This document discusses laboratory diagnosis of renal diseases. It covers renal function tests like glomerular filtration rate (GFR) and clearance tests which are used to detect early renal impairment. GFR is estimated using creatinine clearance tests or formulas using serum creatinine. Urine analysis and renal biopsy are also used to diagnose and characterize renal diseases by examining features under light and electron microscopy. Renal biopsy can identify conditions affecting the glomeruli, tubules, interstitium or blood vessels. Recent advances include use of genomics and proteomics in renal disease diagnosis and classification.
rft is described in detail . function of kidney, objectives of doing the test. the various test available for assessing the renal function with clinical interpretation is available.
rft is described in detail . function of kidney, objectives of doing the test. the various test available for assessing the renal function with clinical interpretation is available.
Renal function test (RFT), also known as kidney function test is a group of tests used to assess the functions of kidney.
It is used screen for, detect, evaluate and monitor acute and chronic kidney diseases.
These are simple blood and urine tests that are used identify kidneys problems.
Tests of renal function have utility in-
Identifying the presence of renal disease
Monitoring the response of kidneys to treatment
Determining the progression of renal disease
RFT is ordered, if your doctor
thinks your kidneys may not be working properly which is known from signs and symptoms
and if you have other conditions that can harm the kidneys, such as diabetes or high blood pressure
KFT are used for evaluating kidney functions. there are several routine tests such as urea, creatinine and uric acid. Calculation of eGFR is recommended by national kidney organization whenever creatinine serum is measured.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
6. INDICATIONS
• Early identification of renal impairment in patients at risk.
• Diagnosis of renal disease.
• Assess response to treatment.
• Adjust dosage of certain drugs.
• Plan renal replacement therapy in advanced renal diseases.
7. CLASSIFICATION
GLOMERULUS PROXIMAL
TUBULES
DISTAL
TUBULES
Clearance tests Glycosuria Specific gravity
S. Creatinine Aminoaciduria Osmolality
BUN Tubular proteinuria Water deprivation
test
BUN/S.Creatinine Urinary excretion of
sodium
Water loading test
Proteinuria Fractional sodium
excretion
Ammonium
chloride loading test
9. GFR - RATIONALE
• Varies according to age, sex, BSA.
• Normal GFR is 120 – 130 ml/min/1.73m2.
• Declines with age.
• Fall in GFR leads to accumulation of waste products.
• GFR < 60ml/min/1.73m2
- >50% loss of renal function.
10. CHRONIC KIDNEY DISEASES
STAGE DISEASE GFR VALUE
(ml/min/1.73m2
)
Stage I Kidney disease
with
Normal GFR >90
Stage II Kidney disease
with
Mildly reduced
GFR
60-89
Stage III Kidney disease
with
Moderately
reduced GFR
30-59
Stage IV Kidney disease
with
Severely reduced
GFR
12-29
Stage V Kidney failure <15
11. METHODS TO MEASURE GFR
• Direct assessment - Clearance tests
• Indirect assessment from S. Creatinine
12. CLEARANCE TESTS
• Volume of plasma that is completely cleared of that substance
per minute.
• C = UV/ P
• C - Clearance (ml/min)
U - Concentration of substance in urine (mg/dl)
V - Volume of urine per min (ml/min)
P - Concentration of substance in plasma (mg/dl)
13. AGENT FOR CLEARANCE
STUDIES
• Not bind to plasma proteins.
• Freely filtered across glomeruli.
• Not reabsorbed
• Not secreted.
• Not metabolized by kidney.
• Excreted only through the kidney.
15. INULIN CLEARANCE TEST
• Gold standard for measurement of GFR.
Method:
• Bolus dose – 25 ml of 10 % solution.
• 500 ml of 1.5 % solution – 4 ml/ min.
• Timed urine and blood samples are collected.
16. INULIN CLEARANCE TEST
Disadvantage:
• Time consuming
• Expensive
• Need to maintain steady plasma levels
Normal values:
• Males – 125 ml/min/1.73 m2
• Females – 110 ml/min/1.73 m2
18. CREATININE CLEARANCE
TEST
Method:
• 24 hour urine sample.
• A blood sample is obtained at midpoint of urine collection.
• Final calculation is by the formula UV/P.
• Cimetidine can be used to prevent overestimation.
19.
20. CREATININE CLEARANCE
TEST
Disadvantages:
• Small amounts of creatinine secreted by renal tubules can
increase even further in advanced renal failure.
• Collection of urine is often incomplete.
• Creatinine levels are affected by -
- meat and muscle mass.
- certain drugs (cimetidine, trimethoprim)
21. CYSTATIN-C CLEARANCE TEST
Rationale:
• Protease inhibitor produced by all nucleated cells.
Advantages over creatinine:
• More sensitive and specific.
• Not affected by sex, diet and muscle mass.
22. INDIRECT ASSESSMENT OF
GFR
Convenient but insensitive.
Creatinine clearance
(140 – age in years) x Body weight in kg
( 72 x serum creatinine in mg/dl)
=
25. DISADVANTAGES - BUN
• Less sensitive.
• Completely filtered by glomeruli and 30-40 % is
reabsorbed.
• Affected by -
- Protein diet
- Upper G.I haemorrhage
- Liver function
• Considerable destruction of renal parenchyma - blood urea
elevation.
26. METHODS
1. Diacetyl monoxamine method
+ DAM
Yellow diazine derivative
High temp, strong acid, oxidizing
agent
Intensity of color is measured
Urea
27. METHODS
2. Urease Berthelot reaction
Iodophenol
Intensity of color
is measured
Urea
370 C
Urease
Ammonia
Alkaline hypochlorite
Phenol
28. CAUSES OF INCREASED BUN
PRE RENAL RENAL POST RENAL
• Shock
• CHF
• Dehydration
• High protein diet
• Trauma
• Burns
• GI haemorrhage
• Impairment of
renal function
• Obstruction of
urinary tract
29. SERUM CREATININE
Rationale:
• Creatinine is produced in muscles at a constant rate.
• Production is proportional to muscle mass and body weight.
Normal range: 0.7 to 1.3 mg/dl
34. BUN/SERUM CREATININE
RATIO
RATIO >20:1 RATIO <10:1
↑BUN WITH NORMAL
CREATININE
↑CREATININE WITH NORMAL
BUN
High protein diet
Increased protein catabolism
GI haemorrhage
Dehydration
Starvation
Low protein diet
Severe liver disease
↑BUN & CREATININE, BUT ↑IN
BUN IS MORE
↑BUN & CREATININE, BUT ↑ IN
CREATININE IS MORE
Post renal obstruction Acute tubular necrosis
35. PROTEINURIA
Rationale:
• A very small amount of albumin is excreted in urine.
• Microalbuminuria (30 to 300 mg/24 hrs)
• Clinical or overt albuminuria ( >300mg/24 hr)
44. URINE OSMOLALITY
Rationale:
• Most sensitive and most commonly employed method.
• Depends on number of dissolved particles.
• Normal value: 500 - 800 mOsm/kg of water.
46. WATER DEPRIVATION TEST
Rationale:
• Measures concentrating ability of kidney with fluid restriction.
• Differentiate between central DI and nephrogenic DI.
47. WATER DEPRIVATION TEST
Method:
Rise in specific gravity and
urine osmolality
Urinary concentrating ability
maintained
No rise in specific gravity and
osmolality
Administer desmopressin
Rise No rise
Nephrogenic DICentral DI
Restriction of water intake
48. WATER LOADING – ADH
SUPPRESSION TEST
Rationale:
• Measures ability of kidney to dilute urine after water loading.
49. Method:
Over night fast
Drink 20 ml/kg of water in 15-20 min
• <80% excreted
• >1.003
• >100 mOsm/kg
• ADH fails to decrease
• >90% excreted
• Specific gravity <1.003
• Urine osmolality <100 mOsm/kg
• Decreased plasma osmolality and
ADH levels
Normal diluting ability
of kidney
Renal function
impairment
Collect urine for next 4 hours
65. GLOMERULUS: NO / MINIMAL
HYPERCELLULARITY
DISEASE LM IF EM
MCD Normal glomeruli,
lipid vacuolation in
tubules
Negative Loss of foot
processes, no
deposits
FSGS Focal and segmental
sclerosis and
hyalinosis
IgM, C3 Loss of foot
processes, electron
dense deposits
MGN Diffuse thickening
of capillary wall
Granular
IgG, C3
Subepithelial
deposits (spikes)
71. GLOMERULUS: WITH
HYPERCELLULARITY
DISEASE LM IF EM
MPGN Double
contour of
GBM
I – IgG, C3
II – C3,
properdin
III – C3, IgG,
Ig M
I - Sub endothelial deposits
II – Dense intra membranous
deposits
III – Sub endothelial and sub
epithelial deposits.
Acute GN Diffuse
proliferation,
leukocytic
infiltration
Irregular IgG, C3 Subepithelial deposits (humps)
Crescentic
GN
Proliferation,
crescents
I- Linear Ig G, C3
II- Granular Ig G,
C3
III - Negative
I - Linear deposits along GBM
II - Sub epithelial deposits
III - No deposits
85. RECENT ADVANCES
• Genomics and proteomics.
• Laser-capture micro dissection - selection of glomeruli or a
specific tubular segment for study.
• ISH
Advantages:
• Identification of specific mRNA expression pattern and their
correlation with diagnosis, prognosis and response.
86. SUMMARY
• Renal diseases causes no symptoms until 50-75% of kidney
function is destroyed.
• Lab tests often provide the initial recognition of renal
impairment and can be used to direct further therapy.
• The simplest diagnostic test is the examination of the urine.
• Renal biopsy is performed to establish the specific diagnosis
of renal disease.
87. REFERENCES
• U.Satyanarayana, U.Chakrapani, Biochemistry, Arunabha Sen
Books Pvt. Ltd., 2010.
• Gaw A, Murphy MJ, Cowan RA, O’Reilly DSJ, Stewart MJ,
Shepherd J. Clinical Biochemistry: An illustrated colour text
(3rd Ed). Edinburgh: Churchill Livingstone, 2004.
• Stevens LA, Levey AS. Measurement of kidney function. Med
Clin N Am 2005;89:457-73.
• Pathological basis of disease : Robbins and Cotran, 9th edition.