Importance of proteinuria

• Function of the kidney:

  • Produces urine by filtering blood, allowing removal of waste products, excess water, salt, etc., and retention of proteins
  • Synthesizes proteins such as EPO, active vitamin D, and renin
  • Regulates blood pressure and acid-base balance
• Who to test for proteinuria:

  • Should be tested in any routine medical consultation as the test is cheap, non-invasive, reliable, and later aids in management
  • Should be tested in patients with edema, unexplainable ascites or pleural effusion
  • Routinely tested in patients with hypertension, diabetes mellitus, etc.
  • Tested in patients who have a possibility of developing a systemic disease
• Tests for proteinuria is done through dipstick testing
• Albumin/creatinine ration (mg/mmol) can be preformed on small urine sample taken at any time of the day
• ACR x 10 approximates to mg/24 hours (e.g., ACR of 100 mg means it approximates to 1g/24 hours which strongly suggests renal disease)
• In diabetes mellitus, micro-albuminuria is the earliest clinical feature of diabetic nephropathy; may initially be intermittent
• In hypotension, albuminuria suggests a primary renal cause
• In all patients, including in the absence of diabetes or hypertension, albuminuria carries prognostic significance
• Micro-albuminuria is an important risk factor for CVD in the general population
• normal ACR is <3.5
• 3.5 - 3.0 ACR is micro-albuminuria
• > 30 ACR is (macro)albuminuria
• The amount protein in urine is categorised by system of pluses (1+,2+…)
• 2+ proteinuria or more implies intrinsic renal disease and very unlikely to be explained by asymptomatic infection (UTI doesn’t causes major proteinuria or albuminuria)
• Proteinuria quantifies the albumin/creatinine ratio
• proteinuria is used to test kidney renal function (consider systemic disease), and should never be ignored/dismissed
• measurement of excretory renal function can be done by measuring plasma/serum creatinine (plasma is anti-coagulated, so all clotting factors are removed)
• creatinine is produced as a result of muscle metabolism and is normally excreted by kidneys
• creatinine can be used to estimate the GFR, after it is modified for sex, age, race, this is called the modification diet in renal disease (MDRD) formula
• collecting and measuring creatinine in urine and blood to find creatinine clearance rate (urine creatinine/plasma creatinine)
• the excretory renal function can be measured by doing an isotope GFR (usually chromium 51 labeled EDTA), where it is given IV and measured periodically to check how long it takes to dissipate (most accurate way, normally done to ensure kidney unction in donors)
• healthy young adult Caucasian people have approximately 1 million nephrons, black and asian people may have fewer nephrons and the number of functioning nephrons decreases with age
• Around 180 litres of water and small molecules are filtered per day
• congenital nephrotic syndrome causes massive leakage of protein into urine (sometimes occurs in newborn babies), due to podocyte-specific gene (gene for nephrin) and can be treated by dialysis, and may require removal of kidneys
• The presence of blood and protein in the urine implies glomerular disease and an urgent need to test excretory kidney function , consider systemic diseases such as vasculitis, lupus
• investigations for proteinuria include

  • BP, test for diabetes/other systemic diseases, quantify proteinuria, check kidney function, renal ultrasound
  • patients with heavy proteinuria almost certainly need a kidney biopsy (slightly different in young children, doesn’t need biopsy, can be treated by corticosteroids)
• haematuria, whether visible bloods (macroscopic) or non-visible blood (microscopic) can be a sign of serious systemic disease for which diagnosis and treatment is very urgent, weather or not there is also albuminuria
• nephrotic syndrome comprises of oedema, heavy proteinuria, and hypo-albuminaemia (clinically important are thrombotic risk, propensity to infection and often severe hyperlipidaemia)
• nephrotic syndrome may or may not be associated with impairment of excretory kidney function, and dominant symptoms include severe lethargy, reduced exercise tolerance, nausea, and loss of appetite
• causes of nephrotic syndrome include:

  • glomerularnephritis
  • diabetes
  • infection (hepatitis B/C, malaria, HIV)
  • amyloid (deposition of abnormal protein)
• disease where glomerulus is damaged and may present with proteinuria and/or haematuria include:

  • rare genetic/developmental disorders
  • diabetes mellitus
  • vascular disease/ischaemia/age
  • inflammation of blood vessels “vasculitis” isolated or as part of a systemic disease
  • inflammation of glomerulus itself (”glomerulonephritis”, various types)
  • deposition disease e.g., amyloid, myeloma
  • anything which causes damage to blood vessels