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	Formula for GFR		Creatinine clearance formula
	Acute on chronic		Proteinuria
	Hypertension		Low-protein diet
	Secondary hyperparathyroidism		Anaemia
	Hyperlipidaemia		Hyperhomocystinaemia

The separation of renal failure into mild, moderate or severe is arbitrary. The British National Formulary (BNF) definition of mild renal failure as a glomerular filtration rate (GFR) of between 20-50ml/min is the one used here.

Most clinicians use serum creatinine as a measure of renal function. But it must be related to the patient's age, weight and sex to avoid an underestimation of GFR. For example, 75kg, 25-year-old male and a 50kg, 75-year-old female with the same GFR (25ml/min) will have serum creatinines of approximately 414umol/l and 136umol/l, respectively.

A useful approach, therefore, is to calculate the GFR using a formula such as the Cockcroft and Gault formula. Here:

GFR	=	(140 - age) x weight in kg x 1.2 for males [or x 1.05 for females]
		Serum Creatinine

This formula is reasonably accurate in mild to moderate renal failure. Alternatively, a 24-hour urine collection for creatinine clearance may be used.

Creatinine Clearance (ml/min)	=	Urinary creatinine (umol/l) in 24 hours x 0.7
		Serum Creatinine (umol/l)

(you can access a calculator for this formula - by clicking here)

An incomplete collection of urine is the major source of error in this test. It also tends to overestimate GFR at more severe levels of chronic renal failure (CRF).

When an accurate test of glomerular filtration is needed, it is best to measure the clearance of a radioisotope such as 51CrEDTA or 99Tc DTPA.

Principles of management

Identify and treat any reversible cause of renal dysfunction

Patients with mild CRF can experience a sudden worsening of renal function which is potentially reversible, so-called "acute on chronic renal failure".

They are more susceptible to the effects of hypotension, fluid losses or sepsis. Early and adequate fluid replacement can minimise the risk of acute renal dysfunction.

Controlled trials have shown that intravenous (IV) 0.9% saline administered at rate of 1ml/kg patient weight/hour for 12 hours to patients with mild CRF, both before and after angiography or pancreatic surgery decreases the risk of acute renal failure (ARF). Nephrotoxic drugs, such as non-steroidal anti-inflamatory drugs, aminoglyosides, radiocontrast agents, ACE inhibitors and angiotension receptor blockers, should be used only with caution and renal function monitored closely.

A renal ultrasound to rule out urinary-tract obstruction is indicated in all patients with unexplained acute renal dysfunction.

Reducing rate of progression of renal failure

Reduce proteinuria: To compensate for nephron loss in CRF, hyperfiltration of the remaining nephrons occurs. This produces glomerular hypertension and hypertrophy, and eventually sclerosis. This manifests histologically as focal segmental glomerulosclerosis and, clinically, as proteinuria.

The proteinuria also believed to contribute to the renal injury.

The severity of the proteinuria correlates with the rate of progression of the renal failure: for each gram proteinuria/24 hours, the approximate loss in GFR = 1ml/min/year.
Evidence-based medicine supports the use of ACE inhibitors to reduce proteinuria and slow the progression of CRF in

		all forms of diabetic nephropathy; and
		patients with proteinuria > 1g/24 hours and mild CRF.

The effect appears to be greatest if this treatment is begun early.

Patients with proteinuria should have yearly, 24-hour urine collection to quantify risk and to monitor response to treatment. The target should be to decrease proteinuria to <1g/24 hours.

Hypertension: Hypertension is present in most patients and adds to the renal injury. The target should be to normalise blood pressure (=130/85 mmHg). Combination therapy is needed to achieve adequate control.

Hypertension in CRF is volume dependent and loop diuretics are particularly important. (Thiazide diuretics lose their efficacy in moderate CRF).

An ACE inhibitor appears to confer additional benefit.

Low-protein diet: Despite animal studies suggesting that a low-protein diet improves renal haemodynamics and decreases proteinuria, results from human studies are conflicting.

The benefit from very-low-protein diets appears to be slight and carries the risk of malnutrition. An acceptable compromise is to restrict protein intake to 0.8 -1.0 g/kg/day biased in favour of first-class protein.

Treating complications

In mild CRF, fluid and electrolyte balance is usually well preserved. The main problems related to renal osteodystrophy and anaemia.

Secondary hyperparathyroidism is very common. Hypocalcaemia due to calcitrol deficiency is the main contributing factor to this in mild CRF.

Serum phosphate is generally low/normal until the GFR <20mls/min (owing to parathyroid-hormone (PTH) induced phosphaturia).

If hyperphosphataemia develops, restrict phosphate in diet and use a phosphate binder such as calcium carbonate to limit absorption of phosphate.
In mild CRF, normalising the PTH does not appear to induce adynamic bone disease. (This is in contrast to moderate or severe CRF, where a PTH two to three times normal is recommended to avoid this complication).

Calcitrol, or 1alpha-hydroxylcholecalciferol, in low doses (125-250ug/day) has been advocated for patients with hyperparathyroidism or hypocalcaemia in mild CRF. The major side-effect here is hypercalcaemia.

Anaemia of chronic renal failure is due primarily to reduced production of erythropoietin by the kidney. Anaemia, defined as a haemoglobin (Hb) < 11g/dl, typically develops with a GFR < 30ml/min.

Anaemia is treated with subcutaneous erythropoietin administered twice or three times weekly.

Other problems to watch for include metabolic acidosis, which can develop as GFR falls. Normalisation of serum bicarbonate is recommended and sodium bicarbonate may be needed to achieve this. The major drawback with this treatment is volume expansion and hypertension.

Hyperlipidaemia is common, particularly hypertriglyceridaemia. This should be treated in the standard way. A lower target level for cholesterol should be considered, given the high cardiovascular morbidity in CRF.

Hyperhomocysteinaemia is a documented independent risk factor for atherosclerosis in both the normal and the CRF patient. In CRF, there is altered renal metabolism of homocysteine and resistance to high dose folic acid supplementation has been documented. Whether reduction of homocysteine levels in this population improves vascular risk has yet to be demonstrated.

Referral to a nephrologist
The Renal Association recommends that all patients who appear to have progressive renal insufficiency and a plasma creatinine above 150umol/l and/or rapidly rising creatinine concentrations should be referred to a nephrology service for assessment and follow up.

Early referral of patients with mild CRF:
		Results in lower costs and/or decreased morbidity and mortality.
		May delay or prevent the need for dialysis.
		Helps prepare the patient psychologically for dialysis.