Summary

Chronic renal failure involves a long-standing and often deteriorating reduction in renal function. It is irreversible and generally appears over a period of years. initially, CRF begins as only biochemical abnormalities, but eventually it will result in clinical symptoms. When it does so, it is often referred to as uraemia.
Once reaching a stage where death is imminent without renal replacement therapy, it is referred to as ESRF, i.e. end-stage renal failure.

Epidemiology

  • Chronic renal failure is of particular importance in terms of cost to the NHS; about 630 patients per 1 million are kept alive by renal replacement therapy, and the incidence of new patients having such treatment is about 110 per 1 million.
  • In the USA, incidence is about 3 times higher than in the UK; over half of CRF patients in the US are diabetics.
  • There is a much higher incidence of ESRF in black populations than in white populations.
  • CRF due to atherosclerotic vascular disease in the renal artery is more common in elderly patients than in young patients.

Causes

  1. Congenital/inherited, e.g. polycystic kidney disease, Alport’s syndrome, medullary cystic disease, tuberose sclerosis
  2. Renal artery stenosis
  3. Hypertension
  4. Glomerular disease, e.g. IgA nephropathy, Wegerner’s granulomatosis, amyloidosis, diabetic glomerulosclerosis, thrombotic thrombocytopaenic purpura, sickle cell disease
  5. Interstitial diseases, e.g. reflux neuropathy, TB, schistosomiasis, multiple myeloma
  6. Systemic inflammatory disease, e.g. SLE, vasculitis
  7. Diabetes mellitus
  8. Unknown – accounting for between 5 and 20% of cases

Signs and symptoms

One of the most useful signs is bilaterally small kidneys on USS.   The early stages of CRF are often completely asymptomatic.   Urea and creatinine levels are usually measured, and there is a rough correlation between these levels and the severity of disease. Symptoms become apparent when serum urea concentration reaches 40 mmol/L.; however, many patients experience symptoms at lower concentrations than this, which may include malaise, loss of appetite, insomnia, nocturia and polyuria due to inability to concentrate urine, itching due to high levels of urea, N/V/D, symptoms of anaemia, peripheral and pulmonary oedema, bruising, bone pain due to metabolic bone disease.
In more advanced uraemia, i.e. 50-60 mmol/L , the forementioned symptoms tend to be more severe, and there may be CNS symptoms such as mental slowing, seizures, or myoclonus.
Eventually there may also be oliguria, which tends to occur in ARF and in the very late stages of CRF.

Disease Staging

There are 5 stages of CKD. Symptoms only usually occur once stage 4 is reached.
Stage
Description
GFR (ml/min/1.73cm2)
Action
1
Some sort of kidney damage present which has been detected by urine test or imaging studies. GFR is normal or high
>90
Investigate more thoroughly – check for proteinuria and haematuria.
2
Kidney damage with slightly low GFR
60-89
Renoprotection control blood pressure and modify diet, i.e. low protein.
3
Moderate reduction in GFR
30-59
4
Severely low GFR
15-29
Prepare for renal replacement therapy if appropriate.
5
Kidney failure
<15 or dialysis

Investigations

Blood

  • Reduced haemoglobin, i.e. normochromic, normocytic anemia
  • ESR – if this is raised it suggests myeloma or vasculitis
  • U+E – raised urea and raised creatinine
  • Glucose – check for diabetes
  • Decreased calcium
  • Increased phosphates
  • Raised parathyroid

Urine

  • Haematuria – can differentiate glomerulonephritis from chronic renal failure; also rules out other conditions.
  • Proteinuria – if this is heavy it is strongly suggestive of glomerular disease.
  • Glycosuria – this is common even with normal blood glucose in CRF.
  • Casts – suggestive of renal disease; highly suggestive of glomerulonephritis.
  • White cells – suggestive of infection.
  • Red cells – can come from anywhere along the urinary tract, so their presence is not particularly useful in diagnosing CRF.
  • 24-hour creatinine clearance – useful in determining the level of renal failure.
  • Urinary electrolytes – an unhelpful investigation.
  • Urine osmolality – this is low in cases of high fluid intake, but it is also low when fluid intake is inadequate in renal disease; demonstrates that the kidney is unable to concentrate urine.

Progression of CRF

CRF progression can be monitored by examining creatinine levels. Normal creatinine is 70-150 μmol/L. Once levels exceed 300 μmol/L there is usually trouble! Beyond this stage, renal replacement therapy is inevitable.

Further Information

Differentiating ARF and CKD
The following factors can help differentiate between chronic and acute renal failure, but remember they are not always present!
Acute renal failure (ARF)
Chronic renal failure (CRF)
Normal sized kidneys
Small kidneys, increased echogenicity
No anaemia
Anaemia, i.e. normochromic, normocytic – check Hb
No diabetes
Diabetes
Low BP
Raised BP
Rapid change in urea/creatinine
Gradual onset of symptoms
Oliguria normally present
Oliguria only present in later stages; polyuria and nocturia often present in less advanced disease
Not often CNS symptoms
CNS symptoms in later disease
Symptoms a bit like “shock”
Symptoms more like serious extensive disease
Chronic renal failure involves a long-standing and often deteriorating reduction in renal function.  It is irreversible and generally appears over a period of years.  Initially, CRF begins as only biochemical abnormalities, but eventually it will result in clinical symptoms.  When it does so, it is often referred to as uraemia.
Once reaching a stage where death is imminent without renal replacement therapy, it is referred to as ESRF, i.e. end-stage renal failure.
In most cases, nothing can be done reverse the disease process.  Exceptions involve cases of UT obstruction, Goodpasture’s syndrome, and cases where narrowing of the renal arteries can be corrected.  Although irreversible, the rate of deterioration can usually be slowed.

Epidemiology

  • Chronic renal failure is of particular importance in terms of cost to the NHS.  About 630 patients per 1 million are kept alive by renal replacement therapy, and the incidence of new patients having such treatment is about 110 per 1 million.
  • In the USA, incidence is about 3 times higher than in the UK; over half of CRF patients in the US are diabetics.
  • There is wide geographic variation in the incidence of conditions that cause CRF.
    • Malaria is the main cause of CRF throughout Africa.
    • Schistosomiasis – this is a parasitic disease caused by several species of fluke. The disease is most commonly found in parts of the Far East, Middle East and Africa where the water supply contains numerous freshwater snails carrying the parasite. After penetrating the skin, snail larvae affected by the parasite move into systemic circulation and then into portal circulation, maturing in the liver. Moving into veins surrounding the bladder, they then lay eggs which cross the urethral or bladder wall causing long-standing urinary obstruction which results in CRF.
  • There is a much higher incidence of ESRF in black populations than in white populations.  In this ethnic group CRF tends to be caused by hypertensive nephropathy.
  • The incidence of diabetes, and thus diabetic nephropathy tends to be higher in Asian populations than in white populations.
  • CRF due to atherosclerotic vascular disease in the renal artery is more common in elderly patients than in young patients.

Causes

As there are numerous causes of CRF, only the most common ones are listed below.
Cause
Proportion accounting for all cases of ESRF
Examples
Congential/inherited
5%
Polycystic kidney disease, Alport’s syndrome, medullary cystic disease, tuberose sclerosis
Renal artery stenosis
5%
Hypertension
5-25%
The wide variation here could be due to racial difference or diagnostic differences – we do not know!
Accelerated hypertension
Glomerular diseases
10-20%
IgA nephropathy, Wegener’s granulomatosis, amyloidosis, diabetic glomerulosclerosis, thrombotic thrombocytopenic purpura, sickle cell disease
Interstitial diseases
5-15%
Reflux nephropathy, tuberculosis, schistosomiasis, multiple myeloma, renal papillary sclerosis, Chinese herb nephropathy
Systemic inflammatory disease
5%
SLE, vasculitis
Diabetes mellitus
20-40%
There are significant racial and regional differences in numbers diagnosed with DM who go on to develop ESRF.
Unknown
5-20%
A very careful history needs to be collected, paying close attention to…
  • The duration of symptoms
  • Drug history – including NSAIDs, anti-inflammatories and other medication use; don’t forget to  take into account the use of herbal remedies
  • Family history of renal disease
  • Diabetes
  • Known hypertension
  • Previous occasions on which a kidney function test has been taken, e.g. for medical insurance, new job or new patient check, etc.
CRF can be caused by any pathology that destroys the normal structure and function of the kidney.
One of the most useful signs is bilaterally small kidneys on USS.

Symptoms

The early stages of CRF are often completely asymptomatic.
 
Urea and creatinine levels are usually measured, and there is a rough correlation between these levels and the severity of disease.
  • Although urea on its own is not a particularly toxic substance, the overall effect of all the metabolites of protein metabolism is what accounts for the problematic nature of living with CRF.  This is confirmed by the fact that restricting dietary protein can reduce the symptom severity.
Symptoms become apparent when serum urea concentration reaches 40 mmol/L. However, many patients experience symptoms at lower concentrations than this.  Symptoms may include:
  • Malaise
  • Loss of appetite
  • Insomnia
  • Nocturia and polyuria due to inability to concentrate urine
  • Itching due to high levels of urea
  • Nausea, vomiting and diarrhoea
  • Parasthesia due to polyneuropathy
  • ‘Restless leg syndrome’
  • Bone pain due to metabolic bone disease
  • Peripheral and pulmonary oedema due to salt retention
  • Symptoms of anaemia
  • Amenorrhoea
  • Erectile dysfunction
  • Bruising
In more advanced uraemia, i.e. 50-60 mmol/L , the aforementioned symptoms tend to be more severe, and there may be others, including CNS symptoms:
  • Mental slowing, clouding of consciousness, seizures
  • Myoclonic twitching – myoclonus is where a particular group of muscles will twitch involuntarily, e.g. hiccups are a kind of myoclonic jerk affecting the diaphragm; in severe disease, it is generally one of the last signs to show after other symptoms are already present.
Eventually there may also be oliguria, which tends to occur in ARF and in the very late stages of CRF.
Urine output is NOT a good guide for renal function.  A low GFR can still result in a very high urine output due to failure of reabsorptive mechanisms.

Examination

There are generally very few signs of uraemia.  There may or may not be apparent:
  • Short stature – due to chronic renal failure in childhood
  • Pallor – i.e. pale colour due to anaemia
  • Increased photosensitive pigmentation – which may make the patient appear misleadingly healthy
  • Brown discolouration of the nails
  • Scratch marks – the patient may feel itchy due to the high levels of urea in the body
  • Signs of fluid overload – see under ‘Management of ARF’ for details of these
  • Pericardial friction rub
  • Glove and stocking sensory loss – rare
The kidneys themselves are generally not palpable unless they are enlarged from polycystic disease, obstruction or tumour.
Always perform rectal and vaginal examination – this may disclose the underlying cause of the disease, for example, urinary tract obstruction.
There may also be signs of other underlying conditions, such as retinopathy in diabetes, evidence of peripheral vascular disease, evidence of spina bifida, and other causes of neurogenic bladder.

Disease Staging

There are 5 stages of CKD. Symptoms only usually occur once stage 4 is reached.
Stage
Description
GFR (ml/min/1.73cm2)
Action
1
Some sort of kidney damage present which has been detected by urine test or imaging studies.  GFR is normal or high
>90
Investigate more thoroughly – check for proteinuria and haematuria.
2
Kidney damage with slightly low GFR
60-89
Renoprotection control blood pressure and modify diet, i.e. low protein.
3
Moderate reduction in GFR
30-59
4
Severely low GFR
15-29
Prepare for renal replacement therapy if appropriate.
5
Kidney failure
<15 or dialysis

Investigations

Blood

  • Reduced haemoglobin, i.e. normochromic, normocytic anemia
  • ESR – if this is raised it suggests myeloma or vasculitis
  • U+E – raised urea and raised creatinine
  • Glucose – check for diabetes
  • Decreased calcium
  • Increased phosphates
  • Raised parathyroid

Urine

  • Haematuria – can differentiate glomerulonephritis from chronic renal failure; also rules out other conditions.
  • Proteinuria – if this is heavy it is strongly suggestive of glomerular disease.
  • Glycosuria – this is common even with normal blood glucose in CRF.
  • Casts – suggestive of renal disease; highly suggestive of glomerulonephritis.
  • White cells – suggestive of infection.
  • Red cells – can come from anywhere along the urinary tract, so their presence is not particularly useful in diagnosing CRF.
  • 24-hour creatinine clearance – useful in determining the level of renal failure.
  • Urinary electrolytes – an unhelpful investigation.
  • Urine osmolality – this is low in cases of high fluid intake, but it is also low when fluid intake is inadequate in renal disease; demonstrates that the kidney is unable to concentrate urine.

Progression of CRF

CRF progression can be monitored by examining creatinine levels.  Normal creatinine is 70-150 μmol/L. Once levels exceed 300 μmol/L there is usually trouble!  Beyond this stage, creatinine levels tend to rise exponentially; thus, by plotting  1/creatinine, a straight, declining line graph will result, parallel to a straight, declining line graph of GFR.  The rate of decline varies between individuals, but will be fairly constant for one particular individual.  This graph can be used to predict when dialysis will be needed.

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