• Albuminuria (AER ≥30 mg/24 h; ACR ≥30 mg/g [≥3 mg/mmol])
• Urinary sediment abnormality
• Electrolyte and other abnormalities due to tubular disorders
• Abnormalities detected by histology
• Structural abnormalities detected by imaging
• History of kidney transplantation
• GFR <60 mL/min/1.73 m2
1.3 Staging
The KDIGO 2012 Clinical Practice Guideline suggested that CKD could be classified according to cause, GFR category, and albuminuria category (CGA) [3].
Assign causes based on observed or presumed pathological–anatomical findings within the kidney and presence or absence of systemic disease.
GFR categories in CKD
GFR category | GFR (mL/min/1.73 m2) | Terms |
|---|---|---|
G1 | ≥90 | Normal/high |
G2 | 60–89 | Mildly decreased (relative to young adult level) |
G3a | 45–59 | Mildly to moderately decreased |
G3b | 30–44 | Moderately to severely decreased |
G4 | 15–29 | Severely decreased |
G5 | <15 | Kidney failure |
Albuminuria categories in CKD
Category | AER (mg/24 h) | ACR | Terms | |
|---|---|---|---|---|
(mg/mmol) | (mg/g) | |||
A1 | <30 | <3 | <30 | Normal to mildly increased |
A2 | 30–300 | 3–30 | 30–300 | Moderately increased (relative to young adult level) |
A3 | >300 | >30 | >300 | Severely increased (including nephrotic syndrome) |
Categories of proteinuria in CKD
Category | PER (mg/24 h) | PCR | Protein reagent strip | |
|---|---|---|---|---|
(mg/mmol) | (mg/g) | |||
A1 | <150 | <15 | <150 | Negative to trace |
A2 | 150–500 | 15–50 | 150–500 | Trace to positive |
A3 | >500 | >50 | >500 | Positive or greater |
1.4 Causes and Risk Factors
Risk factors for CKD
Clinical factors | • Diabetes • Hypertension • Autoimmune disease • Systemic infection • Urinary tract infection • Urinary stones • Lower urinary tract obstruction • Urolithiasis • Family history of CKD • Recovery from acute kidney injury • Kidney mass reduction • Exposure to certain drugs • Low birth weight |
Sociodemographic factors | • Older age • Race • Exposure to certain chemical and environmental conditions • Low income/education |
In China, the current leading causes of CKD are glomerular disease, diabetic kidney disease, and hypertension. IgA nephropathy is one of the most common glomerular diseases.
These differences among countries are primarily related to disease burden shifting from infections toward chronic lifestyle-related diseases, increased life expectancy, and decreased birth rates in industrialized countries. In contrast, infectious diseases continue to be prevalent in less developed countries secondary to poor sanitation, lack of safe water, and high concentrations of disease-transmitting vectors. Furthermore, environmental pollution, pesticides, analgesic abuse, herbal medications, and use of unregulated food additives contribute to the burden of CKD in underdeveloped countries.
Rapid urbanization and globalization have accelerated the transition and led to an overlap in disease burden in Latin American and South Asian countries, with continued high prevalence of infectious diseases and increasing prevalence and severity of lifestyle-related diseases, such as diabetes, hypertension, and obesity.
1.5 Prevalence
Approximately 10% of the population is affected by CKD worldwide, with millions annually dying because of lack of access to affordable treatment [1]. In China, the adjusted prevalence rate of estimated GFR (eGFR) <60 mL/min/1.73 m2 and albuminuria is 1.7% and 9.4%, respectively. The overall prevalence rate of CKD is approximately 10.8%; therefore, 119.5 million patients are estimated to have CKD in China [4].
CKD can affect individuals of any race. In particular, African American, American Indians, Hispanics, and individuals of South Asian origin (Bangladesh, India, Sri Lanka, or Pakistan) have a high risk of CKD. The prevalence of CKD is high in the northern (16.9%) and southwest (18.3%) regions of China compared with that in other regions. In rural areas of China, the prevalence of albuminuria positively correlates with the level of local economic development.
Although CKD can occur at any age, it becomes more common with increasing age and in the female gender. It has been known for decades that eGFR declines in parallel with age. The mean age of 9614 patients presenting with stage 3 CKD in India and 1185 patients in China is 51.0 and 63.6 years, respectively. It is estimated that one in five males and one in four females among individuals aged 65–74 years worldwide have CKD. The prevalence rate of CKD in the Chinese females population increases from 7.4% among those aged 18–39 years to 18.0% and 24.2% among those aged 60–69 and 70 years, respectively. Relative increases in the prevalence of CKD with age are equally striking in the USA, Canadian, and European populations despite between-country differences in the absolute prevalence. Moreover, it is estimated that the number of CKD cases will disproportionately increase in China, where the elderly population is growing. This effect will be further magnified if the trends of increasing prevalence of diabetes and hypertension persist, competing cardiovascular diseases- and stroke-caused deaths are reduced and access to treatment improves.
When CKD finally progresses to kidney failure, renal replacement therapy becomes essential for patients’ survival. However, the current treatment situation is appalling. Over two million patients worldwide presently undergo dialysis or transplantation, yet this number may only represent 10% of those who actually require treatment to live. The majority of these patients receiving therapy for kidney failure reside in only five countries, namely the USA, Japan, Germany, Brazil, and Italy, which represent only 12% of the global population. More than 80% of all patients receiving therapy for kidney failure are from affluent countries, with the remaining 20% being treated in approximately 100 developing countries, which constitute over 50% of the global population. The point prevalence of patients with kidney failure on maintenance dialysis (including hemodialysis and peritoneal dialysis) in 2008 was estimated to be 71.9 per million population in mainland China, with an annual increase in the prevalence rate of 52.9%, and reached 2584, 1106, and 1870 per million population in 2010 in Taiwan, Hong Kong, and the USA, respectively. Approximately 90% of patients with kidney failure on dialysis in China underwent hemodialysis at the end of 2012, meaning that 270,000 patients underwent hemodialysis compared with just 30,000 patients on peritoneal dialysis [1, 4, 5–7].
CKD resulted in 956,000 deaths in 2013. According to the 2010 Global Burden of Disease Study, the rank of CKD in the list of causes of total number of deaths worldwide rose from 27th in 1990 to 18th in 2010, with such movement of ranking up the list being second only to that for human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS). The overall increase in years of life lost due to premature mortality caused by CKD is 82%, being only behind HIV infection and AIDS (396%) and diabetes mellitus (93%). The raw annual mortality in patients on maintenance hemodialysis in Beijing, China, was 76.8 per 1000 patient-years in 2010, which was relatively low compared with 236.3 per 1000 patient-years in 2009 in the USA. The three leading causes of death in patients on hemodialysis in China are cardiovascular disease (31.0%), stroke (20.3%), and infection (19.9%).
Despite the high prevalence, screening individuals without risk factors or symptoms for CKD is not recommended. Current recommendations suggest screening those with structural diseases of the renal tract, hypertension, cardiovascular disease, diabetes, autoimmune diseases with potential for kidney involvement, family history of kidney disease, marked obesity, and age >60 years during routine primary health encounters. Despite screening for CKD in individuals with diabetes is cost-effective, it remains unclear whether screening for CKD in the general population is cost-effective.
1.6 Costs
The cost of treatment for this dramatically growing epidemic represents an enormous burden on healthcare systems worldwide. Patients with kidney failure require dialysis or transplantation, which are exceedingly costly and consume a sizeable portion of the health budget.
In low- and middle-income countries, treatment with dialysis or transplantation imposes a huge financial burden upon most patients who require it. In another 112 countries, long-term dialysis is unaffordable for many patients, resulting in death due to untreated kidney failure in over one million individuals.
CKD was defined as a major chronic disease by the Chinese government and enrolled in three basic medical insurance systems in China. The economy will lose US$558 billion over the next decade owing to effects on death and disability attributable to heart and kidney diseases [7, 8].
An extreme example is in Uruguay, the annual cost of dialysis is close to 30% of the National Resources Fund’s budget for specialized therapies.
The high cost of long-term dialysis for an increasing number of patients is also a problem even in high-income countries. Kidney failure is a major cost driver among patients and their families as well as taxpayers.
In the USA, the treatment for CKD is likely to exceed $48 billion per year. Less than 1% of the covered population consumes 6.7% of the total Medicare budget for treatment for kidney failure.
CKD costs more than breast, lung, colon, and skin cancers combined in England, recently reported by NHS Kidney Care.
Treatment for all current and new cases of kidney failure up to 2020 will cost about $12 billion in Australia.
1.7 Diagnosis
The diagnosis of CKD includes the evaluation of chronicity, causes, GFR, albuminuria, and progression [6].
1.7.1 Evaluation of Chronicity
For individuals with kidney damage or GFR <60 mL/min/1.73 m2 (Table 1.1), reviewing their history and past measurements is necessary to determine the course of kidney disease.
CKD is confirmed if the course exceeds 3 months; otherwise, not confirmed. Tests should be accordingly repeated to differentiate CKD, acute kidney disease, or both.
1.7.2 Evaluation of Causes
Review family and personal history, environmental and social factors, and medications, and perform physical examination, lab and imaging measurements to determine the causes of CKD and establish a pathological diagnosis.
1.7.3 Evaluation of GFR
It is recommended to use serum creatinine (SCr)-based GFR-estimating equation for initial assessment.
Sources of error in GFR estimation using creatinine
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