potassium to acid base.) Potassium levels are tightly controlled by the kidneys.
Hypokalaemia (K <3.5mmol/L)
Patient 1 has been affected by inappropriate use or dosage of diuretics, although most are now K sparing.
Patient 2 has severe, acute diarrhoea and vomiting.
Patient 3 is an elderly patient, living alone, with a very poor diet, who also enjoys liquorice.
Some types of liquorice contain mineralocorticoid-type compounds that act on the renal tubules and retain sodium, and thus water. This can lead to hypertension and oedema, and can also increase excretion of potassium.
Patient 4 has had an ileostomy.
Patient 5 abuses laxatives due to bulimia, and also induces vomiting.
Hyperkalaemia (K >5.5mmol/L)
Patient 1 had blood taken using an over-tight and prolonged tourniquet. The blood was then syringed into a vacutainer, shaken and placed in a fridge. The raised potassium is probably a result of this poor phlebotomy technique, and represents the muscular damage at the draw site and the subsequent red cell lysis in the tube (haemolysis).
Patient 2 has had a muscular crush injury and the rise in potassium is due to cellular destruction. The patient is also likely to have raised CKmm (muscular skeletal) and may need to be monitored for a subsequent cardiac event.
Patient 3 has an acidosis, such as diabetic ketoacidosis. This leads to an increase in H+ ions, which enter the cell and displace K+ into the blood.
Patient 4 is taking potassium-sparing diuretics or KCl supplements.
Patient 5 has renal dysfunction and thus cannot excrete potassium effectively.
Patient 6 is taking ACE inhibitors, ibuprofen and an antibiotic. All of these could interfere with the urinary excretion of potassium.
Patient 7 has a mineralocorticoid deficiency, such as Addison’s disease.
For all of the above patients, additional tests such as HbA1c (diabetes), pH, bicarbonate (acid base), hormone screening (adrenal, pituitary), Na, Urea (renal), LFTs (liver), full blood count (sickle cell and other blood disorders), as well as MRI scans, ECGs and patient histories, can help differentiate.
One of the treatments for acute hyperkalaemia involves shunting the potassium back into the cells. This can be done by using a dose of insulin, bicarbonate or a β2-selective catecholamine (such as salbutamol), as clinically appropriate.
Whilst Na and K are helpful in determining electrolyte and water balance, urea and creatinine are useful in order to specify a pre-, true and post-renal location, and to assess acute versus chronic conditions.
Urea and creatinine
The kidney is very sensitive to urea and actively excretes it into the urine. We have a lot of urea so when the kidney is dysfunctional, urea tends to rise rapidly in the blood (see p. 22). Given that we have much more urea than creatinine in our blood, we wouldn’t expect creatinine levels to increase rapidly in a short period of say five days. If it does, this could be serious and the creatinine level is measured by the Acute Kidney Injury (AKI) blood report.
Creatinine is a product of muscle turnover and is a marker of chronic renal failure, demonstrating prolonged damage to the nephrons. A renal stone or a prolonged urinary tract infection (UTI) may slightly increase creatinine over time.
Urea is produced from the breakdown of protein, and is cleared via the urea cycle, which controls nitrogen stores in the body. In practice, it is commonly used as a marker of acute renal dysfunction. As discussed earlier, urea can rise sharply in acute dehydration, and also as an artefact following the intake of a high protein meal. Urea levels rise in acute renal dysfunction due to renal stones, viral infection and prostate cancer.
Patient 1 is a 70-year-old man with a history of lower back pain and infrequent urine production. He is almost anuriac. His urea, Na, and Alk Phos were all significantly raised. This could have been due to a renal stone, or UTI. Dehydration is unlikely, given the increased Alk Phos. However, a significantly increased prostate specific antigen (PSA) revealed an underlying prostatic tumour, with raised Ca and Alk Phos results from a bone profile, suggesting bone metastasis. On initial presentation to primary care, given that the patient had had a prostatectomy, prostate cancer was not thought to be likely.
Patient 2 is a 35-year-old woman with lower back, pelvic and abdominal pain. Her U&Es were normal, so CA-125 was performed. CA-125 is highly correlated with ovarian cancer, with about 80% accuracy. It is also linked to very severe endometriosis. Following a laparoscopy, this was indeed diagnosed.
The urea:creatinine ratio can commonly be used to determine the site of renal failure and for suspected gastric bleeds. To work this out, you should first take the median (middle) value of the reference range for both urea and creatinine. In this example, the units have been standardised to µmol/L, the range of urea is 3000–8300 and creatinine is 40–130. The medians are therefore 5650 for urea and 85 for creatinine, which is a baseline value of 66:1. To help remember the distinction between creatine and creatinine, think about the test for kidney function, U&E or Ewes and Knees; this has an ‘n’ sound, as does creatinine (found in the kidney).
In pre-renal dysfunction, such as arterial stenosis, congestive heart failure or dehydration, urea reabsorption is increased and the U:C ratio will favour urea <100:1. A U:C of 40–100:1 (normal) is usually seen in post-renal obstructions. In true renal damage, urea reabsorption is compromised and the U:C ratio will be 1–40:1.
Patient 3 is a child with an upper gastrointestinal (GI) bleed and an expected U:C may be 30–40:1.
The overall renal function can be monitored by testing estimated glomerular filtration rate (eGFR). The rate is ‘estimated’ because, unlike an actual GFR (which involves urine collection), eGFR is measured using only blood. The glomerulus is a structure within the kidney, which connects the vasculature and renal architecture and provides an initial filter for large proteins and cells. Storytelling: The glomerulus is a bit like a sieve filled with cotton wool, under a running tap.
A normal eGFR is around 100ml/min. But age, even without specific disease pathology, affects the glomerulus. From the age of about 35, the eGFR value falls by about 10% per decade. It may therefore be ‘normal’ for an 80-year-old patient to have an ‘abnormal’ eGFR of 60. However, an eGFR of 60 in a 19-year-old would be more worrying. Since eGFR is based on creatinine clearance (and thus muscle turnover), patients with an African or Caribbean heritage, or with a large muscle mass, should consider having their eGFR adjusted by multiplying by 1.2.
Glomerular filtration rate
The eGFR forms the basis for chronic kidney disease (CKD) staging and sets the scene for a differential or adjunct diagnosis where renal function can affect the pathology, such as COPD, acid base, anaemia, vitamin D deficiency, diabetes and so on. In clinical practice, an eGFR >60ml/min is usually adequate. Some laboratories will therefore not return a numerical value if greater than this and simply report eGFR >60. Some may give numerical values, and more commonly a narrative about CKD status. However, there is some debate about the clinical relevance of some mild staging, particularly in the elderly, for the reasons discussed above.
Table 15.1: CKD stages and eGFR values
|Stage 1 with normal or high GFR||>90ml/min|
|Stage 2 Mild CKD||60–89ml/min|
|Stage 3A Moderate CKD||45–59ml/min|
|Stage 3B Moderate CKD||30–44ml/min|
|Stage 4 Severe CKD||15–29ml/min|
|Stage 5 End Stage CKD||<15ml/min|
Urate and gout
White blood cells contain uric acid. When a white blood cell is broken down at the end of its lifespan, uric acid is released into the blood. The uric acid is then removed by the kidneys. If uric acid levels in the blood get too high (either due to excessive input or insufficient removal), the uric acid may form a crystalline structure in the joint and the patient may present with gout. Interestingly, if the patient has gout, a blood test for uric acid may produce a normal result. This is because the uric acid is not in the blood any more – it’s now in the joint, in the form of gout. We should therefore measure uric acid levels 4–6 weeks after the patient develops gout. Urate or uric acid is often raised in patients with gout.
Urate is a breakdown product of cellular metabolism, and – more specifically – DNA breakdown. Urate is held in the blood as soluble crystal. However, if the levels of urate rise or a renal impairment affects blood volume and flow (or both), it will quickly precipitate out of solution and form a solid crystal, usually at the interphalangeal joints of the toes.
Storytelling: Imagine floating sticks down a shallow river that is flowing over rocks. The more sticks (urate) you throw in, the more likely they are to get stuck. Also, if the level of the river (blood volume or flow) falls, the sticks will get stuck amongst the rocks.
Urate levels can be raised through poor diet, chemicals called purines and eating food high in DNA such as liver and pâté. High urate may also be seen in leukaemia patients due to the high DNA turnover in the breakdown of large numbers of white blood cells. ( gout to FBC: WBC.) However, in view of the inflammation, a rise in white blood cell count (WBC) and inflammatory markers may be expected.
Renal impairment, with an eGFR less than 60mL/min may predispose a patient to gout. Raised Ca may be an indication of pseudo-gout, especially if the gout is non-responsive to allopurinal (which blocks urate production). A comparison of the crystal structure will provide a helpful differential.