Presentation involves the data from the Clinical trials and animal experiments.

1. RECENT ADVANCES IN
MANAGING AND UNDERSTANDING
DIABETIC NEPHROPATHY
Presented by :
Mr. Prashant Shivgunde
Assistant Professor,
University Department of Interdisciplinary Research and Technology,
Maharashtra University Health Sciences, Nashik
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2. Contents
• Introduction
• Pathophysiology of Diabetic Nephropathy
• Current Standard of Approach to Diabetic Nephropathy
• Novel Therapeutic Modalities
• Some of the Newer Drugs and Terminated RCTs
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3. Introduction
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4. Diabetes Mellitus
• Prevalence of diabetes mellitus (DM) is 8.5% and increasing
• Most affected with Type 2 DM
• Epidemic for several decades
• Associated with many complications
• Diabetic kidney disease (DKD) is a leading complication of
diabetes, which can lead to serious consequences, including
kidney failure and cardiovascular morbidity and mortality
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5. Chronic Kidney Disease
• 8% to 16% prevalence of CKD globally and is steadily rising
• QOL
• Medical expenses are costly
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6. CKD prognosis example
100%
Patients
Stage 3 CKD
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27%
8%65%
Patients
Stage 3 CKD RRT Dead Patients
After 10
Years

7. CKD and Diabetes
• As a cause of ESRD, diabetic nephropathy (DN) ranks first
• DN is clinically characterized by
• Proteinuria (mostly albuminuria),
• Elevated serum creatinine levels, and
• Decreased eGFR
• More than 20% of patients starting dialysis are dead within the
first year and more than 70% of diabetic patients starting
dialysis are dead within 5 years
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8. Percentage of diabetic patients who are likely to progress through
each stage
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Normal albumin excretion
Persistent
MicroalbuminuriaMicroalbuminuria
Proteinuria
Renal Failure
20-30%
~50% (2-4% per annum)
40%
30%
Raising blood
pressure and
cardiovascula
r disease risk

9. Table 1: Likelihood of DKD based on UACR and GFR
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Albuminuria
GFR* CKD Stage† None‡ UACR 30-299 mg/g UACR ≥300 mg/g
>60 1+2 At risk Possible DKD DKD
30–60 3 Unlikely DKD Possible DKD DKD
<30 4+5 Unlikely DKD Unlikely DKD DKD
*GFR expressed in mL/min.
†The NKF recommends using albuminuria data before initiation of RAAS inhibitor therapy to determine the
staging.
‡UACR <30 mg/g

10. Diabetic Nephropathy
• Affects approx. one-third of individuals with diabetes mellitus
• NHANES program during 1988–2008
• Prevalence of DKD increased (2.2%–3.3%) in proportion to the prevalence
of diabetes (6.0%–9.4%)
• The excess mortality risk of DM is practically exclusively
correlated with the occurrence of DN
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11. Diabetic Nephropathy
• Burden of ESRD from type 2 diabetes mellitus(T2DM) is
expected to burgeon by four fold
• Why some diabetic patients develop nephropathy whereas
others do not- ?
• DN pathogenesis remains obscure
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12. Drug Development
• Fewer interventional trials to develop therapeutics
• Obstacles are
• Slow patient enrolment (in part because of a lack of disease awareness),
• Regulatory requirements for hard patient outcomes for drug
registration, and
• Lack of payer engagement
• Only unmet medical need attract some pharmaceutical
companies.
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13. Pathophysiology of Diabetic Nephropathy
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14. Pathogenetic Mechanisms
• Heavy inflammatory element triggered by metabolic disorders,
protein overload, and hemodynamic abnormalities
• Traditionally, Glomerular in origin
• Emerging data suggest that the tubular epithelial cell
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15. Effects of - High Glucose
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Increases
NADH:NAD
Ratio
High Glucose
Aldose Reductase
Pathway
DAG synthesis
PKC
ROS
AGE
RAGE

16. 1/25/2017
16Free Amino Groups (Proteins ,
Lipids, & Nucleic Acids
Reducing Sugar
Under High
Glucose
Ambience
Non-Enzymatic
Interaction
Labile Schiff Base
Amadori Rearrangement
Dehydration
Polymerization
AGE’s
ROS

17. Interact
With
RAGE and Other
Binding Protein
(OST-48, 80 K-H,
Galectin)
Induce Various
Intracellular
Events
Activate PKC, MAP Kinase
and Transcription factor
such as NF-κβ
Increased synthesis of
Type I & IV Collagens
Activate Transcription
factor such as TGF-β and
alter expression of ECM
proteins
Decreased Expression
Of Proteoglycans
Anomalous ECM
polymerization and
expansion
Covalently Bind With Proteins Thus Compounding
With Various Deleterious Effect in Tissues
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18. 18
Membrane Barrier
High Glucose and Ang II-induced JAK/STAT pathway
in kidney mesangial cell growth
O2
NADPH oxidase
Angiotensin II
AT1
High Glucose
Polyol Pathway
RAGE
PKC-beta
AGE
PLD2
JAK2 and
STATs
SHP-1 and SHP-2
PLC-gamma1
DAG
Aldose
Reductase

19. Current Standard of Approach to
Diabetic Nephropathy
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20. The Triumvirate
• Intensive control of Blood Glucose
• Intensive control of Blood Pressure
• RAAS Blockade
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21. What Can be Achieved with Glycaemic Control?
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22. Glycaemic Optimization
• Study - EDIC (Epidemiology of Diabetes Interventions and
Complications- Cohort)
• Type 1 diabetics clearly demonstrated a legacy effect of early
intensive diabetic control-
• 44% reduction in developing CKD with eGFR lower than 60 ml/min/1.73m2
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23. Glycaemic Optimization
• Study- UK Prospective Diabetes Study (UKPDS)
• 3,867 Patients (newly diagnosed)
• Conventional Group HbA1c 7.9%
• For type 2 diabetics the risk in the intensive group was
• 12% lower for any diabetes-related endpoint;
• 10% lower for any diabetes-related death; and
• 6% lower for all-cause mortality
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24. Glycaemic Optimization
• Study- ADVANCE (Action in Diabetes and Vascular Disease:
Preterax and Diamicron Modified Release Controlled Evaluation)
trial
• 11,140 patients
• Demonstrated the value of tight glycaemic control
• Reduction of albuminuria (9% and 30% for micro- and macro-albuminuria,
respectively) and 65% risk reduction of ESRD
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25. Glycaemic Optimization
• Encouraging data must be interpreted with caution
• UKPDS, patients in the intensive group had significantly more
hypoglycaemic episodes
• Study - ACCORD (Action to Control Cardiovascular Risk in
Diabetes)
• Terminated early due to excess mortality in the intensive therapy arm
(HbA1c target <6.0%) versus the standard arm (HbA1c 7.0–7.9%)
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26. Glycaemic Optimization
• What constitutes optimal diabetic control?
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Aim- to strike a balance between the risk of hypoglycaemia
and the clear benefit of reno-protection
The American Association
of Clinical Endocrinologists
Target of HbA1c <6.5%
American Diabetes
Association
Target of HbA1c <7%

27. Glycaemic Optimization
• The Steno-2 study (microalbuminuria)-
• Target-driven, long-term, intensified intervention aimed at
multiple risk factors
• Blood pressure < 130/80 mmHg,
• Proteinuria < 0.3 g/day,
• Low density lipoprotein [LDL] < 100 mg/dL,
• ldl + very low density lipoprotein < 130 mg/dL,
• HbA1c < 7.0%, smoking cessation, and
• Near normalization of anemia of hemoglobin of 11 to 13 g/dL
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28. Glycaemic Optimization
• Reduced the risks of cardiovascular and microvascular events,
by approximately 50%
• In elderly, stricter established target levels
• hypoglycaemia and cerebrovascular ischemic events chances
• Thus, treatment targets should be tailored
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29. Glycaemic Vs Blood Pressure Control
• Depends on the clinical circumstances of the individual
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Significance
Glycaemic
control
Normoalbuminuria to
microalbuminuria progression
Blood
pressure
control
Once microalbuminuria has
shifted into a macroalbu-
minuric state

30. Blood Pressure Control
• Hypertension an independent, modifiable variable
• Predisposes individuals to the development and acceleration of micro- and
macro-vascular problems
• Various attempts to optimize RAAS inactivation
• Several trials have been conducted to validate the efficacy
• Angiotensin converting enzyme inhibitors (ACEI) or Angiotensin II type 1
receptor blockers (ARBs) alone,
• Combined use of ACEI and ARBs,
• Renin inhibitors (aliskiren),
• Aldosterone inhibitors (spironolactone or eplerenone), and
• Angiotensin II type 2 receptor enhancement
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31. Blood Pressure Control
• UKPDS showed for every 10 mmHg reduction in SBP, there was a
decrease in
• All DM-related complications by 12%
• Death by 15%
• Echoed in the RENAAL (Reduction of Endpoints in NIDDM with
the Angiotensin II Antagonist Losartan) trial
• 1,513 type 2 DM patients with confirmed DN and hypertension
• Risk of ESRD or death was raised by 6.7% for each 10 mmHg increase in
baseline SBP
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32. Renin-angiotensin-aldosterone Axis Blockade
• Type 2 DM-
• ACEi or ARB is superior to using other anti-hypertensive agents
• Provide other renoprotective benefits, (MARVAL -Micro-Albuminuria
Reduction with Valsartan study)
• Type 1 DM –
• Study- meta-analysis of 698 non-hypertensive type 1 DM patients with
micro-albuminuria
• Treatment with ACEi restricted development to macro-albuminuria by
60%
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33. Renin-angiotensin-aldosterone Axis Blockade
• Sub-study of the IRMA-2 (Irbesartan in Patients with Type 2
Diabetes and Microalbuminuria) trial
• Reduction in micro-albuminuria by RAS blockade persisted even after
treatment withdrawal
• IDNT (Irbesartan Diabetic Nephropathy Trial)
• 1,715 hypertensive type 2 DN patients
• 33% decrease in the risk of serum creatinine doubling
• 23% decrease in progression to ESRD
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34. Renin-angiotensin-aldosterone Axis Blockade
• Similar observations of RENAAL (Reduction of Endpoints in
NIDDM with the Angiotensin II Antagonist Losartan)
• 50% decrease in albuminuria after 6 months of losartan treatment
correlated with a 45% decreased risk for ESRD
• Findings recapitulate the renoprotective effect of captopril in
type 1 diabetics with overt nephropathy
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Drug Trial Notes
Valsartan MARVAL
(Micro-Albuminuria Reduction with
Valsartan)
Reduction in BP +
micro-albuminuria
Irbesartan IRMA-2
(Irbesartan in Patients with Type 2
Diabetes and Microalbuminuria)
Reduction in micro-albuminuria
persisted, even after treatment withdrawal,
implies that glomerular structural normalization
may be occurring
Irbesartan IDNT
(Irbesartan Diabetic Nephropathy
Trial)
GFR decline,
33% and 23% Risk reduction of serum creatinine
doubling and progression to ESRD respectively
losartan RENAAL
RENAAL (Reduction of Endpoints in
NIDDM with the Angiotensin II
Antagonist Losartan)
GFR decline,
50% & 45% decrease in albuminuria & risk for
ESRD respectively after 6 months treatment

36. Renin-Angiotensin-Aldosterone Axis Blockade
• Comparison between ACEi and ARB
• Appear to have comparable efficacy in DN,
• Intractable dry cough may be associated with ACE inhibition
• Findings are reinforced by the DETAIL (Diabetics Exposed to
Telmisartan and Enalapril) trial
• RCT in 250 type 2 DN patients
• No difference after 5 years- degree of GFR decline, albuminuria and
ESRD incidence
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37. Renin-Angiotensin-Aldosterone Axis Blockade
• Secondary prevention trials have so far provided all existing
data for RAS blockade
• The NKF KDOQI clinical practice guidelines have not
recommended using ACEi or ARB for the primary prevention of
DN in normotensive individuals with normo-albuminuria
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38. Exploiting the Renin-Angiotensin-Aldosterone
Axis
• Combining ACEi and ARB to maximize RAS blockade
• CALM (Candesartan and Lisinopril Micro-albuminuria) study
• A combination of candesartan and lisinopril
• Lowered micro-albuminuria more effectively than either drug alone at 12
weeks
• Longer follow-up studies were never able to reproduce these
short-term results
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39. Exploiting the Renin-Angiotensin-Aldosterone
Axis
• RCT—ONTARGET (Ongoing Telmisartan Alone and in
Combination with Ramipril Global Endpoint Trial),
• Ramipril, telmisartan or both were administered to 25,620 high vascular
risk patients (37.5% diabetics)
• Combination therapy was shown to increase the composite outcome of
dialysis, doubling of serum creatinine and death
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40. Exploiting the Renin-Angiotensin-Aldosterone
Axis
• VA NEPHRON-D (Veterans Affairs Nephropathy in Diabetes)
• 1,448 type 2 DN patients with eGFR 30–89.9 mL/min/1.73m2
• Treated with losartan alone or in combination with lisinopril
• Trial ended early- no renal benefit and an excessive risk of hyperkalemia
(9.9% vs. 4.4%) and acute kidney injury (18% vs. 11%)
• In DN patients with more advanced CKD, dual RAS inhibition
would carry an even greater risk
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41. Aldosterone Antagonism
• Mineralocorticoid receptor antagonist (MRA)
• Meta-analyses have demonstrated that a supplement of MRA given to
those treated with ACEi or ARB produces a decrease in proteinuria
• Likewise beneficial effects observed in administration of non-
selective and selective MRA
• But, Several studies, in combination with RAS inhibition showed
• A greater risk of hyperkalemia
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42. Non-steroidal MRA Antagonism
• Finerenone
• Increased receptor selectivity compared to spironolactone and
• Greater receptor affinity than eplerenone in vitro,
• A less frequent occurrence of hyperkalemia than spironolactone
• Finerenone added to ACEi or ARB
• Produced a dose-dependent decrease in UACR without inducing
hyperkalemia at day 90
• The study had several important limitations
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43. Lipid Lowering Therapy
• Statins are the most widely used class of drug for lipid lowering in
individuals with type 2 diabetes
• reflects the indisputable evidence
• The role of lipid-lowering treatments in renoprotection for patients
with diabetes, however, is debatable.
• In the Heart Protection Study by MRC/BHF with subgroup analysis
for participants with diabetes, allocation to simvastatin (40 mg/day)
• Significantly decreased the rise in serum creatinine values
• Limitation- Subjects with late stage CKD were not studied
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44. Lipid Lowering Therapy
• SHARP
• comprising 23% diabetic subjects did not produce significant reductions
in any of the prespecified measures of renal disease progression among
the subgroup of 6,247 nondialysis patients with a mean eGFR of 26.6
ml/min/1.73m2.
• Whether lipid lowering could only confer tangible
renoprotection during early rather than late CKD requires
further investigation
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45. Lipid Lowering Therapy
• GREACE study
• Patients given atorvastatin had a significant reduction in urinary albumin
excretion;
• However, separate analysis for type2 diabetes was not included in the study
• Findings echoed by the PLANET I study
• Treatment with atorvastatin 80 mg lowered UPCR substantially more than
rosuvastatin 10 mg or rosuvastatin 40 mg
• It must be cautioned that such doses of atorvastatin are unusually
high for the average CKD patient.
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46. Lipid Lowering Therapy
• Statins-
• Lowered mortality and cardiovascular events with early stages of
CKD
• Little or no effects in those on dialysis
• Had uncertain effects in kidney transplant recipients
• Effects on stroke and kidney function remain to be elucidated
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47. Novel Therapeutic Modalities
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48. Pleiotropic Renoprotective Effects of
Anti-diabetic Drugs Beyond Glycaemic Control
PPAR-γ agonists
Incretin- based Agents
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49. PPAR-γ Agonists
• TZDs- Pioglitazone and Rosiglitazone
• Varied reports from clinical studies
• Heightened cardiovascular risks and malignancy
• TZDs are unlikely to be a major player in the therapeutic
armamentarium for DN
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50. Incretin- Based Agents
• Incretins secreted into the circulation postprandially
• Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like
peptide 1 (GLP-1)
• Exert insulinotropic activity
• Impaired incretin regulation is implied in type 2 diabetes
• GLP-1 exerts antidiabetogenic properties by
• stimulating insulin secretion, increasing β-cell mass, inhibiting glucagon
secretion, delaying gastric emptying and inducing satiety
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51. Incretin- Based Agents
• GLP-1gets rapidly degraded by dipeptidyl peptidase 4 (DPP-4)
• Limitation can be overcome by using
• DPP-4 resistant GLP-1 receptor agonists and
• DPP-4 inhibitors.
• Other than glycaemic effects reduce-
• Blood pressure,
• Dyslipidemia, and
• Inflammation to a certain degree
• Risk of hypoglycaemia
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52. Incretin- Based Agents
• Sitagliptin/ Alogliptin/ Saxagliptin
• Experimental models indicated renoprotective benefits
• Lowered albuminuria in patients with type 2 DM
• 6 months of sitagliptin or 12 weeks of alogliptin
• Data from small, uncontrolled studies
• Findings must be interpreted with caution
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53. Incretin- Based Agents
• Four phase III studies, comprising 217 patients with DN on RAS
inhibition
• 24 weeks of linagliptin significantly reduced albuminuria (32% reduction),
independent of HbA1c
• Advantages of DPP-4 inhibitors
• Tolerability,
• Weight neutral benefit and
• Low risk of hypoglycaemia
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54. Incretin- Based Agents
• GLP 1 Agonists- Exenatide, liraglutide, dulaglutide
• Exenatide treatment in Type 2 DM
• Reductions in both albuminuria and urinary levels of TGF-β and type IV
collagen
• The anti-fibrotic effect of linagliptin was demonstrated in a type 1
model of DN after 4 weeks of treatment
• Limited clinical evidence of the effect of targeting TGF-β
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55. Vitamin D Receptor Activators
• Anti-inflammatory and anti-proteinuric effects in animal models
of DN
• Phase III VITAL trial in Patients with Type 2 Diabetes
• Adjuvant paricalcitol at 2 μg/day lowers residual albuminuria in DN
• Drawbacks-
• Poor tolerance- 42% of patients needed a reduced dose of paricalcitol,
• High cost of treatment
• Concrete evidence demonstrating the successful use of VDR
activators to retard the progression of DN is still awaited
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56. Sodium-Glucose Co-transporter 2 Inhibition
• Along with aiding glycemic control, SGLT-2 inhibitors appear to
promote an attractive cardiovascular portfolio
• EMPA-REG study,Empagliflozin added to standard care
• Over 7,000 type 2 diabetics at high cardiovascular risk
• Reduced the rates of
• Death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38%
RRR),
• Hospitalization for heart failure (2.7% Vs 4.1%, 35% RRR), and
• Death from any cause (5.7% Vs 8.3%, 32% RRR)
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57. Sodium-Glucose Co-transporter 2 Inhibition
• Renoprotective effect of SGLT2 inhibitors attributed to a
decrease in high glucose-induced inflammatory and fibrotic
markers in human proximal tubular cells
• By blocking glucose entry into the cell empagliflozin attenuated
High glucose-induced-
• Expression of Toll-like receptor-4, binding of nuclear deoxyribonucleic
acid to nuclear factor κB and activator protein 1, and secretion of
collagen IV and interleukin-6
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58. Sodium-Glucose Co-transporter 2 Inhibition
• Reporting with negligible clinical impact-
• Drug dose-dependent hyperkalemia and urogenital infections
• Dapagliflozin in the most recent trial involving diabetic patients
with moderately decreased renal function group showed
favorable results in terms of reduced albuminuria
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59. Selective C-C Chemokine Receptor Type 2
Antagonism
• MCP-1 overexpression plays an indispensable role in promoting
monocyte and macrophage migration and activation
• CCR2 antagonist- CCX140-B is a small molecule
• Inhibits CCR2 and blocks MCP-1-dependent monocyte activation and
chemotaxis
• Improved glycaemia and albuminuria in animal models
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60. Selective C-C Chemokine Receptor Type 2
Antagonism
• The first evidence that CCR2 inhibition lowers albuminuria in DN
came from a recent European study
• Patients with type 2 DM, Age: 18–75 years with UACR 100–3000 mg/g,
eGFR ≥25 mL/min/1.73m2, and taking stable antidiabetic treatment and
an ACEi or ARB for at least 8 weeks
• Stratified to once a day
• Oral placebo,
• 5 mg CCX140-B, or
• 10 mg CCX140-B
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61. Selective C-C Chemokine Receptor Type 2
Antagonism
• UACR changes (during 52 weeks)
• -2% for placebo (95% CI -11% to 9%),
• -18% for 5 mg CCX140-B (-26% to -8%), and
• -11% for 10 mg CCX140-B (-20% to -1%)
• No significant difference in adverse events or renal events
during the study.
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62. 5’ Adenosine Monophosphate-activated
Protein Kinase Activators
• AMPK is a metabolic master switch that regulates downstream
signals based on shifts in surrounding energy reservoirs
• Evidence of dysregulation of AMPK in relevant tissues is
implicated in the development of metabolic syndrome and
diabetes
• Insulin-resistant animal models
• AMPK activation proven to improve glucose and lipid homeostasis
coordinating anabolic processes
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63. 5’ Adenosine Monophosphate-activated
Protein Kinase Activators
• Metabolic stress –
• Adenosine triphosphate (ATP) consumption -increase in the adenosine
monophosphate (AMP)/ATP ratio
• Several upstream kinases or compound molecule that consists of
three proteins:
• STE-related adaptor (STRAD), mouse protein 25 (MO25), and the tumor-
suppressor liver kinase B1 (LKB1)
• Upstream enzymes
• Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) and
• TGF β-activated kinase (TAK1) 1/25/2017
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64. 5’ Adenosine Monophosphate-activated
Protein Kinase Activators
• Response to oxidative stress- Activated AMPK phosphorylates
its main downstream targets of lipid homeostasis
• ACETYL-COA carboxylase and hydroxymethylglutaryl CoA reductase.
These are primarily involved in the rate-limiting steps
• Promote fatty acid oxidation
• Adaptive responses for cell survival
• Fortify cellular autophagy, antioxidant defense and mitochondrial bio-
genesis
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65. 5’ Adenosine Monophosphate-activated
Protein Kinase Activators
• Sirtuin 1 (Sirt1) protein
• founding member of a family of NAD+-dependent deacetylases and is
linked to longevity associated with calorie reduction
• Expression and activity significantly reduced in type 2 diabetic animal
models and human kidneys the
• Mechanism of Sirt1 reduction in the diabetic condition has not
been clarified,
• Recent publications showed - AMPK activation by resveratrol and
theobromine leads to Sirt1 activation, which protects the diabetic kidney
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66. 5’ Adenosine Monophosphate-activated
Protein Kinase Activators
• Conventional activators of AMPK providing additional
renoprotective effects in addition to their intrinsic activities –
• 5-aminoimidazole-4-carboxamide ribonucleoside,
• Metformin,
• Adiponectin, and
• Resveratrol
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67. Some of the Newer Drugs and
Terminated RCTs
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68. Endothelin Receptor Antagonist
• Avosentan on Time to Doubling of Serum Creatinine, End Stage
Renal Disease or Death in Patients With Type 2 Diabetes Mel-
litus and Diabetic Nephropathy (ASCEND) trial
• Favorable effect of reducing albuminuria when added to standard
treatment
• Terminated due to-
• An increased risk of fluid overload and consequent congestive heart
failure resulting from proximal tubular sodium reabsorption
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69. Endothelin Receptor Antagonist
• Ongoing Study of Diabetic Nephropathy With Atrasentan
(SONAR) phase III trial
• Approaching its closing date, though some safety issues concerning
edema and heart disease are constantly being raised
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70. Antioxidative and Anti-inflammatory Agent
• Bardoxolone
• Powerful antioxidative and anti-inflammatory effects through the
activation of the nuclear 1 factor-related factor 2 transcription factor
• Failed to produce promising results
• Dropped from BEAM and BEACON trials,
• Trivial muscle cramps to serious issues including heart failure,
• Non-fatal myocardial infarction, stroke, and cardiovascular mortality
• Also increased urine albumin excretion and blood pressure
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71. Glycosaminoglycans
• Sulodexide
• Potentiates the antiprotease activities of both antithrombin III
and heparin cofactor II, shown
• Beneficial effects in diabetic animal models
• Failed to prove efficacious in the sulodexide macroalbuminuria (Sun-
MACRO) trial
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72. Others
• Xanthine oxidase inhibitors
• Proven efficacy in terms of delaying the decline in the rate of eGFR in a
relatively small sample of CKD patients
• Need to be validated in a larger population
• Anti-transforming growth factor β (TGF-β) antibody
(LY2382770),
• Effect demonstrated in an animal model, has not yet been translated into
human data
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73. Others
• Pentoxifylline- methylxanthine derivative and nonspecific PDI
• Effects anti-inflammatory, antiproliferative, and ant-fibrotic actions
• Pentoxifylline for Renoprotection in Diabetic Nephropathy
(PREDIAN) trial,
• Rate of eGFR decline and the change in urinary albumin excretion were
significantly lower
• Stem cell therapy in experimental DN models has not yet shown
efficacy in either diabetic mice or rat models
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74. Points to Remember
• Diabetes is the leading cause of chronic kidney disease (CKD)
• Screened regularly for kidney disease
• key markers- glomerular filtration rate (eGFR) and urine albumin
• Intensive management of blood glucose has shown great promise
for people with diabetes, especially for those in the early stages
of CKD.
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75. Points to Remember
• Agents proven blood pressure lowering and slowing the
progression of kidney disease
• Angiotensin-converting enzyme (ACE) inhibitors and
• Angiotensin receptor blockers (ARBs)
• ACEi and ARBs dual blockade is not recommended
• In people with diabetes, excessive consumption of protein may
be harmful.
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76. Any Questions?
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77. 1/25/2017