KIDNEY FUNCTION TESTSRamzi Shawahna, PhD

An-Najah National University, Nablus

CHAPTER OUTLINES

Kidney function testing Urea, Creatinine, Cystain C, and the concepts

of GFR Urine analysis Creatinine, proteins and urine protein

electrophoresis. Renal diseases Interpretation of kidney function testing and

determination of renal diseases. Pre-renal, renal (tubular, glumular, or both), and post-renal disease

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• A major part of homeostasis is maintaining the composition, pH, and volume of body fluids within normal limits

• The urinary system removes metabolic wastes and substances in excess, including foreign substances like drugs and their metabolites that may be toxic

• The urinary system consists of a pair of kidneys, a pair of ureters, a urinary bladder and a urethra

INTRODUCTION

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Kidney

Hilum

Ureters

Urethra

Renalvein

Renalartery

Inferiorvena cava

Abdominalaorta

Urinarybladder

Copyright © The McGraw-Hill Companies, Inc.

Copyright © The McGraw-Hill Companies, Inc.

Inferior vena cava

Renal cortex

Renal pyramid

Renal medulla

Minor calyx

Renal column

Renal papilla

Renal pelvis

Suprarenal artery

Abdominal aorta

Adrenal gland

Renal capsule

Hilum

Renal vein

Suprarenal vein

Ureter

Renal artery

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Glomerulus

Collecting duct

Nephronloop Ascending

limb

Descendinglimb

Peritubularcapillary

Efferentarteriole

Proximalconvolutedtubule

Renalmedulla

Renalcortex

Cortical radiateartery

Cortical radiatevein

Glomerularcapsule

Afferentarteriole

Distal convolutedtubule

From renalartery

To renalvein

NEPHRON

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• The main function of the kidneys is to regulate the volume, composition, and pH of body fluids

• The kidneys remove metabolic wastes from the blood and excrete them to the outside of the body, including nitrogenous and sulfur-containing products of protein metabolism

• The kidneys also help control the rate of red blood cell production, regulate blood pressure, and regulate calcium ion absorption

•Endocrine function: 1- erythropoietin production 2- activation of vitamin D 3- renin-angiotensin production

• Urine contains wastes, excess water, and electrolytes

• Urine is the final product of the processes of:

• Glomerular filtration

• Tubular reabsorption

• Tubular secretion

FUNCTION OF THE KIDNEYS

ENDOCRINE FUNCTION OF THE KIDNEY

WHY TEST RENAL FUNCTION?

To asses the functional capacity of kidney Early detection of possible renal impairment Severity and progression of the impairment Monitor response to treatment Monitor the safe and effective use of drugs

which are excreted in the urine

WHEN?

Older age Family history of Chronic Kidney disease (CKD) Decreased renal mass Low birth weight Diabetes Mellitus (DM) Hypertension (HTN) Autoimmune disease Systemic infections Urinary tract infections (UTI) Nephrolithiasis Obstruction to the lower urinary tract Drug toxicity

WHAT?

Renal function tests are divided into the following:

Urine analysis Blood examination Glomerular Function Test Tubular Function Test

URINE

URINE

Color: pale yellow r due to pigments urochrome, urobilin and uroerythrin

Cloudiness: cellular material or protein, crystallization or precipitation of salts

Volume: 1-2.5 L/day (anuria, oliguria, polyuria)

Specific gravity: 1.001- 1.040 pH: 4.5 to 8 (normally it is slightly acidic lying

between 6 – 6.5).

GLOMERULAR FUNCTION Plasma is filtered by glomeruli @ 140 mL/min. The glomerular filtrate has the same composition as the

plasma without most of the proteins. Normal glomerular filtration rate (GFR) depends on:

Blood flow and pressure Body size Higher in men than women Decline in elderly

Impaired renal function is indicated by higher levels of some metabolites like creatinine and urea.

Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body depending on muscle mass

Creatinine is filtered but not reabsorbed in kidney Urea is major nitrogenous end product of protein and amino

acid catabolism, produced by liver and distributed throughout intracellular and extracellular fluid

CLEARANCE Amount of substance cleared from a volume of plasma over a period

of time

Volume of plasma cleared of “S” = (urine conc. of a substance S per L of plasma X volume of urine collected in a given time period)/(plasma conc of S)

Creatinine is a product of muscle metabolism is collected over a period of 24h and used to measure GFR

GFR is dependent on: Volume collection accuracy Ketones and heavy proteinuria

SERUM CREATININE AND UREA

Serum creatinine conc. is often used as convenient but insensitive

60-120 μmol/L

RENAL TUBULAR FUNCTION

Clearing the body from waste and toxic products

Water, sodium, glucose, and amino acids are reabsorbed

180 L of fluids pass and >90% is recovered Efficient clearance of waste products and

efficient reabsorption of essential consitiuents ensure prober renal functioning

INVESTIGATION OF TUBULAR FUNCTION

Osmolality: the number of moles of solute in 1 kg of solvent

Inability to concentrate urine: Intact tubular function and presence of

arginine vasopressin (AVP) ensure water reabsorption

The osmolality of urine is compared to that of plasma (ratio range 1-3), urine is more concentrate than plasma

WATER DEPRIVATION TEST

To understand the reasons behind polyuria WDT is conducted which involves depriving the patient from water for a period of 24h and measuring uring osmolality during the second 12h

Osmolality >700 mmol/kg should be attained and urine to plasma osmolality ratio of ≥2

In diabetes insipidus (AVP is lacking): ratio 0.2-0.7

In some hospitals patients are restricted from water from 8:00 pm till 10:00 am

Test is unpleasant and should be discontinued if more than 3L of urine lost

ACID LOAD TEST

Diagnosis of renal tubular acidosis: metabolic acidosis due to reduced tubular secretion of hydrogen ions.

Ammonium chloride is administered PO and urine is collected for 8h

In normal renal function: a sample pH should be 5.3 Type I: defective hydrogen ion excretion Type II: reduced capacity to reabsorb bicarbonate Type III: a pediatric variant of type I Type IV: impaired bicarbonate reabsorption due to

aldosterone deficiency, aldosterone receptor defect, or a drug that interfere with aldosterone actions

PROTEINURIA

The glomerular basement membrane does not usually allow passage of albumin and large proteins

A small amount of protein 25 mg/day

SPECIFIC PROTEINURIA: CAUSES

GLYCOSURIA Presence of glucose in urine when the glucose levels

in blood are normal Reflects inability of tubules to reabsorb glucose

Presence of amino acids in the urine Indicate excessive blood conc, reabsorption failure,

metabolic disorders or tubular damage

Describes occurrence of generalized tubular defects as renal tubular acidosis, aminoaciduria, tubular proteinuria.

Heavy metal poisoning, toxins, or cystinosis

AMINOACIDURIA

FANCONI SYNDROME

BILIRUBIN

In blood conjugated and unconjugated Conjugated is water soluble Bilirubinuria is the presence of conjugated

bilirubin in urine Bilirubin is secreted in the bile and

reabsorbed in the gut through enterohepatic circulation

Urobilinogen: conjugated bilirubin is broken in the gut to urobilinogen which is present in the circulation

KETONES

Ketones are products of fatty acid breakdown Indicates that the body is using fat instead of

glucose

Presence of blood and leucocytes in urine indicates acute urinary tract inflammation

Presence of blood may indicate malignancy

BLOOD AND LEUCOCYTES

RENAL STONES

Types: Calcium phosphate: hyperthyrodism or renal

tubular acidosis Magnesium, ammonium and phosphate:

urinary tract infection Oxalate: hyperoxaluria Uric acid: hyperuricaemia Cystine: inherited metabolic disorder

(cystinuria)

RENAL FAILURE

Renal failure is the cessation of kidney function.

It can be acute or chronic. In the acute type, kidneys fail over a period of hours or days while in chronic it develops over months or years and eventually leads to end stage failure.

Acute failure can be reversed whereas chronic is irreversible

CLASSIFICATION: ACUTE

PRE-RENAL

Decreased plasma volume: e.g. bleeding Diminished cardiac output Local factors like occlusion of renal artery

Findings:

Elevated serum urea and creatinine levels Metabolic acidosis Hyperkalaemia High urine osmolality

POST-RENAL

Renal stones Carcinoma of cervix, prostate or bladder

Acute blood loss Severe trauma Septic shock renal diseases like glomerulonephritis Nephrotoxins like aminoglycosides or

analgesics

ACUTE TUBULAR NECROSIS

MANAGEMENT OF RENAL FAILURE

Correction of pre-renal factors Treatment of underlying disease Biochemical monitoring Dialysis

CHRONIC: PROGRESSIVE AND IRREVERSIBLE

Sodium and water metabolism: may retain ability to reabsorb sodium but not water

Potassium metabolism: hyperkalaemia Metabolic acidosis Calcium and phosphate metabolism Erythropoietin synthesis

MANAGEMENT

Water and sodium intake balance Ion exchange resins (Resonium A) for

hyperkalaemia Aluminum or magnesium salts to sequester

phosphate ingestion in the gut Hydroxylated vitamin D to prevent secondary

hypothyroidism Protein restriction Dialysis Renal transplantation