Chronic kidney disease (CKD) is defined as abnormalities to the structure or function of the kidney that is present for >3 months. It tends to be both permanent as well as progressive (and for this reason we are able to stage it).
It is estimated to have a prevalence of 15% in those aged >35 years old, within England.
Pathophysiology
We will discuss the causes of renal injury, however, the initiating factor sets in place a cascade of events which ultimately results in a decline of renal function:
- Glomerular hypertrophy in response to injury increases intra-glomerular pressure as the kidney tries to adapt to nephron loss to maintain the GFR.
- Increased glomerular permeability to oxidative and pro-inflammatory substances leads to inflammation, fibrosis and scarring of the glomerulus.
- Increased angiotensin II production increases the production of TGF-ß which promotes collagen synthesis and renal scarring further.
- Tubulo-interstitial diseases associated with CKD form due to a reduction in the blood supply, coupled with lymphocyte infiltration and inflammation. This ultimately ends up in interstitial fibrosis and tubular atrophy.
So what are the causes of renal injury in the first place?
- 🥇 Diabetes nephropathy - the most common cause.
- 🥈 Hypertension - the second most common cause. It is a complex interaction as hypertension can cause CKD but CKD can also cause/worsen hypertension.
- Chronic glomerulonephritis
- PKD
- Obstructive uropathy
- Chronic pyelonephritis
- Lupus nephritis
- Genetic causation - 1/3rd of adults with CKD have a positive family history of CKD.
- Vasculitis and renal artery stenosis
⚠️ Risk factors
- Age >50 years
- Male
- Black or Hispanic ethnicity
- Family history
- Smoking
- Obesity
- Long-term analgesic use
- Diabetes
- Hypertension
- Autoimmune disorders such as SLE.
😷 Presentation
It is usually asymptomatic and diagnosed with routine testing either incidentally or when following up for chronic diseases (such as hypertension, heart failure, diabetes). Some patients with late-stage disease may become symptomatic with features such as:
- Lethargy and fatigue - either due to ureaemia or anaemia as we have a lack of erythropoietin in the blood (anaemia of renal disease)
- Oedema - due to salt and water retention as the GFR declines. It can be exacerbated due to hypoalbuminaemia.
- Polyuria
- Uraemic pruritus - thought to be due to accumulation of urea under the skin.
- Anorexia
- Insomnia
- Nausea and vomiting - due to an accumulation of toxic waste products in circulation, especially urea. Patients may also report a metallic taste in their mouth.
- Hypertension
- Muscle cramps
- Peripheral neuropathy
🔍 Investigations
- 🥇 U&Es
- Electrolyte abnormalities
- Raised serum creatinine
- eGFR - we will discuss this below
- 🥇 Albumin:creatinine ratio (ACR) - this indicates proteinuria. NICE states that an ACR >3mg/mmol is regarded as clinically significant proteinuria. To gather a sample, a first-pass morning urine specimen should be collected. If the initial sample is between 3-70mg/mmol then it should be confirmed with a subsequent early morning specimen. However, if it is initially >70mg/mmol then there is no need for a subsequent sample. We will discuss the scoring below.
- Protein:creatinine ratio (PCR) may also be used, but ACR has a greater sensitivity. PCR can be used for monitoring of proteinuria as an alternative.
- Urinalysis - to assess for haematuria and proteinuria. Haematuria should be investigated for malignancy.
- Renal ultrasound - usually shows bilateral small kidneys (this is a method of differentiating between AKI and CKD).
ACR (mg/mmol) | PCR (mg/mmol) | Urinary protein excretion (g/24hrs) |
30 | 50 | 0.5 |
70 | 100 | 1 |
250 | 300 | 3 |
🔢 Staging
We can calculate what stage of CKD the individual is at based on their eGFR. This is known as their G score and it ranges from G1-G5. We can also calculate an A score based on the ACR, and this ranges from 1-3.
The eGFR is calculated using the Modification of Diet in Renal Disease (MDRD) formula - it takes into account serum creatinine, age, gender and ethnicity.
G score/stage of CKD:
Stage | eGFR (ml/min/1.73m²) |
G1/Stage 1 | >90 |
G2/Stage 2 | 89 - 60 |
G3a/Stage 3a | 59 - 45 |
G3b/Stage 3b | 44 - 30 |
G4/Stage 4 | 29 - 15 |
G5/Stage 5 | <15 |
A score
A score | ACR |
A1 | <3mg/mmol |
A2 | 3-30mg/mmol |
A3 | >30mg/mmol |
☝️ To be considered CKD, the eGFR needs to be <60ml/min/1.73m² OR markers of kidney damage (albuminuria, electrolyte abnormalities, structural or histological changes) for 3 months or more.
We need to have an eGFR <60 on 3 occasions within 3 months for a diagnosis of CKD to be established. Upon the first instance of detecting an eGFR <60, the patient should be reviewed within 1 week to ensure that they are not having a rapid decline in their kidney function.
🧰 Management
Aims of management include:
- Slowing progression of the disease
- Reducing risk of complications and CVD
- Treating complications
This can be done by optimising diabetic and hypertensive control.
If glomerulonephritis is present, we need to treat it or treat underlying cause.
- Exercise, smoking cessation, dietary management of weight etc.
- Specialist advice about phosphate, sodium, potassium and water intake.
- Atorvostatin 20mg for primary/secondary prevention of CVD.
- Metabolic acidosis - oral sodium bicarbonate
- End-stage renal failure - dialysis or renal transplant
We will discuss some more complications in a little more detail below.
- Oedema
🥇 Fluid and salt restriction
Diuretics such as furosemide may be given if needed.
- Proteinuria and hypertension
🥇 ACEIs or ARB are the first-line option in patients with co-existent hypertension with an ACR >30mg/mmol.
- If ACR >70mg/mmol → give ACEI/ARB regardless of their BP.
- ACR <70 - target BP is 140/90
- ACR >70 - target BP is 130/80
All diabetics over the age of 12 should undergo an ACR screen for microalbuminuria.
→ If microalbuminuria is detected (>2.5mg/mmol in men or >3.5mg/mmol in women) then start on ACEI.
It is important to monitor serum potassium as CKD and ACEIs can cause hyperkalemia
⭐️ After starting an ACEI, a decrease in eGFR up to 25% and a rise in creatinine of up to 30% is acceptable.
[ADD UPDATE ON GUIDELINES FOR DAPAGLIFLOZIN]
- Anaemia
🥇 If the Hb falls <100g/L and there are symptoms of anaemia, we can consider an erythropoietin-stimulating agent.
- Epoetin alfa
- Darbepoeitin alfa
- Mineral and bone disorders - this will be discussed in depth in the complications section of this CCC.
🏥 Referral
Referral to nephrology can be made if:
- Urinary ACR >70mg/mmol unless known to be caused by diabetes and is being treated appropriately.
- Urinary ACR >30mg/mmol + persistent haematuria (2/3 urine dipsticks show 1+ or more of blood in urine) after exclusion of UTI.
- ACR 3-29mg/mmol + persistent haematuria and other risk factors (declining eGFR, CVD)
- Sustained decrease in eGFR of 25% or more and change in G score within 12 months
- 5-year risk of needing renal replacement therapy >5%. This is done using the 4-variable Kidney Failure Risk Equation.
- Decrease in eGFR of >15ml/min/1.73m² per year
- Poorly controlled hypertension despite using 4 or more anti hypertensives.
🚨 Complications
Mineral and bone disorder (CKD-MBD)
CKD-MBD refers to the bone disease experience with CKD.
Let’s take a look at the pathophysiology quickly:
The kidneys need are used to hydroxylate vitamin in D into its active form (1,25-dihydroxycholecalciferol, also known as calcitriol). Calcitriol is needed for absorption of calcium from the intestines and kidneys. It also regulates bone turnover. A deficiency in calcitriol → hypocalcaemia.
Reduced phosphate excretion leads to hyperphosphataemia.
The parathyroid glands react to hypocalcaemia and hyperphosphataemia by releasing more parathyroid hormone. Parathyroid hormone is used increase osteoclast activity to turnover bone for calcium release.
- We then get osteomalacia (softening and weakening of bones) due to increased turnover of bones without sufficient calcium supply to replenish the bones.
- Osteosclerosis occurs as osteoblasts attempt to match the osteoclast hyperactivity, however, without adequate calcium supply the new bone tissue is not mineralised properly. If this occurs in the spine it is known as Rugger Jersey spine.
- Osteoporosis may also occur due to age and steroid use that coincides with CKD.
- Restrict dietary phosphate - which can be found in dairy and eggs.
- Sevelamer - a non-calcium based phosphate binder that helps manage the hypocalcaemia.
- Calcitriol or alfacalcidol can also be considered for the hypocalcaemia.
- Parathyroidectomy is an options with tertiary hyperparathyroidism (PTH >28mmol/L)
Other complications that may arise from CKD can be remembered through the acronym CRF HEALS:
C - CVD
R - Renal osteodystrophy
F - Fluid (oedema)
H - Hypertension
E - Electrolytes (hyperkalaemia and acidosis)
A - Anaemia
L - Leg restlessness
S - Sensory neuropathy