFINITION: Gastric polyps are sessile or pedunculated lesions that originate in the gastric epithelium or submucosa and protrude into the stomach lumen. MALIGNANT POTENTIAL: Depending on histological type, some gastric polyps (adenomas and hyperplastic polyps) have malignant potential and are precursors of early gastric cancer. They may also indicate an increased risk of intestinal or extra-intestinal malignancy.
    • The pathophysiology of the chronic cardiorenal syndrome: a magnetic resonance imaging study

      Breidthardt, Tobias; Odudu, Aghogho; Eldehni, Mohamed; McIntyre, Christopher (2015-06)
      OBJECTIVE: To study the association of renal function with renal perfusion and renal parenchymal structure (T1 relaxation) in patients with chronic heart failure (HF) METHODS: After IRB approval, 40 participants were enrolled according to HF and renal function status [10 healthy volunteers < 40 years; 10 healthy age-matched volunteers; 10 HF patients eGFR > 60 ml/min/1.73 m(2); 10 HF patients eGFR < 60 ml/min/1.73 m(2)] and assessed by MRI. To be eligible for enrolment all HF patients with renal dysfunction (RD) needed to be diagnosed as having chronic cardiorenal syndrome based on current guidelines. Patients with primary kidney disease were excluded. RESULTS: Renal cortical perfusion correlated with eGFR values (r = 0.52;p < 0.01) and was similar between HF patients with and without RD (p = 0.27). T1 relaxation correlated negatively with eGFR values (r = -0.41;p > 0.01) and was higher in HF patients compared to volunteers (1121 ± 102 ms vs. 1054 ± 65 ms;p = 0.03). T1 relaxation was selectively prolonged in HF patients with RD (1169 ms ± 100 vs. HF without RD 1067 ms ± 79;p = 0.047). In linear regression analyses coronary artery disease (p = 0.01), hypertension (p = 0.04), and diabetes mellitus (p < 0.01) were associated with T1 relaxation. CONCLUSION: RD in HF is not primarily mediated by decreased renal perfusion. Instead, chronic reno-parenchymal damage, as indicated by prolonged T1 relaxation, appears to underly chronic cardiorenal syndrome.
    • The reimbursement and cost of acute kidney injury: a UK hospital perspective.

      Kolhe, Nitin; Eldehni, Mohamed; Selby, Nicholas; McIntyre, Christopher (2014-02)
      BACKGROUND: Despite the great interest in acute kidney injury (AKI), there have been very few studies that examined the economic impact and costing methodologies of AKI. We aimed to examine the cost and income of AKI in hospitalised patients over a period of 1 year using the NHS costing system related to that year. METHODS: A total of 627 patients discharged between January 2008 and December 2008 with AKI were identified by International Classification of Disease 10 codes (ICD-10). Basic demographic data were collected using the hospital electronic records, and the severity of AKI was classified according to the Acute Kidney Injury Network (AKIN) classification. We calculated the total income and isolated the AKI income related to AKI-specific finished consultant episodes. Then we conducted a patient level costing exercise using relative value units (RVU) to compare the cost of AKI to the actual income. RESULTS: The total spell income for all patients was GBP 1,954,922.7; the mean total income per patient was GBP 3,752.3 (95% CI 3,594.6-3,903.9). AKIN stage 3 generated significantly higher total spell and AKI income. The estimated overall cost of treating AKI was higher than the AKI income to the Primary Care Trust (GBP 1,984,543.9 vs. 1,755,395). CONCLUSION: AKIN stage 3 has a significant economic impact when compared with AKIN stages 1 and 2. The move towards a patient level costing using RVU could be a more efficient way to match cost and income.
    • The relationship between obstructive sleep apnea and intra-epidermal nerve fiber density, PARP activation and foot ulceration in patients with type 2 diabetes.

      Piya, Milan (2016-06)
      BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased nitrosative stress, endothelial dysfunction, and peripheral neuropathy in patients with type 2 diabetes. We hypothesized that OSA is associated with Poly ADP ribose polymerase (PARP) activation, lower intra-epidermal nerve fiber density (IENFD), and diabetic foot ulceration (DFU). METHODS: A cross-sectional study of adults with type 2 diabetes recruited from a secondary care hospital in the UK. OSA was assessed by multi-channel home-based cardio-respiratory device (Alice PDX, Philips Respironics). DPN was assessed using the Michigan Neuropathy Screening Instrument (MNSI). IENFD and % PAR stained nuclei were assessed using immunohistochemistry staining on skin biopsies. DFU was assessed based on MNSI. RESULTS: Skin biopsies and DFU data were available from 52 and 234 patients respectively. OSA was associated with lower IENFD (12.75±1.93 vs. 10.55±1.62 vs. 9.42±1.16 fibers/mm of epidermis for no OSA, mild OSA and moderate to severe OSA respectively, p<0.001). Following adjustment, mild (B= 2.19, p=0.002) and moderate to severe OSA (B=-3.45, p<0.001) were independently associated with IENFD. The apnea hypopnea index (AHI) was associated with IENFD following adjustment (B=-2.45, p<0.001). AHI was associated with percentage of PAR stained nuclei following adjustment (B=13.67, p=0.025). DFU prevalence was greater in patients with OSA (7.1% vs. 28.1% vs. 26.2% for patients with no OSA, mild OSA and moderate to severe OSA respectively, p=0.001). Following adjustment, OSA was associated with DFU (OR 3.34, 95% CI 1.19-9.38, p=0.022). CONCLUSIONS: OSA is associated with lower IENFD, PARP activation and DFU in patients with type 2 diabetes. Our findings suggest that OSA is associated with small fiber neuropathy. PARP activation is a potential mechanisms linking OSA to DPN and endothelial dysfunction in patients with type 2 diabetes. Whether OSA treatment will have a favorable impact on these parameters and DFU requires interventional studies.