History and exam

Key diagnostic factors

common

presence of risk factors

Risk factors include age >50 years, male sex, black or Hispanic ethnicity, family history, smoking, obesity, long-term analgesic use, diabetes, hypertension, and autoimmune disorders.

fatigue

Signs and symptoms of CKD are often vague and commonly include fatigue, which may be due to uraemia or anaemia.[44] Anaemia is associated with CKD due to the lack of erythropoietin produced by the kidney, usually once the glomerular filtration rate declines to <50 mL/minute/1.73 m².[3] There can also be other deficiency anaemias (e.g., iron) that manifest during the assessment of CKD.

oedema

Periorbital and peripheral oedema develop as a result of salt and water retention as the glomerular filtration rate declines, and may be exacerbated by hypoalbuminaemia.[3]

nausea with/without vomiting

Thought to be due to an accumulation of toxic waste products in the circulation, such as urea that is not excreted by the kidney. As kidney failure progresses to the more advanced stages of uraemia, patients may report vomiting. They may also report a metallic taste in the mouth further worsening the nausea.

pruritus

Thought to be due to an accumulation of toxic waste products in the circulation and under the skin, such as urea that is not excreted by the kidney.[44]

restless legs

A symptom of uraemia.[44] Present in all stages of CKD.[54]

anorexia

Thought to be due to an accumulation of toxic waste products in the circulation, such as urea that is not excreted by the kidney.

uncommon

infection-related glomerular disease

Infections such as hepatitis B and C, syphilis, and streptococcal pharyngitis are associated with glomerular disorders.

A kidney biopsy is critical in these cases to determine the correct diagnosis.[2]

Other diagnostic factors

common

arthralgia

If the patient has concomitant autoimmune disorder.

enlarged prostate gland

Prostate examination in men should be performed to exclude obstructive uropathy.

uncommon

foamy-appearing urine

Indicative of proteinuria.

cola-coloured urine

Indicative of haematuria.

rashes

Ecchymosis and purpura are signs of haematological consequences of CKD.

The patient may have a concomitant autoimmune disorder: for example, systemic lupus erythematosus and butterfly rash.

dyspnoea

Associated with pulmonary oedema due to reduced urine output in worsening disease.

orthopnoea

Associated with pulmonary oedema due to reduced urine output in worsening disease.

seizures

Occurs in advanced-stage disease.[46]

Thought to be due to an increase in neurotoxins that are not excreted by the kidney.

retinopathy

Fundoscopy is a key examination in determining the presence of diabetic or hypertensive retinopathy, as evidence of microvascular damage, which occurs in uncontrolled diabetes/hypertension. Diabetic and hypertensive patients should be screened for such changes.

Risk factors

strong

diabetes mellitus

This is the most common cause.[6]

It is estimated that approximately 20% to 40% of people with diabetes will have CKD, as documented by albuminuria and/or a reduction in the glomerular filtration rate, within 15 years of diagnosis.[12][13] CKD rarely develops in patients with type 1 diabetes before 10 years following diagnosis, whereas CKD is present at time of diagnosis in around 3% of patients with type 2 diabetes.[13]

Glycaemic control directly correlates with the development of diabetic kidney disease and the rapidity of progression to end-stage renal disease.[12]

Hyperglycaemia results in formation of advanced glycated end products.[20] This leads to mesangial oxidative stress, which results in matrix expansion and increased vascular permeability, which in turn attracts inflammatory mediators.[21] These promote collagen production, leading to glomerular sclerosis.

hypertension

This is the second most common cause of CKD.[6]

Hypertension is also a consequence of CKD (including from other causes such as diabetic kidney disease, and glomerular nephrotic and nephritic syndrome), and contributes to its progression to end-stage renal disease.[14]

Hypertension is thought to affect both the vasculature and tubulo-interstitial components of the kidney, resulting in ischaemic damage from arterial narrowing. The end result is loss of nephron mass, and atrophy and fibrosis of the tubules and interstitium.

age >50 years

Older age is a key predictor of CKD. Healthy ageing is associated with structural changes in the kidney and a decrease in glomerular filtration rate (GFR).[22] Typically the GFR declines by 0.75 mL/minute/1.73 m² per year in healthy ageing, but urine albumin excretion does not change, thus, the increase in the prevalence of criteria-defined CKD in healthy older adults is due more to a GFR decline than to increasing albuminuria and has a much lower risk of progression to end-stage renal disease.[22] However, increasing age is associated with an increased likelihood of comorbid conditions that are risk factors for CKD, such as diabetes, hypertension, and cardiovascular disease.[23]

childhood kidney disease

A history of childhood kidney disease is a risk factor for adult CKD and end-stage renal disease (ESRD). Children with a medical history of congenital anomalies, glomerular disease, or pyelonephritis with normal kidney function and blood pressure have a four-fold increased risk for ESRD as compared to children without kidney disease.[24]

weak

smoking

Smoking has been associated as a risk factor for the development and progression of the disease, probably because of accelerated atherosclerosis and vascular disease, as well as exacerbating underlying hypertension.[25][26]

obesity

Obesity is an associated risk factor.[27] It may contribute to the development of diabetes, exacerbate poor control of hypertension, contribute to renal ischaemia and hypertension with associated sleep apnoea, and cause glomerular strain with hypertrophy and glomerulosclerosis.[28]

black or Hispanic ethnicity

Black or Hispanic people are at higher risk than white people.[29][30] The mechanism is not known, but is thought to be due in part to a higher incidence of diseases such as diabetes and hypertension in these populations. Additionally, in black and Hispanic populations, genetic factors such as apolipoprotein L1 risk variants increase the risk for non-diabetic kidney disease.[31]

family history of CKD

People with a close family member with the disease are at a higher risk themselves of developing CKD.[9][15] The mechanism is thought to be due in part to genetic susceptibility to certain disease states, such as diabetes, hypertension, polycystic kidney disease, Alport syndrome, and possibly glomerular syndromes, such as IgA nephropathy and focal segmental glomerulosclerosis.

autoimmune disorders

Autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and Sjogren syndrome may cause glomerular or tubulo-interstitial CKD.[32][33]

male sex

Men are at a higher risk of CKD progression than women.[34]

The mechanism of renal injury is not known but is thought to be related to differences in sex hormones and the differential effect of sex on lifestyle and traditional risk factors.[34]

long-term use of non-steroidal anti-inflammatory drugs

Long-term use of anti-inflammatory analgesics for rheumatological disorders and pain control have been associated with the development of CKD.[35][36] Non-steroidal anti-inflammatory drugs, and previously phenacetin, have been described as causing analgesic nephropathy.

high uric acid levels

There is an expected increase in uric acid levels with advancing CKD. Literature also discusses uric acid as a contributory factor to CKD worsening.[37][38][39] However, trials of urate-lowering treatment did not result in clinically meaningful benefits to kidney outcomes.[40][41]

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