Kidney Function Tests PDF

J.M.U kidney Kidney function tests Theoretical lec. 1 Date 27\1\2025 Semester 2nd Presenter name: Dr. Iman M. Jebur Learning objectives Identify common laboratory tests used to assess kidney function: Blood Urea Nitrogen (BUN), serum creatinine, and the Glomeru...

J.M.U kidney Kidney function tests Theoretical lec. 1 Date 27\1\2025 Semester 2nd Presenter name: Dr. Iman M. Jebur Learning objectives Identify common laboratory tests used to assess kidney function: Blood Urea Nitrogen (BUN), serum creatinine, and the Glomerular Filtration Rate (GFR). Define uremia (abnormally high BUN in the blood) and azotemia (elevated plasma concentrations of both urea and creatinine in renal insufficiency). Differentiate among prerenal, renal (intrinsic), and postrenal causes of elevated BUN and how each reflects different pathophysiological processes. Use the BUN/Creatinine ratio as a crude indicator to discriminate prerenal, renal, and postrenal azotemia. Calculate creatinine clearance and explain how it estimates GFR. Identify factors that can affect plasma creatinine levels (e.g., muscle mass, certain drugs, age, sex). Define GFR as the volume of filtrate formed per unit time by all nephrons in both kidneys. List substances used to measure/estimate GFR (e.g., inulin, creatinine, cystatin C). [email protected] https://jmu.edu.iq/ar/ 2 Learning objectives Classify acute renal failure as prerenal (reduced renal perfusion), intrinsic (renal parenchymal damage), or postrenal (obstruction to urine flow). Explain how purine catabolism leads to uric acid production and how it is excreted (70% via kidney, 30% via the gut). Define hyperuricemia and outline its clinical consequences (e.g., gout, renal stones). Distinguish between primary and secondary causes of gout (overproduction vs. reduced excretion of uric acid). Classify proteinuria into three main types: glomerular, overflow, and tubular proteinuria. Correlate glomerular damage with increased filtration of larger proteins (e.g., albumin). Define microalbuminuria (30–300 mg/day) and recognize its significance as an early indicator of diabetic or hypertensive nephropathy. Interpret protein/creatinine ratio to assess the degree of proteinuria and identify nephrotic-range proteinuria (>1000 mg/day). Clinical Applications Integrate the above concepts to interpret laboratory data in patients with suspected kidney disease, gout, or diabetic nephropathy. Explain how understanding BUN, creatinine, GFR, uric acid, and proteinuria contributes to diagnosing and managing kidney dysfunction. [email protected] https://jmu.edu.iq/ar/ 3 Functions of kidney The functions of the kidneys include: Regulation of water, electrolyte and acid–base balance excretion of the products of protein and nucleic acid metabolism: e.g. urea, creatinine and uric acid. The kidneys are also endocrine organs, producing a number of hormones, and are subject to control by others Fig (2). Arginine vasopressin (AVP) acts to influence water balance, and aldosterone affects sodium reabsorption in the nephron. Parathyroid hormone promotes tubular reabsorption of calcium, phosphate excretion and the synthesis of 1,25-dihydrocholecalciferol (the active form of vitamin D). Renin is made by the juxtaglomerular cells and catalyses the formation of angiotensin I and ultimately aldosterone synthesis. [email protected] https://jmu.edu.iq/ar/ 4 Functions of kidney Make the photos take enough space [email protected] https://jmu.edu.iq/ar/ 5 Renal Function Tests Some of tests are used for assessment of renal function : 1-Blood urea and blood urea nitrogen (BUN). 2-Serum creatinine 3-Glomerular filtration rate ( GFR) Note: nitrogen (N) containing substances are classified into two main groups 1- Protein nitrogen (proteins) : like different proteins 2- Non protein nitrogen (NPN) : Urea is the major NPN and form more than 75% of the total NPN. Other NPNS are amino acid, uric acid , creatinine , creatine and , ammonia. [email protected] https://jmu.edu.iq/ar/ 6 Renal Function Tests Urea (CO{NH2}2 ) is the major nitrogen containing metabolic product of protein catabolism in human.The biosynthesis of urea is from ammonia (NH3) which derived amino nitrogen which is carried out exclusively by hepatic enzymes of the urea cycle. Proteolysis Transamination and oxidative deamination In liver Urea cycle Protein--------------→ amino acid-------------------------→ NH3 ---------------------→urea Note : more than 90% of urea is excreted through the kidneys. Losses of urea through the gastrointestinal tract and skin account for most of the remaining fraction. [email protected] https://jmu.edu.iq/ar/ 7 Renal Function Tests Uremia : it is abnormal high urea nitrogen in blood. Aazotemia: it is significant increase in the plasma concentration of urea and creatinine in kidney insufficiency Causes of uremia Prerenal uremia : urea concentration is increased but creatinine concentration may be normal. prerenal uremia is caused by extra-renal factor like High protein diet Increase protein catabolism as in stress ,fever, sever burn Reabsorption of of blood protein after gastrointestinal hemorrhage. Treatment with cortisol. Dehydration. Heart Failure (decrease [email protected] renal perfusion ) https://jmu.edu.iq/ar/ 8 Renal Function Tests 2-Renal uremia: it is caused by diminished glomerular filtration as in acute or chronic renal disease ex. Acute and chronic glomerulonephritis ,polycystic kidney disease. in which the urea and creatinine may be increased 3-Postrenal uremia :it is usually result from obstruction in pathway of urine , in which the urea is reabsorbed into the circulation ex. malignancy , stones, prostate gland enlargement. in this condition there is often greater increase in plasma urea than creatinine. [email protected] https://jmu.edu.iq/ar/ 9 Serum Creatinine Creatinine is the cyclic anhydride of creatine that is produced as a the final product of decomposition of phosphocreatine.It is excreated in urine. Creatine is synthesis in the kidneys ,liver and pancreas ,then creatine is transported by blood to other organs such as muscle and brain where it is phosphorylated to phosphocreatine ,it is a high energy compound.The stored creatine phosphate in the muscle serves as an immediate store of energy in the muscle which is used in muscle contraction. The amount of creatinine is related to the muscle mass. [email protected] https://jmu.edu.iq/ar/ 10 Serum Creatinine Clinical Significance 1-Creatinine is freely filtered by glomeruli of the kidney with small percentage (7-10%) secreted by the renal tubules and not reabsorbed under normal circumstances. 2-There is relatively constant excretion of creatinine in the urine. 3-In renal disease the creatinine excretion is impaired and reflected by increased creatinine in the blood. 4-S.Creatinine is somewhat higher in males than in females. 5-Sustained high protein diets and catabolic states probably affect the plasma creatinine concentration less than that of urea. [email protected] https://jmu.edu.iq/ar/ 11 Serum Creatinine 6-Plasma urea concentration tend to rise faster than creatinine in case of reduction of GFR in renal dysfunction. 7-Creatinine is affected by age, sex, exercise, certain drugs ( cimetidine ,trimethoprim) , muscle mass. Creatinine clearance: It is milliliters of plasma that are cleared of creatinine by the kidneys per minute. Creatinine clearance is calculated as : Creatinine clearance(ml/min) = U/P X V X 1.73/A U: urine creatinine concentration (mg/dl) ( 24hrs collection) P: plasma creatinine concentration (mg/dl) V: is the volume in milliliter of urine excreted per minute. [email protected] https://jmu.edu.iq/ar/ 12 A: is the body surface area in sequare meters and 1.73 is the standard body surface area Glomerular filtration rate (GFR) Glomerular filtration rate (GFR) It is the quantity of glomerular filtrate formed per unit of time in all nephrons of both kidney. The substance was used to measure the GFR are Inulin , Cystatin C and creatinine. The aim of measurement of GFR is to Detect the onset of renal insufficieny ( help to diagnosis ) Adjust drug dosage for drugs excreted by the kidney.( calculate the dose of drug according to the degree of failure ) GFR (ml/min) = (140 – age in yrs) X wt (kg) X(0.85 if female) 72 X S.Cr (mg/dl) [email protected] https://jmu.edu.iq/ar/ 13 Acute Renal Failure (ARF) Acute Kidney Injury abrupt decline in renal function, clinically manifesting as low GFR with a reversible acute increase blood urea nitrogen (BUN) and serum creatinine levels. Classification of ARF 1-Pre-renal ARF: this occur because the blood supply to kidney is reduced either due to vascular obstruction or reduced renal perfusion and decrease GFR. The most common cause , blood loss ,sever water loss like burn ,vomiting and diarrhea Body response : increase ADH and aldestrone secretion. [email protected] https://jmu.edu.iq/ar/ 14 Acute Renal Failure (ARF) Q: What are some of the biochemical finding in patients with pre –renal failure A: Biochemical finding The blood supply to kidney is reduced leading to reduced renal perfusion and decrease GFR causing 1-High urea and creatinine in serum but urea more than creatinine 2-Hyperkalemia due to decrease GFR and acidosis 3-Metabolic acidosis due to the inability of the kidney to excrete H+ 4-High urine osmolality 2-Renal : there is renal damage either due to disease or consequence of prolong pre-renal or post- renal proplems effecting kidney , the causes are: Prolonged renal circulatory insufficiency, acute glomerulonephritis , septicaemia and Poisons or drugs or myoglobulinuria [email protected] https://jmu.edu.iq/ar/ 15 Acute Renal Failure (ARF) 3-Post –renal :post renal obstruction causes back pressure leading to reduction of glomerular filtration , the causes are either renal calculi , Ca of prostate or cervix or bladder or prostate hypertrophy [email protected] https://jmu.edu.iq/ar/ 16 Uric Acid Purine metabolism Nucleic acids contain two different bases , pyrimidines and purines. The catabolism of the purines ( adenine and guanine AMP , GMP ) produces uric acid. uric acid is mostly ionized and present in plasma as sodium urate. Hyperuricaemia : Abnormal high level of uric acid concentration in blood. Uric acid and sodium urate are relatively insoluble molecules that readily precipitate in aqueous solutions such as urine or synovial fluid. The consequence of this is the medical condition known gout. [email protected] https://jmu.edu.iq/ar/ 17 Uric Acid Urate is formed in three ways 1- De novo synthesis 2- The metabolism of endogenous DNA, RNA 3- The breakdown of dietary nucleic acids. Urate is excreted in two ways: The kidney: the majority of urate (70%) is excreted via the kidney. The gut: Smaller amounts(30%) of urate are excreted into the gut where it is broken down by bacteria. [email protected] https://jmu.edu.iq/ar/ 18 Uric Acid Gout : is a clinical syndrome occure due to accumulation of urate crystals in the synovial fluid resulting in inflammation leading to acute arthritis. uric acid is deposited in the joints to cause tophi like distal joints of foot. Increased excretion of uric acid may cause deposition of uric acid crystals in the urinary tract leading to stone formation with renal damage Type of gout : Primary Gout : About 10% of cases of primary gout are idiopathic and primary gout may be familial ,it can be enzyme deffect like abnormal PRPP Synthetase [email protected] https://jmu.edu.iq/ar/ 19 Uric Acid Secondary gout : a-Increased Production of Uric Acid : It may be due to increase turnover rate of nucleic acid as seen in rapid growing malignant tissues e.g. leukemias ,or in radiotherapy or chemotherapy or trauma or Increase intake of meat. b-Reduced Excretion Rate : e.g Renal failure , Treatment with thiazide diuretics , Lactic acidosis and keto-acidosis due to interference with tubular secretion. [email protected] https://jmu.edu.iq/ar/ 20 Proteinuria Types of proteinuria 1. Glomerular proteinuria :increase infilteration load of protein due to glomerular damage and vascular permeability. 2. Overflow proteinuria : increased circulating concentration of low molecular weight proteins. 3. Tubular proteinuria : decrease in reabsorptive capacity of protein due to tubular damage. 1-glomerular proteinuria : The glomeruli of kidney are not permeable to substances with molecular weight more than 69,000 and so plasma proteins are absent in normal urine. When glomeruli are damaged or diseased, they become more permeable and plasma proteins may appear in urine. [email protected] https://jmu.edu.iq/ar/ 21 Proteinuria The smaller molecules of albumin pass through damaged glomeruli more readily than the heavier globulins. Albuminuria is always pathological. Protein /Creatinine ratio : is calculated to decide whether the patient has nephrotic range proteinuria or not. If proteinuria are 1000 mg/day = Glomerular proteinuria [email protected] https://jmu.edu.iq/ar/ 22 Proteinuria Microalbuminuria : It is identified, when small quantity of albumin (30–300 mg/day) is seen in urine. Microalbuminuria is an early indication of nephropathy in patients with diabetes mellitus and hypertension. Hence, all patients who are known diabetics and hypertensive should be screened for microalbuminuria. It is an early indicator of onset of nephropathy. The test should be done at least once in an year. [email protected] https://jmu.edu.iq/ar/ 23 Proteinuria 2-Overflow Proteinuria When small molecular weight proteins are increased in blood, they overflow into urine. For example, Hb having a molecular weight of 67,000 can pass through normal glomeruli, and therefore, if it exists in free form (as in hemolytic conditions), hemoglobin can appear in urine (hemoglobinuria). Similarly, myoglobinuria is seen following muscle crush injury. another example is the Bence-Jones proteinuria in multiple myeloma. [email protected] https://jmu.edu.iq/ar/ 24 Proteinuria 3-Tubular Proteinuria This occurs when tubular damage or functional nephrons are reduced, so low molecular weight proteins appear in urine. e.g alpha-1 microglobulin are synthesized in liver and are readily filtered by the glomerulus. Tubular damage results in the release of intracellular components to the urinary tract and may be used as markers of tubular damage. Transient proteinuria: it associated with physical exertion ,trauma, cardiac failure, fever Orthostatic ( postural) proteinuria: It may be severe proteinuria in the upright than in prone position, it glomerular origin. [email protected] https://jmu.edu.iq/ar/ 25 Lecture summary Summary of Kidney Lecture This lecture covers laboratory assessments of renal function, focusing on key analytes and conditions that indicate kidney health or disease. 1. Tests for Renal Function 1. Blood Urea & Blood Urea Nitrogen (BUN) Urea is the major end product of protein catabolism (urea cycle in liver). More than 90% is excreted by the kidneys. BUN is calculated by: Uremia: Abnormally high BUN in blood. Azotemia: Significant increase in both urea and creatinine, often indicating renal insufficiency. [email protected] https://jmu.edu.iq/ar/ 26 Lecture summary Causes of High BUN (Uremia) Prerenal Uremia: Due to reduced renal perfusion or extra-renal factors (e.g., high protein diet, catabolism, dehydration, heart failure). Urea rises more than creatinine. Renal Uremia: Intrinsic kidney disease (acute/chronic glomerulonephritis, polycystic kidney disease) => both urea & creatinine increase. Postrenal Uremia: Obstruction in urine flow (stones, prostate enlargement, malignancy) => reabsorption of urea into circulation, often raising BUN more than creatinine. BUN/Creatinine Ratio Used to distinguish prerenal (>20), renal (~10-15), and postrenal causes (often >20) in azotemia. Normal ratio ~12-20. [email protected] https://jmu.edu.iq/ar/ 27 Lecture summary 2. Serum Creatinine Creatinine is the end product of phosphocreatine breakdown in muscle; production depends on muscle mass. Freely filtered by glomeruli, with minimal tubular secretion (~7-10%). Elevated serum creatinine usually reflects decreased renal excretion (renal dysfunction). Key Points Serum creatinine is slightly higher in males (more muscle mass). High protein diets/catabolic states affect serum creatinine less than urea. Creatinine levels can be influenced by age, sex, muscle mass, certain drugs (e.g., cimetidine), and exercise. [email protected] https://jmu.edu.iq/ar/ 28 Lecture summary 3. Creatinine Clearance and Estimated GFR Creatinine Clearance (mL/min) = : Urine creatinine (mg/dL) : Volume of urine (mL/min) : Plasma creatinine (mg/dL) : Body surface area (m²); 1.73 is standard average BSA. Glomerular Filtration Rate (GFR): The volume of filtrate formed per unit time by all nephrons. Measured or estimated using inulin, cystatin C, or creatinine. Clinical Uses: Early detection of renal insufficiency & adjusting dosage of renally-excreted drugs. An example of estimated GFR: [email protected] https://jmu.edu.iq/ar/ 29 Lecture summary 2. Acute Renal Failure (ARF) / Acute Kidney Injury (AKI) Definition: Abrupt decline in renal function (low GFR), causing sudden rise in BUN & creatinine. Often reversible if treated early. Classification: 1. Prerenal: Reduced blood flow to kidney (e.g., hemorrhage, dehydration). Lab findings may show high serum urea & creatinine (urea rises more), hyperkalemia, metabolic acidosis, high urine osmolality. 2. Renal (Intrinsic): Direct kidney damage from prolonged prerenal/postrenal problems or diseases (glomerulonephritis, toxins, myoglobinuria). 3. Postrenal: Obstruction in outflow (stones, prostate issues) => back pressure reduces GFR. [email protected] https://jmu.edu.iq/ar/ 30 Lecture summary 3. Uric Acid Purine Metabolism: Catabolism of purines (adenine, guanine) → uric acid, which is mostly present as urate (sodium urate) in plasma. Hyperuricemia: Elevated uric acid (e.g., in gout or renal failure). Gout: Urate crystals deposit in joints → inflammation (arthritis). Uric Acid Excretion: ~70% via kidneys; ~30% via gut bacteria. Types of Gout: 1. Primary Gout: Often familial or due to enzyme defects (↑ synthesis). 2. Secondary Gout: Increased production (malignancy, cell turnover) or reduced excretion (renal failure, certain drugs). [email protected] https://jmu.edu.iq/ar/ 31 Lecture summary 4. Proteinuria Definition: Presence of abnormal amounts of protein in urine, indicating kidney pathology. Types: 1. Glomerular Proteinuria: Damage to glomeruli → ↑ permeability to larger proteins (albumin). 2. Overflow Proteinuria: Excess low-molecular-weight proteins in blood overflow into urine (e.g., hemoglobinuria, myoglobinuria, Bence-Jones proteins in multiple myeloma). 3. Tubular Proteinuria: Tubular damage → ↓ reabsorption of normally filtered proteins (e.g., alpha-1 microglobulins). [email protected] https://jmu.edu.iq/ar/ 32 Case Scenario Q2: Susan is a 42 yrs old female with heart failure history , a random blood sample was obtained and the following biochemical results Na+ 120 ( nv 135 - 145) , K+ 5.9 (3.5 – 5) , HCO3- 15 ( nv 24 -32) , urea 55 ( 15 -42) , creatinine 4.3 (0.7 -1.4) What do these biochemistry results indicate about patient s condition ? Comment on these biochemical findings ? Could the edema appear in this case ? why? the patient is a case of heart failure but increase level of blood urea and creatinine and potassium and blood acidosis (low bicarbonate ) all indicate renal failure which may be secondary to heart failure. Low cardiac output in heart failure stimulate ADH secretion which causes water retention leading to formation edema which causing fall in S.Na+. Renal failure also causes stimulation to secretion of ADH as a result to decrease of GFR this lead to retention of fluid causing edema and hyponatremia. [email protected] https://jmu.edu.iq/ar/ 33 Clinical Biochemistry and Metabolic Medicine Martin Andrew Crook [email protected] https://jmu.edu.iq/ar/ 34  Jaber Ibn Hayyan University for Medical & Pharmaceutical Sciences Contact: presenter email address [email protected] https://jmu.edu.iq/ar/ 35