Management of hypertension in older people.

Introduction: As the population ages, the prevalence of hypertension is increasing. Treatment of hypertension is associated with a reduction in cardiovascular risk. However, the optimal blood pressure targets in older people are not clearly defined due to paucity of randomised clinical trials specific to this age group.

Early and asymptomatic cardiac dysfunction in chronic kidney disease.

Background: Heart failure (HF) is highly prevalent and associated with high mortality in chronic kidney disease (CKD). However, the pathophysiology of cardiac dysfunction in CKD, especially in the early asymptomatic stage, is not well understood. We studied subclinical cardiac dysfunction in asymptomatic CKD patients without comorbid cardiac disease or diabetes mellitus by evaluating peak cardiac performance.

Renin-Angiotensin-Aldosterone system blockade in diabetic kidney disease: A critical and contrarian point of view.

Diabetes mellitus is the most common cause of end-stage renal disease (ESRD) worldwide. Diabetic kidney disease (DKD) is associated with high morbidity and cardiovascular mortality. A number of guidelines and recommendations have been issued over the years recommending the use of renin-angiotensin-aldosterone system (RAAS) blockade in the management of DKD.

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy.

Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN.

Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial.

Background: Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin-angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in patients with advanced progressive CKD.

The mortality and hospitalization rates associated with the long interdialytic gap in thrice-weekly hemodialysis patients.

Excess mortality and hospitalization have been identified after the 2-day gap in thrice-weekly hemodialysis patients compared with 1-day intervals, although findings vary internationally. Here we aimed to identify factors associated with mortality and hospitalization events in England using an incident cohort of 5864 hemodialysis patients from years 2002 to 2006 inclusive in the UK Renal Registry linked to hospitalization data. Higher admission rates were seen after the 2-day gap irrespective of whether thrice-weekly dialysis sequence commenced on a Monday or Tuesday (2.

Management of diabetic nephropathy in older patients: a need for flexible guidelines.

As the population ages and diabetes mellitus increases in prevalence, the incidence of diabetic nephropathy (DN) is becoming a disease of older people (aged ≥ 75 years). As the epidemiology of diabetes mellitus and DN shifts toward this patient population, the pathogenesis of DN in old age is changing: the pathologic findings suggest ischemia and hypertension, and the classic Kimmelstiel-Wilson lesions may be absent. The demographic shift in the epidemiology and the associated changes in pathology because of aging and atherosclerosis will have a significant impact on various aspects related to the disease in old age.

Estimated albumin excretion rate versus urine albumin-creatinine ratio for the estimation of measured albumin excretion rate: derivation and validation of an estimated albumin excretion rate equation.

Background: Glomerular filtration rate estimation equations use demographic variables to account for predicted differences in creatinine generation rate. In contrast, assessment of albuminuria from urine albumin-creatinine ratio (ACR) does not account for these demographic variables, potentially distorting albuminuria prevalence estimates and clinical decision making.

Study Design: Polynomial regression was used to derive an age-, sex-, and race-based equation for estimation of urine creatinine excretion rate, suitable for use in automated estimated albumin excretion rate (eAER) reporting.

Variation in centre-specific survival in patients starting renal replacement therapy in England is explained by enhanced comorbidity information from hospitalization data.

Background: Unadjusted survival on renal replacement therapy (RRT) varies widely from centre to centre in England. Until now, missing data on case mix have made it impossible to determine whether this variation reflects genuine differences in the quality of care. Data linkage has the capacity to reduce missing data.

Natural history and predictors of faster glomerular filtration rate decline in a referred population of older patients with type 2 diabetes mellitus.

Aim: To study the natural history and predictors of faster glomerular filtration rate (GFR) decline in a referred population of older patients (aged ≥ 65 years) with type 2 diabetes mellitus.

Methods: A retrospective medical record analysis in an outpatient diabetes clinic for older patients. Baseline characteristics and blood pressure readings for each clinic visit were recorded.

Transplantation in the obese: separating myth from reality.

The prevalence of obesity among patients requiring renal replacement therapy continues to increase inexorably. While observational data have suggested that obesity may be associated with better outcomes among patients on dialysis, many centres have been reluctant to transplant obese patients because of concerns over adverse outcomes in the short and long term. In this review, we evaluate data about the safety of weight loss on dialysis and critically review the impact of pre-transplant body mass index and sarcopenia on post-transplant outcomes.

Chapter 13 The linkage of incident renal replacement therapy patients in England (2002-2006) to hospital episodes and national mortality data: improved demography and hospitalisation data in patients undergoing renal replacement therapy.

Introduction: Missing data has hampered the comprehensive and inclusive reporting of adjusted outcomes for patients on renal replacement therapy (RRT) captured by the UK Renal Registry (UKRR). Furthermore the information collected by the UKRR does not currently include morbidity after starting RRT, details on hospital admission rates or location of death. Linking datasets offers the opportunity to enhance existing data and describe new measures of centre performance.

Urinary matrix metalloproteinase activity in diabetic kidney disease: a potential marker of disease progression.

Background: Progressive kidney fibrosis, associated with chronic kidney disease (CKD), results from an imbalance in extracellular matrix (ECM) homeostasis. Reduced matrix metalloproteinases (MMP) activity causing lower clearance of ECM proteins has been implicated mainly through an overproduction of tissue inhibitors of metalloproteinases (TIMP), but also by reduced MMP synthesis. We tested the hypothesis that MMP activity can be measured in human urine and can be used as a potential biomarker of the progression of diabetic kidney disease (DKD).

Changes in matrix metalloproteinases and their inhibitors in kidney transplant recipients.

Objectives: Chronic allograft nephropathy remains one of the main causes of late graft loss after kidney transplant owing to multifactorial development of kidney scarring. Chronic allograft nephropathy is characterised by an excess accumulation of extracellular matrix. A key system regulating extracellular matrix homeostasis are matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases.

Do albuminuria and hs-CRP add to the International Diabetes Federation definition of the metabolic syndrome in predicting outcome?

Background: To investigate the added value of elevated urinary albumin excretion (UAE) and high high-sensitive C-reactive protein (hs-CRP) in predicting new-onset type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD) and chronic kidney disease (CKD) in addition to the present metabolic syndrome (MetS) defining criteria.

Methods: The PREVEND Study is a prospective population-based cohort study in the Netherlands, including 8592 participants. The MetS was defined according to the 2004 International Diabetes Federation criteria, elevated UAE as albuminuria ≥ 30 mg/24 h and high hs-CRP as ≥ 3 mg/L.

Stopping renin-angiotensin system inhibitors in chronic kidney disease: predictors of response.

Background/aims: Renin-angiotensin system (RAS) inhibitors are considered first-line agents for hypertensive patients with progressive chronic kidney disease (CKD). In a previous study, we showed that stopping RAS inhibitors increased estimated glomerular filtration rate (eGFR) in a significant number of advanced CKD patients. The present study tries to address who would benefit and whether this benefit is predictable.

A study of the natural history of diabetic kidney disease (DKD).

Background: In view of the alarming increase in the number of people with diabetes mellitus (DM), a rising number of patients with diabetic kidney disease (DKD), end-stage renal disease (ESRD) and cardiovascular disease (CVD) is forecasted. It is therefore imperative to re-visit the natural history of DKD and to identify potential risk factors, which may enhance the progression of the disease and its complications.

Methods: The medical records of 270 Type 2 diabetic chronic kidney disease patients followed up at the Sheffield Kidney Institute between 2000 and 2008 were reviewed.