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Estimating GFR using serum urea and creatinine

Urea and creatinine excreted by kidneys, accumulate in the blood when renal function is impaired.

Excess renal capacity - neither one rises substantially until GFR falls to around 30mL/min from a normal value of around 120ml/min.

Urea increased by: high protein intake or catabolic state
Urea decreased by: liver disease, over hydration

Urea is freely filtered, but there is also some tubular reabsorption, which is increased (along with sodium) by dehydration or reduced renal perfusion, causing a greater elevation in urea than creatinine.

Creatinine is increased in patients with large muscle bulk.


What is the clearance method for estimating GFR?

When substance is filtered, initial concentration in the filtrate is the same as plasma. If there is neither reabsorption or secretion, the quantity of the substance excreted in final urine, in 1 min, is equal to quantity removed from plasma by filtration in 1 min.

Amount is excreted is calculated by multiplying urine concentration by urine flow rate per min. This concentration MUST equal the plasma concentration multiplied by GFR (volume of filtrate formed in 1 min). By measuring plasma and urine concentration of a substance and the urine flow rate per minute, the GFR can be calculated.


Use of creatinine clearance

Creatinine clearance provides routine estimate of GFR. But 24h urine collection is needed to calculate urine flow rate in ml per min. Creatinine clearance overestimates GFR because of tubular creatinine secretion. This secretion, and the error, increase when GFR is low. Cimetidine and trimethoprim inhibit creatinine secretion and so raise blood concentration and reduced measured creatinine clearance.


Most common method of measuring GFR

Modification of diet in renal disease (MDRD) is MC method
- uses serum creatinine and factors in patients age, weight, height, ethnicity and gender


When should creatinine over estimated GFR (eGFR) be used for monitoring in CKD?

eGFR is decreased by 50% once serum creatinine rises above reference range, therefore creatinine is not useful for identifying early CKD use eGFR instead. eGFR is not useful for monitoring late CKD, use creatinine instead.


Other biochemical tests useful in renal disease

Serum albumin levels - low in nephrotic syndrome
Lipids - raised in nephrotic syndrome
Electrophoresis of plasma proteins can demonstrate excess of monoclonal immunoglobulins - myeloma or B cell neoplasms
- urine electrophoresis may show leakage of free Ig light chains into the urine

Myoglobin in the blood or urine suggests rhabdomyolysis
Free haemoglobin in the blood or urine suggests haemolysis
ABG - acid base disturbances


Urinary dipstick

Standard dipsticks - presence of protein, blood and glucose; "multi-stix" also assess pH (normally 5-6; pH >8 may suggest renal tubular acidosis), leukocytes (vaginal contamination or infection) and nitrite (broken down from nitrates by some bacteria - infection)

Do not detect urinary free light chains (Bence Jones proteins) so urine immunoelectrophoresis is required

Microalbuminuria will not be detected with standard dipsticks


How much protein is normally lost in the urine?

Normal urinary protein excretion is <150 mg/day; should consist of <20 mg albumin, tubular secreted proteins and immunoglobulin



Hallmark of early diabetic nephropathy; also prognostically important for cardiovascular mortality risk in hypertensive patients

= albumin excretion 30-250 mg/day


How should proteinuria be quantified?

Either urinary albumin: creatinine ratio (uACR) or protein: creatinine ratio (uPCR). The uACR is routinely used in screening of patients with diabetes.

Individuals pass around 10 mmol urinary creatinine each day:
- uPCR or ACR of 100 mg/mmol = 1000mg protein or albumin/ day
- uACR of 5 mg/mmol = 50 mg albumin/ day = microalbuminuria


What causes significant non nephrotic proteinuria?

(e.g. dipstick + to +++, 0.2-3.5 g/24h) is usually suggestive of renal parenchymal disease (unless due to a urinary tract infection).

Nephrotic range proteinuria (>3.5 g/24h, dipstick ++++) is virtually always due to glomerular disease.


Non renal causes of proteinuria

Severe exercise
Skin disease (e.g. severe exfolitation, psoriasis)
Lower urinary tract infection (e.g. cystitis)


What is orthostatic proteinuria?

Describes proteinuria detectable after the patient has spent several hours in the upright position; it disappears when the patient is lying flat so first early morning urine should test negative.

Proteinuria is usually <1 g/24h; there is no heamaturia and renal function and BP are normal. Renal biopsy samples are usually normal, benign condition


What can be tested for on urine microscopy?

1) Red cells: >2-3/ high power field is pathological (microscopic haematuria); cells are dysmorphic in glomerular bleeding, but appear normal when from the lower urinary tract

2) Leukocytes: infection, and some cases of glomerular and interstitial disease

3) Crystals: e.g. oxalate, struvite, cystine and with polarised light, uric acid

4) Casts: there are several types:
- TUBULAR CELLS - ATN or interstitial nephritis
- HYALINE - Tamm-Horsfall glycoprotein (normal)
- GRANULAR - non specific
- RED CELLS - GTN or tubular bleeding
- LEUKOCYTES - pyelonephritis or ATN


Causes of urinary discolouration

Myoglobinuria (brown)
Beetroot consumption
Alkaptonuria (urine brown on exposure to the air)
Obstructive jaundice (yellow)
Drugs (e.g. rifampicin, aminosalicylic acid)
Porphyria (urine dark brown or red on standing)

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