Diabetic nephropathy is a major complication of diabetes that can progress to kidney failure. The document discusses the pathophysiology, risk factors, stages of progression, biomarkers and pathology of diabetic nephropathy. Key factors that contribute to its development include genetic susceptibility, hypertension, activation of the renin-angiotensin-aldosterone system, increased levels of growth factors like TGF-β, and chronic high blood glucose levels which can activate biochemical pathways like protein kinase C. Left untreated, diabetic nephropathy can progress through five stages and ultimately lead to end-stage renal disease.
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
My Nephrology Registrar Seminar Talk from September 2013
Topics Covered
Pathogenesis of Diabetic Nephropathy
Other Renal Disease in Diabetes
Treatment of Diabetic Kidney Disease + The Joint Renal Diabetic Clinic
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
My Nephrology Registrar Seminar Talk from September 2013
Topics Covered
Pathogenesis of Diabetic Nephropathy
Other Renal Disease in Diabetes
Treatment of Diabetic Kidney Disease + The Joint Renal Diabetic Clinic
a detailed description of pain and therpaeutic options available and clinical assessment of pain, approach to the patient with pain, assessment of intensity of pain, nsaids and opioids, tca. WHO pain ladder, chronic opioid therapy
Diabetic nephropathy considered one of the most common complications of DM. This presentation answer the question are some diabetic patient immune to diabetic nephroapthy
New Therapeutics in Diabetic Kidney Disease
Conjoint Meeting of the Iraqi Society of Nephrology and Renal Transplantation and The Iraqi Diabetes Association.
Diabetic nephropathy is a clinical syndrome characterized by the following :
Persistent albuminuria (>300 mg/d or >200 μg/min) that is confirmed on at least 2 occasions 3-6 months apart.
Progressive decline in the glomerular filtration rate (GFR).
Elevated arterial blood pressure.
Three major histologic changes occur in the glomeruli of persons with diabetic nephropathy:
First, mesangial expansion is directly induced by hyperglycemia, perhaps via increased matrix production or glycation of matrix proteins.
Second, thickening of the glomerular basement membrane (GBM) occurs.
Third, glomerular sclerosis caused by intraglomerular hypertension (induced by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli).
These different histologic patterns appear to have similar prognostic significance.
Several issues are key in the medical care of patients with diabetic nephropathy.
These include glycemic control, management of hypertension, and reducing dietary salt intake and phosphorus and potassium restriction in advanced cases.
A meta-analysis from the Cochrane Database shows a large fall in blood pressure with salt restriction, similar to that of single-drug therapy
By Dr Ahmed Mohammed Abd El Wahab. It describes nature of hyperuricemia, gout, pathophysiology evidence to treat or not and different treatment modalities
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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.
- 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
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
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.
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
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.
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
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.
2. Global Epidemic of Type 2
Diabetes
•Aging Population
•Global Lifestyle “Westernization”
•Surging Obesity
3. The facts
• Almost one in three people with type 2
diabetes develops overt kidney disease.
• Diabetes is the single most common cause of
end stage renal failure.
• Kidney disease accounts for 21 per cent of
deaths in type 1 and 11 per cent of deaths in
type 2.
4. Russo E, et al. Diabetes Metab Syndr Obes. 2013; 6: 161–170.
6. Afkarian M et al., J Am Soc Nephrol. 2013
Feb;24(2):302-8
7. Definition of Diabetic Nephropathy
• Persistent albuminuria from 3 to 6 months in at
least two out of three consecutive urine
collections,with longstanding history of diabetes.
• With presence of Diabetic retinopathy
,hypertention & decreased eGFR.
• With absence of clinical or laboratory evidence of
other kidney or urinary system diseases.
13. Stages of Diabetic Nephropathy
Stage I II III IV V
GFR H H H L L
uAER N HN MIA MAA MAA
BP N N HN H H
Hypertrophy + ++ +++ + +/-
BM thicken. N + ++ +++ +++
Mesang. Expan. N +/- ++ +++ +++
G.Closure & A. hyalinosis N N N ++ +++
15. A1 A2 A3
Normal to
mildly
increased
Moderately
increased
Severely
increased
<30 mg/g
<3 mg/mmol
30-300 mg/g
3-30 mg/mmol
>300 mg/g
>30 mg/mmol
• CKD is defined as abnormalities of kidney structure or function, present for >3 months, with
implications for health and CKD is classified based on cause, GFR category, and albuminuria
category (CGA).
KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:136-150.
http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf Accessed February 26, 2013
G1 Normal or high ≥90
G2 Mildly decreased 60-89
G3a
Mildly to moderately
decreased
45-59
G3b
Moderately to
severely decreased
30-44
G4 Severely decreased 15-29
G5 Kidney failure <15
Persistent albuminuria categories
Description and range
Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red, very high risk.
Prognosis of CKD by GFR
and Albuminuria Categories:
KDIGO 2012
16. Category
Spot collection (µg/mg
creatinine)
Normal <30
Increased urinary albumin
excretion* ≥30
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S44; Table 11
*Historically, ratios between 30 and 299 have been called microalbuminuria and those 300
or greater have been called macroalbuminuria (or clinical albuminuria).
20. Factors involved in the pathophysiology of diabetic
nephropathy
Genetic susceptibility
Haemodynamic raised intraglomerular pressure
Biochemical
Growth factors
Vasoactive factors
glucose, protein kinase C, diacyl
glycerol, etc.
IGF-1, TGF-ß, connective tissue
growth factor
VEGF, angiotensins, endothelin
21. Genetic predisposition
• Genetic predisposition to or protection from diabetic
nephropathy appears to be the most important
determinant of diabetic nephropathy risk in both type 1
and type 2 diabetics.
• A polymorphism in the gene that encodes the ACE has
been associated with diabetic nephropathy
• Genes for pyrophosphatase/phosphodiesterase-1,
peroxisome proliferator-activated receptor-γ2 (PPAR-γ2),
glucose transporter 1, apolipoprotein E, and lipoprotein
lipase (HindIII) have been associated with diabetic
nephropathy risk.
• A1a12 allele of PPAR-γ2 may confer protection
24. Hypertension
• In diabetics who have disordered autoregulation at the
level of the kidney, systemic hypertension can contribute to
endothelial injury.
• Systemic blood pressure levels are implicated in
progression and, as noted earlier, lack of normal
nocturnal blood pressure dipping may be implicated in
the genesis of diabetic nephropathy.
• Intensive blood pressure control has been associated with
decreased rates of progression of diabetic nephropathy in
both normotensive and hypertensive diabetics.
25. Aldosterone
Sympathetic
activation
Growth
factor
stimulation
↑TGF β, ECM
↑CTGF,PAI-1
NA+
retention
H2O retention
K+
excretion
Mg+
excretion
Vascular
smooth muscle
constriction
↑GP
↓RBF
Angiotensin
converting
enzyme
(ACE)
Angiotensin II
Liver secretes
angiotensinogen
Kidneys secrete
renin
The Renin-Angiotensin-Aldosterone (RAA)
System activation and diabetic nephropathy
Angiotensinogen Angiotensin I
Adrenal cortex
secretes aldosterone
Blood Renin
Non ACE
AT2 R
VD
↑NO
↓ tissue
proliferation
AT1 R
26. Angiotensin II stimulates release of growth factors
through NF-B activation
Wiecek et al. Nephrol Dial Transplant (2003)
27. Role of angiotensin II in the progression of
diabetic nephropathy – 2
The renin–angiotensin system, angiotensin receptors and their action
31. CV mortality and systolic pressure in diabetics and nondiabetic
SYSTOLIC BP
CVmortalityrateper10000person-yrs
Adapted from Stamler J et al Diabetes Care 1993;16(2):435-444
32. Klotho-FGF23 axis
• CKD patients sarting from stage G1 onwards have increased
vascular stiffness.
• This stiffness is related to vascular calcification.
• V.C. in CKD pts affects both intima and tunica media.
• Intimal calcification is related to atherosclerosis.
• Medial calcification is related to Klotho-FGF23 axis.
33.
34. Górriz JL ,et al., Clin J Am Soc Nephrol. Apr 7;10(4):654-66, 2015.
Nasrallah MM, et al., Nephrol Dial Transplant, Aug; 25(8): 2679-85, 2010.
35. Chang Hu M, et al., Nephrol. Dial. Transplant.
(2012) 27 (7): 2650-2657
38. So,
• CKD inflammation Klotho gene decrease
in Klotho FGF23 resistance increase in FGF23 &
phosphate retension transformation of VSMC to
osteoblasts calcification of vessel wall.
39. Inflammation
• Chronic inflammation is one of the hallmarks of DKD.
– Increased secretion of MCP1 in urine
– It is triggered by the uremic status itself
– periodontal disease
– infection of vascular access for hemodialysis
– Diabetic foot
– cholecystitis
40.
41. Klotho
• Possible strategies that can be used to increase
endogenous Klotho include:
– Control of hyperphosphatemia .
– Angiotensin II blockade.
– Vitamin D repletion .
Komaba H and Fukagawa K , Kidney International (2012) 82, 1248–1250
42. Results Valsartan/hydrochlorothiazide treatment significantly increased mean soluble
Klotho (from 432.76179 to 506.46226.8 pg/ml; P=0.01) and reduced serum phosphate
compared with amlodipine. Attained BP was similar in the two groups.
Conclusions Treatment with a RAS blocker, valsartan, is associated with an increase
in soluble Klotho, which may contribute to the BP-independent cardiorenal benefits of
these drugs in DKD.
Effect of Renin-Angiotensin System Blockade on Soluble Klotho in
Patients with Type 2 Diabetes, Systolic Hypertension, and
Albuminuria
Karalliedde J., et al., CJASN November 07, 2013 vol. 8 no. 11 1899-1905
43. Chang Hu M, et al., Nephrol. Dial. Transplant.
(2012) 27 (7): 2650-2657
44. Other mechanisms possibly associated
with diabetic nephropathy
• ROS.
• abnormalities of the endothelin and prostaglandin
pathways .
• ↓glycosaminoglycan content in basement membranes.
• Insulin resistance gene polymorphisms.
• ↑Plasma levels of ICAM-1.
• ↑ expression of human mesangial cell MCP-1 mRNA and
downregulation of MCP-1 receptor mRNA expression.
• ↑ Plasma and urinary MCP-1 levels and fluorescent
products of lipid peroxidation and malondialdehyde
content.
45. Biomarkers of onset and progression of DN
1121 titles and abestracts screened
15 articles on 27 different biomarkers included
• Beacause of the heterogeneous quality of biomarker
studies in this field, in serum, plasma and urine, a more
rigorous evaluation of these biomarkers and validation
in larger trials are advocated.
46. New urinary biomarkers for diabetic kidney disease
• Transferrin.
• IgG.
• IgM.
• Cystanic C.
• Podocytes.
• Type IV collagen.
• Cerulospasmin.
• MAP-1.
• 8-oxo-7,8 dihydro-2-
deoxyguanosine .
48. Diabetic Glomerulopathy
• Mesangial expansion, Glomerular hypertension.
• Diffuse thickening of GBM.
• Broading of foot process, Loss of podocytes.
• Reduced slit pore proteins.
• Glomerulomegally.
• Kimmelstiel- Wilson lesion.
• Adhesion to bowman,
s capsule.
• Neovascularization.
• Diffuse and nodular glomerosclerosis.
• Arteriolar hyalinosis .
49. Diabetic Tubulopathy
• Tubuloepithelial cell hypertrophy,
• Tubular BM thickening and reduced tubular brush border.
• Epithelial-mesenchymal transition,and the accumulation
of glycogen.
• Expansion of the interstitial space with infiltration of
various cell types, including myofibroblasts and
macrophages.
• Abnormal tubuloglomerular feedback mechanisms
• Abnormal lysosomal processin.
• Increases tubular salt reabsorption & Impaired tubular
acidification
50.
51. Clinical diagnosis of diabetic
nephropathy
– Albuminuria.
– Diabetic retinopathy.
– No evidence for another renal disease:
• HTN, renovascular disease, SLE,
vasculitis, paraproteinemia
52. When to suspect non diabetic
nephropathy?
• Significant proteinuria with short term DM .
• Absence of retinopathy.
• Progresssive renal insufficiency occurs without
concomitant proteinuria.
• Micro/ macroscopic hematuria with dysmorphic RBCs.
• Active sediments.
• Shrunken kidneys on ultrasound .
• Coexisting illness : SLE, Hepatitis C.
53. Renal function assessment
• Urinary ACR: spot sample (mg/gm).
• 24 hour urine protein.
• Serum creatinine & electrolytes.
• GFR calculated by equations ( MDRD/Cockroft-Gault)
• Renal ultrasound and Doppler .
• Serum creatinine levels should be measured and
creatinine clearance estimated annually in those patients
with diabetes without albuminuria and at least every 6
months in those with albuminuria .
55. Primary prevention of nephropathy
• Tight blood glucose control:
– <7.5% on insulin.
– <6.5% not on insulin.
• Tight blood pressure control:
– <140/80 mm Hg for type 2.
• ?Non-smoking.
• ?Statin therapy.
56. What is the Proper Therapy of
Kidney Disease in patients with
Diabetes?
57. Stratton IM et al. BMJ. 2000;321:405-412.
Improved Glycemic Control Has Been
Shown to Reduce the
Risk of Complications
According to the United Kingdom Prospective Diabetes
Study (UKPDS) 35, Every 1% Decrease in A1C Resulted in:
Decrease
in risk of
microvascular
complications
(P<.0001)
Decrease
in risk of any
diabetes-related end
point
(P<.0001)
Decrease
in risk of MI
(P<.0001)
Decrease
in risk of stroke
(P=.04)
21% 14% 12%
37%
62. Other novel therapies
• Pirfenidone –antifibrotic agent
• Sulodexide, an agent postulated to restore
the glomerular charge by repleting the loss of
glycosaminoglycans.
• Histone deacetylase inhibitors
• Raloxifene, a selective estrogen receptor
modulator.
63. Endothelin antagonists
• Endothelin antagonists have antifibrotic, anti-
inflammatory, and antiproteinuric effects in
experimental studies.
• Wenzel et al conducted a study on the effect of
the endothelin-A antagonist avosentan on UAER
in 286 patients with diabetic nephropathy.
• Avosentan, treatment, were found
to reduce the mean relative urinary albumin
excretion rate (-16.3% to -29.9%, relative to
baseline) in the study's patients.
68. Emapticap Pegol
• Pegol means: pegylated monoclonal antibodies
• Emapticap pegol is a Spiegelmer
• Binds and neutralizes CCL2/MCP-1 (C-C
Chemokine Ligand / Monocyte Chemoattractant
Protein-1), a pro-inflammatory chemokine that plays
an important role in diabetic kidney disease.
69. Emapticap Pegol
• Treatment was for 12 weeks with twice-weekly subcutaneous
emapticap pegol or placebo.
• This treatment period was followed by a 12 week
observational period to study the long-term effect of
emapticap pegol treatment on albuminuria.
• Emapticap pegol was found to be safe and well tolerated.
• For the primary efficacy analysis, patients with major protocol
violations, on dual RAS blockade, or with concomitant
hematuria and leukocyturia were excluded.
70. Emapticap Pegol
• Results showed relevant, statistically significant reductions in
urinary albumin excretion and improved glycemic control.
• Importantly, these effects were independent of hemodynamic
changes and maintained after cessation of treatment,
suggesting that emapticap pegol interferes with the
underlying pathophysiology of diabetic nephropathy.
• Long-lasting effects on urinary albumin after cessation of
treatment are not seen with agents currently approved to
71. • Rapamycin (sirolimus): m-TOR inhibitor
– systemic administration of rapamycin, a systemic and
potent inhibitor of mTOR, markedly ameliorated
pathological changes and renal dysfunction in Diabetic
db/db mice as a model of ESRD associated with DN
– Sirolimus lowered the expression and activity of
glomerular TGF-β and VEGF
72. • Pentoxifylline
– Pentoxifylline administration has prevented Renal
expression of proinflammatory cytokines, such as tumor
necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6
– Pentoxifylline treatment caused regression and
prevented the progression of renal damage
74. Management of DM with Failing Kidney
.Early referral to a nephrologist (Scr >2 mg/L ).
• Structured physical and psychological
preparation for RRT.
• Younger patients will usually be offered
transplantation .
• Before transplantation, full cardiovascular
assessment is essential.
• PTCA or even CABG may be required before
transplantation.
76. Summary
• Identifying nephropathy by screening for
albuminuria.
• Multiple risk factors intervention for preventing
DN progression.
• RAAS blockade is the key to prevent
progression.
• Manage acute deterioration of renal function in
DN.
Diabetic nephropathy occurs in 20–40%
of patients with diabetes and is the
single leading cause of ESRD.
This table defines abnormalities of albumin excretion and the linkage between albumin-to-creatinine ratio and 24-hour albumin excretion
Historically, ratios between 30 and 299 have been called microalbuminuria and those 300 or greater have been called macroalbuminuria (or clinical albuminuria)
Because of variability in urinary albumin excretion, two of three specimens collected within a 3- to 6-month period should be abnormal before considering a patient to have developed increased urinary albumin excretion or had a progression in albuminuria
Exercise within 24 hours, infection, fever, CHF, marked hyperglycemia, and marked hypertension may elevate urinary albumin excretion over baseline values
Other factors affecting urinary albumin excretion such as listed in the table should be excluded.
Uncontrolled hyperglycemia can lead to diabetes-related complications.
Findings from the United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that lowering A1C reduces the risk of diabetes-related complications.
In patients with A1C &gt;6%, every 1% decrease in A1C resulted in a 21% decrease in the risk of any diabetes-related endpoint, a 14% decrease in risk of myocardial infarction, a 12% decrease in the risk of stroke, and a 37% decrease in the risk of microvascular complications.
There is no threshold of A1C below which the benefits of reduced complications are not seen.
Results from this study highlight the importance of improving glycemic control in the management of diabetes.
Let us now consider the role of anemia in the CKD and CVD relationship and new data supporting anemia as the “critical link” between CKD and CVD.
Accumulation of polyol by the reduction of galactose rather than glucose owing to the higher affinity of aldose reductase for galactose
Osmotic cell damage
Decrease in intracellular myoinositol
Decrease in Na-K-ATPase activity
Shift in redox potential
Glucose competitively interferes with myoinositol via a sodium-myoinositol cotransporter
Sorbinil Retinopathy Trial (Pfizer)