History and exam

Your Organisational Guidance

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Chronisch nierlijden (multidisciplinaire aanpak)Published by: WORELLast published: 2017GPC pluridisciplinaire sur la néphropathie chronique (IRC)Published by: Groupe de travail Développement de recommandations de première ligneLast published: 2017

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 chronic kidney disease (CKD) are often vague and commonly include fatigue, which may be due to uraemia or anaemia.[49][50]

Anaemia of CKD occurs due to reduced erythropoietin production by the kidney, usually once the glomerular filtration rate declines to <50 mL/minute/1.73 m².[2]

There can be other deficiency anaemias (e.g., iron) that manifest during the assessment of CKD.

oedema

Peri-orbital and peripheral oedema develop as a result of salt and water retention as the glomerular filtration rate declines, and may be exacerbated by hypoalbuminaemia.[2]

In patients with fluid overload/congestion, leg oedema is usually bilateral and pitting.

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.[49][67]

Most common in patients with advanced chronic kidney disease (CKD) and end-stage kidney disease, uraemic pruritus occurs in about 40% to 50% of adults with CKD undergoing dialysis.​[68][69]

skin and nail changes

Xerosis (abnormal dryness of the skin), acquired ichthyosis (dry, scaly skin), changes to skin pigmentation, and nail changes ('half-and-half nails') may occur, especially in patients with advanced chronic kidney disease.[67][70]​​​

Xerosis, caused by atrophy of sweat glands and sebaceous glands, is commonly seen in end-stage kidney disease. Hyperpigmentation may be attributed to melanin deposition. Sallow or yellow skin may be due to urochrome deposition.

restless legs

A symptom of uraemia.[49] Present in all stages of chronic kidney disease.[71]

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.[63]

A kidney biopsy is critical in these cases to determine the correct diagnosis.[58]

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- or tea-coloured urine

Indicative of haematuria.

rashes

Ecchymosis and purpura are signs of haematological consequences of chronic kidney disease.

The patient may have a concomitant autoimmune disorder: for example, systemic lupus erythematosus and malar [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.[52]

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 20% to 40% of people with diabetes will develop chronic kidney disease (CKD), as defined by albuminuria and/or a reduction in the glomerular filtration rate, within the 15-year period following the diagnosis of diabetes.[15][16]

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.[16]

Glycaemic control directly correlates with the development of diabetic kidney disease and the rapidity of progression to end-stage kidney disease.[15]

See Diabetic kidney disease.

hypertension

Hypertension is the second most common cause of chronic kidney disease (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 kidney disease.[17]

age >50 years

Older age is a key predictor of chronic kidney disease (CKD).

In the US, prevalence of CKD is 38.4% in people aged 70 years and over, 18.5% in those aged 60-69 years, 10.9% in those aged 40-59 years, and 6.1% in those aged 18-39 years (2017-2020 data). CDC Kidney Disease Surveillance System: tracking and preventing kidney disease in America Opens in new window

Healthy ageing is associated with structural changes in the kidney and a decrease in glomerular filtration rate (GFR).[26]

Increasing age is associated with an increased likelihood of comorbid conditions that are risk factors for CKD, such as diabetes, hypertension, and cardiovascular disease.[27]

childhood kidney disease

A history of childhood kidney disease is a risk factor for adult chronic kidney disease and end-stage kidney disease.

Children with a history of congenital anomalies, glomerular disease, or pyelonephritis with normal kidney function and blood pressure have a four-fold increased risk for end-stage kidney disease as compared with children who do not have kidney disease.[28]

weak

smoking

Smoking has been associated with the development and progression of chronic kidney disease, probably because of accelerated atherosclerosis and vascular disease, as well as exacerbating underlying hypertension.[29][30]

obesity

Obesity is associated with the development of chronic kidney disease (CKD) and the progression to end-stage kidney disease, irrespective of blood pressure control and glycaemic control, in high-risk populations.[31][32]

Obesity 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.[32]

Obesity is also an independent risk factor for microalbuminuria and CKD, possibly due to endothelial dysfunction and tubulo-interstitial fibrosis, although the precise mechanism is unclear.[32][33]

non-Hispanic black ethnicity

Black people are at higher risk than white people.[34][35]

Chronic kidney disease (CKD) is associated with significant disparities with respect to race and socioeconomic status.[10][11]​​ In the US, prevalence of CKD is higher in non-Hispanic black adults (20%) than other ethnic groups (non-Hispanic Asian adults 14%; Hispanic adults 14%; and non-Hispanic white adults 12%).[8]

Higher incidence of diseases such as diabetes and hypertension in non-Hispanic black people may contribute to increased risk. Additionally, in people of African ethnic origin, genetic factors such as apolipoprotein L1 (APOL1) risk variants increase the risk for non-diabetic kidney disease.​[21][36]

family history of CKD

People with a close family member with the disease are at a higher risk themselves of developing chronic kidney disease (CKD).[18][19]

Monogenic disorders may account for up to 30% of non-diabetic CKD in adults and up to 50% in children.[20]​ The most common monogenic disorder is autosomal dominant polycystic kidney disease (caused by genetic variants in PKD1 and PKD2 genes).[21] Genes associated with complex kidney diseases (where risk of disease depends on both genotype and environment) have been described, such as the apolipoprotein L1 (APOL1) gene. People of African ethnic origin are more likely to have an APOL1 risk variant than people of other ethnic origins.[21]

autoimmune disorders

Autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis, and Sjogren syndrome may cause glomerular or tubulo-interstitial chronic kidney disease.[37][38]

Drugs used to treat these conditions (e.g., the long-term use of non-steroidal anti-inflammatory drugs [NSAIDs]) may cause kidney disease or contribute to its progression.[39][40][41]​​​​​

male sex

Chronic kidney disease is generally more prevalent in women; men, however, are at greater risk for disease progression.​[3][42]​​​[43]

The mechanism of kidney 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.[43]

long-term use of non-steroidal anti-inflammatory drugs (NSAIDs)

Long-term use of NSAIDs for rheumatological disorders and pain control has been associated with the development of chronic kidney disease.[39][40][41]​​​

NSAIDs have been described as causing analgesic nephropathy.

high uric acid levels

There is an expected increase in uric acid levels with advancing chronic kidney disease (CKD). Literature also discusses uric acid as a contributory factor to CKD worsening.[44][45][46]

However, uric acid-lowering therapy is not recommended in people with CKD and asymptomatic hyperuricaemia to delay CKD progression.[1]

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