5. Renal Function Tests.pptx

The main function of the kidney is excretion of water soluble waste products from our body.
Derangement of any of these function would result in either decreased excretion of waste products and hence their accumulation in the body or loss of some vital nutrient from the body.

1. Laboratory Evaluation of Kidney Function Tests Rajendra Dev Bhatt, PhD Scholar Asst. Professor Clinical Biochemistry & Laboratory Medicine Dhulikhel Hospital-Kathmandu University Hospital Fellow: Translational Research (2018-2022) in CVD in Nepal, NIH, USA

2. The main function of the kidney is excretion of water soluble waste products from our body The kidney has various filtration, excretion and secretary functions . Derangement of any of these function would result in either decreased excretion of waste products and hence their accumulation in the body or loss of some vital nutrient from the body.

3. We are able to accurately calculate the kidney's ability to perform its various tasks based on the concentration of these excretory products and nutrients in the blood and urine. The functional unit of the kidney is called a nephron. It consists of two main parts , the glomerulus and the tubular system. The glomerulus is composed of a bowman’s capsule and a tuft of leaky blood vessels encapsulated by the bowman’s capsule.

4. The primary purpose of the glomerulus is filtrations. The leaky vessels filter into the glomerulus almost all the water, electrolytes, small proteins, nutrients such as sugar etc and excretory products such as urea etc. The Tubular system is responsible for re-absorption of most of the water , electrolytes , nutrients as well as excretion of the remaining nutrients by means of secretion into the tubules. These tubules are responsible for the concentration of urine.

5. Renal Functions Excretory Functions: Formation and excretion of urine Glomerular filtration Tubular reabsorption Tubular secretion Excreting toxic substances in synergy with liver

6. Renal Functions Homeostatic function Regulation of blood volume Regulation of blood pH Regulation of serum electrolytes; Na, K, Cl and Ca Reabsorption of essential nutrients

7. Renal Functions Endocrine function Erythropoietin Renin Angiotensin system Vitamin D activation Degradation of hormones like insulin and aldosterone Metabolic function Along with liver site for gluconeogenesis

8. Why Renal F unction Tests needed ? To assess functional capacity of kidneys To diagnose renal impairment To assess the severity and progression of renal impairment To assess the effectiveness of treatment

9. Causes of renal disease Pre-renal Any condition that results in reduced blood flow to kidneys Severe blood loss Hemolysis Renal Damage to renal tissue, glomerular basement membrane or tubules Glomerulonephritis Diabetic or hypertensive nephropathy Tubular damage due to toxic substances

10. Post Renal Obstruction to urine outflow Ureteric or urethral stone Prostatic cancer This list is not complete, these are only few common causes of renal disease

11. Renal function test Can be divided into two categories: Test for glomerular function Serum Urea Serum Creatinine Clearance tests Tests for tubular function Urine concentration test Dilution test Para amino hippuric acid clearance test Acidification test Urine examination: Important for assessing both glomerular and tubular function

12. Test for glomerular function The following parameters are commonly included in assessing glomerular function Serum Urea ( 10-45 mg/dl) Serum Creatinine (0.6 –1.2 mg/dl) Serum Uric acid (males 3.5-7.2 mg/dl, females 2.6-6 mg/dl) Total protein ( 6.0-8.0 g/dl) Serum albumin ( 3.0-5.0 g/dl ) Serum electrolytes Na ( 135-150 mEq /L) K ( 3.5-5.0 mEq /L) Cl (96-106 mEq /L) Phosphate (2.8-4 mg/dl) Calcium (8.0-10.2 mg/dl)

13. Glomerular Filtration Rate (GFR) Glomerular filtration rate (GFR) represents the flow of plasma from the glomerulus into Bowman's space over a specified period. Glomerular filtration rate (GFR) is an important indicator of the filtering capacity of kidneys and is considered the best overall index of renal function currently used. Estimated glomerular filtration rate ( eGFR ) is the most important variable in the assessment of patients with suspected or known kidney disease in clinical practice. GFR measures the rate at which the kidneys' two million glomeruli filter plasma in order to process it and remove waste products from it.

14. GFR is decreased when BP is below 80 mm of mercury. The GFR is reduced when there is obstruction to the renal flow (calculi, enlarged prostate, etc.). It also decreases with age. The renal blood flow is about 700 mL of plasma or 1200 mL of blood per minute. The glomerular filtration rate (GFR) is 120–125 mL per minute in a person with 70 kg body weight. Glomerular filtrate formed is about 170 to 180 liters per day, out of which only 1.5 liters are excreted as urine. This means that most of the water content of glomerular filtrate is reabsorbed.

15. Markers for GFR Ideal characteristics: Freely filtered at the glomerulus No tubular secretion or reabsorption No renal/tubular metabolism Exogenous or endogenous: Exogenous – not normally present in the body: Inulin Endogenous – normally present in the body Creatinine

16. Advantages: Endogenous Produced at relatively constant rate per day Routinely measured Freely filtered at glomerulus Not reabsorbed or metabolized by renal tubules Assays are standardized Disadvantages: Estimate of GFR Is secreted by renal tubules

17. Direct Measures of GFR: Creatinine Clearance C = (U x V)/P C = clearance U = urinary creatinine concentration V = urinary Volume P = plasma creatinine concentration Clearance = GFR

18. Inulin Clearance Gold standard for renal clearance : Freely filtered at glomerulus No tubular metabolism No tubular reabsorption or secretion Protocol: IV infusion Blood samples Urine catheter Limitations : Expensive, hard to obtain Difficult to assay Invasive

19. Estimated Glomerular Filtration Rate ( eGFR ) Modification of Diet in Renal Disease (MDRD): The original Modification of Diet in Renal Disease (MDRD) equation was based on 6 variables: age, sex, ethnicity, serum creatinine, urea, and albumin (often referred to as MDRD 6). Subsequently , the MDR was simplified to a 4-variable version (MDRD-4) that included age, sex, ethnicity, and serum creatinine. This 4-variable version was later re-expressed using serum creatinine values that were standardized to reference methods. The equation shown here is the re-expressed 4-variable MDRD equation . GFR in mL/min per 1.73 m 2  = 175 x SerumCr -1.154  x age -0.203  x 1.212 (if patient is black) x 0.742 (if female)

20. Urine Albumin Reference interval: Urine micro-albumin<30 mg/d Albuminuria = Micro-Albumin to creatinine ratio (ACR) >30 mg/g

21. Cystatin C Cystatin C is a relatively small protein that is produced throughout the body by all cells that contain a nucleus and is found in a variety of body fluids, including the blood. It is produced, filtered from the blood by the kidneys, and broken down at a constant rate. This test measures the amount of cystatin C in blood to help evaluate kidney function.

22. The rate at which the fluid is filtered is called the glomerular filtration rate (GFR). A decline in kidney function leads to decreases in the GFR and to increases in cystatin C and other measures of kidney function, such as creatinine and urea  in the blood.  In normal it is around 0.8-1.2mg/L

23. Serum Urea Urea is the end-product of protein metabolism. Normal value is 15 to 45 mg/dl . Serum urea is increased in all forms of kidney diseases . In acute glomerulonephritis values may be as high as 300 mg/dl. In early stages of nephrosis , serum urea may be normal, but in late stages serum urea increases along with decreasing renal functions. Urea concentration in serum may be low in late pregnancy, in starvation , in diet grossly deficient in proteins and in hepatic failure .

24. Serum Creatinine Creatinine is the waste product of creatine phosphate, a compound found in the skeletal muscle tissue . It is excreted entirely by the kidneys . The creatinine level is affected primarily by renal dysfunction and is thus very useful in evaluating renal function . Increased levels of creatinine indicate a slowing of the glomerular filtration rate. Female: 0.6–1.2 mg/dL Male: 0.8–1.4 mg/dL

25. Possible Meanings of Abnormal Values: Congestive heart failure Glomerulonephritis Nephritis Pyelonephritis Renal failure Urinary obstruction Dehydration

26. Serum Uric acid Uric acid is produced by the breakdown of purines, chemicals that are the building blocks for DNA and RNA . M ost uric acid is excreted in the urine Excess serum uric acid can become deposited in joints and soft tissues, causing gout, an inflammatory response to the deposition of the urate crystals . Female: 2.3–6.6 mg Male: 3.5–7.2 mg/dL

27. Possible Meanings of Abnormal Values: Increased (hyperuricemia ) Congestive heart failure Glomerulonephritis Alcoholism Gout Dehydration Decreased ( hypouricemia ) Liver disease Renal tubular defects

28. Total protein and albumin Both serum total protein and albumin is decreased in chronic kidney disease (CKD) due to increased proteinuria Even though proteinuria may also be seen in acute kidney disease but it usually does not alter the total protein and albumin

29. Serum electrolytes Sodium is decreased ( hyponatremia ) and potassium is increased (hyperkalemia) in chronic kidney disease (CKD) as kidney reabsorb sodium in exchange of potassium Chloride and phosphate is increased in CKD Calcium is decreased as vitamin D is deficient

30. Tests for tubular function Specific Gravity of Urine: Specific gravity depends on the concentration of solutes, whereas osmolality depends on the number of osmotically active particles. Hence in cases of proteinuria, the specific gravity is elevated considerably , but osmolality is only mildly elevated. Normal specific gravity of urine is 1.015–1.025. The specific gravity will be decreased in excessive water intake , and in diabetes insipidus. It is increased in diabetes mellitus, in nephrosis

31. Review Questions Which of the following conditions is associated with an elevated blood urea nitrogen (BUN) level ? Dehydration Liver cirrhosis Hyperthyroidism Hypoalbuminemia Dehydration

32. 2. Which renal function test is used to evaluate the concentrating ability of the kidneys ? Serum creatinine Blood urea nitrogen (BUN ) Urine specific gravity Serum sodium Urine specific gravity

33. 3. Which of the following electrolyte abnormalities is commonly associated with renal failure ? Hyperkalemia Hyponatremia Hypocalcemia Hypomagnesemia Hyperkalemia

34. 4. Which of the following substances is normally not present in the urine ? Urea Creatinine Glucose Albumin Glucose

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