Chronic kidney disease

Chronic kidney disease (CKD), previously called chronic renal failure is defined as the presence of either kidney damage or decreased kidney function for more than 3 months. Decreased kidney function is measured by decreased GFR. In practice, the presence of any of the following criteria for more than 3 months establishes CKD:

• Abnormal GFR
• Abnormal albuminuria
• Abnormal urinary sediment
• Abnormal electrolyte balance
• Abnormal histology
• Abnormal kidney morphology on imaging (usually ultrasound)
• Previous kidney transplant

According to the definition, a person does not require a decreased GFR to have CKD. A person with proteinuria but normal GFR for more than 90 days has CKD. Also, the term “abnormal GFR” is used rather than “decreased GFR” because hyperfiltration (high GFR) is also pathological.

CKD is a progressive disease. Progression can not be reversed significantly, but the progression can be slowed or even stopped. It’s a problematic condition because CKD increases mortality and morbidity significantly, but it’s mostly asymptomatic until the very late stages.

It’s a very common condition. In Hungary alone, 1,3 million people are affected. The prevalence in Western countries is around 10%.

The disease is nowadays called chronic kidney disease, not chronic renal failure, because the definition has been expanded to not only include those conditions where the glomerular filtration is decreased, but also those cases where other kidney function functions are pathological.

Etiology

The most common causes of CKD by far are diabetes mellitus and hypertension. Other cases include:

• Glomerulonephritis
• Tubulointerstitial diseases
• Polycystic kidney diseases

Other risk factors include:

• Cardiovascular risk factors
• Old age
• Low socioeconomic status

Classification

CKD is classified according to the GFR and the degree of albuminuria:

GFR category	GFR (mL/min)
G1	> 90
G2	60 – 89
G3a	45 – 59
G3b	30 – 44
G4	15 – 29
G5	< 15

We usually call stage G4 and G5 “chronic kidney failure”, while stage G5 is referred to as end-stage kidney disease (ESKD).

Albuminuria can be categorized either by measuring the total albumin amount in a 24-hour urine sample, or from a single sample where the ratio between albumin and creatinine is measured.

Albuminuria category	Albumin excretion rate (AER) (mg/24 hours)	Albumin creatinine ratio (ACR) (mg/mmol)	Old term
A1	< 30	< 3	–
A2	30 – 300	3 – 30	Microalbuminuria
A3	> 300	> 30	Macroalbuminuria

As such, a person with GFR of 43 and AER of 100 is stage G3bA2. A person with a GFR of 100, AER of 5, and polycystic kidney disease has stage G1A1 CKD.

Clinical features

Chronic kidney disease is asymptomatic until the late stages, when the patient may develop oedema due to hypervolaemia.

In end-stage kidney disease, toxic substances accumulate due to the low GFR. This is called uraemia. The symptoms of uraemia include:

• Nausea, vomiting
• Anorexia
• Itching
• Headache
• Oedema
• Uraemic pericarditis
• Uraemic encephalopathy

Diagnosis and evaluation

The diagnosis of CKD is based on alterations in laboratory parameters, imaging, biopsy, etc., as already explained, as soon as it is established that these alterations have lasted 3 months or more.

For the evaluation of kidney function in CKD, estimated GFR (eGFR) must be used rather than serum creatinine.

All patients with recently discovered decreased kidney function should undergo evaluation to determine the cause and to determine if this is acute kidney injury or CKD. If previous kidney function tests are available it may be trivial to determine whether this is acute or chronic, but these are not available in all cases. Tests for diabetes, hypertension, urine analysis and kidney ultrasound are obligatory.

Kidneys with CKD have abnormal morphology. On ultrasound the following features are seen:

• Decreased size of kidney (< 100 mm)
• Thinning of cortex (< 10 mm)
• Irregular surface

Renal scintigraphy may be used to precisely determine the kidney function of each kidney.

The following laboratory alterations may be present:

• Elevated creatinine and urea, decreased eGFR
• Hyperkalaemia
• Hypocalcaemia with hyperphosphataemia
• Metabolic acidosis
• Dyslipidaemia (especially triglycerides)
• Elevated PTH
• Proteinuria
• Haematuria

Hyperkalaemia can be a problem in CKD, because of the decreased renal elimination of potassium and because of the RAAS inhibitors’ tendency to cause it. Treatment may be necessary.

Treatment

The management of CKD includes slowing the progression, treating the complications, and identifying those who require renal replacement therapy.

Not all cases of CKD need referral to nephrologist. When the GFR is below 30, referral is needed. Other cases can usually be managed by the primary care physician.

Non-pharmacological treatment:

• Sodium restriction (< 5 g/day NaCl)
• Fluid restriction
  • Only if oliguria/anuria, to prevent hypervolaemia and oedema
• Protein restriction
• Normalization of BMI
• Regular exercise
• Smoking cessation
• Avoid nephrotoxic substances (NSAIDs, ABs)
• Restriction of potassium-rich foods

Pharmacological treatment:

• Anti-proteinuric treatment
  • Only if proteinuria
  • ACEi or ARB
• Blood pressure normalization
  • Only if hypertension (most patients have)
  • First-line: ACEi or ARB
  • Target < 140/90 mmHg
• Blood glucose normalization
• Blood lipid normalization
  • Statin first choice
  • + ezetimibe if necessary
• Vitamin D supplementation
• Loop diuretics
  • Only if GFR low (< 15)
• Allopurinol
  • Only if hyperuricaemia
• EPO
  • Only if renal anaemia

Some CKD patients, mostly ESKD ones, require renal replacement therapy.

When adding new drugs to CKD patients with low GFR, it’s important to check if the drug has any special considerations for low GFR, like dose adjustment.

Complications

• Dyslipidaemia (especially increased triglycerides)
• Anaemia
• Hyperkalaemia
• Bone disease
• Cardiovascular disease

Not only do CKD patients usually have cardiovascular risk factors, but CKD is a very strong independent risk factor for cardiovascular diseases. Cardiovascular disease is the most common cause of death in end-stage renal disease patients.