Chronic Kidney Disease (CKD)

Table of contents
Key points ⚡
Succinct notes to superpower your revision
Chronic kidney disease\: abnormal kidney function/structure >3 months, a
Causes\: diabetes, vascular disease, glomerular disease (e.g. IgA nephropathy), nephrotoxic drugs (e.g aminoglycosides,
NSAIDs), obstructive uropathy, multisystem diseases (e.g. lupus, vasculitis), hereditary kidney disease (e.g. polycystic kidney
disease).
Risk factors\: age >50, history of AKI, history of childhood kidney disease, diabetes, cardiovascular disease, obesity, smoking,
male gender, black/Hispanic ethnicity, gout.
Symptoms\: often asymptomatic; in advanced stages, fatigue, nausea, polyuria,
sexual dysfunction.
Clinical
peripheral neuropathy, microvascular damage.
Investigations\: BP, urinalysis, plasma glucose, ECG, FBC, U&Es, serum albumin, urinary albumin, serum calcium,
phosphate, PTH, alkaline phosphatase, cholesterol and triglycerides, imaging (renal ultrasound, CT/MRI).
Management\: exercise, weight loss, smoking cessation, glycaemic control, BP control (ACE inhibitors/ARBs), immunisations
(in
hydroxycholecalciferol for hyperparathyroidism and addressing cardiovascular risk factors.
Renal replacement therapy\: dialysis (haemodialysis or peritoneal dialysis), kidney transplantation, conservative
management for some patients. Generally patients begin dialysis when GFR reaches approx. 5-10 mL/min/1.73m.
Complications\: metabolic acidosis, pulmonary oedema, anaemia, uraemic encephalopathy, cardiovascular disease,
hyperkalaemia, CKD-mineral bone disorder.
Article 🔍
A comprehensive topic overview

Introduction

Chronic kidney disease (CKD) is de
with subsequent implications for health.
1
CKD is a common condition estimated to a
2

Aetiology

Causes of CKD
The most common causes of CKD in adults are diabetes and vascular disease.
3
Other causes of CKD include\:
3
Glomerular disease\: such as IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis
Nephrotoxic drugs\: aminoglycosides, bisphosphonates, calcineurin inhibitors (such as ciclosporin or tacrolimus), lithium,
proton pump inhibitors, mesalazine and NSAIDsObstructive uropathy or re
hypertrophy, urinary diversion surgery, recurrent urinary tract calculi, or pathology outside the urinary tract such as
malignancy or retroperitoneal
Multisystem diseases with renal involvement\: systemic lupus erythematosus, vasculitis, myeloma, hepatitis B, hepatitis
C, HIV
Hereditary kidney disease\: polycystic kidney disease, Alport syndrome
Pathophysiology4
Chronic kidney disease is the end-stage for any cause of severe and/or long-standing kidney injury. Regardless of the
cause, once half the nephrons are damaged CKD will progress.
Damage to the kidneys reduces the number of functioning nephrons, which leads to several adaptations. There is
hyper
Another adaptation is the activation of the renin-angiotensin-aldosterone system causing an increase in blood pressure,
which furthers the hyper
factors.
The increase in capillary pressure within the glomerulus and in
reduces the
to systemic complications, which are discussed later in this article.
Classi
Figure 1. The classi
eGFR and proteinuria
CKD is classi
represents "low risk"
, yellow represents "moderate risk"
, orange represents "high risk" and red represents "
very high risk"
.

Risk factors

Risk factors for chronic kidney disease include\:
Age greater than 50 years
History of acute kidney injury
History of childhood kidney disease
Family history of CKD stage 5
Diabetes mellitus
Cardiovascular disease
Obesity with metabolic syndrome
Gout
Solitary functioning kidney
Smoking
Black or Hispanic ethnicity
Male gender

Clinical features

History
CKD is primarily asymptomatic, and symptoms usually only start developing when it is advanced (stages 4-5).
3CKD is usually detected through the presence of hypertension, haematuria and/or proteinuria upon urinalysis, or a
reduction in GFR with increased serum creatinine.
6
In advanced CKD, typical symptoms may include\:
3,6
General symptoms\: such as fatigue, nausea and vomiting, cramps, insomnia, restless legs, taste disturbance, bone pain,
and pruritus
Abnormal urine output\: such as polyuria, oliguria, or nocturia
Fluid overload\: may present as dyspnoea and orthopnoea
Sexual dysfunction
Severe uraemia may also cause hiccups, pericarditis, coma and seizures
Clinical examination
Typical clinical
3,6
Uraemic fetor\: ammonia-like smell of the breath
Pallor\: due to anaemia
Cachexia
Cognitive impairment\: speci
Tachypnoea\: may be due to
Hypertension
Volume disturbance\: volume overload (e.g. peripheral oedema, pulmonary oedema, pleural e
depletion
Peripheral neuropathy
Fundoscopy may reveal microvascular damage in patients with diabetes or hypertension
There may be speci
Bilateral masses upon palpation of
hepatomegaly due to liver cysts.
Palpable bladder\: may suggest obstructive uropathy, often accompanied by prostatic enlargement in men

Di

Di
Acute kidney injury\: the presence of chronic symptoms of fatigue, weight loss, anorexia, nocturia and pruritus suggest a
diagnosis of CKD over AKI
Acute on chronic kidney disease\: where patients with features of CKD experience an acute further deterioration in their
renal function, often following a precipitant such as infection or diarrhoea

Investigations

Bedside investigations
Relevant bedside investigations include\:
3
Blood pressure\: hypertension is common in patients with CKD
Urinalysis\: may reveal haematuria and/or proteinuria, particularly in glomerular disease
Plasma glucose\: to detect undiagnosed diabetes or assess control of diabetes
ECG\: particularly to assess for evidence of left ventricular hypertrophy or ischaemia
Laboratory investigations
Relevant laboratory investigations include\:
3,7
Full blood count\: may reveal normochromic normocytic anaemia due to erythropoietin de
de
present (e.g. raised potassium, low bicarbonate)
Serum albumin\: hypoalbuminaemia in patients who are nephrotic and/or malnourished
Urinary albumin (albumin to creatinine ratio)\: may be increased
Serum calcium\: may be low, normal, or high
Serum phosphate\: often elevated
Serum PTH\: rises as GFR falls (secondary and tertiary hyperparathyroidism)
Serum alkaline phosphatase\: may be raised when in the presence of hyperparathyroidism
Cholesterol and triglycerides\: hyperlipidaemia is common
Other speci
Serum protein electrophoresis and free light chain measurement\: for evidence of a monoclonal gammopathy such as
multiple myeloma, primary amyloidosis
Serology\: autoantibodies such as ANCA (anti-neutrophil cytoplasmic antibodies, speci
myeloperoxidase) anti-nuclear antibodies (ANA) and serum complement (C3 and C4) when secondary glomerular
disease is suspected
Hepatitis B and C and HIV serology\: if suspected as a cause of CKD or if a patient requires dialysis
Imaging
Relevant imaging investigations include\:
3
Plain abdominal radiograph\: may reveal radio-opaque stones or nephrocalcinosis
Renal ultrasound\: may reveal structural abnormalities (e.g. polycystic kidneys), hydronephrosis, in
of cortex, increased echogenicity, and reduction in kidney size (advanced CKD often leads to small, echogenic kidneys)
CT or MRI scan\: may be used to de

Diagnosis

A diagnosis of CKD requires evidence of kidney damage and/or a persistent reduction in renal function.
2
CKD stages 3 - 5 can be diagnosed based on GFR alone (\<60 mL/min/1.73m ).
CKD stages 1 - 2 require additional evidence of renal disease such as\:
2
Proteinuria
Urine sediment abnormalities\: particularly red blood cells or casts, or white blood cells
Electrolyte abnormalities due to tubular dysfunction
Structural abnormalities
Histological abnormalities
History of kidney transplantation
Accelerated progression of CKD
Accelerated progression of CKD is de
category within 12 months, or a persistent decrease in eGFR of 15 mL/min/1.73 m 2 2within 12 months.Figure 2. Identi
permission.

Management

General management
General measures for the management of CKD include\:
3,8
Exercise
Healthy weight loss
Smoking cessation
Good glycaemic control
Control of blood pressure
Immunisations\: in
Avoidance of nephrotoxic medication
Diet\: adequate protein intake, restricted sodium and phosphate intake
Patients should be assessed for cardiovascular risk factors (lipid pro
consumption) and o
3,8
Good blood pressure control is vital in slowing the progression of CKD. In patients with diabetic renal disease or signi
proteinuria, an ACE inhibitor or an angiotensin receptor blocker are the
be used with care in patients with renovascular disease or those who are at risk of volume depletion or impaired renal
perfusion.
8
An SGLT-2 inhibitor may be o
that they can tolerate.
9
Dietary phosphate restriction and phosphate binders (e.g. calcium acetate, sevelamer, lanthanum) to control
hyperphosphataemia.
3
1-alpha-hydroxycholecalciferol is administered if secondary hyperparathyroidism is present.Figure 3. Interventions for CKD in Primary Care (Medscape UK). Reproduced with
permission.
Monitoring
Monitoring requirements include a full blood count and iron studies (for anaemia), serum calcium, phosphate, and
parathyroid hormone level (for renal bone disease).
8
Risk level, determined by eGFR and albuminuria, guides the frequency of monitoring\:
5
Low-moderate risk\: monitor annually
High risk\: monitor every 6 months
Very high risk\: monitor every 3-4 months
Renal replacement therapy
Renal replacement therapy is an important aspect of the treatment of end-stage CKD. This includes dialysis (either
haemodialysis or peritoneal dialysis) and kidney transplantation.
Generally, patients begin dialysis when their GFR reaches approximately 5-10 mL/min/1.73m.
2,5
Some patients, particularly those who are elderly or have signi
(best supportive care) rather than renal replacement therapy.
Haemodialysis
Haemodialysis involves pumping blood from the patient’s body through a dialyser (arti
di
based regimens are typically for 4 hours three times a week.
10
Good blood
typically takes 6-8 weeks to become usable after formation) or a tunnelled central venous catheter. 10
A
preferred option due to the higher rate of complications with lines (particularly infection).
Complications of haemodialysis include\:
10
Access-related\: infection (including bacteraemia leading to endocarditis, discitis), venous stenosis, access failure
Haemodynamic instability
Nausea and vomiting, headache, cramps
Reactions to dialysis membranes
Peritoneal dialysis
Peritoneal dialysis involves infusing dialysate into the peritoneal cavity through a tunnelled catheter. Solutes and
from the peritoneal vessels move across the peritoneal membrane into the dialysate and are removed.
10
This requires a functional peritoneal membrane, so patients may not be suitable if they have had previous intra-abdominal
pathology (e.g. previous peritonitis, surgery, adhesions).
The two typical regimens, which may be combined\:
11
Continuous ambulatory peritoneal dialysis\: manual dialysate exchanges are typically performed four times per day
Automated dialysis\: a machine performs exchanges overnightComplications of peritoneal dialysis include\:
10
Bacterial or fungal peritonitis
Catheter problems\: infection, blockage, kinking, leaks, displacement (more likely if a patient becomes constipated)
Weight gain
Worsening glycaemic control in patients with diabetes
Failure of peritoneal membrane requiring a switch to haemodialysis
Encapsulating peritoneal sclerosis
Transplantation
Transplantation provides the best long-term outcome for a patient with CKD and has numerous bene
need for dialysis, can ameliorate anaemia and renal bone disease and improves quality of life and long-term survival.
10
Kidneys may be obtained either from cadaveric donors (heart beating or non-heart-beating) or live donors (genetically
related or unrelated).
The patient’s native kidneys are normally left in situ, and the donor kidney is placed in the iliac fossa. Patients receive
induction and maintenance immunosuppression to prevent graft rejection.
10
Figure 3. Kidney transplantation.
12
Contraindications to transplantation include active or recent malignancy, active infection, or signi
ischaemic heart disease).
10
Complications of renal transplantation
Complications of renal transplantation include\:
10
Operative complications\: infection, bleeding, arterial or venous thrombosis, problems with ureteric anastomosis
Stenosis of graft artery or ureter
Side e
ciclosporin
Opportunistic infections particularly Cytomegalovirus (CMV)
Malignancy\: Epstein Barr virus-driven non-Hodgkin B cell lymphomas, and non-melanoma skin cancers
(squamous cell and basal cell carcinomas)
Recurrence of original renal disease in the transplant
Hyperacute graft rejection\: untreatable and should not occur if appropriate cross-matching has been performed
Acute graft rejection\: presents with creatinine rise, diagnosed by graft biopsy, initial treatment normally with
intravenous steroids
Chronic allograft nephropathy\: can occur for multiple reasons, does not usually respond to increased
immunosuppression

Complications

The complications of CKD can be related to the functions of the kidney. The mnemonic 'A WET BED' is a useful way to
recall the functions of the kidney and associated complications of CKD.
Table 1. A WET BED\: the functions of the kidney and associated complications of CKD
Function of the kidney CKD complicationsA Acid-base balance
W Water removal
E Erythropoiesis
T Toxin removal
B
Blood pressure
control
E Electrolyte balance
D Vitamin D activation
Metabolic acidosis
Due to the inability of the kidneys to excrete acid
Managed with oral bicarbonate supplements or dialysis
Pulmonary oedema
Due to
Patients should avoid excessive water and sodium intake
It is treated with loop diuretics (e.g.\: furosemide) or dialysis
Anaemia of chronic kidney disease
Due to the insu
Can be treated with erythropoietin-stimulating agents
Patients often also require iron supplementation for functional iron de
Uraemic encephalopathy
Due to the build-up of toxins in the blood which can a
Treated with dialysis to remove the toxins
Cardiovascular disease
Due to a combination of salt and water overload, hypertension, and accelerated
atherosclerosis
Management of cardiovascular risk factors, as discussed above, is important
Hyperkalaemia
Due to the kidney's inability to excrete potassium
Treatment includes restriction of dietary potassium intake, avoidance of drugs
that promote hyperkalaemia (e.g. ACE inhibitors), use of oral potassium binders, or
dialysis
Bone-mineral disorder of chronic kidney disease (CKD-BMD), previously referred
to as renal osteodystrophy
Due to increased secretion of PTH (
secondary hyperparathyroidism
), because of impaired renal hydroxylation of vitamin D, and renal phosphate
retention
Management includes administration of hydroxylated vitamin D and control of
hyperphosphataemia by restriction of dietary phosphate and administration of
phosphate binders
Prognosis14
CKD is a long-term condition and may progress to end-stage renal disease. It cannot be cured, but many aspects can be
managed as outlined above. CKD is a strong risk factor for vascular disease, which is often the cause of death in patients
with CKD.

References

NICE CKS. C h r o n i c K i d n e y D i s e a s e - D e LINK]
Singh, M. and Krause, M.,. C h r o n i c K i d n e y D i s e a s e . E p i d e m i o l o g y . 2021. Available from\: [LINK]
Tidy C, Jarvis S. C h r o n i c K i d n e y D i s e a s e ( C h r o n i c R e n a l F a i l u r e ) . 2021. Available from\: [LINK]
Oiseth S, Jones L, Maza E. Chronic Kidney Disease | Concise Medical Knowledge. 2021. Available from\: [LINK]
Wilkinson I, Raine T, Wiles K, Goodhart A, Hall C, O'Neill H. Oxford handbook of clinical medicine. 10th ed. Oxford University
Press; 2017.Singh, M. and Krause, M. C h r o n i c K i d n e y D i s e a s e . A p p r o a c h . 2021. Available from\: [LINK]
Singh, M. and Krause, M. C h r o n i c K i d n e y D i s e a s e . I n v e s t i g a t i o n s . 2021. Available from\: [LINK]
NICE CKS. M a n a g e m e n t o f c h r o n i c k i d n e y d i s e a s e . 2021 [cited 15 January 2022]. Available from\: [LINK]
NICE Guideline. C h r o n i c k i d n e y d i s e a s e \: a s s e s s m e n t a n d m a n a ge m e n t . 2021 [cited 22 February 2022]. Available from\: [LINK]
Rull G, Bonsall A. R e n a l R e p l a c e m e n t T h e r a p y a n d T r a n s p l a n t a t i o n . 2016. Available from\: [LINK]
National Institute of Diabetes and Digestive and Kidney Diseases. P e r i t o n e a l D i a l y s i s . 2022. Available from\: [LINK]
Bruce Blaus. K i d n e y T r a n s p l a n t . 2015. License\: [CC BY-SA]
Singh, M. and Krause, M. C h r o n i c K i d n e y D i s e a s e . C o m p l i c a t i o n s . 2021. Available from\: [LINK]
Singh, M. and Krause, M. C h r o n i c K i d n e y D i s e a s e . P r o g n o s i s . 2021. Available from\: [LINK]

Reviewer

Dr Mahzuz Karim
Consultant nephrologist
Norfolk and Norwich University Hospital

Acute Kidney Injury (AKI)
Glomerular Disease (Glomerulonephropathies)
Haemodialysis
Source\: geekymedics.com