1. Nephrotic syndrome is characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia. The majority of cases in children are idiopathic or minimal change disease.
2. Secondary causes include systemic diseases, infections, medications, and genetic conditions.
3. Treatment involves corticosteroids as first line, with recurrence being common in minimal change disease. Kidney biopsy may be needed to identify secondary causes or steroid resistance.
Management Of Nephrotic Syndrome
Objectives
To briefly review the definition & etiology of nephroticsyndrome.
To understand the terminology pertaining to clinical course of nephroticsyndrome.
To understand the management of nephroticsyndrome:Specific management & Supportive care and management of complications
Management of congenital nephrotic syndrome
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
Management Of Nephrotic Syndrome
Objectives
To briefly review the definition & etiology of nephroticsyndrome.
To understand the terminology pertaining to clinical course of nephroticsyndrome.
To understand the management of nephroticsyndrome:Specific management & Supportive care and management of complications
Management of congenital nephrotic syndrome
This presentation was done by Dr. Julius P. Kessy,MD. An intern Doctor at Dodoma Regional Referral Hospital (DRRH) during pediatrics unit clinical meeting and supervised by Dr. Christina K. Galabawa,MD,Mmed2, Pediatrics and Child Health, University of Dodoma (UDOM) in November, 2017.
Description of Urinary tract infections of pediatric age group, signs and symptoms, presentations, diagnosis, investigations, prognosis and management plan
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Description of Urinary tract infections of pediatric age group, signs and symptoms, presentations, diagnosis, investigations, prognosis and management plan
download link : https://www.dropbox.com/s/xc0fpdul47g1gu8/IgA%20Nephropathy.ppt?m
Join us on our facebook group: NephroTube...............Follow our blog: www.nephrotube.blogspot.com
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
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.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- 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
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
2. Nephrotic Syndrome
1. Massive proteinuria - 40 mg/m2/hr
(50 mg / kg / d or 3.5 gm/day)
2. Hypoalbuminemia (<2.5 g/dL)
3. Hypercholesterolemia (>220 mg/dL)
With or without
4. Edema
ISKDC Definition :
•Nephrotic range of proteinuria =
Urine Protein 3+ or 4+
•Urine protein / creatinine ratio of > 2.0
3. Nephrotic Syndrome
• 2 to 7 cases per 100,000 childre
• 10-fold lower in adults
• Male-to-female ratio is reported to be 2:1
for children and 1:1 in adolescents and
adults
• MCNS peaks between 2-5 years of age
• 92% of these will experience remission of
their disease when treated
• Adolescents are more likely to have a
more aggressive cause of the nephrotic
syndrome
Incidence of Idiopathic form
4. Nephrotic Syndrome - Children
Etiology
• 90 % - primary
glomerular
abnormality
(Idiopathic)
• Rest – part of renal
involvement in
different diseases
15. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
(mesangiocapillary glomerulonephritis)
• MPGN types 1, 2, and 3 account for 44%, 20%, and 36%
of cases, respectively.
• All 3 types appear similar by light microscopy and have
increased mesangial cellularity and matrix expansion.
• By electron microscopy,
– type 1 shows normal-appearing GBM, with subendothelial electron-
dense deposits.
– MPGN type 2, also known as dense-deposit disease, appears to
be a distinct disease and has thickening and increased electron
density of the lamina densa of the GBM.
– In MPGN type 3, deposits are present on both the subepithelial and
the subendothelial sides of the GBM, as well as within the GBM. With
special stains the GBM appears fenestrated, and deposits are
covered by layers of new GBM
16. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
(mesangiocapillary glomerulonephritis)
• Etiology:
– Type-1 MPGN:
• Caused by immune complex formation and deposition
• Of the classical pathway of complement consumption
– MPGN type 2:
• (Dense Deposit Disease), Mesangiocapillary GN
• thought to be the result of the presence of circulating
autoantibodies called nephritic factors (NFs) that stabilize the C3
convertases activating the alternative (NFa) and respectively
– MPGN type 3:
• Activation of (NFt) pathways of complement activation
• Candidate gene on Chromosome 1
17. Idiopathic Nephrotic Syndrome - Children
Pathological Types
3 Focal Segmental Glomerular Sclerosis (10%)
idiopathic or secondary to a number of different causes (e.g., heroin abuse,
HIV infection, sickle cell disease, obesity, reflux of urine from the bladder to the
kidneys, and lesions associated with a single or remnant kidneys).
18. Disease processes associated with FSGS
lesions
• Diabetic nephropathy
• Sickle cell disease
• HIV nephropathy
• Glomerulonephritides
– IgA nephropath
– MPGN
– Lupus nephritis
• Frasier syndrome, consisting of male
pseudohermaphroditism (Mutations in WT1 gene)
• Diffuse mesangial sclerosis
– May be part of Denys-Drash syndrome
19. Idiopathic Nephrotic Syndrome
Pathological Types
4 Membranous nephropathy (1%)
most common pattern of idiopathic NS in white Americans
- Hepatitis B, Sjögren's syndrome, Systemic lupus erythematosus
(SLE), Diabetes mellitus, Sarcoidosis, Syphilis, Drugs, Malignancy
20. MCNS Nephrotic Syndrome
(Nil Disease or Lipoid Nephrosis)
– In 3 months to 16 years of age, 76%
have minimal change nephrotic
syndrome (MCNS)
– No glomerular abnormalities in light
microscope
– Effacement of foot processes in electron
microscopy
– Minimal deposition of mesangial matrix
– Serum complement (C3) normal
– Circulating immune complexes absent
21. Pathophysiology of NS
Increased permeability of glomerular capillary
wall, which leads to massive proteinuria and
hypoalbuminemia.
In MCNS :
T Cell dysfunction leads to alteration of cytokines which
causes a loss of negatively charged glycoproteins within
capillary wall
In FSGS:
A plasma factor produced by lymphocytes responsible
Mutations in podocyte proteins (podocin, a – actinin 4)
In Steroid resistant NS:
Mutations in NPHS 1(nephrin) & 2(podocin) and WT1 or
ACTN4 (a-actinin) genes
22. Clinical Features
• Age of onset : 85 - 90% < 6 yrs yrs
• 30% adolescents may have MCNS
• Onset : insidious
• Initial episode & subsequent
relapses may follow minor
infections or insect bites, bee
stings, poison ivy, etc.
23.
24. Clinical Features
COMMON:
• Anorexia, irritability, abdominal pain, diarrhoea
and genital edema
• Frothy urine (high concentrations of protein)
• Edema may cause dyspnea (pleural effusion or
laryngeal edema),
• Chest discomfort (pericardial effusion), arthralgia
(hydrarthrosis), or abdominal pain (ascites or, in
children, mesenteric edema).
• Edema may obscure signs of muscle wasting and
cause parallel white lines in fingernail beds
(Muehrcke's lines).
UNCOMMON:
• Hypertension, Gross hematuria
26. Massive Proteinuria - Mechanism
• Loss of negatively charged
sialoproteins and glycoproteins
• Increased size of pores
• Loss of foot processes
• Increased excretion or decreased
absorption
• Release of platelet factor in
glomeruli
• Increased thromboxane production
27. Protein Loss
– Albumin
– Thyroxine-binding protein
– Cholecalciferol-binding protein
– Transferrin
– Metal binding proteins
– Anti Thrombin III, Proteins C & S
29. Oedema - Mechanism
Massive proteinuria – hypoalbuminemia - i
plasma oncotic pressure -> transudation of fluid
from intravascular compartment to interstitial
space.
Under Fill Theory :
Reduced renal perfusion leading to h production of renin-
angiotensin aldosterone system
Reduction of intravascular volume stimulates ADH
Over Fill Theory :
Defective excretion of sodium and water from kidney due
to dysfunction
h absorption of sodium and water from renal tubules
Circulation of unknown antigen causing h
capillary permeability
i production of atrial natriuretic peptide
Increased activity of aldosetrone & vasopressin
Activities of various cytokins and physical factors
within the vasa recti
30. Hyperlipidemia - Mechanism
i conversion of VLDL in to LDL by i of
lipoprotein lipase
Loss of apolipoprotein (apo CII) in urine
i levels of HDL
h synthesis of lipoproteins
Abnormalities in regulatory enzymes like licithin-
cholesterol acyltranferase and cholesterol ester
transfer protein, lipoprotien lipase
• VLDL content is more increased
• Triglyceride levels are decreased when albumin level is < 1 g
31. Hypercoagulable State
Occur when serum albumin < 2g/dL
Causes :
– Urinary loss of antithrombin III, Factor
IX, X, XI - > thrombin activity increase
– Protein C, S activity or level decrease
– Hyperfibrinogenemia
– Platelet activation increase
– Hyperlipidemia
• Combined with hypovolemia, immobility, increased incidence of infection
40. Blood
• S.Cholesterol ( > 250 mg/dL)
• S.Albumin (<2.5 gm/dL)
• S. A/G ratio - reversal
• S.Creatinine
• Bl. Urea
• S . C3 and C4 levels
• CBC : Increased Hb, Platelets, Hct
Normal
41. Imaging
• U/S : Nonspecific.
– Enlarged kidneys – due to tissue edema
– Increased echogenicity/Small Kidneys : Chronic kidney
disease other than MCNS
• CXR:
– Pleural effusion
– Pulm edema - rare
42. Kidney Biopsy
Indications:
• Patients younger than 1 year and older than 8 yrs
• Symptoms of systemic disease ( fever, rash, joint
pain)
• Labs suggestive of sec nephrotic syndrome
(Positive Ana, Positive anti-double stranded DNA
antibody, Low complement)
• Elevated creatinine levels unresponsive to
correction of volume depletion
• Family history of kidney disease
• Patients initially or subsequently unresponsive to
steroid treatment.
43. Management - Principles
• Admission
– For establishment of diagnosis
– For exclusion of infection
– To wait for spontaneous remission
• Treat infections
• Supportive therapy
• Steroid therapy
44. Supportive Care
• Diet : Balanced
– adequate protein (1.5 – 2 gm/kg)
– Not > 30% calories from fats
– Avoid saturated fats
– Reduction in salt intake (1-2 g/d) for
those with persistent edema
– Ensure physical activity
– Calcium and Vitamin D supplementation
45. Treatment of Initial Episode
• Prednisalone
– 2mg / kg / d in 2-3 divided doses for
4-6 weeks [60 mg / m2/d]
• Antacid dose steroid to prevent gastric
irritation ??
• After 6 wks, reduce dose
– 1.5 mg/kg/d [40 mg / m2/d ] as a
single dose every other day morning
slowly tapering in 2-3 months
• Then discontinue
Shorter duration of initial therapy in not recommended.
Steroid Therapy
46. Treatment of Initial Episode
• Acting through the nuclear
factor kappaB (NF-kB)
transcription pathway –
inhibiting cytokine production
and inhibiting T-Cell prouction
and proliferation.
Steroids – Mechanism of action
47. Diuretic Therapy
Indications
• To prevent secondary infections after breakdown
of skin
• To prevent GI and Resp. embarrassment
• To prevent urethral obstruction due to massive
edema of scrotum
Drugs
• Furosemide : 1-3 mg / kg / dose IV q12h
• Chlorthiazide : 10 mg / kg / d
• Spiranolactone : 3-4 mg /kg/ d in 3-4 div. doses
• 25% salt free albumin 0.5g / kg over 60 min
Patients with persistent edema and weight gain above 7 - 10% are
treated with oral frusemide
48. ISKDC Terminology
• Remission
– Urine albumin : Nil or Traces or <4 mg/m2/hr
for 3 consecutive early morning specimen
• Response
– Urine free of protein in 8 wks. (Steroid
sensitive)
• Late Response
– A response beyond 8 weeks
49. ISKDC Terminology
• Relapse
– Proteinuria 3+ plus edema or
40 mg/m2/ hr for 3 consecutive early
morning specimen
– (having been in remission previously)
• Frequent Relapse
– SSNS with 2 or more relapses in 6 mo. or
> 4 relapses in 1 year
50. ISKDC Terminology
• Steroid Dependent NS
SSNS with 2 or more consecutive relapses
during tapering or within 14 days of stopping
steroids.
• Steroid Resistant:
Either do not respond to the initial treatment
with prednisalone within 8 weeks of therapy
60mg/m2/d, or do so transiently and later
cease to respond [2-5%]
(FSGS= 80%, MPG = 20%, MCNS– rarely)
51. Treatment of Relapse
Relapse often precipitated by URI
• Prednisalone
– 2 mg/kg/d until the urine is protein free
for 3 consecutive days
– Thereafter – 1.5 mg/kg/d on alternate
days for 4 wks and stop.
(Total duration of therapy = 5 to 6 wks.)
52. Management of pt. with steroid sensitive NS
Prednisalone 2 mg/kg daily forr6 wks., followed by 1.5 mg/kg on alt
day for 6 wks.
Infrequent relapses Frequent relapses Steroid resistant
Therapy for relapse
Prednisalone 2 mg/kg daily
until remission, then 1.5
mg/kg on alt. days for 4
weeks
Alternate day prednisalone
to maintain remission
Therapy based on
renal histology
Threshold <0.5 mg/kg
on alt. days
Threshold >0.5 mg/kg on
alt. days / Steroid toxicity
Alt. day prednisalone
for 9-18 mo.
•Levamisole
•Cyclophosphamide
•Mycophenolate
•Tacrolimus
•Cyclosporine
53. Management of pt. with steroid sensitive NS
Infrequent relapses
• Examine for infections, which
should be treated before initiating steroid therapy.
• Prednisolone is administered at a dose of
2 mg/kg/day (single or divided doses) until urine protein is
trace or nil for 3 consecutive days.
• Subsequently, prednisolone is given in a single
morning dose of 1.5 mg/kg on alternate days for
4 weeks, and then discontinued.
• The usual duration of treatment for a relapse is 5-6 weeks.
Prolongation of therapy is not necessary for patients with
infrequent relapses
54. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
• Following treatment of a relapse, prednisolone is gradually
tapered to maintain the patient in remission on alternate
day dose of 0.5-0.7 mg/kg, which is administered for 9 -
18 months.
(a)Levamisole at a dose of 2-2.5 mg/kg on alternate days for 12-
24 months.
Co-treatment with prednisolone at a dose of 1.5 mg/kg on
alternate days is given for 2-4 weeks; its dose is gradually
reduced by 0.15-0.25 mg/kg every 4 weeks to a maintenance
dose of 0.25-0.5 mg/kg that is continued for 6 or more months.
The chief side effect of levamisole is leukopenia; flu-like symptoms, liver
toxicity, convulsions and skin rash. The leukocyte count should be monitored
every 12-16 weeks.
55. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
(b) Cyclophosphamide at a dose of 2-2.5 mg/kg/day for 12
weeks.
Prednisolone is co-administered at a dose of 1.5 mg/kg on
alternate days for 4 weeks, followed by 1 mg/kg for the next 8
weeks;steroid therapy is tapered and stopped over the next 2-
3 months.
Therapy with cyclophosphamide should be instituted preferably
following remission of proteinuria. Total leukocyte counts are monitored
every 2 weeks; treatment is temporarily discontinued if the count falls below
4000/mm3. An increased oral fluid intake and frequent voiding prevents the
complication of hemorrhagic cystitis; other side effects are alopecia, nausea
and vomiting.
The risk of gonadal toxicity is limited with a single (12 weeks) course of
cyclophosphamide. The use of more than one course of this agent should
preferably be avoided.
56. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
(c) Calcineurin inhibitors: Cyclosporin (CsA) is given at a
dose of 4-5 mg/kg daily for 12-24months.
Prednisolone is co-administered at a dose of 1.5 mg/kg on alternate days
for 2-4 weeks; its dose is gradually reduced by 0.15- 0.25 mg/kg every 4
weeks to a maintenance dose of 0.25-0.5 mg/kg that is continued for six
or more months. Occasionally, treatment with corticosteroids may be
discontinued.
Side effects of CsA therapy include hypertension, cosmetic
symptoms (gum hypertrophy, hirsutism) and nephrotoxicity;
hypercholesterolemia and elevated transaminases.
Estimation of blood levels of creatinine is required every 2-3 months and a
lipid profile annually. A repeat kidney biopsy, to examine for histological
evidence of nephrotoxicity, should be done if therapy with calcineurin
inhibitors is extended beyond 2 years
57. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
Tacrolimus is an alternative agent, administered
at a dose of 0.1-0.2 mg/kg daily for 12-24 months.
Side effects include hyperglycemia, diarrhea and rarely
neurotoxicity (headache, seizures). The use of tacrolimus
is preferred especially in adolescents, because of lack of
cosmetic side effects(13). Blood levels of creatinine and
glucose should be estimated every 2-3 months.
58. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
(d) Mycophenolate mofetil (MMF) at a dose of 800-1200
mg/m2 along with tapering doses of prednisolone for 12-24
months.
The principal side effects include gastrointestinal discomfort,
diarrhea and leukopenia.
Leukocyte counts should be monitored every 1-2 months;
treatment is withheld if count falls below 4000/mm3.
59. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
Choice of agent
1. Levamisole has a modest steroid sparing effect and is a
satisfactory initial choice for patients with frequent
relapses or steroid dependence.
2. Treatment with cyclophosphamide is preferred in patients
showing:
(i) significant steroid toxicity,
(ii) severe relapses with episodes of hypovolemia or
thrombosis, and
(iii) poor compliance or difficult follow up, where 12 weeks
therapy possible to ensure than long-term compliance.
60. Management of pt. with steroid sensitive NS
Frequent relapsers & Steroid Dependent
Choice of agent
3. Treatment with CsA or tacrolimus is recommended for
patients who continue to show steroid dependence or
frequent relapses despite treatment with the above
medications
4. The lack of renal, hemodynamic and metabolic toxicity
with Mycophenolate maleate makes it an attractive
alternative to calcineurin inhibitors.
61. Frequent relapsers FRNS &
Steroid Dependent SDNS
• Prednisalone 2 mg/kg/d (60 mg/m2/d) as single morning
dose until patient has been free of protinuria for at least 3
consecutive days. Following remission, Prednisalone
reducetd to 1.5 mg/kg/d (40mg/m2) given as single dose on
alt days and tapered over 3 months.
• A steroid sparing agent conisered once protinuria is in
remission
• Alkylating agent : Cyclophosphamide, Chlorambucil
• Calcinurin inhibitors: Cyclosporin A, Tacrolimus
62. Management of NS
• ACE Inhibitors : to prevent proteinuria
– Act by alteration of capillary permeability
and reduction in glomerular hydrostatic
pressure
• HMG coenzyme-A reductase inhibitors
to reduce s. cholesterol
• Albumin Infusion : controversial
– Abdominal pain
– Hypotension
– Severe Oliguria
– Renal insufficiency
63. Management of NS
Immunization
• Patients on prednisalone therapy
are considered immunosuppressed
– avoid live attenuated vaccines
• All patients should receive
pneumococcal vaccine
64. Management of NS
Investigational Treatments
• Rituximab : A chimeric anti-CD20 antibody
that results in depletion of B Cells
• Plasmapheresis – esp with FSGS patients
who have received kidney transplans
• Galactose : high affinity for circulating
permeability factor (FSGS) after kidney
transplant
• Zinc
65. Initial Steroid Resistance
• Mesangial proliferative GN
• Focal segmental
glomerulosclerosis (FSGS)
• Membrano-proliferaive GN (MPGN)
– Type 1 : with intact BM
– Type 2: (30%) with dense deposits,
persistent low serum C3, abundant
immunonglobulin & C3 deposits
• Membranous nephropathy
66.
67.
68.
69. Initial Steroid Resistance
• Trial of pulse methylprednisalone
(30 mg/kg) or dexamethasone
– First 6 doses given every other day
followed by tapering for periods upto
18 months
• Cyclosporin A
• IVIG
• Mycophenolate mofetil
70. Steroid Adverse Effetcts
• Infection
• Obesity
• Growth delay
• Osteopenia
• Avascular necrosis of the hip
• Cataracts
• Hypertension
• Hyperglycemia
• Nephrolithiasis
• Hyperlipedemia
72. A. Complications Due to Disease
• PEM due to protein loss
• Infections:
– S.pneumonia, H. influenza - VPDs
• Thrombotic complications
• Iron, copper, zinc, and vitamin D
deficiencies
• Laryngeal edema - rarely
73. Infections
• Factors responsible :
– Urinary loss of Factor B and
immunoglobulins, properdin B
– Defective CMI
– Defective opsonization
– Ascitic fluid – good culture medium
– Immunosuppressive drugs
– Malnutrition
• Peritonitis
• Pneumonia
• Osteomyelitis
• Cellulitis
• Arthritis
74. B. Complications Due to Treatment
• Steroids
– Cushingoid syndrome
– Hypertension due to salt retention
– Osteoporosis
– Susceptibility to infections
– Growth failure
– Cateracts
– Glaucoma
– Gastritis
– Peptic ulcer
– Hypokalemia
– Behavioural changes
• Cyclophosphamide
– Alopecia
– Leucopenia
– Infertility
– Hemorrhagic cystitis
75.
76. Outcome of MCNS
• Most stop getting relapses by 11 to
15 yrs
• Full recovery
• Very small proportion – develop
late steroid resistance
• Mortality : 1-4 % sec. to infections
& hypovolemia
77. NS Variants
Congenital:
• Develop within first 3 mo.
• Cong. Syphilis, Intrauterine infections
Finnish Type :
• Autosomal recessive
• Mutations in the NPHS1 gene encoding nephrin or
NPHS2 gene encoding podocin
• Leads to renal failure
• Elevated alpha fetoprotein in amniotic fluid &
maternal serum
Dany-Drash Syndrome :
• Wilms tumor, NS, Genital anomalies
• Diffuse mesangial sclerosis