Diabetic Kidney Disease

DIABETIC KIDNEY DISEASE
DIABETIC KIDNEY DISEASE
• Diabetic kidney disease (DKD) is a clinical diagnosis in a patient with usually long-
standing diabetes (>10 years) with albuminuria and/or reduced estimated glomerular
filtration rate (eGFR) in the absence of signs or symptoms of other primary causes of
kidney damage.
• It is a chronic kidney disease, which involves gradual loss of kidney function.
RISK FACTORS FOR CHRONIC KIDNEY DISEASE (CKD)
• Diabetes
• Hypertension
• Family history of kidney disease
• Cardiovascular disease
• Obesity
• Acute kidney injury

KIDNEY:
ANATOMY AND
PHYSIOLOGY
KIDNEYS AND THE COLLECTING SYSTEM
• Kidneys
• Ureters
• Bladder
• Urethra
Slide 5 of 53
THE NEPHRON
• Glomerulus
• Proximal tubule
• Loop of Henle
• Distal tubule
• Collecting duct
THE KIDNEYS MAINTAIN BALANCE
• They have a regulatory function:
 Control composition and volume of blood
 Maintain stable concentrations of inorganic anions such as sodium (Na), potassium (K),
and calcium (Ca)
 Maintain acid-base balance
• They have an excretory function:
 Remove metabolic wastes
 Including nitrogenous waste
 Produce urine
THE KIDNEYS HAVE OTHER FUNCTIONS
• Their hormonal function affects many systems:
 Produce renin for blood pressure control
 Produce erythropoietin which stimulates marrow production of red blood cells
 Activate 25(OH)D to 1,25 (OH)2D (active vitamin D) needed for bone health
• They have metabolic functions:
 Gluconeogenesis
 Metabolize drugs and endogenous substances (e.g., insulin)

CKD IS REDUCED KIDNEY FUNCTION
AND/OR KIDNEY DAMAGE
• CKD
• Kidney function
• Glomerular filtration rate (GFR) < 60 mL/min/1.73 m 2 for > 3 months with or without kidney damage
AND/OR
• Kidney damage
• > 3 months, with or without decreased GFR, manifested by either
• Pathological abnormalities
• Markers of kidney damage, i.e., proteinuria (albuminuria)
• Urine albumin-to-creatinine ratio (UACR) > 30 mg/g
Reference: Kidney International Supplements, 2013; 3(1): 5-14

DIAGNOSING KIDNEY DISEASE
• 1. ASSESS KIDNEY FUNCTION

WHAT IS THE GFR?
• The GFR is equal to the sum of the filtration rates in all of the
functioning nephrons.
• GFR is not routinely measured in clinical settings.
• An estimation of GFR (eGFR), using serum creatinine level, gives a
rough measure of the number of functioning nephrons.
Slide 11 of 53
What is the GFR?
• Cardiac output (CO) = 6 L/min
• x 20% of CO goes to kidneys = 1.2 L/min
• x Plasma is 50% blood volume = 600 mL/min
• x Filtration Fraction of 20% = 120 mL/min
Slide 12 of 53
ESTIMATING EQUATIONS FOR EGFR
• The Modification of Diet in Renal Disease (MDRD) and CKD Epidemiology (CKD-EPI)
equations are most widely used for estimating GFR.
• The variables include serum creatinine (Scr), age, race, and gender.
• MDRD eGFR = 175 x (Scr) -1.154 x (age) -0.203 x (0.742 if female) x (1.212 if African American)
• CKD-EPI eGFR = 141 × min (Scr /κ,1)α × max (Scr /κ,1)-1.209 × 0.993 age × (1.018 if female) ×
(1.159 if African American)
• The estimate is normalized to body surface area.

Slide 13 of 53
References: Levey et al. Ann Intern Med. 1999; 130:461–470;
Levey et al. Ann Intern Med. 2009:150:604–612.
EGFR ESTIMATES THE MEASURED GFR
• eGFR is not the measured GFR.
• eGFR provides an estimate of GFR which is within +/- 30% of the measured GFR in
approximately 85% of people.
• MDRD and CKD-EPI results are based on serum creatinine levels.
• Previous methods to estimate kidney function also are based on serum creatinine.
Slide 14 of 53
CREATININE-BASED ESTIMATES OF KIDNEY
FUNCTION HAVE LIMITATIONS
• Results may be inaccurate with:
 Rapidly changing creatinine levels (Example: acute kidney injury)
• Extremes in muscle mass, body size, or altered diet patterns
• Medications that interfere with the measurement of serum creatinine
• Use of creatine supplements
Slide 15 of 53
SERUM CREATININE ALONE IS NOT ADEQUATE
• Serum creatinine levels reflect muscle mass, age, sex and race.
• A typical “normal” reference range of 0.6–1.2 mg/dL listed on many lab reports does not
account for muscle mass, age, sex and race.
• A 28-year-old African American man with serum creatinine of 1.2 has an eGFR > 60.
• A 78-year-old white woman with serum creatinine of 1.2 has an eGFR of 43.
Slide 16 of 53
DECREASED KIDNEY FUNCTION VERSUS KIDNEY DISEASE
• Estimating equations are less reliable at higher GFR.
• Kidney function declines with age.
• While there is an association between decreased eGFR and morbidity, even in elderly, this
association does not mean causality.
• Use diagnostic terms denoting disease with caution, especially in older people without
evidence of kidney damage (e.g. elderly with eGFR 55).
Slide 17 of 53
KIDNEY FUNCTION AND EGFR DECLINE WITH AGE
Reference Table for Population Mean eGFR from NHANES III

Age (years) Mean eGFR (mL/min/1.73 m2)
20–29 116
30–39 107
40–49 99
50–59 93
60–69 85
70+ 75
In healthy kidney donors the number of glomeruli per kidney decrease 25% by age
60-69 and GFR declines proportionately.
Slide 18 of 53
Reference: Coresh et al. Am J of Kidney Dis. 2003;41(1):1–12.

Denic et al. J Am Soc Nephrol. 2017;28(1):313–320.
DIAGNOSING KIDNEY DISEASE
• 2. ASSESSING KIDNEY DAMAGE

URINE ALBUMIN IS A MARKER FOR KIDNEY DAMAGE
• An abnormal urine albumin level is a marker for glomerular disease,

including diabetes.
• Urine albumin is a marker for cardiovascular disease and is a

hypothesized marker of generalized endothelial dysfunction.
• May be associated with increased mortality.
Slide 21 of 53
DAMAGED KIDNEYS ALLOW MORE ALBUMIN TO CROSS
THE FILTRATION BARRIER INTO THE URINE
• Increased glomerular permeability allows albumin and other proteins to cross

the glomerulus into the urine.
• Higher levels of protein which exceed the tubule’s capacity to reabsorb that
protein may exacerbate kidney damage through injury to the tubules.
Slide 22 of 53
USE URINE ALBUMIN-TO-CREATININE RATIO (UACR)
FOR URINE ALBUMIN ASSESSMENT
• UACR uses a spot urine sample.
• In adults, ratio of urine albumin to creatinine is used to estimate 24 hour albumin

excretion.
• Ratio is between two measured substances (not dipstick).
• UACR < 30 mg/g is generally the most widely used cutoff for “normal.”
Slide 23 of 53
https://www.niddk.nih.gov/health-information/professionals/clinical-tools-patient-education-
outreach/quick-reference-uacr-gfr
UACR QUANTIFIES ALL LEVELS OF URINE ALBUMIN
• UACR is a continuous variable.

• The term albuminuria describes all levels of urine albumin. The
modifiers micro and macro are going out of use.
• The term microalbuminuria has been used to denote
 30 mg/g – 300 mg/g
• The term macroalbuminuria has been used to denote

 > 300 mg/g
Slide 24 of 53
WHICH URINE TEST TO USE?
• Dipstick
 Semi-quantitative, screening only
 Affected by urine concentration, highly variable
 Detection of urine albumin > 300 mg/day
(1+ approximates albumin excretion of 30 mg/day)
• Urine protein/creatinine ratio
 All proteins, not just albumin
• Urine albumin-to-creatinine ratio (UACR)
 Other common names for UACR include microalbumin, urine albumin, albumin-to-
creatinine ratio or microalbumin/creatinine ratio.
Slide 25 of 53
CONFIRM HIGH UACR
• There is significant variation within individuals.

• Diagnosis of kidney injury requires confirmation with a second test.
Slide 26 of 53
RISK FACTORS FOR ALBUMINURIA
Known risks Possible risks Transient increases may be

due to:
• Diabetes • High sodium intake • Episodic hyperglycemia

• Hypertension • High protein intake • Exercise within 24 hrs.
• Smoking • Inflammation • Fever
• Obesity • Urinary tract infection
References: De Jong et al. Kidney International. 2004;66:2109–2118;

Slide 27 of 53
Tuttle et al. Diabetes Care; 2014: 37:2864–2883
LOWERING UACR MAY LOWER RISK OF PROGRESSION
Slide 28 of 53
Reference: De Zeeuw et al. Kidney Int 2004; 65(6):2309–2320.
INTERVENTIONS FOR REDUCING URINE ALBUMIN
• Control blood pressure

• Reduce sodium intake
• Achieve good control of diabetes early; may help prevent albuminuria
• Reduce weight, if obese
• Reduce protein intake, if excessive
• Achieve tobacco cessation
Slide 29 of 53
EXPLAINING URINE ALBUMIN
Slide 30 of 53
2018 Diabetes Canada CPG – Chapter 29. Chronic Kidney Disease in Diabetes
ACR ≥2.0 mg/mmol
CKD and / or
IN DIABETES
eGFR <60
mL/min/1.73 m2
ACR, albumin to creatinine ratio; CKD, chronic kidney disease; eGFR, estimated
glomerular filtration rate
DIABETIC NEPHROPATHY
“ Progressive increase in proteinuria in people with longstanding

diabetes, followed by declining function which can eventually lead
to End-Stage Renal Disease (ESRD)”
NATURAL HISTORY OF DIABETIC NEPHROPATHY: HYPERGLYCEMIA CAUSES
HYPERF ILTRATION, FOLLOWED BY ALBUMINURIA AND DECREASED GF R
Reference: Adapted from Friedman, 1999
Slide 31 of 53
HYPERGLYCEMIA IS ASSOCIATED WITH
HYPERFILTRATION
• The initial response to hyperglycemia is an increase in GFR, or

hyperfiltration, followed by a slow decline.
• The increased pressure and flow within the glomerular capillary may damage
the nephrons.
• Diabetic kidney disease (DKD) is generally, but not always, associated with
progressive albuminuria.
Slide 32 of 53 References: Molitch et al. Diabetes Care 2010; 33(7):1536–1543;

Retnakaran et al. Diabetes 2006; 55(6):1832–1839.
DIABETES IS THE LEADING CAUSE OF ESRD,
FOLLOWED BY HYPERTENSION
Slide 36 of 53
Reference: USRDS Annual Data Report (NIDDK, 2016)

TRENDS IN ESRD PREVALENCE BY MODALITY, 1980-
2015
Slide 37 of 53
ESRD IS VERY COSTLY
• Hemodialysis $ 26.7 billion ($88,195 per patient)

• Peritoneal Dialysis $ 2.1 billon ($75,140 per patient)
• Transplantation $ 3.3 billion ($34,800 per patient)
ESRD data do not include Medicare Part D cost Reference: USRDS Annual Data Report (NIDDK, 2017)
Slide 38 of 53
SCREENING AND
DIAGNOSIS OF
CKD IN DIABETES
BEWARE OF TRANSIENT
ALBUMINURIA
2
BEWARE
OF
OTHER
CAUSES
OF CKD
CKD, chronic kidney disease

WHEN TO CONSIDER OTHER CAUSES

OF CKD
CKD, chronic kidney disease

ONCE CKD IS IDENTIFIED, FURTHER EVALUATION IS
NEEDED AND OFTEN INCLUDES:
• Basic panel including glucose, creatinine, blood urea nitrogen, electrolytes, albumin, calcium
and phosphorus
• Fasting lipid panel
• Complete blood count
• Complete urinalysis
• Screening serologies
• Renal ultrasound
• Dilated retinal exam
• A1C
• Additional data may include iron studies, 25(OH) vitamin D and intact parathyroid hormone
(iPTH) Slide 39 of 53
DIABETES IS THE MOST LIKELY CAUSE OF CKD IF:
• Albuminuria is present.
• Diabetic retinopathy is present.
• The patient has diabetes of at least 10 years duration.
However, kidney disease in diabetes may manifest differently in

different people. In the future, individualized treatment may be
guided by kidney biopsy and advanced biochemical or genetic
testing.
Am J Kidney Dis. 2012;60(5):850-886
Clin J Am Soc Nephrol. 2017;12(9):1544-1547
Slide 40 of 53
KEY ISSUES IN MANAGING DKD
• Ensure the diagnosis is correct

 Assess UACR and eGFR
• Implement appropriate therapy
• Monitor progression
• Screen for CKD complications
• Educate the patient about DKD
• Prepare appropriately for kidney failure
Slide 46 of 53
MUCH OF THE NECESSARY CARE MAY BE MANAGED
IN THE PRIMARY CARE SETTING
• Many CKD interventions are similar to those for diabetes care.
• Other key interventions include co-morbidity screening.
• Timing of nephrology referral varies depending on patient status and
provider experience.
 Lack of appropriate care is associated with more rapid progression, worse health status
at time of dialysis initiation, higher mortality after starting dialysis, and decreased
access to transplant.
• Refer to a Registered Dietitian who is familiar with CKD for Medical
Nutrition Therapy.
Slide 47 of 53
CONSIDERATIONS FOR NEPHROLOGY REFERRAL
• Prepare for renal replacement therapy, especially when eGFR is less than 30.
• Assist with diagnostic challenges.
• Rapid decrease of eGFR.
• Assist with therapeutic challenges related to CKD complications such as
blood pressure, anemia, abnormal mineral metabolism and bone disorders,
hyperkalemia, hyperphosphatemia, malnutrition, and secondary
hyperparathyroidism.
• Assist with acute kidney injury.
Slide 48 of 53
IDENTIFY DIABETIC KIDNEY DISEASE (DKD)
• Albuminuria may be the first sign of DKD.

• Confirm abnormal levels.
• Recommend annual urine and blood tests.
• Check UACR to assess kidney damage.

• A spot urine sample can be used.
• A normal level is less than 30 milligrams per gram.
• Check eGFR to assess kidney function.

• Serum creatinine, age, gender and race are needed.
• An eGFR less than 60 identifies kidney disease.
• An eGFR less than 15 identifies kidney failure.
Slide 49 of 53
PREVENTION OF CHRONIC KIDNEY

DISEASE IN DIABETES
• Optimal glycemic control in type 1 and type 2 diabetes has

been shown to reduce the development and progression of
nephropathy
DCCT: REDUCTION IN ALBUMINURIA

Primary Prevention Secondary Intervention
34% RRR 43% RRR

(p<0.04) (p=0.001)
56% RRR
(p=0.01)
Solid line = risk of developing microalbuminuria RRR = relative risk reduction

Dashed line = risk of developing macroalbuminuria CI = confidence interval
The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.
EDIC: CONTINUED REDUCTION IN

ALBUMINURIA Macroalbuminuria
Return to normoalbuminuria
HR 1.92 HR 0.64
(p<0.05) (95% CI 0.40-1.02)
HR = hazard ratio
CI = confidence interval
deBoer IH et al. Arch Intern Med 2011;171(5):412-420.

E D I C : E A R LY G LY C E M I C C O N T R O L R E D U C E S L O N G - T E R M
R I S K O F IM PA I R E D G F R
Risk reduction with intensive therapy

50%
(95% CI 18-69; p=0.006)
DCCT/EDIC Research Group. N Engl J Med 2011;365:2366-76.

UKP DS: POS T-T RIAL MONITOR ING “LEGACY EF F ECT”
After median 8.5 years post-trial follow-up

Aggregate Endpoint 1997 2007
Any diabetes related endpoint RRR: 12% 9%
P: 0.029 0.040
Microvascular disease RRR: 25% 24%
P: 0.0099 0.001
Myocardial infarction RRR: 16% 15%
P: 0.052 0.014
All-cause mortality RRR: 6% 13%
P: 0.44 0.007
Holman R, et al. N Engl J Med 2008;359.

ADVANCE: PRIMARY
MICROVASCULAR
25
New/worseningOUTCOMES
nephropathy, retinopathy
20
HR 0.86 (0.77-0.97)
15 p = 0.01 Standard
Cumulative control
incidence (%) 10
5 Intensive
control
0
0 6 12 18 24 30 36 42 48 54 60 66
Follow-up (months)
Intensive Standard HR p
Nephropathy/retinopathy (%) 9.4 10.9 0.86 0.01

Nephropathy (%) 4.1 5.2 0.79 0.006
Retinopathy (%) 6.0 6.3 0.95 NS
Adapted from:
ADVANCE
ADVANCE Collaborative
Collaborative Group.
Group. N Engl N Engl J Med
J Med 2008;358:2560-72. 2008;358:24.
REDUCING PROGRESSION OF DIABETIC

NEPHROPATHY
• Optimal glycemic control
• Optimal BP control
• ACE-inhibitor or ARB
ACE, angiotensin converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure
ACE-I NHIB ITOR IN TYP E 1 DIABET ES WITH M AU

REDUCE S PROGRE SS ION TO CL INICAL P ROTE INURIA
Proportion with Event
Months of Therapy
Laffel LM et al. Am J Med 1995;99(5):497-504.
MAU, microalbuminuria
ACE-INHIBITOR IN TYPE 1 DIABETES WITH

MACROALBUMINURIA REDUCES RENAL
OUTCOMES
Lewis EJ et al. N Engl J Med 1993;329:1456-62.

ARB IN TYPE 2 DIABETES WITH MAU

REDUCES PROGRESSION
Primary endpoint: Time to onset of diabetic nephropathy* (n=590)
Placebo
Irbesartan
150mg
Irbesartan
300mg
*defined by persistent albuminuria in overnight specimens,

with urinary albumin excretion rate <200 μg/min and ≥30% higher than baseline level
Parving et al. N Engl J Med 2001;345:870-8

MAU, microalbuminuria
ARB IN TYPE 2 DIABETES WITH

MACROALBUMINURIA REDUCES RENAL OUTCOMES
Primary endpoint: Time to doubling of serum creatinine,

ESRD, or death (n=1513)
50 Placebo
patients with event
Risk reduction = 16%

Cumulative % of
40
p=0.02
30
20 Losartan
10
0
0 12 24 36 48
Months
Brenner et al. N Engl J Med 2001;345:861-9

ESRD, end stage renal disease
ARB in T2DM with Macroalbuminuria

Reduces Renal Outcomes
Primary endpoint: Time to doubling of serum creatinine,
70 ESRD, or death (n=1,715)
Irbesartan
60 RRR 23%
Amlodipine p=0.006
RRR 20%
p=NS p=0.02
50
Placebo
Patients (%)
40
30
20
10
0 6 12 18 24 30 36 42 48 54 60
Lewis et al. N Engl J Med 2001;345:851-60 Follow-up (mo)
ESRD, end stage renal disease
E M PA G L I F L O Z I N R E D U C E D D O U B L I N G O F S E R U M
C R E AT I N I N E * , I N I T I AT I O N O F R E N A L R E P L A C E M E N T
T H E R A P Y, O R D E AT H D U E TO R E N A L D I S E A S E
Hazard ratios are based on Cox regression analyses. *Accompanied by eGFR [MDRD] ≤45 ml/min/1.73m2.
HR, hazard ratio; CI, confidence interval. Post-hoc analyses.
Wanner et al. N Engl J Med 2016; 75:323-334

CANAGLIFLOZIN REDUCED COMPOSITE ENDPOINT OF

40% REDUCTION IN EGFR, REQUIREMENT FOR RENAL
R E P L A C E M E N T T H E R A P Y O R D E AT H F R O M R E N A L C A U S E S
Neal B et al. N Engl J Med 2017; 377:644-657

ANTIHYPERGLYCEMIC AGENTS AND RENAL FUNCTION
CKD Stage 5 4 3b 3a 1 or 2
eGFR (mL/min/1.73 m ): 2 <15 15–29 30–44 45-59 ≥ 60
Alpha-glucosidase
Inhibitors
Acarbose 30
Biguanides Metformin 30 500-1000 mg daily 45
Alogliptin 6.25 mg daily 30 12.5 mg daily 60
DPP-4
Linagliptin 15
Inhibitors Saxagliptin 15 2.5 mg daily 50
Sitagliptin 25 mg daily 30 50 mg daily 50
Dulaglutide 15
GLP-1
Exenatide 30 50
Receptor Exenatide QW 30 50
Agonists
Liraglutide 15
Lixisenatide 30
Gliclazide 30 60
Insulin
Glimepiride 30 60
Secretagogues Glyburide 60
Repaglinide 60
Canagliflozin* 25 45 100 mg daily 60
SGLT2
Inhibitors
Dapagliflozin 60
Empagliflozin 30 45
Pioglitazone 60
Thiazolidinediones
Rosiglitazone Fluid retention 60
Insulins 30
Use alternative agent Dose adjustment required Caution Do not initiate Dose adjustment not required
* May be used for cardiorenal benefits in those with clinical CVD, A1C above target and eGFR >30 mL/min/1.73m 2
KEY TAKEAWAYS
• Identiﬁcation of CKD in people with diabetes requires screening for proteinuria, as

well as an assessment of serum creatinine converted into an estimated glomerular
function rate (eGFR)
• All individuals with CKD should be considered at high risk for CV events and should
be treated to reduce these risks
• The development and progression of renal damage in diabetes can be reduced and
slowed through intensive glycemic control and optimization of BP. Progression of
CKD in diabetes can also be slowed through the use of medications that disrupt the
renin angiotensin aldosterone system
CKD, chronic kidney disease; CV, cardiovascular
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Diabetic Kidney Disease

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Diabetic Kidney Disease

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DIABETIC KIDNEY DISEASE

DIABETIC KIDNEY DISEASE

• Family history of kidney disease

• Acute kidney injury

 Produce renin for blood pressure control

 Produce erythropoietin which stimulates marrow production of red blood cells

• They have metabolic functions:

 Metabolize drugs and endogenous substances (e.g., insulin)

Reference: Kidney International Supplements, 2013; 3(1): 5-14

• 1. ASSESS KIDNEY FUNCTION

• x 20% of CO goes to kidneys = 1.2 L/min

• x Plasma is 50% blood volume = 600 mL/min

• x Filtration Fraction of 20% = 120 mL/min

• The estimate is normalized to body surface area.

• eGFR is not the measured GFR.

• MDRD and CKD-EPI results are based on serum creatinine levels.

• Results may be inaccurate with:

 Rapidly changing creatinine levels (Example: acute kidney injury)

• Extremes in muscle mass, body size, or altered diet patterns

• Medications that interfere with the measurement of serum creatinine

• Use of creatine supplements

• Estimating equations are less reliable at higher GFR.

• Kidney function declines with age.

Reference Table for Population Mean eGFR from NHANES III

Reference: Coresh et al. Am J of Kidney Dis. 2003;41(1):1–12.

• 2. ASSESSING KIDNEY DAMAGE

• An abnormal urine albumin level is a marker for glomerular disease,

• Urine albumin is a marker for cardiovascular disease and is a

• May be associated with increased mortality.

• Increased glomerular permeability allows albumin and other proteins to cross

• UACR uses a spot urine sample.

• In adults, ratio of urine albumin to creatinine is used to estimate 24 hour albumin

• Ratio is between two measured substances (not dipstick).

• UACR is a continuous variable.

• The term macroalbuminuria has been used to denote

• There is significant variation within individuals.

Known risks Possible risks Transient increases may be

• Diabetes • High sodium intake • Episodic hyperglycemia

References: De Jong et al. Kidney International. 2004;66:2109–2118;

• Control blood pressure

ACR ≥2.0 mg/mmol

“ Progressive increase in proteinuria in people with longstanding

Reference: Adapted from Friedman, 1999

• The initial response to hyperglycemia is an increase in GFR, or

Slide 32 of 53 References: Molitch et al. Diabetes Care 2010; 33(7):1536–1543;

Reference: USRDS Annual Data Report (NIDDK, 2016)

Reference: USRDS Annual Data Report (NIDDK, 2017)

• Hemodialysis $ 26.7 billion ($88,195 per patient)

CKD, chronic kidney disease

WHEN TO CONSIDER OTHER CAUSES

CKD, chronic kidney disease

However, kidney disease in diabetes may manifest differently in

• Ensure the diagnosis is correct

• Albuminuria may be the first sign of DKD.

• Check UACR to assess kidney damage.

• Check eGFR to assess kidney function.

PREVENTION OF CHRONIC KIDNEY

• Optimal glycemic control in type 1 and type 2 diabetes has

DCCT: REDUCTION IN ALBUMINURIA

34% RRR 43% RRR

Solid line = risk of developing microalbuminuria RRR = relative risk reduction

EDIC: CONTINUED REDUCTION IN

deBoer IH et al. Arch Intern Med 2011;171(5):412-420.