This review was built on a broad and intensive search of published papers, including some related clinical practice guidelines, clinical trials, and meta-analyses. This search was supplemented with a systematic MEDLINE search for publications on the subject with the key words: “chronic kidney disease”; “CKD”, “chronic kidney failure”; “CKF”, “end-stage renal disease”; “ESRD”, “early detection”, “prevention”, “management”, “risk factors”, “pathophysiology”, up to September, 2004. Only papers
SeminarChronic kidney disease: the global challenge
Section snippets
Epidemiology
The worldwide rise in the number of patients with CKD is reflected in the increasing number of people with ESRD treated by renal replacement therapy—dialysis or transplantation.2 In the UK, the annual incidence of ESRD has doubled over the past decade to reach about 100 new patients per million of population,3 well below the European average (about 135 per million) and rates in the USA4 (table 1). The UK trend, like trends in other more developed countries, is expected to continue to rise at an
Risk factors and CKD
Much epidemiological and clinical evidence has shown a link between several factors and the initiation and the progression of CKD. These can be classified into two distinct categories: those proven to be causal (risk factors) and those that are associated with CKD in the absence of established causal relations (risk markers).
Glomerulosclerosis
Progressive glomerulosclerosis has many similarities to atherosclerosis.52 They share risk factors, notably hypertension, dyslipidaemia, and smoking. They are both characterised by endothelial damage and dysfunction, proliferation of smooth-muscle or mesangial cells, and injury to the pericyte or podocyte (figure 1). As with atherosclerosis, hypertension-induced shear stress leads to injury, activation, and dysfunction of the glomerular endothelium, which in turn initiates glomerular
Role of stem cells in renal remodelling
Renal remodelling (repair/healing or scarring) might depend on influx into the injured kidneys of haemopoietic stem cells with the potential for repair or scarring. The detection of cells showing embryonic mesenchymal characteristics in glomeruli has led to the hypothesis that haemopoietic stem cells are involved in normal turnover of glomerular cells as well as in the response of glomeruli to injury. Experiments based on bone-marrow transplantation have shown that bone-marrow-derived cells are
Mediators of renal scarring
Interactions between cells during renal remodelling rely on the release of chemokines, cytokines, and growth factors.58 Autacoids such as angiotensin II and endothelin have also been implicated in renal scarring. Among growth factors, TGF β1 is thought to be the most fibrogenic, directly or indirectly through the action of connective-tissue growth factor.64 By contrast, hepatocyte growth factor, vascular endothelial growth factor, and osteogenic protein 1 seem to have beneficial or protective
Primary prevention: lifestyle modification
Primary prevention will rely on controlling the global epidemic of obesity and associated type 2 diabetes as well as hypertension. Lifestyle modifications, such as weight reduction, exercise, and dietary manipulations can be effective, as shown in clinical trials in which the incidence of type 2 diabetes in overweight individuals with impaired glucose tolerance was substantially lowered by these means.69, 70 Approaches to control hypertension by means of dietary salt restrictions and diets rich
Recommendations and strategies
Detection and prevention research programmes are essential. Early detection of CKD and subsequent management has met many, but not all, the criteria of an ideal screening programme.92, 93 The stages of CKD are reasonably well defined (panel 1), but the natural history of the early phases is variable and unpredictable. Screening tests for the measurement of serum creatinine, urinary albumin, and urinary protein are subject to sex-related and racial variability94 but are generally sensitive when
Search strategy and selection criteria
References (105)
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ESRD in Australia and New Zealand at the end of the millennium: a report from the ANZDATA registry
Am J Kidney Dis
(2002) - et al.
Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey
Am J Kidney Dis
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Validation of the modification of diet in renal disease formula for estimating GFR with special emphasis on calibration of the serum creatinine assay
Am J Kidney Dis
(2004) - et al.
Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate
Am J Kidney Dis
(2002) - et al.
Should the K/DOQI definition of chronic kidney disease be changed?
Am J Kidney Dis
(2003) - et al.
Early detection of kidney disease in community settings: the Kidney Early Evaluation Program (KEEP)
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Kidney disease in the first-degree relatives of African-Americans with hypertensive end-stage renal disease
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Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury
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Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64)
Kidney Int
(2003) - et al.
Reappraisal of the pathogenesis and consequences of hyperuricaemia in hypertension, cardiovascular disease, and renal disease
Am J Kidney Dis
(1999)
Obesity-related glomerulopathy: an emerging epidemic
Kidney Int
Obesity-associated focal segmental glomerulosclerosis: pathological features of the lesion and relationship with cardiomegaly and hyperlipidemia
Am J Kidney Dis
Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephropathy
Am J Kidney Dis
Smoking as a risk factor for end-stage renal failure in men with primary renal disease
Kidney Int
Recreational drug use: a neglected risk factor for end-stage renal disease
Am J Kidney Dis
Plasticity of kidney cells: role in kidney remodelling and scarring
Kidney Int
Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease
Kidney Int
Cell cycle regulatory proteins in glomerular disease
Kidney Int
Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial
Lancet
Preserving renal function in adults with hypertension and diabetes: a consensus approach
Am J Kidney Dis
Effects of lipid reduction on the progression of renal disease: a meta-analysis
Kidney Int
Preventing end-stage renal disease: the potential impact of screening and intervention in developing countries
Kidney Int
Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency
Kidney Int
Proteinuria, albuminuria, risk assessment, detection, elimination (PARADE): a position paper of National Kidney Foundation
Am J Kidney Dis
Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification
Am J Kidney Dis
Maintenance dialysis population dynamics: current trends and long-term implications
J Am Soc Nephrol
UK Renal Registry. The Sixth annual report
Annual data report: incidence and prevalence of ESRD (2003)
Am J Kidney Dis
Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections
Diabetes Care
Healthcare systems and end-stage renal disease: an international review—costs and reimbursement of ESRD therapies
N Engl J Med
Estimating the prevalence of low glomerular filtration rate requires attention to the creatinine assay calibration
J Am Soc Nephrol
Prevalence of kidney damage in Australian adults: the AusDiab Kidney Study
J Am Soc Nephrol
The Okinawa Screening Program
J Am Soc Nephrol
Microalbuminuria is common, also in a non-diabetic, non-hypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity
J Intern Med
Diabetes and renal failure in Indo-Asians in the UK: a paradigm for the study of disease susceptibility
Nephrol Dial Transplant
End-stage renal disease in African-Americans and white men: 16-year MRFIT findings
JAMA
Cholesterol and risk of renal dysfunction in apparently healthy men
J Am Soc Nephrol
Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland
J Am Soc Nephrol
Urinary albumin excretion predicts cardiovascular and non-cardiovascular mortality in general population
Circulation
Kidney disease as a risk factor for development of cardiovascular disease (AHA Scientific Statement)
Circulation
Chronic kidney disease and the risks of death, cardiovascular events, and hospitalisation
N Engl J Med
World Health Report 2003: shaping the future
Age and gender-related incidence of chronic renal failure in a French urban area: a prospective epidemiologic study
Nephrol Dial Transplant
Factors affecting progression in advanced chronic renal failure
Clin Nephrol
Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States
J Am Soc Nephrol
The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal failure
N Engl J Med
Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition; a patient level metaanalysis
Ann Intern Med
Proteinuria and the risk of developing end stage renal disease
Kidney Int
Pathophysiology of progressive nephropathies
N Engl J Med
Effect of intensive therapy on the development and progression of diabetic nephropathy in the DCCT
Kidney Int
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