Chronic renal failure (CRF)

Causes of CRF:

Congenital/inherited:

• Polycystic kidney disease
• Congenital hypoplasia

Glomerular disease:

• SLE
• DM
• Amyloidosis
• Vasculitis

Vascular disease:

• Arteriosclerosis
• Microscopic polyarteritis
• SLE
• Systemic sclerosis

Tubulointerstitial disease:

• Tubulointerstitial nephritis
• Reflux nephropathy
• TB
• Schistosomiasis

Urinary tract obstruction:

Calculi

Prostatic disease

Pelvic tumours

Retroperitoneal fibrosis

Symptoms of CRF:

When serum urea >40mmols/L:

• Anorexia
• Insomnia
• Nocturia/Polyuria
• Pruritus
• Nausea/vomiting
• Diarrhoea
• Paraesthesiae/tetany (due to polyneuropathy/hypocalcaemia)
• Bone pain (due to metabolic bone disease)
• Peripheral/pulmonary oedema
• Anaemia
• Amenorrhoea in women
• Erectile dysfunction in men

When serum urea >50-60mmols/L:

• Mental slowing
• Clouding of consciousness
• Seizures
• Myoclonic twitching

Examination:

• Short stature – in patients who have had CRF in childhood
• Pallor – due to anaemia
• Increased photosensitive pigmentation – may make the patient look misleadingly healthy
• Brown discolouration of the nails
• Scratch marks – due to uraemic pruritus
• Signs of fluid overload
• Pericardial friction rub
• Flow murmurs:
• Mitral regurgitation - due to mitral annular calcification
• Aortic/pulmonary regurgitation – due to volume overload

Investigations:

Urinalysis:

• Haematuria (e.g. GN)
• Proteinuria (e.g. UTI, DM, if heavy it suggests glomerular disease)
• Glycosuria with normal BM is common in CRF

Urine microscopy:

• WBCs in the urine indicate active bacterial urinary infection
• Eosinophiluria:
• Allergic tubulointerstitial nephritis
• Cholesterol embolism

• Red cell casts strongly suggest GN

Urine biochemistry:

• 24 hour creatinine clearance to assess the severity of CRF
• Urine osmolality

Serum biochemistry:

• Urea and creatinine
• Serum electrophoresis to detect myeloma
• Extreme elevation of CK and hyperkalaemia suggest rhabdomyolysis

Haematology:

• Eosinophilia:
• Vasculitis
• Allergic tubulointerstitial nephritis
• Cholesterol embolism
• Raised viscosity or ESR:
• Myeloma
• Vasculitis

• Haemolysis indicates haemolytic uraemic syndrome

Immunology:

• Autoantibody screening:
• SLE
• Scleroderma
• Wegener’s granulomatosis
• Microscopic polyarteritis
• Goodpasture’s syndrome

Microbiology:

• Urine culture

Radiological investigations:

• Renal US (for renal size and to exclude hydronephrosis)
• Plain AXR (renal calculi)

Renal biopsy:

• Should be considered in every patient with unexplained renal failure and normal-sized kidneys, unless there are strong contraindications

Complications of CRF:

• Anaemia
• Renal osteodystrophy
• Skin disease
• GI complications
• Metabolic abnormalities
• Endocrine abnormalities
• CNS disturbances
• ANS disturbances
• PNS disturbances
• CVS disease

Anaemia:

Anaemia is present in the great majority of patients. Several factors have been implicated:

• EPO deficiency (most important)
• Bone marrow toxins (retained in renal failure)
• Bone marrow fibrosis (secondary to hyperparathyroidism)
• Haematinic deficiency (Fe, folate B₁₂)
• Haemolysis
• Increased blood loss (e.g. occult GI haemorrhage)
• ACE inhibitors (interfere with endogenous EPO release)

Renal osteodystrophy:

• Decreased production of 1α-hydroxylase results in decreased production of 1,25(OH)₂D₃
• Decreased production of 1,25(OH)₂D₃ leads to secondary hyperparathyroidism
• The increased PTH causes:
• Bone resorption
• Hypercalcaemia
• Raised serum ALP

Skin disease:

Pruritus (itching) is common in severe renal failure and is caused (mainly) by the retention of nitrogenous waste products of protein catabolism. Other causes of pruritus include:

Hypercalcaemia

Hyperphosphataemia

Hyperparathyroidism (even if calcium and phosphate levels are normal)

Fe deficiency

GI complications:

• Decreased gastric emptying and increased risk of reflux oesophagitis
• Peptic ulceration
• Acute pancreatitis
• Constipation (especially patients on CAPD)

Metabolic abnormalities:

• Gout
• Decreased insulin catabolism/excretion (therefore, dose must be decreased in insulin-dependent diabetics)
• Dyslipidaemia

Endocrine abnormalities:

• Hyperprolactinaemia
• Increased LH levels in both sexes
• Decreased serum testosterone
• Oligomenorrhoea/amenorrhoea
• Decreased thyroid hormone levels

CNS abnormalities:

Severe uraemia causes:

• Depressed cerebral function
• Asterixis
• Tremor
• Myoclonus

ANS abnormalities:

Increased circulating levels of catecholamines

Impaired baroreceptor sensitivity

Impaired efferent vagal function

PNS abnormalities:

• ‘Restless legs’ syndrome
• Median nerve compression in the carpal tunnel is common

CVS disease:

Increased risk of:

• MI
• Cardiac failure
• Sudden cardiac death
• Stroke

Pericarditis is common and occurs in 2 clinical settings:

• Uraemic pericarditis:
• Haemorrhagic pericardial effusion and atrial arrhythmias are often associated
• Is a danger of pericardial tamponade
• Anticoagulants should be use with caution

• Dialysis pericarditis:

Management of CRF:

BP control:

• Aim for around 130/80mmHg
• ACE inhibitors are believed to be the most beneficial in renal failure

Hyperkalaemia:

• Usually responds well to dietary restriction of potassium
• Drugs which cause potassium retention should be stopped

Acidosis:

• Correction of acidosis helps to correct hyperkalaemia in CRF and may also decrease muscle catabolism
• Sodium bicarbonate supplements are often effective, but may cause oedema and HT (owing to ECF expansion)

Control of calcium and phosphate levels:

• Hypocalcaemia and hyperphosphataemia should be treated aggressively, preferably with regular (e.g. 3 monthly) measurements of serum PTH to assess how effectively hyperparathyroidism is being suppressed
• Oral calcium carbonate acts as a calcium supplement and also reduces the bioavailability of dietary phosphorus

Dietary restrictions:

• In advanced renal disease, reduction of protein lessens the amount of nitrogenous waste products generated, and this may delay the onset of the symptoms of uraemia
• Most patients with renal impairment will require a diet restricted in sodium and potassium
• Prolonged dietary protein restriction should be avoided. It is preferable to commence renal replacement therapy a little earlier than to cause malnutrition