Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. Strict control of blood glucose, blood pressure, angiotensin system inhibitors, and other risk factors can help prevent or slow the progression of kidney damage. The stages include early hyperfiltration, development of microalbuminuria, progression to macroalbuminuria and renal failure. Management focuses on glycemic control, blood pressure reduction, angiotensin blockade, cholesterol control, and management of anemia and cardiovascular risk factors to preserve kidney function for as long as possible.
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of...Dr. Om J Lakhani
Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD).
Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India
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
Effects of Sodium Glucose contransporter (SGLT2) inhibition on renal outcomes in patients with (diabetic) chronic kidney disease.
Presentation given during the East by Southwest, Annual Update in Nephrology, September 17th 2017, Santa Fe, NM
http://medicine.unm.edu/academic-divisions/nephrology/east-by-southwest.html
Calcium channel blockers are useful treatments in the management of hypertension. In this presentation by Dr Vivek Baliga, we look at the added benefits of newer types of CCBs in treating high blood pressure. Read more from Dr Baliga here - http://drvivekbaliga.net
MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of...Dr. Om J Lakhani
Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD).
Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India
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
Effects of Sodium Glucose contransporter (SGLT2) inhibition on renal outcomes in patients with (diabetic) chronic kidney disease.
Presentation given during the East by Southwest, Annual Update in Nephrology, September 17th 2017, Santa Fe, NM
http://medicine.unm.edu/academic-divisions/nephrology/east-by-southwest.html
Calcium channel blockers are useful treatments in the management of hypertension. In this presentation by Dr Vivek Baliga, we look at the added benefits of newer types of CCBs in treating high blood pressure. Read more from Dr Baliga here - http://drvivekbaliga.net
ABSTRACT- Background: Viral hepatitis B and C can lead to the end stage liver disease and diabetes mellitus is also
a life-long chronic disease. Simultaneous presences of both of these conditions lead to synergistic detrimental outcome.
So identification of diabetes mellitus at the initial evaluation of a patient having chronic hepatitis B and C is essential.
Materials and methods: This study was designed as a retrospective single center cross-sectional study. The association
of viral hepatitis B and C with diabetes mellitus was investigated at the Liver Centre Dhaka, Bangladesh for a period of
12 years. HBsAg was tested for hepatitis B virus infection and anti-HCV for hepatitis C virus infection. Demographic
profile and biochemical data were retrieved from records.
Results: A total of 29425 cases were analyzed in the study [median age 31(19–95) years, 24615(84%) males]. HBsAg
positive were 27475 and hepatitis C were 1950. Patients with hepatitis C were older than hepatitis B (p<0.001).
Although previous history of jaundice was similar in both infections but history of blood transfusion was more common
among hepatitis C patients (p<0.001). Analyzing different conditions of liver disease, it was observed that hepatitis B
virus infection was highly responsible for acute hepatitis than hepatitis C (10.7% vs 1.1%) (p<0.001). Chronic hepatitis
was similar in rate (73.3% vs 59.9%). But in both conditions of cirrhosis of liver like compensated and decompensated
states, hepatitis C virus was significantly responsible than the hepatitis B virus 24.7% vs 9.6% (p<0.001) and 14.3% vs
6.4% (p<0.001) respectively. The most significant finding was very higher rate of diabetes among hepatitis C which
was 22.6% while only 1.8% among hepatitis B virus infection (p<0.001).
Conclusion: Hepatitis C virus was highly related with the presence of diabetes than hepatitis B.
Key-words- Diabetes mellitus, Prevalence, Hepatitis B virus, Hepatitis C virus
Management of coronary disease in diabetes - Is it different?Dr Vivek Baliga
The management of diabetes and coronary artery disease go hand in hand. This presentation by Dr Vivek talks on whether it varies from usual management.
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
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
We all have good and bad thoughts from time to time and situation to situation. We are bombarded daily with spiraling thoughts(both negative and positive) creating all-consuming feel , making us difficult to manage with associated suffering. Good thoughts are like our Mob Signal (Positive thought) amidst noise(negative thought) in the atmosphere. Negative thoughts like noise outweigh positive thoughts. These thoughts often create unwanted confusion, trouble, stress and frustration in our mind as well as chaos in our physical world. Negative thoughts are also known as “distorted thinking”.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
This is a presentation by Dada Robert in a Your Skill Boost masterclass organised by the Excellence Foundation for South Sudan (EFSS) on Saturday, the 25th and Sunday, the 26th of May 2024.
He discussed the concept of quality improvement, emphasizing its applicability to various aspects of life, including personal, project, and program improvements. He defined quality as doing the right thing at the right time in the right way to achieve the best possible results and discussed the concept of the "gap" between what we know and what we do, and how this gap represents the areas we need to improve. He explained the scientific approach to quality improvement, which involves systematic performance analysis, testing and learning, and implementing change ideas. He also highlighted the importance of client focus and a team approach to quality improvement.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Palestine last event orientationfvgnh .pptxRaedMohamed3
An EFL lesson about the current events in Palestine. It is intended to be for intermediate students who wish to increase their listening skills through a short lesson in power point.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
How to Create Map Views in the Odoo 17 ERPCeline George
The map views are useful for providing a geographical representation of data. They allow users to visualize and analyze the data in a more intuitive manner.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
2. Current Terminology
• Kidney, not Renal (or Reno)
• CKD, not CRF
• DKD (= diabetic nephropathy)
• AKI, not ARF
• Still ESRD (End Stage Renal Disease)
• Still RRT (Renal Replacement Therapy)
3. Definition of CKD
Structural or functional abnormalities of
the kidneys for >3 months, as manifested
by either:
1. Kidney damage, with or without decreased
GFR, as defined by
• pathologic abnormalities
• markers of kidney damage, including
abnormalities in the composition of the blood
or urine or abnormalities in imaging tests
2. GFR <60 ml/min/1.73 m2, with or without
kidney damage
4. Definition and Problem
• Progressive in UAE a/w BP and GFR
• 35-50% DN in Type 1 after 20 years of disease
• 10- ? 20% DN Type 2 in patients on diagnosis ??
• Renal risk is equal in both Type I and II DM
• Progressive rise in ESRD: Up to 40% of patients
on RRT due to DN
• Strong association with cardiovascular risk
(20-40 fold higher)
5. Stages of Chronic Kidney Disease
Stage Description
GFR
(mL/min)
1
Kidney damage
normal or GFR
≥90
2
Kidney damage
mild GFR
60-89
3 Moderate GFR 30-59
4 Severe GFR 15-29
5 Kidney Failure <15
Use e-GFR and not S Creat in practice
6. Stages of Diabetic Nephropathy
• Hyperfilteration
• Stage of Clinical Latency
• Incipient Nephropathy
• Overt Nephropathy
• Renal Failure
(Mogensen Staging for T1DM)
11. Definitions of abnormalities in albumin
excretion
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 crossed one of these diagnostic thresholds.
Exercise within 24h, infection, fever, congestive heart failure, marked
hyperglycemia, marked hypertension, pyuria, and hematuria may elevate urinary
albumin excretion over baseline values.
Diabetes care 2004; 27(1): S79-S83
13. Type II
Renal failure
Diagnosis
Perkins BA, Et al. N Engl J Med 2003;348:2285-93.
Diagnosis
Hyperfiltration
Clinical Latency
Microalbuminuria
Macroalbuminuria
Renal failure
Type 1
14. Microalbuminuria & Proteinuria
Normal Microalbuminuri
a
Overt
proteinuria
F M F M
Albumin/creatinine
ratio (mg/mmol)
<3.5 <2.5 >3.5 >2.5 >30
Equivalent Albumen
excretion (mg/day)
<30 30-300 300
•Diagnosis of microalbuminuria based on 2 out of 3
urine samples in absence of UTI
•After 5 years of Dx in T1DM & than annually.
•At the time of diagnosis in T2DM.
15. U/A at Diagnosis
(Type 2 patients)
Random spot collection
Albumin:creatinine
Repeat 3x in 3-6 months
2 of 3
≥ 30mg/g
creatinine
Microalbuminuria,
begin treatment
Nephropathy
Quantify µalb:Cr
Consider referral
No microalbuminuria
Re-screen yearly
Negative
Positive
No Yes
16. 16
What are Diabetics with Nephropathy Dying
From?
Stroke
Myocardial
Infarction
Heart
Failure
Sudden
Death
17. Risk Factors : Non Modifiable
• Race: Indo-Asians, Africans, Hispanics, Native Americans.
• Familial clustering:
In Type 1 DM if 1* relative > 80% chances of developing DN.
In Type 2 DM (Pima Indians) 14%, 23% and 46% (0,1,2 parents DM)
• Genetic influence
ACE gene polymorphism (DD in Type 2)
Ag-II type 2 receptor gene (AT2) on X-chromosome. (AA haplotype
risk than GT haplotype in type 1 DM)
Inheritance of one allele of the aldose reductase gene,
• Low Birth weight
• Age Type 1 onset < 5 risk of ESRD but risk in T2DM in Pima
indians <20 yrs. Type 1 no proteinuria till age 25 risk <1 %
• Elevated pro-renin levels.
19. Natural History in Type 2 DM
• GFR decline once proteinuria present 12
ml/min/year untreated
• Patients often die of other causes (CVS
disease) before ESRF
• CVS risk rises 2-3X with microalbuminuria,
9-10X with clinical proteinuria
• Higher rates of ESRF in T1DM
20. Hypertension
• Greater than 140/90 increases the risk of
diabetes
• 50-60% of newly diagnosed patients also
have HTN at diagnosis
• An interesting note: A family history of
HTN in a child with Type 1 diabetes their
risk of developing nephropathy
21. Undesirable lipid levels
• HDL less than 35 mg/dL
• Triglycerides greater than 150 mg/dL
• Think diabetes or hypothyroidism with the
above lipid profile
• Draw a FBS and a TSH
22. Predictors of progression
• In normoalbuminuric person
• Glycemic control
• In established DN
• Hypertension
• Degree of proteinuria
• In renal biopsy
• Mesangial expansion
• Tubulointerstitial lesions
23. • Hyperglycaemia
Early histological lesions reversible
with normoglycaemia
• Hypertension
Predicts microalbimunuria,
proteinuria paralleled by gradual rise in BP
Correlation between BP and rate of of GFR
• Proteinuria
Induces tubulointerstitial damage/ contributes to
progression
Highly selective in early disease
Pathogenesis of DN
24.
25. Oparil et al. Ann Intern Med 139:761-76, 2003.
ANG II ANG II
26. Cross-talk between the Insulin and Aangiotensin- II
Angiotensin II insulin
sensitivity & insulin
secretion, explaining
the antidiabetogenic
effect of RAS blockade
Hyperinsulinemia
enhances Ang II-
induced transcriptional
activity in vascular
smooth muscle cells
28. DCCT
1400 T1DM
Intensive Conventional
HbA1C 7.3% 9.1%
Reduction in
Retinopathy- 47%
Microalbumnuria- 39%
Clinical Nephropathy- 54%
Neuropathy- 60%
Benefits of intensive control persisted even after study
concluded and glycemic control worsened.
After 17 years 50% reduction in macrovascular
complications.
29. Strict glycemic control prevents microalbuminuria in patients with
type 1: 2.2%/year DN in Intensive and 3.4% in conventional
30. Randomized prospective trial of
treatment strategies in type II diabetes
ukpdsType 2 diabetic patients 5,102
Person years follow-up 53,000
Intensive Conventional
HbA1c 7% 7.9%
At 12 years 23 % 34 %
Each 1% decrease in HbA1C decreases microvascular
complications by 35%.
Macrovascular advantage is seen after 10 years.
Strict BP control decreased microvascular complications.
31. Benefits of Glycemic Control
•Delay the development of albumin excretion
•Stabilize or protein excretion in pts with UAE
•Slow the progressive renal injury in Macroalb.
•May reverse early structural changes
UKPDS Study :
Glycemic control is less than the
benefit from blood pressure control
33. 33
Ang I
Ang II
Progressive Diabetic Nephropathy
ACE
Renal Injury
and Proteinuria
ACEi
AT1 Receptor
Non-ACE
Pathways
Aldosterone
MRA
ARB
Can Dual Blockade of the RAAS Improve
Renal Outcomes in Diabetic Nephropathy?
+
+
34. CALM Study
• N= 200
• Type II DM with
microalbuminuria
• Randomized to:
• Lisinopril 20 mg qd
• Candesartan 16 mg qd
• Combination of lisinopril
20 mg and candesartan
16 mg
Mogensen CE, Et al. BMJ 2000; 321: 1440-4.
Candesartan and Lisinopril
Microalbuminuria (CALM)
24
39
50
0
10
20
30
40
50
ReductioninAlbuminuria(%)
Candesartan Lisinopril Combination
35. Calcium channel blockers
• Verapamil does not delay
development of microalbuminuria
• Verapamil does reduce proteinuria
in diabetics independent of changes
in BP. Side effect: FGGS & TIF.
Aldosterone antagonists
• Spironolactone reduces
proteinuria in diabetics
• Change in proteinuria is
independent of blood pressure
• All patients were treated with an
ACEi or ARB
• 24-Hr ambulatory BP fell 6/2
Schjoedt KJ, Et al. Kidney International 2006; 70: 536-542.
36. ARBs: Evolution of protective benefits
↓BP
↓Stroke
↑Glycemic control
↓Heart failure
↓Renal dysfunction
↓CHD (?)
37. ONTARGET
• Telmisartan (16.7%) noninferior; combination
(16.3%) not superior to ramipril (16.5%) for
primary endpoint (CV death, MI, stroke, heart
failure)
• Greater incidence of hypotension in combination
(4.8%) and telmisartan (2.7%) groups,
compared with ramipril group (1.7%) (p < 0.001)
Trial design: Patients at high risk for cardiovascular events, but without heart failure, were
randomized to telmisartan, ramipril, or the combination. Patients were followed for a
median of 56 months.
Results
Conclusions
The ONTARGET investigators. N Engl J Med 2008;358:1547-59
Telmisartan
(n = 8,542)
Combination
(n = 8,502)
• Either telmisartan or ramipril, but not both,
can be used in hypertensive patients at high
risk for cardiovascular events
• Side effects greater with combination therapy
16.7
16.3
%
0
10
Primary endpoint
20
Ramipril
(n = 8,576)
16.5
0
10
15
5
Mortality
11.6
12.5 11.8
%
(p < 0.004*)
(p = ns)
* Telmisartan vs. ramipril for noninferiority
40. Aliskiren Trial in Type 2 Diabetes Using
Cardio-Renal Endpoints (ALTITUDE):
• To determine whether aliskiren 300 mg once
daily, reduces CV and renal morbidity and
mortality compared with placebo when added to
conventional treatment (including ACEi or ARB)
• Included high-risk type 2 diabetes patients
45. < 2 % pts of DRD require RRT because others often
die of CVD before reaching ESRD.
Dialysis
Get an early vascular access for HD
Offer PD to patients with adequate manual dexterity
I P Insulin therapy in PD pts
Offer HD to diabetic with severe vascular disease
Transplantation
Renal and renal-pancreas transplantation
Preemptive transplantation (GFR<30 mL/min)
Evaluation for CAD
Post-Tx UTI, Allograft Rejection, Glycemic Control
Management of ESRD in DN
46. How Should We Manage Patient
With Diabetic Nephropathy Today?
Parameter
• Lower BP……………
• Block RAAS……
• Improve glycemia ….
• Lower LDL cholesterol..
• Anemia management ...
• Endothelial protection…
• Smoking……………
Target
< 130/80 mmHg
ACEi or ARB to max
HbA1c < 6.5% (Insulin)
< 100 (70) mg/ statin + other
Hb 11-12 g/dl (Epo + iron)
Aspirin daily
Cessation
47. Conclusions
• Diabetic nephropathy is
the most common
cause of ESRD in the
world
• ESRD is a rare out-
come among diabetics
• Just over half of
diabetics will develop
nephropathy
• Blood pressure control
• Glycemic control
• Angiotensin 2 reduction
• Proteinuria reduction
• ACEi + ARB
• Statins
• Aldosterone antagonists
• Dihydropyridine calcium
channel blockers
48. Key messages
• Screening for diabetic renal disease is easy and should
be performed annually
• Good glycaemic control is the main Pry prevention
therapy
• Once microalbuminuria confirmed RAS blockade is
must
• BP targets should be individualised
• Treatment aims to stabilise e-GFR & maintain/ UAER
• Attention to all vascular risk factors is vital
• If RRT becomes necessary this needs to be carefully
planned well in advance
49. Diabetic Nephropathy
Over 40% of new cases of
end-stage renal disease
(ESRD) are attributed to
diabetes.
In 2001, 41,312 people with
diabetes began treatment for
end-stage renal disease.
In 2001, it cost $22.8 billion
in public and private funds
to treat patients with kidney
failure.
Minorities experience higher
than average rates of
nephropathy and kidney
disease
Incidence of ESRD
Resulting from Primary
Diseases (1998)
43%
23%
12%
3%
19%
Diabetes
Hypertension
Glomerulonephritis
Cystic Kidney
Other Causes
50. Five Stages of Kidney Disease
Stage 1: Hyperfiltration, or an increase in
glomerular filtration rate (GFR) occurs. Kidneys
increase in size.
Stage 2: Glomeruli begin to show damage and
microalbuminurea occurs.
Stage 3: Albumin excretion rate (AER) exceeds 200
micrograms/minute, and blood levels of creatinine
and urea-nitrogen rise. Blood pressure may rise
during this stage.
51. Investigations
Urinary Protein assessment
Dipstick
24hour urinary protein estimation
Albumin: Creatinine ratio > 2.5 in males and > 3.5 in
females is abnormal
Confirm with Albumin excretion rate (AER) of 20-
200ug/min or 30-300mg/24hrs. This requires timed
urine collection
52. Five Stages of Kidney Disease
(con’t.)
Stage 4: GFR decreases to less than 75 ml/min, large
amounts of protein pass into the urine, and high blood
pressure almost always occurs. Levels of creatinine and
urea-nitrogen in the blood rise further.
Stage 5: Kidney failure, or end stage renal disease
(ESRD). GFR is less than 10 ml/min. The average length
of time to progress from Stage 1 to Stage 4 kidney
disease is 17 years for a person with type 1 diabetes.
The average length of time to progress to Stage 5, kidney
failure, is 23 years.
53. Screening for Diabetic
Nephropathy
Test When Normal Range
Blood
Pressure1
Each office visit <130/80 mm/Hg
Urinary
Albumin1
Type 2: Annually
beginning at diagnosis
Type 1: Annually, 5-years
post-diagnosis
<30 mg/day
<20 g/min
<30 g/mgcreatinine
1American Diabetes Association: Nephropathy in Diabetes (Position Statement).
Diabetes Care 27 (Suppl.1): S79-S83, 2004
55. • Glycemic Control
– Preprandial plasma glucose 90-130 mg/dl
– A1C <7.0%
– Peak postprandial plasma glucose <180
mg/dl
– Self-monitoring of blood glucose (SMBG)
– Medical Nutrition Therapy
• Restrict dietary protein to RDA of 0.8
g/kg body weight per day
Treatment of Diabetic
Nephropathy (cont.)
56. Treatment of End-Stage Renal
Disease (ESRD)
There are three primary treatment
options for individuals who experience
ESRD:
1. Hemodialysis
2. Peritoneal Dialysis
3. Kidney Transplantation
57. Hemodialysis
• Procedure
– A fistula or graft is created to access the
bloodstream
– Wastes, excess water, and salt are
removed from blood using a dialyzer
– Hemodialysis required approx. 3 times per
week, each treatment lasting 3-5 hrs
– Can be performed at a medical facility or at
home with appropriate patient training
58. • Hemodialysis Diet
– Monitor protein intake
– Limit potassium intake
– Limit fluid intake
– Avoid salt
– Limit phosphorus intake
• Complications
– Infection at access site
– Clotting, poor blood flow
– Hypotension
Hemodialysis (cont.)
59. Peritoneal Dialysis
• Procedure
– Dialysis solution is transported into the
abdomen through a permanent catheter
where it draws wastes and excess water
from peritoneal blood vessels. The
solution is then drained from the
abdomen.
– Three Types of Peritoneal Dialysis
• Continuous Ambulatory Peritoneal Dialysis
(CAPD)
• Continuous Cycler-Assisted Peritoneal Dialysis
(CCPD)
• Combination CAPD and CCPD
60. Peritoneal Dialysis (cont.)
• Peritoneal Dialysis Diet
– Limit salt and fluid intake
– Consume more protein
– Some potassium restrictions
– Reduce caloric intake
• Complications
– Peritonitis
61. Kidney Transplant
• Procedure
– A cadaveric kidney or kidney from a related
or non-related living donor is surgically
placed into the lower abdomen.
– Three factors must be taken into
consideration to determine kidney/recipient
match:
• Blood type
• Human leukocyte antigens (HLAs)
• Cross-matching antigens
63. 63
Albuminuria then Proteinuria
• Microalbuminuria first (lower MW)
– Raised by GFR (i.e. BSL, protein diet,
fever, exercise)
• Spot urine ACR or PCR
– more convenient than 24hr collection
– more accurate than urinalysis
– adjusts for fluid intake
– underestimates the muscular patient
64. 64
Diabetic Nephropathy
• From haemodynamic & metabolic
stresses
• Metabolic stress
– deposition of advanced glycosylation end
products in connective tissue & sml vessels.
• May take 10-20 yrs but many T2DM
asymptomatic for several yrs, hence
nephropathy may already be present at
Dx
65. 65
Nephropathy Risk Factors
• DM Type & Duration
– 20% of Type I after 20 years
– 40% of Type II any duration
• Poor diabetic control
• Hypertension
• Aboriginal > Indian > Caucasian
• Smokers
• Family history
66. 66
• 1st clinical sign is microalbuminuria (ACR)
• Kidney not able to catabolise albumin
• This can also occur transiently with
– Fever
– Exercise
– Short term hyperglycaemia
– High protein meal
• Hence, repeat at a later date/rule out reversible
• DM + HPT, x 20 risk of progressive nephropathy
• DM + HPT + poor diabetic & lipid control, x 40 risk
67. 67
Nephropathy Risk Factors
• DM Type & Duration
– 20% of Type I after 20 years
– 40% of Type II any duration
• Poor diabetic control
• Hypertension
• Aboriginal > Indian > Caucasian
• Smokers
• Family history
68. 68
Nephropathy Risk Factors
• Modifiable
– HbA1c, BP & total cholesterol (Odds Ratio 43)
– Obesity, smoking
• Non-modifiable
– Age, ethnicity, male sex
69. 69
Delaying Complications
• Tight diabetic control
– Prevention of microvascular Cmplx
• Risk of hypos
• Tight BP control
– Prevention and management of micro &
macro Cmplx
– Use ACEI, ARB’s or both combined
70. 70
ACE Inhibitors can prevent
progression of renal failure
120
160
200
240
280
320
350
400
80
0 1 2 3 4 5 6
Years
Ann Intern Med 118 577-581.1993
Placebo
Enalapril 85
90
95
100
105
110
80
0 1 2 3 4 5 6
Years
Placebo
Enalapril
Normotensive Type 2 Diabetics
Proteinuria
(mg/day)
% Initial GFR
72. 72
Q. Which features are typical of
diabetic CKD at presentation ?
• Haematuria NO
• Small scarred kidneys NO
• Progress to ESKD in <2yrs NO
• Associated retinopathy YES
• -blockers better than ACE-I Rx NO
73. 73
Diabetes and ESKD
• Reducing insulin requirements
• Difficult vascular access
• Accelerated macrovascular disease
• Advanced microvascular disease
• Frequent sepsis
• Silent ischaemia
• 2-3 x death rate vs non-DM patients
74. 74
How can DM effect Dialysis?
• Autonomic neuropathy – may suffer hypotension
increased by large fluid shift in HD
• Uncontrolled blood sugars – may absorb some glucose
in PD fluid
• Severe PVD – difficult to get vascular access for HD
• PVD may also affect peritoneum and reduce PD
success
• Increased risk of infections – problem in both
• Transplants – new kidneys develop nephropathy, hence
good glycaemic control important
75. 75
Strict BSL Control in early Type I
• Target HbA1c < 7%
• For every 1% HbA1c:
– 10% CVD
– 40% Microvascular Cmplx
• BUT:
• Doubles risk of hypoglycaemia
• Loss of control with DM duration:
– 50% at 3yr
– 30% at 6yr
– 15-25% at 9yr (= % patients with HbA1c < 7% on Met or OHA alone)
76. 76
Strict BSL Control in DM CKD
• AND:
• Minimal benefit if overt proteinuria
• Diabetes “cured” by advancing CKD
– reduced appetite and CHO intake
– prolonged insulin half-life
– false elevation of HbA1c by 0.5-1%
77. 77
Metformin in CKD
• No hypos or weight gain
• Inexpensive
• BUT:
– Renally-excreted
– Excess doses anorexia, diarrhoea
– Dose adjust to GFR: 2g to 250mg/day
– Protocol says
• eGFR 30 – 59 max 1gm/day
• cease when eGFR <30 but…
– Risk of fatal lactic acidosis if unwell
78. 78
Glitazones in DM
• Av.1% fall in HbA1c as monoRx or add-on
• Preserves beta-cell fn - use early
• Durable effect >3yrs
• BUT:
– 1-2/12 delayed onset
– Average 4kg SC fat gain, visceral fat loss
– Oedema (Na+/H20, vasc. permeability)
– Expensive
79. 79
Strict BP Control at any stage
• ½’s (or even stops) rate of fall in GFR
• Greater benefit than tight BSL control
• Falling BP Target = 120/70 currently
• Preferential use of ACEi/ARBs
• Complete regression of proteinuria
possible
• Helps all micro- & macrovascular disease
• (Parving, UKPDS, Captopril Trial, MicroHOPE, IRMA/IDNT, JNC VI)
80. 80
Use of ACEi/ARBs: actions
• Antihypertensive
– by salt excess, by thiazides
– need mean of 3 agents in mild CKD
• Antiproteinuric
– 30-50% alone, 40-70% together
• Renoprotective
– corrects GFR, expected 30% creatinine
82. Rough GFR
Equations should be
used only in the steady
state
Not useful in ARF
Reasonable criteria
◦ CrCl> 50ml/min
◦ CrCl 10 – 50 ml/min
◦ Crcl< 10 ml/min
◦ Oliguric and non oliguric
Creatinine GFR
1 100
2 50
3 25
4 12.5
5 6.125
6 3.06125
85. Problems
Precautions
Blood pressure control
Dietary protein restriction
Management of MBD
Management of anemia
Vaccination
Volume control
Cardiovascular disease screening
Options of renal replacement
86. Precautions
No nephrotoxics
◦ Impair glomerular function: NSAIDS
◦ Impair tubular function: Aminoglycosides
◦ NO contrast agent exposure
Drug dose adjustment
Treat intercurrent infections properly
Educate about native drugs
Early referral to nephrologist
87. Blood pressure management
Systemic BP reduction Intra-glomerular BP reduction
Anti-proteinuric effect
Blood pressure control
Beta blockers
Alpha -blockers
Vasodilators
ARB
ACEi
Preservation of other target organs Preservation of kidneys
88. Protein restriction
Preservation of organ repair
Daily dietary requirement (FAO)
◦ 0.6 g/Kg/d plus 2 SD= 0.8 g/Kg/d
MDRD study
◦ Dietary protein restriction may offer a
benefit
Remember to preserve adequate
calories
92. Diabetic Nephropathy
DN occurs in 35-40% of patients with type I
diabetes (IDDM) whereas it occurs only in
15-20% of patients with type II diabetes
(NIDDM).
Definition or Criteria for diagnosis of DN
Presence of persistent proteinuria in sterile urine
of diabetic patients with concomitant diabetic
retinopathy and hypertension.
93. BMD
Dietary phosphate
restriction
Phosphate binders
◦ Aluminium
◦ Calcium
◦ Magnesium
◦ Non aluminium,
calcium, magensium
binders
Replenishment of
vitamin D stores
Activated vitamin D
1, 25 (OH)2D3
Vitamin D
analogues
◦ Paricalcitrol
◦ Doxercalcitriol
94. Anemia management
EPO deficiency
Defect in iron absorption
B12 and folate
deficiency
Diseases like myeloma
Hyperparathyroidism
Drugs like ARB
Aluminum toxicity
Blood loss
Hemolysis
Pure Red Cell Aplasia
95. Correction of anemia
Identify iron
deficiency
Oral iron vs
parenteral iron
Iron sucrose
Don’t overload iron
Avoid transfusions
EPO therapy if iron
replete
Target 11 to 12 g/dl
Start at small dose
and titrate upwards
Twice weekly to
thrice weekly
Newer analogues
may be used less
frequently
96. Vaccinations
Hepatitis B
◦ 20 mcg each deltoid IM 0, 1, 2, 6 months
◦ Check Anti HBS titre post vaccination
after 3rd dose
◦ Only 60 % seroconvert in ESRD
Pneumococcal vaccine
Influenza vaccine
97. Volume control
Problems with salt and water excretion
in CKD is relatively later
Proteinuric conditions may develop
this problem early
Diabetic remain proteinuric even while
fibrosis continues to proceed
Fluid restriction and salt restriction is
important
98. Diabetes
Asymptomatic bacteriuria is more common
(20%)
UTIs are likely to be more severe in diabetic
than nondiabetic women
Asymptomatic bacteriuria often precedes
symptomatic UTI in type 2 diabetes [RR]
1.65
Risk factors for UTI in diabetics includes
those
who take insulin (relative risk 3.7)
longer diabetes duration (>10 years, relative risk
2.6)
○ but not glucose control
Emphysematous pyelonephritis,
xanthogranulomatous UTI and fungal UTI are
118. Diabetic nephropathy (DN) is a major
cause of ESRD, and the incidence of
diabetes
mellitus is rising rapidly.
119. Diabetic Nephropathy
DN occurs in 35-40% of patients with type I
diabetes (IDDM) whereas it occurs only in 15-
20% of patients with type II diabetes (NIDDM).
Definition or Criteria for diagnosis of DN
Presence of persistent proteinuria in sterile urine of
diabetic patients with concomitant diabetic retinopathy
and hypertension.
120. Effect of Angiotensin Blockade
Afferent arteriole
Efferent arteriole
Glomerular pressure
( GFR)
Glomerulus
Bowman’s Capsule
Angiotensin II
Proteinuria
A II blockade:
121. Irbesartan in patients with type 2 diabetes &
microalbuminuria study
590 NIDDM patients with HTN and
microalbuminuria with nearly normal GFR.
Randomly assigned to placebo, 150 mg or 300 mg
of irbesartan for 2 years.
Primary outcome was time to the onset of diabetic
nephropathy (urinary albumin excretion rate >200
mcg/min and at least 30% greater albuminuria)
14.9% patients on placebo group, 9.7% of
irbesartan 150mg group and 5.2% of irbesartan
300 mg group reached the primary point.
(Parving et al, NEJM, 2001)
123. D.N.-Management
ACEI or AII RB- in both expt & human
Reduce glomerular hypertension
Reduce proteinuria independent of
hemodynamic effects
Reduce glomerular hypertrophy
well tolerated apart from hyperkalemia &
worsening of anemia in severe CRF
Cautious use in presence of severe renovascular
disease
124. DN: ADA Position Statement
Screening:
Perform an annual test for the presence of microalbuminuria in
1) type 1 diabetic patients who have had diabetes > 5 years and
2) all type 2 diabetics patients starting at diagnosis.
Treatment:
• In the treatment of albuminuria/nephropathy both ACE inhibitors and
ARBs can be used:
• In hypertensive and nonhypertensive type 1 diabetic patients with
microalbuminuria or clinical albuminuria, ACE inhibitors are the initial
agents of choice
• In hypertensive type 2 diabetic patients with microalbuminuria or
clinical albuminuria, ARBs are the initial agents of choice.
• If one class is not tolerated, the other should be substituted
American Diabetes Association: Position Statement Diabetes Care 25:S85-S89, 2002
125. UK Prospective Diabetes Study (UKPDS) Major Results:
Powerful Risk Reductions
Better blood pressure control reduces…
Strokes by > one third
Serious deterioration of vision by > one third
Death related to diabetes by one third
Better glucose control reduces…
Early kidney damage by one third
Major diabetic eye disease by one fourth
Turner RC, et al. BMJ. 1998;317:703-
713.
126. National Kidney Foundation Recommendations on
Treatment of HTN and Diabetes
Blood pressure goal: 130/80 mmHg
Target blood pressure: 125/75 for
patients with >1 gram/day proteinuria
Blood pressure lowering medications
should reduce both blood pressure +
proteinuria
Therapies that reduce both blood
pressure and proteinuria have been
known to reduce renal disease
progression and incidence of ischemic
heart disease
Bakris GL, et al. Am J Kidney Dis.
2000;36(3):646-661.
127. Treatment Objectives to Prevent Macrovascular
Disease in Diabetic Patients
Hypertension
◦ BP < 130/80 mmHg
Hypercholesterolemia
◦ LDL < 100 mg/dL
Hyperglycemia
◦ Hgb A1C < 7.0 %
American Diabetes Association Clinical Practice
Recommendations. Diabetes Care. 2001;24(suppl1):S1-
S133.
128. Management of HTN and Chronic Renal Disease (CRD)
in Diabetics
Reduce BP to <130/80 mmHg
Use multiple antihypertensive drugs (ACEI,
ARB, diuretic, CCB, beta-blocker)
Maximal reduction of proteinuria
Treat hyperlipidemia (LDL <100 mg/dL)
Control Hgb A1C to <7%
Low salt diet (<2 gm NaCl/day)
Stop cigarette smoking
133. Screening for Microalbuminuria
Albumin excretion increased due to
Strenuous exercise
Oral Protein intake
Urinary infection
Fluid loading
Pregnancy
137. Protein Kinase C
Renal injury due to hyperglycaemia increase
reactive oxygen species.
Activation of PK C and TGF b results in
increased:
Vascular Contractility
Blood Flow
Cellular Proliferation
Vascular Permeability
138. Inhibition of PKC by
Ruboxistaurin in Rats
Reduces Glomerular Hyperfiltration
Albuminuria
Extra cellular Matrix accumulation
139. Mechanisms for the Renoprotective
Effect of ACE Inhibitors
Lower Systemic Blood Pressure
Lower Intra glomerular Pressure and
filtration rates
Reduce Proteinuria
140. Mechanisms for the Renoprotective
Effect of ACE Inhibitors
Inhibit non Heamodynamic effects of
Angiotensin on various cell types
Reduction in Cytokine and Growth
factor synthesis e.g. TGF β
Mesangium: Reduced Cell
proliferation
Hypertrophy
Matrix Expansion
141. Mechanisms for the Renoprotective
Effect of ACE Inhibitors
Reduction in Oxidative Stress
Inhibit macrophage activation,
proliferation and migration
142. Renal preglomerular vasodilation
Systemic hypertension
Glomerular hypertension
Glomerular sclerosis
Hyperglycemia
Genetic factors
metabolism of glom. cells
Treatment of DM nephropathy:
Glucose control
from T. Hostetter
143. Renal preglomerular vasodilation
Systemic hypertension
Glomerular hypertension
Glomerular sclerosis
Hyperglycemia
Genetic factors
metabolism of glom. cells
Treatment of DM nephropathy:
Hypertension control
from T. Hostetter
144. Blood pressure management
Systemic BP reduction Intra-glomerular BP reduction
Anti-proteinuric effect
Blood pressure control
Beta blockers
Alpha -blockers
Vasodilators
ARB
ACEi
Preservation of other target organs Preservation of kidneys
145. Treatment
• Hypertension control:
– Lower the BP, slower the decline in GFR in patients with diabetic
nephropathy
– JNC VI recommended BP < 130/85 mmHg in patients with renal
insufficiency
– Patients with CKD and > 1g proteinuria, BP goal should be < 125-
130/75-80 mmHg
147. Treatment
• ACE inhibitors:
– Type I diabetes with nephropathy: captopril vs. placebo
– 50% RR of combined end points of death, dialysis and transplantation in ACEI group
independent of BP
Lewis et al. NEJM, 1993
148. Treatment
• Angiotensin-receptor blockers:
– RENAAL study(2001)
• 1513 pts with type II DM and nephropathy. Losartan vs. placebo.
Losartan reduced the rate of doubling of cr by 16% but no effect
on the rate of death.
– IDNT(2001)
• 1715 type II DM pts with nephropathy. Irbesartan vs. amlodipine
vs. placebo. Irbesartan has 20% lower risk of reaching endpoints
compared to placebo and 23% lower incidence than that in the
amlodipine group
149. Renal preglomerular vasodilation
Systemic hypertension
Glomerular hypertension
Glomerular sclerosis
Hyperglycemia
Genetic factors
metabolism of glom. cells
Treatment of DM nephropathy:
Effect of ACEIs and ARBs
from T. Hostetter
151. ACEi- or ARB-Based Regimens for Diabetic
Nephropathy Do Not Go Far Enough!
152. Diabetic Nephropathy: Important Message
• Small short-term studies suggest combinations of
ACEi and ARB reduce proteinuria synergistically
– Greater reductions in proteinuria with or without additional lowering in blood pressure
– Hyperkalemia and Increased creatinine not well documented
• Safety and Efficacy of combination ACEi and ARB in
diabetic with nephropathy not well established
154. Targets
Stage Calcium* Phosphorous PTH
Stage 3 8.4 to 9.5 2.7 to 4.6 35-70
Stage 4 8.4 to 9.5 2.7 to 4.6 70-110
Stage 5 8.4 to 9.5 3.5 to 5.5 150 to 300
*Corrected calcium
155. BMD
• Replenishment of vitamin D stores
• Activated vitamin D 1, 25 (OH)2D3
• Vitamin D analogues
– Paricalcitrol
– Doxercalcitriol
• Dietary phosphate restriction
• Phosphate binders
– Aluminium
– Calcium
– Magnesium
– Non aluminium, calcium, magensium binders
156. Anaemia
• May occur when GFR < 50 % & almost always present
when GFR < 30 %
• Correct deficiencies
– Iron, Folic acid, Vit B12, Pyridoxine
• Erythropoietin 75 - 150 iu/kg SC
– With Iron supplements
– Expensive therapy Rs. 8 - 10, 000 / month
– Hb % maintained at 11 - 12
• > 13 in pts with CAD
157. Vaccinations
• Hepatitis B
– 20 mcg each deltoid IM 0, 1, 2, 6 months
– Check Anti HBS titre post vaccination after 3rd dose
– Only 60 % seroconvert in ESRD
• Pneumococcal vaccine
• Influenza vaccine
158. Fluid management
Many diabetics have nephrotic state and severe
edema and need rigorous salt & fluid restriction
• Severe edema - 600 - 800 ml / day
• Mild to moderate - equal to UOP
• No edema - UOP + insensible
losses
159. Cardiovascular disease screen
• Renal disease is a cardiovascular risk factor
• CKD promotes vascular calcification
• Non invasive evaluation important
• Contrast agents carries risk of RCIN- benefits to risk
163. Diabetic Nephropathy: Some Novel
Therapies Under Investigation
• Pirfenidone –antifibrotic agent
• Aliskerin anti-renin agent
• Robuxistaurin- Protein Kinase C Beta-1 antagonist
• Advanced Glycation Endproduct antagonists
164. Recommendations:
Nephropathy treatment (1)
• Nonpregnant patient with micro- or macroalbuminuria
– Either ACE inhibitors or ARBs should be used (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.
165. Control blood sugars: which drug
to use ?
• Drugs contraindicated: Metformin
• Preferably not used: Glibenclamide,
Chlorpropamide
• Can be used: Glimiperide, Repaglinide,
Pioglitazone
• Insulin: prefer
Target : HbA1c <7 %, FPG: <100 mg/dl, PPBG<140 mg/dl
167. Recommendations:
Nephropathy treatment (2)
• In patients with type 1 diabetes, hypertension, and any
degree of albuminuria
– ACE inhibitors have been shown to delay progression of nephropathy
(A)
• In patients with type 2 diabetes, hypertension, and
microalbuminuria
– Both ACE inhibitors and ARBs have been shown to delay progression to
macroalbuminuria (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S33.
168. Recommendations:
Nephropathy Treatment (4)
• Reduction of protein intake may improve measures of renal
function (urine albumin excretion rate, GFR) (B)
– To 0.8 –1.0 g x kg body wt–1 x day–1 in those with diabetes, earlier
stages of CKD
– To 0.8 g x kg body wt–1 x day–1 in later stages of CKD
• When ACE inhibitors, ARBs, or diuretics are used, monitor
serum creatinine, potassium levels for development of acute
kidney disease, hyperkalemia (E)
169. Adverse effects of ACEI and ARB
• Cough : 0-39%, F>M, class effect
• Angioedema: 0.1-0.2 %: 1hr to <1 wk
• Metallic taste: captopril
• Hyperkalemia
• Worsening renal failure
170. Treatment of DM nephropathy:
Effect of statins
from T. Hostetter
Renal preglomerular vasodilation
Systemic hypertension
Glomerular hypertension
Glomerular sclerosis
Hyperglycemia
ROS
Genetic factors
metabolism of glom. cells
171. • Normalize BP. Target <130/80.
• Treat with ACE inhibitors or ARBs.
• Treat hyperlipidemia and hyperglycemia aggressively.
• Moderate protein restriction (0.8- 1.0 gm/kg/day).
• Treat cardiovascular disease aggressively.
• Refer to nephrologist early in course of azotemia.
Management of Diabetic
Nephropathy-Rx
172. Diabetic Nephropathy: Introduction (2)
Do you know…
• At diagnosis 30% of people with T2DM
have nephropathy
Tobe SW et al. CMAJ; 2002; 167 (5):499-503
173. Category 24-h Timed Spot
collection collection collection
mg/24 h µg/min µg/mg creat
Normal <30 <20 <30
Microalbuminuria 30-300 20-199 30-299
Overt Nephropathy >300 ≥200 ≥ 300
(Macroalbuminuria)
(Alb./Cr.ratio)
Definitions of abnormality in albumin excretion
Diabetic Nephropathy : Introduction (3)
174. Obese, sedentary, “wrong diet”, genetic predisposition,…….
IGT
DM
Incipient Nephropathy
Overt or Clinical Nephropathy
ESRD
Progression of Nephropathy (2)
175. • Glycemic Control means
– FPG= 90-130 mg/dl
– PPPG <180 mg/dl
– HbA1c <7.0%
– Self-monitoring of blood glucose (SMBG)
– Medical Nutrition Therapy
• Restrict dietary protein to RDA of 0.8 g/kg body weight / day
• BP control
– Maintain BP <130/80 mm/Hg
Glycemic control is a must….
Editor's Notes
There are differences in the cumulative incidence rates for the development of end stage renal disease (after patients develop albuminurium) between those who have type I versus type 2 DM. The rate for type 2 DM obviously being quite lower than that for type I. The reasons for these differences are many, but probably include primarily the fact that patients with type 2 DM have a substantial amount of cardiovascular disease and probably die from their cardiovascular disease before they actually develop end stage renal disease, in many cases. Furthermore, a number of patients with type 2 DM have other causes of nephropathy in about 25% of cases, so that there may be other reasons why there may be a slower progression rate. And then finally, patients who have type 2 DM may just have a slower rate of progression of the disease compared to those with type I.There are a number of things that can potentially explain the increase in cardiovascular disease occurring in those patients with diabetes who have increased urinary albumin excretion. Among these is a common genetic predisposition for both of these findings. Endothelial dysfunction certainly occurs in patients with cardiovascular disease, as well as those with increased urinary albumin excretion. Hypertension is a common accompaniment of renal disease in patients with diabetes, and that can certainly make cardiovascular disease worse. Insulin resistance is common to both of these findings. In patients with renal disease, there is an atherogenic dyslipidemia that occurs, and certainly hyperglycemia may contribute to both the development of renal disease as well as cardiac disease.