LA NEFROPATIA DIABETICA

1

• DIABETIC NEPHROPATHY
• Epidemiology
• Natural history

Paola Fioretto Università di Padova
MGSD Postgraduate Course, Padova, 14/2/2004
2
ESRD Incidence Rates by Primary Diagnosis
150
Rate/Million Pop./Year
100
Diabetes
Hypertension
50
Other
Glomerulonephritis
0
1988
89
90
91
92
93
94
95
96
1997
Year
USRDS 1999
3
Percent of Incident ESRD Patients with Diabetic
Nephropathy, 2000
45.2
36.1
25
22

15.9
14.6
4
AER GFR BP
LESIONS
I N/? ? N ? glomerular and
kidney size II N
N/? N glomerular
lesions III MA N/? N/? glomerulopathy
(20-200µg/min) mild/moderate IV
gt200 µg/min N/? ? glomerulopathy
advanced V gt200 µg/min ??
?? global GS, tubulo- int. Fibr.
5

• In Dipstick negative patients
• Morning spot urines
• Albumin concentration
• (N lt20 mg/l)
• Albumin/Creatinine
• (N lt2.5 mg/mM in M, 3.5 in F)
• Timed urine collections
• AER
• (N lt 20 µg/min)

6
Microalbuminuria

• Timed urine collections
• 24 hours
• Overnight
• Timed (ex 4 hours)

7
MICROALBUMINURIA

• Not reliable in presence of
• UTI
• Menstrual period
• Intense physical activity
• Poor metabolic control
• Fever
• Heart failure
• In absence of these problems, the variability is
  40

8
MICROALBUMINURIA

• NORMOALBUMINURIA
• AER lt 20 µg/min
• MICROALBUMINURIA
• AER 20-200 µg/min in at least 2 out of 3 timed
  urine collections over 6 months
• PROTEINURIA
• AER gt 200 µg/min

9
MICROALBUMINURIA-WHEN?

• At diagnosis in type 2 diabetes
• After 5 year duration in type 1 diabetes
• Once a year if the patient is normoalbuminuric
• Every 3-6 months if microalbuminuric

10
Microalbuminuria in Diabetes

• predicts the development of overt nephropathy
• predicts cardiovascular disease and early
  mortality

11

• Viberti GC et al, Lancet 1982 1 1430-2
• Parving H-H et al, Acta Endocrinol (Copenh)
  1982, 100 550-5
• Mogensen CE et al, NEJM 1984 311 89-93

Progression to overt proteinuria over 6-14
years 60-85
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Risk of Progression in Diabetic Patients
N Follow-up NA MA
P (years)
() () () Type 1
Diabetes NA 861 9
(5-10) 80 15 5 MA
193 9 (5-10) 20-25
30-50 30-40
Type 2 Diabetes NA 279
7 (6-9) 70 25 5 MA
150 5 (5-6) ? ? 30

Caramori ML, Diabetes, 2000
13
Regression of microalbuminuria in type 1
diabetes Perkins BA, Ficociello LH, Silva KA,
Finkelstein DM, Warram JH, Krolewski AS New
Engl J Med, 348 2285-2293, 2003
14
TYPE 2 DIABETS

• Mogensen CE et al, NEJM 1984, 310 356-360
• Mogensen CE. Kidney Int 1987, 31 673-682
• Schmitz A, et al, Diabetic Med 1988, 5 126-134

Progression to clinical nephropathy in 10 yrs
20-25
15
This observation should not be misunderstood to
indicate that MA in an unreliable indicator.
Rather, it leads a note of optimism, since it
provides indirect evidence that aggressive
management does pay dividends regression was
seen in patients with low levels of HbA1c,
systolic blood pressure and cholesterol or
triglycerides.
Ritz E, NEJM, 2003
16
Low glomerular filtration rate in
normoalbuminuric type 1 diabetic patients An
indicator of more advanced glomerular lesions
Caramori ML, Fioretto P, Mauer M, Diabetes, 2003
17
GFR

• Plasma or urinary clearance of
• Inulin
• Ioexol
• Iodotalamathe
• 51-Cr-EDTA
• Creatinine clearance
• Creatinine
• Cystatin C

18
CREATININE CLEARANCE

• Timed urine collections
• Blood sample

UCr x V
Cr Cl
PCr
19
Creatinine clearance and serum creatinine

• The generation rate of creatinine varies serum
  creatinine is muscle mass and gender dependent
• Creatinine is secreted by the renal tubules.
  Overestimation of GFR by a factor of 1.2 or
  greater.
• Coefficient of variation for urinary creatinine
  excretion in a single individual is never less
  than 6 and may be greater than 20
• In advanced renal failure extrarenal clearance of
  creatine occurs
• Accurate timed urine collections may be difficult
  to obtain.
• The inverse of serum creatinine is simple and
  cheap, but is not useful to monitor renal
  function until serum creatinine has risen above
  200 ?mol/L
• Serum creatinine does not increase untill GFR is
  reduced by 50.

20
COCKROFT and GAULT Formula

• Creatinine clearance (140-age) x K x BW x
  (1/S-creatinine)
• K1.23 for men and 1.05 for women
• S-creatinine in ?mol/l
• BW in Kg
• Age in yrs
• This formula gives an accurate estimate of GFR in
  evaluation of mean decline in renal function in
  cohort studies.
• Inaccurate in individual patient

21
CYSTATIN C

• Cystatin C cannot return into the blood stream
  after filtration
• Meets criteria for a GFR marker
• Cystastin C levels rise prior to that of
  creatinine
• Determined by immunoassay

22
BP MONITORING

• In type 1 diabetes abnormalities in 24h BPM
  precede the occurrence of MA
• (Lurbe A, NEJM, 2002)
• In patients with borderline or with white coat
  Ht
• In evaluating the adequacy of antihypertensive
  treatment

23
Increase in nocturnal blood pressure and
progression to microalbuminuria in type 1
diabetes

• Lurbe E et al, NEJM, 347 797-804,2002