RENAL (/MEDICINE/RENAL/NOTES)

Chronic kidney disease

NOTES

Overview

Chronic kidney disease (CKD) can be defined by the presence of kidney damage or
reduced kidney function for three or more months.

Reduced kidney function is suggested by a reduction in the glomerular filtration rate (GFR).

Kidney damage can be characterised by the presence of one of more of the following pathological
markers.

Albuminuria (e.g. albumin:creatinine ratio > 3 mg/mmol or > 30 mg/g)

Urinary sediment abnormalities (e.g. white cell or red cell casts)
Radiological abnormalities (e.g. polycystic kidneys)
Pathological abnormalities (e.g. seen on renal biopsy)
History of kidney transplantation.

CKD is a common condition with a progressive nature. As CKD progresses towards end-stage renal
disease (ESRD) it is associated with more symptoms, increasing complications and need for renal
replacement therapy (RRT).

The inability of the kidneys to carry out their normal function can lead to problems with volume
regulation, acid-base balance, calcium and phosphate handling and electrolyte abnormalities.

Classification

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 1 of 12
 The classification of CKD is now based on two factors: the estimated glomerular filtration
rate (eGFR, ml/min/1.73m2) and the albumin:creatinine ratio (ACR, mg/mmol).

The change towards using ACR in the classification of CKD reflects the increased risk of acute on
chronic injury, end stage disease and all-cause mortality in patients with a high ACR.

CKD is increasingly common with advancing age and stages 3-5 affect up to 8.5% of the adult
population. The higher the stage of CKD, the more frequent monitoring patients require. This
helps to identify and manage complications and plan for RRT.

Aetiology & pathophysiology

There are numerous causes of CKD, but the majority of cases are secondary to diabetes
mellitus, hypertension and glomerulopathies.

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 2 of 12
 Major causes include:

Hypertensive nephropathy
Diabetic nephropathy
Glomerulopathties
Inherited kidney disorders (e.g. PCKD)
Ischaemic nephropathy (e.g. vascular disease)
Obstructive uropathy
Tubulointerstitial diseases
Medications

Approximately 1 million nephrons are present in each kidney from birth. These nephrons
contribute to the kidneys ability to maintain adequate glomerular filtration and allows the kidney
to perform its normal functions (e.g. volume regulation, acid-base balance).

As we age there is a progressive loss in renal mass and a number of structural changes occur (e.g.
glomerulosclerosis) leading to a decline in renal function. Following a peak in the third decade of
life, there is an estimated annual decline of 1 mL/min/year in eGFR.

Regardless of the underlying cause, renal disease leads to progressive loss of nephrons and a
subsequent reduction in the GFR. As the disease progresses, structural abnormalities may occur
leading to kidney damage (e.g. albuminuria), and eventually, the kidneys start to lose their ability
to carry out normal functions.

Clinical features

Patients are generally asymptomatic with CKD, but start to develop non-specific symptoms
at more advanced stages (e.g. eGFR < 45ml/min).

It is always important to look for evidence of an underlying cause of CKD (e.g. large bilateral
abdominal masses could be suggestive of PCKD).

Symptoms

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 3 of 12
 Asymptomatic
Anorexia & nausea
Fatigue & weakness
Muscle cramps
Pruritus
Dyspnoea
Oedema

Signs
Pallor (e.g. anaemia)
Hypertension
Fluid overload (e.g. raised JVP, peripheral & pulmonary oedema)
Skin pigmentation
Excoriation marks
Peripheral neuropathy​

Diagnosis

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 4 of 12
 The diagnosis and subsequent monitoring of CKD is based on evidence of kidney damage
and the measurement of the serum creatinine and urinary ACR.

There are a number of ways to calculate the eGFR from serum creatinine, all should be used with
caution. Serum creatinine levels have a high individual variation changing with disease states,
muscle mass, pregnancy and dietary intake.

Many laboratories will use the Modification of Diet in Renal Disease (MDRD) equation; however,
NICE recommend the use the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
equation for calculating the eGFR.

Indications for CKD testing include the following:

Diabetes
Hypertension
Acute kidney injury
Obesity with metabolic syndrome
Cardiovascular disease
Structural renal tract disease
Proteinuria or persistent haematuria
Family history

Depending on the results of the eGFR and ACR, patients can be classified into a particular stage of
CKD. In patients with stable CKD (e.g. eGFR < 60ml/min without acute deterioration or ACR
between 3 and 70 mg/mmol), it is important to repeat these tests within 3 months. Those with
pronounced albuminuria (> 70mg/mmol) or significantly reduced eGFR (G4 or G5) require referral
to a nephrologist.

Those with evidence of persistent haematuria in the absence of infection should be investigated
for malignancy. There are a number of other referral criteria that are beyond the scope of these
notes.

Investigations

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 5 of 12
 Investigations may be used to help diagnose, monitor and assess for complications of CKD.

Urine
Urine dipstick
Urine microscopy
ACR (spot test)
ACR (24-hour collection)
Electrophoresis (e.g. myeloma)

Bloods
FBC
U&Es (inc. eGFR)
Bone profile
PTH
Bicarbonate
LFTs
Lipid profile
Autoimmune screen (e.g. ANCA, ANA)

Imaging
Renal ultrasound
Magnetic resonance angiography
Echocardiogram
ECG (high risk of CVS disease)

A renal ultrasound scan should be offered to patients with visible or persistent non-visible
haematuria, evidence of obstructive uropathy, family history of PCKD, reduced eGFR (< 30ml/min)
or accelerated progression of CKD.

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 6 of 12
 Special
Renal biopsy (useful in the identification of intrinsic causes of CKD)

Management

The principles of CKD management are to treat the underlying cause, prevent or slow
progression (e.g. renoprotective therapy), treat associated complications and plan for
RRT.

Renoprotective therapy

Renoprotective therapy is aimed at slowing the progression of CKD, independent of the

aetiology.

Renoprotective therapy is centered around blood pressure control and reducing proteinuria.
Specific blood pressure targets depend on whether CKD is secondary to diabetes and the
presence of proteinuria.

A standard BP target is < 130/80 mmHg if the patient is diabetic or has albuminuria. Therapy to
control BP utilises ACE inhibitors and angiotensin receptor antagonists (both renin-angiotensin
system antagonists). These drugs are both antihypertensive and antiproteinuric.

Renin-angiotensin system antagonists should be offered to patients who are:

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 7 of 12
 Diabetic and have an ACR of 3 mg/mmol or more.
Hypertensive and ACR of 30 mg/mmol or more.
ACR > 70mg/mmol independent of CVS disease.

Outside of these parameters, hypertension should be treated in accordance with the usual NICE
hypertension guidance (typical target BP < 140/90 mmHg).

Other important therapies to consider include:

Statin therapy
Smoking cessation
Protein restriction
Antiplatelets for secondary prevention of CVS disease.

Treating complications

A number of important complications develop as a consequence of CKD, which include

anaemia, hyperkalaemia, mineral and bone disorders, fluid overload and acidosis.

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 8 of 12
 Anaemia

A normocytic normochromic anaemia is typical of CKD.

This anaemia is normally multifactorial. A significant factor in advanced disease is a reduction in

the production of erythropoietin (EPO), the hormone that drives erythropoiesis.

It is still important to assess patients for other potential causes of anaemia (e.g. iron-deficiency,
folate deficiency), which can subsequently be corrected. The main management for anaemia in
CKD is the use of erythropoietin-stimulating agents (ESA) such as epoetin alfa.

Hyperkalaemia

The ability of the kidneys to maintain adequate acid-base homeostasis and electrolyte
balance diminishes with worsening renal function.

Many medications, including NSAIDs and potassium-sparing diuretics, may worsen

hyperkalaemia. Furthermore, uncontrolled metabolic acidosis may also worsen potassium
handling.

Acute rises in potassium should be managed as a medical emergency. This involves stabilisation of
the myocardium (with calcium gluconate) and driving potassium into the intracellular
compartment (with insulin/dextrose).

Chronic elevations in serum potassium can be managed with low potassium diets, potassium-
binding resins and correction of acidosis.

Mineral and bone disorders

In CKD, disorders of mineral and bone metabolism reflect a complex spectrum of pathology
that results from abnormal calcium and phosphate handling.

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 9 of 12
 In health, the kidneys have an important role in the maintenance of calcium homeostasis. They are
able to activate vitamin D, a fat-soluble vitamin important for absorption of calcium from the
gastrointestinal tract. They are also involved in the reabsorption of calcium and excretion of
phosphate.

In disease, reduced kidney function (usually associated with a GFR < 30ml/min) leads to
hypocalcaemia, hyperphosphataemia and hyperparathyroidism (secondary
hyperparathyroidism). These biochemical abnormalities may then lead to boney pathology (e.g.
adynamic bone disease, osteomalacia, osteoporosis and osteitis fibrosa cystica). The term ‘renal
osteodystrophy’ is used exclusively for this type of bone pathology seen in CKD.

The management of mineral and bone disorders requires management of the underlying
biochemical abnormalities.

Hypocalcaemia: dietary supplements and calcitriol.

Hyperphosphataemia: dietary restriction and phosphate binders.
Hyperparathyroidism: calcimimetics or surgery.

Fluid overload

In the presence of significantly reduced GFR, the kidneys are unable to adequately
controlled fluid volume.

This leads to hypervolaemia and patients may have evidence of peripheral oedema, ascites,
raised JVP, gallop rhythm and bilateral pleural effusions.

Fluid overload can be managed with a combination of fluid restriction, reduced sodium intake and
the use of oral diuretics (e.g. furosemide).

Acidosis

Patients with CKD have an increased tendency to retain hydrogen ions because of
abnormalities in their acid-base homeostasis.

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 10 of 12
 This leads to low bicarbonate levels and management generally involves the use of oral sodium
bicarbonate therapy.

Renal replacement therapy

Haemodialysis, peritoneal dialysis and renal transplant are all forms of RRT that are
indicated for ESRD.

In-depth analysis of the types of RRT, their indications, contraindications and efficacy are beyond
the scope of these notes. However, we will briefly cover some of the key aspects of each type.

Haemodialysis

Haemodialysis involves the removal of waste products and other substances by passing
blood through a dialysis machine.

Blood comes into contact with a semi-permeable membrane, which contains the dialysate on
the other side. Substances may then diffuse between the two fluids (blood and dialysate).

Haemodialysis requires intravenous access in the form of an arteriovenous fistula or an artificial

line (e.g. portacath). Patients usually have haemodialysis 3-4 times a week for several hours.

Peritoneal dialysis

Peritoneal dialysis is achieved by using the peritoneal cavity as the primary site of
ultrafiltration.

A catheter (e.g. Tenckhoff catheter) is inserted into the abdominal cavity, which allows the infusion
of the dialysate. The dialysate then dwells within the abdomen using the peritoneum as a semi-
permeable membrane for the transfer of waste products. The dialysate can then be removed after
a certain amount of time and the procedure repeated.

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 11 of 12
 In general, peritoneal dialysis can be achieved by continuous ambulatory peritoneal dialysis
(CAPD) where multiple exchanges are made each day, or by automated peritoneal dialysis (APD)
where the exchange is made overnight when the patient sleeps.

Renal transplant

Renal transplant is considered the gold-standard for RRT.

Transplantation may be from living donors or non-living donors as long as there is MHC
compatibility, which may mediate graft rejection. Non-living donors include donors after cardiac
death (DCD) and donors after brain death (DBD).

Renal transplantation requires the use of long-term immunosuppressive therapy to stop the
recipient's immune system from ‘attacking’ the donor tissue.

Despite the overt success of transplantation, it can be associated with a number of complications
including graft rejection, complications from immunosuppressive agents (e.g. malignancy,
infection) and disease recurrence.

Have comments about these notes? Leave us feedback

FURTHER STUDY:

View Video (/medicine/renal/videos/chronic-kidney-disease) Take exam (/exam?exam%5Btopic_ids%5D%5B%5D=95)

https://app.pulsenotes.com/medicine/renal/notes/chronic-kidney-disease 26/03/2019, 1>51 PM

Page 12 of 12