Transcript diabetic nephropathy

DIABETIC NEPHROPATHY
MARITZA BROWN,MD
• Diabetic nephropathy refers to a
progressive disease characterized by
proteinuria, hypertension, reduced
glomerular filtration, and increasing renal
failure.
• 4% of the U.S.A population are known to
have diabetes with another 4% undiagnosed
Diabetes accounts for 14% of the health care
expenditures, of which one half is related to
complications such as heart attacks, strokes,
ESRD, retinopathy and foot ulcers.
• Diabetes is the most common cause of new
patients requiring renal replacement
therapy, accounting for 45% of cases in the
U.S.A
• Diabetic nephropathy now accounts for
aprox. 20% of kidney transplants performed
annually in the USA.
Reduce complications of diabetes
• Many of the complications of diabetes
could be minimized if patients participated
in a comprehensive health maintenance
program that included the following
features
• A 45 y/o man was referred to your clinic
because of elevated glucose on a insurance
screening test.
• FBS 324 mg/dl
• Bun 26/creatinine 1.1
History
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Diabetes
Passing of foamy urine
Diabetic retinopathy
fatigue and foot edema secondary to
hypoalbuminemia
• Other associated disorders such as
peripheral vascular occlusive disease,
hypertension or CAD
Physical
• Generally, diabetic nephropathy is considered after
a routine urinalysis and screening for
microalbuminuria in the setting of
diabetes.Physical findings assoc. with long
standing DM
• Hypertension
• Retinopathy
• Peripheral vascular occlusive disease
• Evidence for diabetic neuropathy
• Nonhealing skin ulcers/osteomyelitis
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Vigorous cardiac risk reductions
Lifestyle modifications
Routine eye exam, ophthalmology referral
Routine foot examination
Optimal treatment of hypertension
Screening and treatment for microalbuminuria
Glycemic control
Appropriate vaccination
Cardiac risk reductions
• Diabetics = increased risk for athesclerosis
• The American Heart Association has stated that a
substantial reduction in cardiovascular mortality(
particularly in type 2 diabetes) coud be achieved
by:
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smoking cessation
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Aspirin 325 mg daily
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aggressive treatment of hypertension and
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lipid abnormalities
• Measure fasting serum lipids annually
• LDL cholesterol goal is <100 mg/dl
Regular exercise which leads to improved
glycemic control
• Diabetic retinopathy is present in virtually
all persons with IDDM who have
nephropathy, whereas only 50-60% of
patients with proteinuric NIDDM have
retinopathy.
• Absence of retinopathy requires further
investigation for nondiabetic
glomerulopathies.
• Patients with type I diabetes should have a
complete examination by an ophthalmologist
• Beginning three –five years after the onset of
diabetes
• **SCREENIG NOT INDICATED BEFORE
PUBERTY
• ***Women with preexisting diabetes who
become pregnant should have ophthalmologic
examiniation during the first trimester. At least 3
exams during the pregnancy.
Routine foot examinations
• Feet should be examined at least annually in
patients with type 2 DM and in those with
type 1 DM for more than five years.
• Test should include a detailed neurological
examination, including use of astandardized
monofilament at specific sites to detect
early loss of sensation in the foot.
• Assesment for peripheral vascular disease
should include:
• Examination of leg and foot pulses,
• Skin temperature
Signs of current or previous ulcers
Lesions between adjacent toes due to pressure
from tight shoes cramming together.
Lab Studies
• Urinalysis
• Including microscopic to help rule out a
potentially nephritic picture
• 24-hour urinalysis for urea, creatinine,and
protein to quantify protein losses and
estimating the GFR
• Renal sonogram
• Increased urinary albumin excretion is the earliest
clinical finding of diabetic nephropathy.
• Normal rate of albumin excretion is less than 20
mg/day(15mcg/min)
• Microalbuminuria : persistant values between 30
and 300 mg/day (20-200 mcg/min)
• Macroalbuminuria: excretion greater than 300
mg/day
Therapy
• ??Strict glycemic control
• The efficacy of strict glycemic control
depends in part upon the stage at which it is
begun and the degree of normalization of
glucose metabolism
Intensive insulin therapy on the
kidney
• It can partially reverse the glomerular
hypertrophy and hyperfiltration
• In type I, it can delay the development of
microalbuminuria. Benefits persist for years
• It can stabilize or decrease protein excretion
in patients with microalbuminuria
• Is strict glycemic control beneficial in patients
with macroalbuminuria?
• Lancet 1993
• 8 recipients of pancreatic transplantation
underwent serial kidney biopsy at 0,5,and 10 years
• Pre-transplant: 3 patients had nl albumin
excretion, 3 had microalbuminuria, 2 had overt
nephropathy.
results
• Mesangial volume significantly decreased
• Width of glomerular and tubular basement
membranes returned to normal and nodular
gomerular lesions had dissaperared
Optimal level of glycemic control is
uncertain, but a level of 7 % or less should
be our goal, particularly if hypoglycemia is
not an important problem
• What is the target b/p?
• What agent or agents to use?
• Should I combine an ACE inbitor with and
ARB?
• Which CCB reduce proteinuria?
• Hypertension is a common problem for both
type 1 and type 2 diabetes
• Early effective treatment is important to
prevent cardiovascular disease and to
minimize the rate of progression of diabetic
nephropathy and retinopathy
Initial therapy
• In the absence of renal disease or high risk
of cardiovascular disease :
• Weight reduction (if obese)
• Exercise
• Sodium restriction
• Smoking cessation and avoidance of excess
alcohol ingestion
• Extensive studies in diabetic animals
suggest that intraglomerular hypertension
and glomerular hypertrophy play an
important role in diabetic nephropathy
• Diabetes induces renal vasodilation and
increases GFR
• Reducing intraglomerular hypertension with
dietary protein restriction or
antihypertensive therapy with an
angiotensin converting enzyme inhibitor or
the prevention of intraglomerular
hypertension because of concurrent renal
artery stenosis can inimize progression of or
even prevent glomerular diasease in the
absence of glycemic control
ACE inhibitors
• ACE inhibitors beneficial in type I diabetes, this
benefit can be demonstrated early in the course of
the disease when microalbuminuria is the only
clinical manifestation.
• ACE inhibitors administration to
NORMOTENSIVE type 1 diabetics with
microalbuminuria decreased albumin excretion
and progression to overt diabetic nephropathy
• Benefit also demonstrated in patients with type 1
diabetes who already had overt nephropathy.
• 409 patients with overt proteinuria and plasma
creatinine <2.5mg/dl randomized to captopril or
placebo
• At four years of equivalent b/p control, patients in
the captopril had a slower rate of increase in the
plasma creatinine, lesser likelihood of progressing
to esrd or death.
• If antihypertensive drugs must be used, the
optimal initial therapy in type 1 diabetics is
an ACE inhibitor( or, if not tolerated an
ARB)
• If b/p goal not reach additonal meds should
be added ie diltiazem, verapamil are
reasonable options
• Target b/p in patients with renal insuf. And
proteinuria above 1-2 g/day should be aprox
120/75 mmHg.
• Lower values may be better
• United Kingdom Prospective Diabetes
Study of patients with type 2 diabetes
Type 2 Dm, ACE inhibitors vs
ARB
• Lack of major trials comparing both agents
• Two major trials have demonstrated a clear
benefit in terms of renoprotection with
ARBs in patients with nephropathy due to
type 2 diabetes.
Irbesartan vs amlodipine
• 1715 patients irbesartan 300mg/day vs
amlodipine 10 mg/d
• 2.5 years f/u
• Irbesartan decrease risk of doubling
creatinine, development of esrd or death
RENAAL Trial
• 1513 patients with type w diabetes and
nephropathy
• Losartan 50-100mg/d vs placebo
• Addition to conventional antihypertensive
but not ACE inhibitors
• Losartan 25% reduction , doubling serum
creatinine
• Losartan 28 % reduction, ESRD
• An ARB should be ussed in type 2 diabetic
hypertensive patients especially with
evidence of left ventricular hypertrophy and
/or nephropathy.
• Do not switch from ACE to ARB
Calcium channel blockers
• Non-dihydropyridine CCBs slow renal
disease progression and proteinuria in
patients with type 2
• Irbesartan vs amlodipine
• ALLHAT trial higher rate of heart failure
with amlodipine
• Avoid initial therapy with a dihydropyridine
ccb. Diltiazem & verapamil are preferred
Dialysis in diabetic nephropathy
• Diabetes most common cause of new
patients requering dialysis
• 45% of cases in USA
• Increasing prevalence of diabetic
nephropathy is due to type 2 diabetes
• Incidence of ESRD due to type 1 may be
decreasing
• Patients survival in diabetics on
maintenance dialysis is lower than in non
diabetics
• USRDS excludes patients who diied within
the firs 90 of initiation of dialysis
• 84 consecutive patients with type 2 DM
requiring HD in France 32% died at 211
days mean f/u
• Cardiovascular disease is the most common
cause of death, accounting for more than
one-half of cases.
• Risk factors– those present prior to the
initiation of dialysis but also due to the
deposition of advanced glycosylation end
products.AGE
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AGE are excreted by the kidney
Accumulate in patients with renal failure
Inadequate removal by dialysis
Plasma AGE levels are 3.5 times > normal
• Death by withdrawal from dialysis is more
likely to occur in diabetics
Renal transplantation
• Diabetics account for 20% of kidney
transplanted in the USA
• Survival post transplant may be suboptimal
• 45-75% in some studies, other studies show
no major difference
• UTI >in diabetic transplant: long term
prophylaxis with dialy bactrim is
recommended
• Recurrent diabetic nephropathy develops in
almost all patients
• Loss of graft due to recurrent disease is
unusual, occurring in less than 5% of cases
• Nodular lesions of diabetic
glomerulosclerosis rarely recur