Elsevier

The Lancet

Volume 365, Issue 9456, 22 January 2005, Pages 331-340
The Lancet

Seminar
Chronic kidney disease: the global challenge

https://doi.org/10.1016/S0140-6736(05)17789-7Get rights and content

Summary

The worldwide rise in the number of patients with chronic kidney disease (CKD) and consequent end-stage renal failure necessitating renal replacement therapy is threatening to reach epidemic proportions over the next decade, and only a small number of countries have robust economies able to meet the challenges posed. A change in global approach to CKD from treatment of end-stage renal disease (ESRD) to much more aggressive primary and secondary prevention is therefore imperative. In this Seminar, we examine the epidemiology of CKD worldwide, with emphasis on early detection and prevention, and the feasibility of methods for detection and primary prevention of CKD. We also review the risk factors and markers of progressive CKD. We explore current understanding of the mechanisms underlying renal scarring leading to ESRD to inform on current and future interventions as well as evidence relating to interventions to slow the progression of CKD. Finally, we make strategic recommendations based on future research to stem the worldwide growth of CKD. Consideration is given to health economics. A global and concerted approach to CKD must be adopted in both more and less developed countries to avoid a major catastrophe.

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

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

References (105)

  • N Kambham et al.

    Obesity-related glomerulopathy: an emerging epidemic

    Kidney Int

    (2001)
  • RR Verani

    Obesity-associated focal segmental glomerulosclerosis: pathological features of the lesion and relationship with cardiomegaly and hyperlipidemia

    Am J Kidney Dis

    (1992)
  • F Bonnet et al.

    Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephropathy

    Am J Kidney Dis

    (2001)
  • SR Orth et al.

    Smoking as a risk factor for end-stage renal failure in men with primary renal disease

    Kidney Int

    (1998)
  • TV Perneger et al.

    Recreational drug use: a neglected risk factor for end-stage renal disease

    Am J Kidney Dis

    (2001)
  • AM El Nahas

    Plasticity of kidney cells: role in kidney remodelling and scarring

    Kidney Int

    (2003)
  • Y Guan et al.

    Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease

    Kidney Int

    (2001)
  • SJ Shankland

    Cell cycle regulatory proteins in glomerular disease

    Kidney Int

    (1999)
  • L Hansson et al.

    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

    (1998)
  • GL Bakris et al.

    Preserving renal function in adults with hypertension and diabetes: a consensus approach

    Am J Kidney Dis

    (2000)
  • LF Fried et al.

    Effects of lipid reduction on the progression of renal disease: a meta-analysis

    Kidney Int

    (2001)
  • A Schieppati et al.

    Preventing end-stage renal disease: the potential impact of screening and intervention in developing countries

    Kidney Int

    (2003)
  • CY Hsu et al.

    Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency

    Kidney Int

    (2002)
  • WF Keane et al.

    Proteinuria, albuminuria, risk assessment, detection, elimination (PARADE): a position paper of National Kidney Foundation

    Am J Kidney Dis

    (1999)
  • Kidney Disease Outcome Quality Initiative

    Clinical practice guidelines for chronic kidney disease: evaluation, classification and stratification

    Am J Kidney Dis

    (2002)
  • MJ Lysaght

    Maintenance dialysis population dynamics: current trends and long-term implications

    J Am Soc Nephrol

    (2002)
  • The Renal Association

    UK Renal Registry. The Sixth annual report

  • United States Renal Data System

    Annual data report: incidence and prevalence of ESRD (2003)

    Am J Kidney Dis

    (2003)
  • H King et al.

    Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections

    Diabetes Care

    (1998)
  • AF De Vecchi et al.

    Healthcare systems and end-stage renal disease: an international review—costs and reimbursement of ESRD therapies

    N Engl J Med

    (1999)
  • CM Clase et al.

    Estimating the prevalence of low glomerular filtration rate requires attention to the creatinine assay calibration

    J Am Soc Nephrol

    (2002)
  • SJ Chadban et al.

    Prevalence of kidney damage in Australian adults: the AusDiab Kidney Study

    J Am Soc Nephrol

    (2003)
  • K Iseki

    The Okinawa Screening Program

    J Am Soc Nephrol

    (2003)
  • HL Hillege et al.

    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

    (2001)
  • K Buck et al.

    Diabetes and renal failure in Indo-Asians in the UK: a paradigm for the study of disease susceptibility

    Nephrol Dial Transplant

    (1999)
  • MJ Klag et al.

    End-stage renal disease in African-Americans and white men: 16-year MRFIT findings

    JAMA

    (1997)
  • ES Schaeffner et al.

    Cholesterol and risk of renal dysfunction in apparently healthy men

    J Am Soc Nephrol

    (2003)
  • MK Haroun et al.

    Risk factors for chronic kidney disease: a prospective study of 23,534 men and women in Washington County, Maryland

    J Am Soc Nephrol

    (2003)
  • HL Hillege et al.

    Urinary albumin excretion predicts cardiovascular and non-cardiovascular mortality in general population

    Circulation

    (2002)
  • MJ Sarnak et al.

    Kidney disease as a risk factor for development of cardiovascular disease (AHA Scientific Statement)

    Circulation

    (2003)
  • AS Go et al.

    Chronic kidney disease and the risks of death, cardiovascular events, and hospitalisation

    N Engl J Med

    (2004)
  • WHO

    World Health Report 2003: shaping the future

    (2003)
  • P Jungers et al.

    Age and gender-related incidence of chronic renal failure in a French urban area: a prospective epidemiologic study

    Nephrol Dial Transplant

    (1996)
  • T Hannedouche et al.

    Factors affecting progression in advanced chronic renal failure

    Clin Nephrol

    (1993)
  • CY Hsu et al.

    Racial differences in the progression from chronic renal insufficiency to end-stage renal disease in the United States

    J Am Soc Nephrol

    (2003)
  • S Klahr et al.

    The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal failure

    N Engl J Med

    (1994)
  • TH Jafar et al.

    Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition; a patient level metaanalysis

    Ann Intern Med

    (2003)
  • K Iseki et al.

    Proteinuria and the risk of developing end stage renal disease

    Kidney Int

    (2003)
  • G Remuzzi et al.

    Pathophysiology of progressive nephropathies

    N Engl J Med

    (1998)
  • The Diabetes Control and Complications Trial (DCCT) Research Group

    Effect of intensive therapy on the development and progression of diabetic nephropathy in the DCCT

    Kidney Int

    (1995)
  • Cited by (944)

    • CKD of Unknown Etiology: Is Taiwan Another Hotspot?

      2024, Kidney International Reports
    View all citing articles on Scopus
    View full text