2. Content
⢠Kidneys & Functions
⢠Presenting Features of Renal Disease
⢠Kidney Failure/ESRD
â Risk factors
â Symptoms
â Treatment
⢠Hemodialysis
⢠Peritoneal Dialysis
⢠Common Kidney Diseases
⢠Laboratory Investigation of Kidney Disorders
ď Urine Examination
-routine
-microscopic
ď Renal Function Test
-Glomerular Function tests
-Renal blood flow test
ď Renal Biopsy
⢠References
3. The Kidneys
⢠A pair of bean-shaped organs located at the
posterior wall of the abdomen
⢠Dimensions
â 11 cm long, 6 cm wide and 3 cm thick
â weighs about 160g
4. The Kidneys
⢠Made up of functioning units called nephrons
Nephron
Glomerulus
Tubules
5.
6. Functions
⢠Removal of waste and excess water from
body; Regulation of fluid, electrolyte and acid-
base balance
7. Functions
⢠Normal kidneys release several hormones
â Renin (regulates blood pressure)
â Erythropoietin (stimulates production of red blood
cells)
â Activated form of Vitamin D (maintain normal
bone structure)
8. Presenting features of renal disease
1. Dysuria
- urethritis(inflammation of urethra) and
cystitis(inflammation of bladder due to
infection)
- inflammation of vagina and penis
2. Polyuria and nocturia(increased urine flow at
night)
- > 3 L/ day
- solute diuresis, diabetes insipidus, CRF(Chronic
Renal Failure)
9. 3. Oliguria
- Decreased urinary output i.e. < 300 ml/ day
- hypotension, hypovolaemia(decreased
volume of circulating blood in body)
- intrinsic renal disease
- urinary tract obstruction
10. 4. Haematuria.
- blood in the urine, arises anywhere in renal
tract
- micturition- urethral disease- tendency to
urinate
11. 5. Renal pain.
- dull constant pain in the loin.
- renal obstruction, acute pyelonephritis, acute
nephritic syndrome, polycystic kidney, renal infart.
6.Ureteric colic.
- Severe loin pain, waxes and wanes, a/w fever,
vomiting, radiate to abdomen, groin, upper thigh.
- Renal calculus, clot.
12. Kidney Failure or End-stage Renal
Disease (ESRD)
⢠Occurs when the kidneys do not function
properly or sufficiently, resulting in the
accumulation of waste products and toxic
materials
â may cause permanent and irreversible damage to
body cells, tissues and organs
â kidneys that function <20% of required capacity
⢠need renal replacement therapy
14. Symptoms
⢠Decreased urination
⢠Blood in the urine
⢠Nausea and vomiting
⢠Swollen hands and ankles
⢠Puffiness around the eyes
⢠Itching
⢠Sleep disturbances
⢠High blood pressure
⢠Loss of appetite
15. Treatment of Kidney Failure
Blood creatinine rises to 900 Âľmol/ L
⢠Dialysis
â Hemodialysis
â Peritoneal Dialysis
⢠Transplant
â the best means of treatment
16. Hemodialysis
⢠A process by which excess waste products and
water are removed from the blood
⢠Requires an access to the patient's blood
stream and the use of a haemodialysis
machine
20. Hemodialysis
⢠âWashout Syndromeâ
â feels weak, tremulous, extreme fatigue
â syndrome may begin toward the end of treatment
or minutes following the treatment
â may last 30 minutes or 12-14 hours in a
dissipating form
21. Hemodialysis
⢠Advantages
â Staff performs treatment in the dialysis centre
â Three treatments per week in the dialysis centre
â Permanent internal access required
â Regular contact with people in the centre
22. Hemodialysis
⢠Disadvantages
â Requires travel to a dialysis centre
â Fixed treatment schedule
â Two needle sticks for each treatment; tie onto a
machine and cannot move about during
treatment
â Diet and fluid intake restriction
23. Peritoneal Dialysis
⢠Dialysis solution flow into the peritoneal
(abdominal) cavity through a catheter
⢠Petrionuem acts as a filter
24. Peritoneal Dialysis
⢠2 forms
â CAPD (Continuous Ambulatory Peritoneal
Dialysis)
⢠4 exchanges during the day, 45 min each
â APD (Automated Peritoneal Dialysis)
⢠exchanges are performed by the machine during the
night while the patient is asleep
25. Peritoneal Dialysis
⢠Advantages
â Patient's involvement in self-care
â Control over schedule
â Less diet & fluid restriction
â More steady physical condition as it provides slow,
continuous therapy
â Most similar to original kidneys. Can be done at
night as in automated peritoneal dialysis
â Provide less severe cardiovascular instabilities in
patients with underlying heart disease
26. Peritoneal Dialysis
⢠Disadvantages
â Four exchanges per day
â Permanent external catheter
â Change of body image
â Some risks of infection
â If on automated peritoneal dialysis, one will be tie
onto a machine in the night
â Storage space is needed for supplies
27. Kidney Transplant
⢠A kidney from either a living related or a brain
dead person is removed and surgically placed
into the kidney failure patient.
⢠Not all kidney failure patients are fit to
undergo transplantation.
â Medication to suppress their immunity given for
the transplant may worsen their general health
28. Kidney Transplant
⢠Advantages
â Absence of need for frequent dialysis treatment
â Better quality of life
â Better health
â Reduced medical cost after first year
â No diet and fluid intake restriction
â Provide less severe cardiovascular instabilities in
patients with underlying heart disease
29. Kidney Transplant
⢠Disadvantages
â Need for frequent physician visits
â Pain, discomfort of surgery
â Risk of transplant rejection
â Prone to infections
â On lifelong medications
31. Polycystic Kidney Disease
⢠Genetically acquired
⢠2 forms - dominant and recessive
⢠In the dominant PKD form, one parent has the
disease and passes it to the child. The chance
of passing the gene to the offspring is 50%.
⢠Cysts are abnormal pouches containing fluid.
Eventually the cysts replace normal kidney
tissue -> suffers ESRD
32. Polycystic Kidney Disease
Signs and Symptoms
⢠Dull pain at the side of the abdomen and back
⢠Blood in the urine
⢠Frequent urine tract infection
⢠High blood pressure (often before cysts
appear)
⢠Upper abdominal
discomfort
(liver and pancreatic cysts)
33. Polycystic Kidney Disease
Treatment
⢠Blood pressure - controlled and treated
⢠Kidney failure - supportive therapy until end-
stage is reached when dialysis or
transplantation is then required
⢠Urine tract infection - treatment with
antibiotics
⢠Pain - analgesics are used. Alternatively,
surgery to shrink or resect the cysts.
37. Glomerulonephritis /
Glomerulosclerosis
⢠Glomerulonephritis - An inflammatory
condition that affects predominantly the
glomeruli.
⢠Causes
â IgA nephropathy
â Streptococcus bacteria
â Autoimmune
⢠Glomerulosclerosis - scarring of the glomeruli
38. Glomerulonephritis /
Glomerulosclerosis
Signs and Symptoms
⢠Blood or protein in urine
⢠Frothy urine (signifying protein in urine)
⢠Dark or pink-coloured urine
⢠Leg swelling
⢠Systemic disease like diabetes or autoimmune
disease will have systemic manifestations, e.g.
weight loss, arthritis, or skin rash
40. Urinary Tract Infection (UTI)
⢠Disease of the urinary tract
â Infection occurs when microorganisms attach
themselves to the urethra and begins to multiply.
⢠May lead to infection of the kidneys
(pyelonephritis) and cause permanent kidney
damage, if left untreated.
⢠Women are especially prone to get urinary
tract infection.
41. Urinary Tract Infection (UTI)
⢠Conditions that increases risk of UTI
â Diabetes
â Situations where a urine catheter is needed
â Abnormalities of the urinary tract
â Obstructed urine flow (large prostate or stone)
â Being pregnant
42. Urinary Tract Infection (UTI)
Signs and Symptoms
⢠Painful urination (burning sensation)
⢠Hot and foul smelling urine
⢠Blood in urine
⢠Fever (sometimes with chills)
⢠Painful lower abdomen
⢠Increased urgency/frequency of wanting to
pass urine
⢠Nausea and/or vomiting
43. Urinary Tract Infection (UTI)
Treatment
⢠Appropriate antibiotics
⢠Drink plenty of water
44. Kidney Stones
⢠Start as salt/chemical crystals that precipitate
out from urine
⢠Occurs when substance in urine that prevents
crystalization are ineffective
45. Kidney Stones
⢠Various forms of kidney stones - the most
common is calcium in combination with either
phosphate or oxalate
⢠More common in
â Males
â 20-40 yo
46. Kidney Stones
Signs and Symptoms
⢠Extreme pain at the site where the stone is
causing the irritation
⢠Blood in the urine (abrasion along the urinary
tract as the stone travels)
⢠Painful and/or difficult urination
⢠Unable to pass urine if the stone is large
enough to obstruct the outlet completely
47. Kidney Stones
Treatment
⢠With plenty of water, most stones can pass
through if small
⢠Pain-killers (as prescribed by the doctor)
⢠Some medications may help 'breakdown' larger
stone
⢠Shockwave therapy (F-SWL) to break the stone
⢠Surgical intervention - cystoscopy or open surgery
48. Diabetic Kidney Disease
⢠Common in chronic and poorly controlled
diabetics
⢠Diabetes damages blood vessels in the kidneys
⢠Occurs in both types of diabetes
⢠Occurrence of high blood pressure in diabetics
is a strong predictor for diabetic nephropathy
⢠Most common cause of ESRD in many
developed countries
49. Diabetic Kidney Disease
Signs and Symptoms
⢠Frothy urine (signifying protein in urine)
⢠Leg swelling (worse after walking/standing)
⢠High blood pressure
⢠Itching
⢠Nausea and/or vomiting
⢠Losing weight
⢠Lethargy
⢠Increased need to urinate at night
50. Diabetic Kidney Disease
Treatment
⢠Good control of diabetes
⢠Good control of blood pressure (aiming for <
130/85 or lower in younger patients)
⢠Medications to decrease protein excretion and
preserve the function of kidneys
⢠Lower protein diet
⢠Treat any urine tract infection (which is
common in diabetics)
51. Analgesic Nephropathy
⢠Chronic kidney disease that occurs when there
is a long period of painkiller/s ingestion
(usually years)
⢠Associated with conditions which require
constant need for painkiller medications
⢠May lead to ESRD
52. Analgesic Nephropathy
Signs and Symptoms
⢠Blood in the urine
⢠Protein in the urine
⢠Signs and symptoms related to kidney failure
such as nausea, vomiting, lethargy, swelling,
and poor appetite.
53. Analgesic Nephropathy
Treatment
⢠Avoid long-term consumption of analgesics
⢠Those already with kidney disease of other
kinds should certainly refrain from harmful
analgesics as much as possible.
54. Laboratory Investigation of Kidney
Disorders
⢠Urine Examination
-routine
-microscopic
⢠Renal Function Test
-Glomerular Function tests
-Renal blood flow test
⢠Renal Biopsy
⢠Imaging
55. Urine Examination
⢠Sample Collection
-the 1st morning specimen is preferred
-collected in a clean container
-for culture, the specimen should be collected in a
sterile container & sent to the lab immediately,
where it should be plated within 15minutes or
stored in a refrigerator at 4 degree Celsius.
Bacteria multiply rapidly at room temp., which
may give false positive results.
56. Methods of Urine Collection
⢠Midstream urine : a clean-catch midstream specimen is widely
used. In older children who can cooperate, midstream specimen is
obtained after proper local cleaning .The initial part of urine is
discarded.
⢠Bag collection : in neonates & infants, urine can be collected in
sterile bags. Not used for microscopic exam.
⢠Bladder catheterisation : a urine specimen can also be safely
obtained, in infants, by strict bladder catheterisation but requires
some skills & experience.
⢠Suprapubic bladder aspiration : the only reliable way to
obtain reliable urine specimen in neonates & young infants. In
children <2 yrs of age it is most suitable method for a definitive
diagnosis of UTI
57. ⢠SPECIFIC GRAVITY : full term infants have a
limited concentrating ability with a maximum
sp.gravity of 1.021 â 1.025. It is measured
with clinical Hydrometer. Increase in sp.gravity
may be ass. with dehydration, diarrhoea, emesis,
excessive sweating etc. while decrease in sp.gravity may be
ass. with renal failure, interstitial nephritis & excessive fluid
intake.
⢠pH : tested with pH meter. UTI with urea splitting organisms
make urine highly Alkaline. Normal pH ranges from 4.6 -8.0. In
fasting, the concentrated urine sample is highly Acidic
-A high urine may be due to RTA(Renal Tubular Acidosis type
I),UTI, Vomitng & a low urinary pH may be due to
DKA(Diabetic Keto-Acidosis), diarrhea & starvation.
Urine Routine Examination:
58. ⢠PROTEIN :
Boiling test : satisfactory but
cumbersome.10-15 ml of urine is taken in a
test tube & upper portion is boiled. If turbidity
appears 3 drops of concentrated acetic acid
are added & specimen is boiled again. A zero
to +4 grading is used.
59. +1 Presence of slight
turbidity,through
which print can be
read
30-100mg of
protein/dl
+2 Turbidity with slight
precipitates
100-300mg of
protein/dl
+3 White cloudiness
with fine precipitate
300-1000mg
protein/dl
+4 Large clumps of
white precipitates
>1mg of protein/dl
Cont.
60. Dipstick methods(e.g uristix) : widely used
test for Proteinuria, more convenient &
equally reliable.
-Colour changes from yellow to green.
-light chain proteins & LMW tubular
proteins are not detected by this method.
-Trace react. ď 5 to 20 mg/dl urinary prtn
+1 ď 30 mg/dl
+2 ď 100 mg/dl
+3 ď 300 mg/dl
+4 ď > 1000 mg/dl
61. ⢠Proteinuria in patients with Nephrotic Syndrome is massive
(+3 or +4 by dipstick) & selective, constituted predominantly
of Albumin, without loss of proteins of higher molecular wt.
⢠In the presence of tubular damage or physical injury to the
glomerular barrier, the proteinuria is non selective.
⢠In renal parenchymal diseases,proteinuria is often quantified
to assess degree of glomerular injury.
⢠Selective Proteinuria : intermediate sized(<1000kDa)
proteins(albumin,transferrin) leaks through glomerulus.
⢠Nonselective proteinuria : range of different sized proteins
leak through,including larger proteins(immunoglobulin)
62. ⢠Quantitative Measurement of Urine Protein
-Accurate collection of urine over 24hr period is required to
quantitate protein excretion.
-A value of >4mg/m2/hr is considered abnormal, & >40/m2/hr
indicates heavy proteinuria.
-The range proteinuria in nephrotic syndrome is massive
proteinuria(>3.5gm/24hrs)
while the range in nephritic syndrome is mild to moderate
proteinuria(<3gm/24hrs)
63. ⢠Urine Protein/Creatinine Ratio : an approx. estimate of the
severity of proteinuria also can be made by measurement of
urine protein & urine creatinine on random urine sample.
-Values >2 indicate Heavy Proteinuria
<0.2 are insignificant.
-Such measurements are of use in following response to
therapy in various disorders, but seldom necessary in
children with nephrotic syndrome.
64. ⢠GLUCOSE :the older methods(e.g benedict
test) that detected reducing substance have
mostly been replaced by Dipstick test,which is
based on Glucose Oxidase Peroxidase linked
reaction.
⢠BLOOD :detection of Hb by dipstick is based on an reaction,
with a spotted +ve reaction indicating intact red blood cells &
uniform +vity suggesting presence of free Hb. However the
use of dipstick to detect hematuria is discouraged, bâcoz
reactions may often be false +ve(e.g myoglobinuria,oxidising
substances, bacterial colonisation) or false âve (e.g ascorbic
acid, other reducing substances)
65. ⢠A fresh,well mixed specimen should be examined.
⢠Presence of cellular elements & casts should be noted.
⢠Red cell casts : indicate glomerular inflammation.
Red cell casts & red cells in a pateint with glomerulonephritis
Microscopic Examination
66. White cell casts :clumping of
neutrophils suggests
acute pyelonephritis
Epithelial cell cast :are noted in patients recovering from Acute
tubular necrosis
67. Hyaline or Fatty casts : may be +nt
in proteinuric states or in normal
in normal individuals with
concenterated urine.
⢠Red blood cells & leukocytes can be counted under the high
power field & more accurately in a counting chamber.
⢠>5 leukocytes/HPF(High Power Field) along with bacteruria
suggests urinary tract infection.
⢠Neutrophils may also be detected in proliferative
glomerulonephritis & interstitial nephritis, while the presence
of Eosinophils in urine is specific of acute interstitial nephritis
68. ⢠Hematuria is defined as presence of >5RBC/HPF in a
centrifuged specimen.
⢠RBC morphology is useful in distinguishing Glomerular & non
glomerular causes of hematuria.
⢠The site of injury is likely to be the lower urinary tract if <25%
urine correlates well with a colony count of over 105
organisms/ml indicating significant bacteriuria.
69. Renal Function Evaluation
⢠Various aspects of renal function are
-GFR(Glomerular Filtration Rate)
-RPF(Renal Plasma Flow)
-Reabsorption & Excretion of various substances like Na+, K+,
Ca+2, inorganic phosphate, glucose, urea, a.a, H2O & osmoles.
⢠In clinical practice
-determination of Creatinine Clearance is a measure of GFR
-water deprivation & vasopressin administration tests to
determine urinary concentrating ability, &
-bicarbonate & ammonium chloride loading test to examine
urinary acidification are usually sufficient for diagnostic
evaluation & measurement of kidney function.
⢠The results of these tests are important in assessing the
excretory function of the kidneys. For example, grading of
chronic renal insufficiency and dosage of drugs that are excreted
primarily via urine are based on GFR (or creatinine clearance).
70. ⢠The concept of clearance is based upon the fact that the rate
of removal of a substance from the plasma must equal its
simultaneous rate of excretion in urine.
⢠Thus if the urinary excretion rate & plasma concentration of a
substance are known, we can calculate the volume of plasma
from which that substance would have been completely
removed. INULIN has been taken as a reference substance.
⢠The standard formula for clearance is : C = U x V
P
C = clearence/min(ml/min)
U = urinary concenteration(mg/dl)
P = plasma concenteration(mg/dl)
V = urine volume/min(ml/min)
Glomerular Function Test
71. ⢠If a given substance is freely filtered & neither reabsorbed nor
excreted, its clearance rate would accurately reflect GFR.
⢠The GFR can be estimated by measuring s.creatinine level &
height. The formula proposed by SCHWARTZ is useful for
children :
⢠GFR(ml/min/1.73m2) = K x Height(cm)
S.Creatinine(mg/dl)
K = 0.34 (in preterm infant)
= 0.45 (in term infants)
= 0.55 (in children & adolescent girls) &
= 0.7 (in adolescent males)
72. Serum Creatinine & Creatinine Clearance :
⢠Creatinine is derived from the metabolism of creatine &
phosphocreatine,the bulk of which is in muscle.
⢠Since creatinine is chiefly excreted by glomerular
filteration,S.creatinine levels reflects changes in GFR.
⢠S.creatinine values are low when the muscle mass is
decreased, as in malnutrition.
⢠Bilirubin interferes with creatinine measurements.
73. ⢠The normal values of S.creatinine are :
AGE RANGE(mg/dl)
Cord 0.6-1.2
Newborn 0.3-1.0
<3 years 0.17-0.35
3-5 years 0.26-0.42
5-7 years 0.29-0.48
7-9 years 0.34-0.55
9-11 years 0.35-0.64
11-13 years 0.42-0.71
13-15 years 0.46-0.81
Adult Male 0.7-1.3
Adult Female 0.6-1.1
74. ⢠CYSTATIN C : It is a LMW nonglycosylated protein produced at
a constant rate by all nucleated cells in the body, freely
filtered by the glomeruli, not secreted, but totally reabsorbed
by the renal tubules.
⢠Little or no cystatin is excreted in urine.
⢠Normal adults have circulating level of approx. 1mg/l.
⢠This is better indicator of renal function as compared to
creatinine in early stages of GFR impairment as it is
independent of age,gender,body composition & muscle mass.
⢠Cystatin C can be estimated in blood by enzyme
immunoassays or immunoturbidometry. Both techniques are
currently kit based & expensive.
75. ⢠SINGLE INJECTION TECHNIQUE : In clinical practice,
radionuclides are often used to estimate total GFR or to
measure difference in clearance bet. one kidney compared to
other in the same patient.
⢠The technique is based on use of a single injection, plasma
disappearance curves to estimate the true GFR.
⢠Briefly, the radionuclide dye is injected & the signal from
radiolabelled form is used to obtain measurment.
⢠The most commonly used Radionuclides for GFR are
-DTPA (Diethyl triamine Penta-acetic acid)
-EDTA (ethylene diamine tetra acetic acid) &
-Iothalamate
⢠Iohexol,a non ionic non radioactive LMW radiocontrast
agent,as an alternative to inulin,measured easily by HPLC(high
performance liquid chromatography)
76. ⢠BLOOD UREA : A normal level of blood urea is often
mistakenly regarded to indicate normal kidney function.
⢠In a steady state the blood urea may not rise beyond the
upper range of normal(40mg/dl) even when 75% of the renal
function is lost.
⢠On the other hand, prerenal factors that decreases renal
perfusion & GFR, such as dehydration, causes an increase in
blood urea levels.
⢠There may be transient rise in blood urea level due to :
-high protein intake & excessive protein catabolism( e.g with
severe infections, tissue break down, trauma, use of large
doses of corticosteroids or tetracyclines)
-gastrointestinal bleeding & inhibition of anabolism.
77. ⢠Renal blood flow measurements are performed using the
clearance of PAH(para aminohippurate)
⢠>90% PAH is extracted from the plasma during the 1st pass
through the kidneys.Therefore, renal clearance of PAH is
commonly used as an estimate of renal plasma flow(RPF).
⢠Plasma clearance following single injection of 131I-hippuran or
99mTc-mercaptoacetyltriglycine(MAG-3)is an alternative
method.
⢠Renal Blood Flow is calculated by dividing RPF by [1-
hematocrit].
⢠Normal value ranges from 500 to 600 ml/min(abt.
1200ml/min/1.73m2).
⢠Other methods-Color Doppler US,Contrast Enhanced US &
MRI.
Renal Blood Flow
78. ⢠Expert evaluation of renal histology is important in the
diagnosis of various renal parenchymal disease involving
glomeruli, tubulo-interstitium & small blood vessels.
⢠The procedure has become has become
much simpler with the use of automatic
(biopsy gun, tru cut) devices & ultrasono
-graphic visualization of kidney.
Renal Biopsy
79. ⢠BIOPSY PROCEDURE
-A renal biopsy is usually made percutaneously
-A history of bleeding & clotting disorders should be obtained.
-PT, BT, Coagulation time & Platelet count is measured.
-BP should be in normal range
-In Patients with acute renal failure,dialysis should be done to
reduce azotemia & correct biochemical abnormalities before
the biopsy.
-Renal size & location are confirmed with an US before biopsy.
-The Patient should be kept fasting for abt 3-4 hrs.
-Local anaesthesia can be used
80. -The child lies in prone position with a
folded towel or bed sheet placed
under his lower ribs & epigastrium to
push the kidneys posteriorly &
stabilize their position.
-The entry of biopsy needle into the kidney, when it pierces the
renal capsule, is indicated by slight resistance & once in kidney
it moves with respiratory excrusions
-2 core of tissue(abt. 8-10 mm long)
are needed for adequate histological
examination.
81. -One core is fixed in buffered formaline & other in saline(for
immunofluorescence study)
Interpretation of Renal Biopsy
⢠The histology should be examined by light microscopy using
Hematoxylin & eosin(H & E),Periodic Schiff (PAS) & Silver
Methanamine staining In all cases, & special stains as
necessary.
⢠Electron microscopy is very useful in several disorders e.g
Alport So, Membranoproliferative GN & thin Basement
Membrane Disease.
81
82. References
Books:
⢠M.N. Chaterjee, Clinical Chemistry (Organ Function Tests and
Laboratory Investigations), Jaypee Brothers Medical Publishers (1999)
⢠Ambika Shanmugam, Fundamentals of Biochemistry for Medical
Students, Revised Edition(2005)
Links:
⢠Kidney Dialysis Foundation (2007). Normal Kidney Functions. Health
Guide[Online]. Available: http://www.kdf.org.sg/health.php (2008, June
01).
⢠National Kidney Foundation (2007). Common Kidney Diseases.
Education[Online]. Available: http://www.nkfs.org/index.php (2008, June
01).
Editor's Notes
AV fistula VS graft
a normally existing antibody (Immunoglobulin A) is deposited in the glomeruli and incites inflammation
This is due to the differences in the anatomy of the urinary tract between men and women. A woman's urethra (which is the urinary tubing that connects the bladder and the outside world) is much shorter and very close to the opening of the vagina.