CHRONIC RENAL FAILURE

DEFINITION
A syndrome of progressive and irreversible loss of kidney function, resulting in permanant impairment of solute waste excretion.
Med school notes.

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INCIDENCE

Relatively common in the elderly.
- 2/10,000 people have end-stage renal failure.
Age
Highest in >75 year old.
Ethnicity
Higher in non-Europeans.
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AETIOLOGY

Congenital:
Polycystic kidney disease
Medullary cystic disease
Alport's syndrome.

Acquired:
Pyelonephritis
Renal tuberculosis.
Haemolytic uraemic syndrome
Glomerulonephritis
Scleroderma / SLE / vasculitis.
Myeloma.
Renal artery stenosis
DM
Nephrocalcinosis
Diuretic therapy
NSAIDs
ACE inhibitors
Interstitial nephritis
Radiation nephritis.
Hypertension.
Amyloidosis.
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BIOLOGICAL BEHAVIOUR

Pathophysiology

Often symptom-free until ~2/3 of renal mass lost
- intact nephrons increase flow and filtration to compensate for initial loss.

An increase in renin secretion causes hypertension and (later) oedema.

The ability for the kidney to concentrate urine is lost early
--> polyuria/nocturia
- especially in medullary disease (concentrating ability is lost earlier).


Complications
Renal impairment and the accompanying buildup in toxins (particularly urea) leads to disease in several organ systems:

Bone
Secondary hyperparathyroidism (with occasional tertiary hyperparathyroidism) due to low calcium levels.
Osteomalacia due to insufficient Vit D synthesis.
Adynamic bone disease.

Blood
Anaemia (lowered EPO production).
Poor platelet function - competitive inhibition of vWF receptor by urea.
Poor neutrophil function - inhibition of chemotactic factors.

Endocrine
Proteinaceous hormones are metabolised by the kidney (e.g. insulin, gastrin, glucagon) -> hypoglycaemia, gastric ulcers.
Lowered testosterone.
Increased LH and prolactin.
Raised renin (5%).
Abnormal growth hormone cycles.

Electrolytes
Urine dilution and concentration deranged.
Acidosis
Hyperkalaemia
Hypocalcaemia.

Cardiovascular
Hypertension, heart failure.
Pericarditis.
Valve calcification.

Gastrointestinal
Anorexia, nausea, vomiting, diarrhoea, uraemic fetor, malnutrition.

Dermatological
Pallor and pigmentation.
Pruritis.
Ecchymoses.

Nervous
Peripheral neuropathy.
Proximal myopathies.
Restless Leg syndrome.
Carpal tunnel syndrome.
Stupor, fits, asterixis.

Psychological
Depression, anxiety.
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MANIFESTATIONS

Symptoms

Local
Oliguria, anuria, polyuria, nocturia
--> any of these changes is possible depending on cause.

Systemic
Progressive lethargy and fatigue
Anorexia & vomiting
Fluid gain & oedema
Itchy and purpuric skin.

Complications
As for conditions outlined above.

Signs

Observe
Increased photosensitive pigmentation, brown nails, pallor, uraemic fetor.
Other physical signs eg vasculitic skin lesions may suggest the diagnosis.

Palpate
Arrythmias, displaced apex beat.
Prostatic enlargement should be noted.

Auscultate
Pericardial friction rub, bibasal lung crackles, hypertension, murmurs.

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INVESTIGATIONS

Biochemistry
Creatinine chronically >0.12mmol/L
Serum urea is >50mmol/L.
Hypocalcaemia, hyperphosphataemia, hyperkalaemia
Partially compensated metabolic acidosis.
Alk phosphatase elevation implies problem is chronic.

FBC
Normocytic, normochromic anaemia.

Urine
Heavy proteinuria or haematuria with casts suggests a primary renal insult
- ?diabetic nephropathy, amyloidosis, focal glomerulosclerosis.
Sterile pyuria suggests analgesic nephropathy or TB.
White cell casts suggest urinary tract infection, red cell casts suggest glomerulonephritis
Eosinophiluria suggests toxic interstitial nephritis.

Radiology
Ultrasound will exclude obstruction and help gauge kidney size
- smaller kidneys tends to mean more chronic disease.
Bone disease may be revealed on plain films of hands, clavicles, pelvis and spine.
Chest X-ray may reveal effusions, oedema and cardiomegaly.

Histology
Only done in normal-sized kidneys to diagnose acute cause.

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MANAGEMENT

Conservative
Extracellular fluid volume
Needs accurate assessment
- via JVP, regular weight monitoring, blood pressure etc.

Diet
Adequate energy, with some protein restriction and low fat.
Phosphate restriction can be achieved through protein restriction.


Medical
Prescribing
Reduce doses in current drug regime to reflect declining renal function.

Rigorous BP control
Aiming for 130/80: ACEis, Ca channel blockers, possibly diuretic.
- talk to a physician
- ACEi lowers intraglomerular pressure and is a first line treatment.
- Ca channel blockers (diltiazem, verapamil, not dihydropyridines) have been shown to slow decline in renal function.

Statins
Lower lipid levels but do not improve the outcome.

EPO
Can be used to correct anaemia (but is expensive).

Bicarbonate
Correction of acidosis with bicarbonate can be considered.

Early referral
Particularly in patients with serum creatinine of 0.6-0.8mmol/L) to a renal physician, for discussion of dialysis and transplant options.

Surgical
Transplant
The most effective and cost-efficient form of renal replacement therapy.
- a healthy donor kidney can come from either a living donor or a brain-dead cadaveric donor.
- matched based on blood-group and HLA match.
Operation is 2-3 hours, patient remains in hospital 7-10 days.
- after transplant, 10-30% develop acute tubular necrosis, as well as massive polyuria.
Transplant patients are given an anti-rejection drug cocktai
- contains cyclosporin, azothiaprine and prednisone, with antimicrobials and antihypertensives.

Complications
Include wound infection, rejection, increased risk of skin cancer (about 50% incidence after 15 years post-transplant).
Negative prognostic factors include comorbid cardiovascular or neoplastic disease, increased age and diabetes.
5 year survival is ~70% for 20-54 year olds, ~20% for older.
- if diabetic, the figures are 20% and 10% respectively.
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