More than 50 years ago, nephrology emerged as a medical subspecialty dealing with the effects of severely impaired kidney function on body homoeostasis. At that time, the understanding of renal physiology and the complex and diverse involvement of kidney function on various body functions was ahead of its clinical application. Few options to treat renal disorders of mineral and electrolyte handling existed, hormonal deficiencies resulting from kidney disease could not be corrected, and almost no techniques were available to prolong the life of individuals with kidney failure.
Nephrology progressed gradually with the establishment of renal pathology and a better understanding of disease entities, but the first major change occurred when dialysis and transplantation became widely available in the 1960s. The ability to provide life-sustaining renal replacement therapy was an outstanding achievement in medicine. Unsurprisingly, nephrologists have since strived to optimise renal replacement therapy and the prevention and treatment of comorbidities in patients with renal failure. However, the costs associated with these achievements are high. In countries that can afford to offer renal replacement therapy to all patients with renal failure, the proportion of health-care expenditure for this group of patients is far out of proportion to its size.1, 2 In most countries, economic constrains allow only restricted access to this expensive chronic treatment, which creates striking social inequalities and pressure on constrained health-care resources.3
By contrast with the importance and obvious relevance of chronic kidney failure requiring replacement therapy, the effect of less severe chronic kidney disease, which affects far more patients, had for a long time been largely ignored by the medical community, policy makers, and the public. Reduced kidney function was thought to be of little importance until the glomerular filtration rate reached less than 15%. This viewpoint resulted in two sets of terms to distinguish between patients with so-called end-stage renal disease and others with a lesser degree of renal impairment, who were often collectively summarised as pre-end-stage renal disease or pre-dialysis patients. Moreover, numerous vague and poorly defined terms were commonly used (eg, renal insufficiency or pre-uraemia) in parallel to nomenclature describing the cause of kidney disease (eg, glomerulonephritis, polycystic kidney disease, or diabetic nephropathy). However a uniform and unequivocal definition of chronic kidney disease was unavailable.
Key messages
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Chronic kidney disease is chiefly defined by a reduction in glomerular filtration rate and increased urinary albumin excretion
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Chronic kidney disease affects more than 10% of the population in many countries worldwide
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Causes of chronic kidney disease are complex and include common diseases such as hypertension, metabolic syndrome, and diabetes, and various less common diseases that mainly affect the kidney
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Chronic kidney disease predisposes to acute kidney injury and vice versa
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Even mild forms of kidney disease are associated with various adverse effects on body functions and an increased risk of mortality and cardiovascular morbidity
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Genetic causes of specific forms of kidney disease and susceptibility to development of kidney disease in the context of other disorders are increasingly recognised
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A multilevel interdisciplinary approach will be needed to address the public health burden of kidney disease
Only in 2002 did the medical community first agree on a uniform definition and staging system for chronic kidney disease, based on measures of kidney function and independent of the cause of impaired kidney function.4, 5 Application of this uniform concept to large databases showed that chronic kidney disease is far more frequent than was appreciated previously.6 More than 10% of people have chronic kidney disease and the overall prevalence at least equals that of diabetes.7 As with many other chronic diseases, the prevalence of chronic kidney disease increases with age, exceeding 20% in individuals older than 60 years and 35% in those older than 70 years.8 The importance of chronic kidney disease became apparent when large analyses showed that even early-stage disease is associated with increased prevalence and severity of numerous disorders and adverse outcomes. In particular, chronic kidney disease is now recognised as a very relevant and independent cardiovascular risk factor (see paper 5 in this Series).9, 10
Similar considerations hold true for acute changes in kidney function. Acute renal failure was well known to be associated with poor prognosis, but was regarded as harmless and reversible for a long time, provided patients survived the critical condition during which it occurred. However, even small, transient changes in serum creatinine (suggesting temporary decreases in glomerular filtration rate) have been associated with significantly worsened prognosis, including a strikingly increased risk of mortality and development and progression of chronic kidney disease.11, 12 After several initiatives were undertaken, a uniform definition and staging of what is now known as acute kidney injury was developed, which could potentially further advance the specialty.13
These developments, which were not based on technical, surgical, or immunological progress, but rather on a consensus for a uniform terminology and its application with rigorous epidemiological methods, has greatly expanded the focus on kidney disease beyond nephrology. Standardised terminology has stimulated research, affected patient care, and influenced public policies. And, as for any major advancement, it has also raised new questions. The seemingly most straightforward, but most pressing, of these questions are why is kidney disease so frequent and why is it associated with such a poor prognosis? To answer these two questions, researchers might need to return to the physiology of the organ to better understand why the kidney is a frequent target of many chronic disturbances and why, conversely, disorders of kidney function affect extrarenal tissues so strikingly, in particular the cardiovascular system. Aspects of renal function generally accepted to be understood need to be revisited. Additionally, linkage of the new definitions and staging of acute and chronic kidney disease with genomic, proteomic, and metabolomic information offers new opportunities to understand underlying mechanisms of disease.
Here, we aim to review the central role of the kidney for body homoeostasis and its fate as a target organ of disease. We will also describe the current definitions and staging systems for chronic kidney disease and acute kidney injury, and advances in understanding of the genetic predisposition to kidney disease. Subsequent articles in this series will focus on the global effects, clinical consequences, and management of chronic kidney disease14 and acute kidney injury;15 the link between kidney disease and cardiovascular disease;16 the effects of maternal, neonatal, and child health on kidney health;17 and future perspectives of the specialty.18