Nefropatia2 DBT

Nefropata Diabtica
Consideraciones en
el Manejo Clnico
Carlos Chiurchiu
cchiurchiu@hospitalprivadosa.com.ar
Servicio de Nefrologa y Programa de Trasplantes Renales

Hospital Privado - Centro Mdico de Crdoba
Mortalidad anual segn los

estados de Nefropata Diabtica
No nefropata
1.4%
(1.3% to 1.5%)
Microalbuminuria
3.0%
(2.6% to 3.4%)
Macroalbuminuria
4.6%
(3.6% to 5.7%)
Elevada creatinina plasmtica o
terapia de reemplazo renal
Adler et al. Kidney Int. 2003;63:225-232.
19.2%
(14.0% to 24.4%)
DIABETES COMO CAUSA DE INSUFICIENCIA RENAL

CRNICA TERMINAL EN ARGENTINA
35
PORCENTAJE
30
25
20
15
10
5
0
1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
SINTRA, Incucai 2007
SUPERVIVENCIA EN HEMODIALISIS
Supervivencia Acumulada
%
100
80
Logrank: p < 0,0001
60
40
No Diabticos
Diabticos
20
n:305
n: 71
0
0
50
100
150
200
250
300
Tiempo (meses)
Hospital Privado-Centro Mdico de Crdoba: perodo 1997-2003
RECOMENDACIONES
Individuos a riesgo de
Enf. Renal Crnica
Medidas a implementar
Diabticos
Hipertensos
Enf Autoinmunes
Infec. Sistmicas
Mayores de 60 aos
Historia fliar enf. Renal
Reduccin masa renal
Antec. de IRA
Medir la creatinina srica

Evaluar la presencia de
proteinuria
Estimar el FG
Monitorear el ndice P/C
Source: Kidney Disease Outcome Quality Initiative of the National Kidney Foundation.
CASO CLINICO
Mujer, 57 aos
Diabtica tipo 2 (15 aos de diagnstico)
HTA (10 aos de diagnstico)
Refiere controles de PA en casa de 120/80
Nunca tabaco
BMI: 31
Probable SAOS (en estudio)
Sin retinopata
Control previo hace 6 meses
PA: 155/95
Sin edemas
Creatinina: 1.10 mg/dl (previa 0.88 mg/dl)
Indice Albmina/Creatinina urinaria: 28 mg/g
K: 5.4 mEq/l
Hb glicosilada: 9.4%
LDL: 155 mg/dl
HDL: 35 mg/dl
Triglicridos: 225 mg/dl
Orina completa: normal
Medicacin: Enalapril 10 mg/da, Atorvastatina 10 mg/da, Metformina 850 mg c/12 hs
Tiene esta paciente cada de la funcin renal?

Es necesario una recoleccin de orina de 24 hs?
El control de la presin arterial debera ser optimizado?
El valor de K srico impide seguir utilizando IECAs o ARA II?
La optimizacin del control metablico mejorara la salud renal ?
Pudo haberse prevenido la aparicin del compromiso renal?
Es necesario interconsultar a un nefrlogo?

RECOMENDACIONES
www.kidney.org/professionals/kdoqi/gfr_calculator.cfm
Estimacin del Clearance de Creatinina:

Ecuacin de Cockroft-Gault
(140-edad) x peso(72 x S.Creat.) (x 0.85 en mujeres)
Desarrollada en 249 hombres

con creatinina estable
300
Sobrestimacin del ClCr en:

1) vegetarianos
2) obesos
3) malnutridos
4) edematosos
5) Bajos FG
Cockroft Gault
250
200
150
100
50
0
50
100
150 200
250
Filtrado Glomerular
300
Datos de 176 pacientes estudiados en el

Hospital Privado Centro Mdico de Crdoba
Ecuacin MDRD:
Generacin de las variables
ECUACIN ABREVIADA
186 x (Creatinina)-1.154 x
(edad)-0.203
(x 0.742 en mujeres,
x 1.212 en Raza Negra)
Levey et al., Ann Int Med, 1999
Ecuacin MDRD: Rendimiento
Puede subestimar el FG en
ERC estadio 1
Puede sobrestimar el FG en
ERC estadios 4-5
4 Estudios en pacientes con ERC:
diferencias medias encontradas:
-5,5 ml/min hasta +0.9 ml/min/1.73m2
Levey et al., Ann Int Med, 1999
Ecuacin MDRD: Limitaciones
Relacionadas a la calibracin de la creatinina

En poblacin con FG > 60 ml/min
En pacientes con IRA
En diabticos con hiperfiltracin
En poblacin oriental (otras etnias?)
Levey et al., N Eng J Med 2006
Subestimacin del FG con MDRD en

Sujetos Diabticos Tipo 2
Gaspari et al.
2005
MDRD (ml/min/1.73m2)
200
160
120
80
40
y = 0.471 x + 36.029
r = 0.560
n = 413
0
0
40
80
120
160
200
Clearance Plasmtico de Iohexol (ml/min/1.73m2)
Estimacin del FG en Diabticos

Influencia del Control Metablico
Deteccin de FG < 60 ml/min
Rigellau V et al. Diabetes Care 2006

GUIDELINE 5. ASSESSMENT OF PROTEINURIA
Criterion Standard
When screening tests are positive, measurement of protein excretion
in a 24-hour collection has been the longstanding gold standard for
the quantitative evaluation of proteinuria.
An alternative method for quantitative evaluation of proteinuria is

measurement of the ratio of protein or albumin to creatinine in an
untimed spot urine specimen. These ratios correct for variations in
urinary concentration due to hydration and provide a more
convenient method of assessing protein and albumin excretion than
that involved with timed urine collections.
American Journal of Kidney Diseases,Vol 39, No 2, Suppl 1 (February), 2002
Por qu es necesario conocer

la proteinuria de nuestros pacientes?
La proteinuria es una caracterstica comn de las
nefropatas crnicas
Mayor proteinuria se asocia con mayor riesgo
de enfermedad renal crnica
Mayor proteinuria se asocia con mayor velocidad en la
prdida del filtrado glomerular
La proteinuria se asocia con aumento en el riesgo CV
Ritmo circadiano de la proteinuria:

Importancia en el Indice P/C
Koopman N, et al .Nephrol Dial Transplant 1989
60Kg
70Kg
80Kg
Indice P/C como indicador de Proteinuria de 24 hs:

Diabticos con Nefropata
Robdy R, et al. Am J Kidney Dis, 1995
Indice A/C como indicador de Albuminuria de 24 hs:

Screening de Microalbuminuria en Diabticos tipo 2
(531 pacientes)
Incerti et al.Nephrol Dial Transplant 2005

INDICATIONS FOR INITIAL TREATMENT AND GOALS

FOR ADULT HYPERTENSIVE DIABETIC PATIENTS
Systolic
Goal (mmHg)
Diastolic
< 130
< 80
Behavioral therapy
alone (maximum
3 months) then add
pharmacologic treatment
130-139
80-89
Behavioral therapy +
pharmacologic treatment
140
90
American Diabetes Association, Diabetes Care 2004

WITHDRAWAL FROM CLINICAL TRIALS ON RAS

INHIBITORS BECAUSE OF SEVERE HYPERKALEMIA
RAS-I
Diabetic nephropathy
Lewis et al., N Engl J Med, 1993
Lewis et al; N Engl J Med, 2001
RENAAL, N Engl J Med, 2001
Total
3/207
11/579
9/751
23/1531 (1.6%)
non RAS-I
0/202
5/1136
2/762
7/2100 (0.3%)
Non-diabetic nephropathy
Kamper et al., Am J Hypertens, 1992 0/35
Hannedouche et al., Br Med J, 1994
2/52
Maschio et al., N Engl J Med, 1994
5/300
GISEN, Lancet, 1997
1/78
Ruggenenti et al., Lancet, 1998
0/99
Total
8/564 (1.4%)
Averall
31/2101 (1.5%)
0/35
2/48
3/283
1/88
1/87
7/521 (1.3%)
14/2621 (0.6%)
In patients with chronic renal disease, ACE inhibitors usually increase serum K + by 0.3 - 0.5 mEq/L, but induce severe
hyperkalemia in no more than 1% to 2 % of cases
EL BLOQUEO DEL SRAA SE ASOCIA CON MENOR

PROGRESIN HACIA LA MACROPROTEINURIA
Incidencia de macroalbuminuria
20
15
Cambio en la albuminuria
10
14.9 %
NNT: 5
5.2 %
5
0
150 mg
Placebo
9%
NNT: 11
9.7 %
% 10
p = 0.006
300 mg
Irbesartan
-6%
% -10
-20
- 30 %
-30
150 mg
Placebo
300 mg
Irbesartan
Parving et al., N Engl J Med, 2001

Reversin de la ND con el Tx de Pancreas

Cl Cr
Album.
Hb Glic
(ml/min)
(mg/da)
(%)
Basal
108.2
103
8.7
5 aos
74.2
30
5.3
10 aos
74.1
20
5.5
Fioretto P, et al. N Eng J Med 1998
INCIDENCIA DE MICRO Y MACROALBUMINURIA

CON CONTROL METABLICO INTENSIVO
Retinopata Basal SI
Retinopata Basal
NO
MICRO
MACRO
MICRO
MACRO
DCCT Research Group N Eng J Med 1993
CONTROL METABLICO INTENSIVO Y EVENTOS

VASCULARES: (11.000 Diabticos tipo 2)
Relative Risk (95% CI)
Eventos Macro
Incidencia Nefropata
-0.60
-0.80
0.80
ADVANCE Collaborative Group. N Eng J Med 2008

THE BENEDICT TRIAL

Patients
1,204 subjects with type 2 diabetes,

high blood pressure and normal
urinary albumin excretion
End point
Progression to microalbuminuria
Target HbA1C
< 7.0 %*
Target BP
120/80 mmHg*
* ADA guidelines, Diabetes Care 1998
Ruggenenti et al., N Eng J Med, 2004
Study design
TREATMENT PERIOD
RUN-IN
RAS inhibitors withdrawal
-6
-5
-4
-3
-2
-1
0
weeks
Randomisation
ndCCBs
withdrawal
Trandolapril (2mg/d)
Verapamil S.R. (240 mg/d)
Trandolapril (2mg/d) plus Verapamil S.R. (180 mg/d)
Placebo
12
18
24
30
36
months
Overnight UAE
Blood pressure and routine laboratory tests
Arterial Blood Pressure (mmHg)
Blood pressure according to treatment group
160
Systolic
150
140
130
120
Trandolapril
Verapamil
Trandolapril plus Verapamil
Placebo
110
100
90
Diastolic
80
70
12
15
18
21
24
27
30
33
36
39
42
45
48
Follow-up (months)
Placebo
(30 events)
Cumulative Incidence
of Microalbuminuria (%)
15
10
Trandolapril
plus
verapamil
(17 events)
A.F. (95 % C.I.) = 0.39 (0.19 - 0.80) p = 0.01
0
0
12
18
24
30
36
42
48
Follow-up (months)
No. at Risk
Trandolapril plus
Verapamil
Placebo
300
249
232
217
210
201
192
162
115
300
229
214
203
187
176
164
136
89
Cumulative incidence of
microalbuminuria (%)
15
Placebo
NNT: 8
(30 events)
10
Trandolapril
(18 events)
A.F. (95 % C.I.) = 0.47 (0.26 - 0.83) p = 0.01
0
0
12
18
24
30
36
42
48
Follow-up (months)
No. at Risk
Trandolapril
301
254
237
224
207
198
188
149
104
Placebo
300
229
214
203
187
176
164
136
89
Verapamil
(36 events)
Cumulative incidence of
microalbuminuria (%)
15
Placebo
(30 events)
10
0
0
12
18
24
30
36
42
48
174
134
98
164
136
89
Follow-up (months)
No. at Risk
Verapamil
303
234
210
202
189
181
Placebo
300
229
214
203
187
176
EFFECTS OF ENALAPRIL (10 mg/day) IN NON-OBESE SUBJECTS WITH

TYPE
2
DIABETES,
NORMAL
BLOOD
PRESSURE
AND
NORMOALBUMINURIA
UAE
(mg/24 h)
40
30
20
10
Mean Blood Pressure

(mmHg )
* p < 0.05 vs. enalapril
110
105
Placebo (n=79)
Enalapril (n=77)
100
95
90
3
Years
6
Ravid et al.,Ann Intern Med 1998

DERIVACION PRECOZ VS TARDIA
Kinchen et al. An Inter Med 2002, 137
MORTALIDAD Y DERIVACION TARDIA
Kazmi et al. NDT 2004, 19, 1808
TRASPLANTE Y DERIVACION TARDIA
Cass et al. AJKD 2003, 42, 1043
SITUACION CLINICA DEL PACIENTE

CON IRC AL MOMENTO DE
DERIVACION AL NEFROLOGO
EXPERIENCIA EN UN HOSPITAL
POLICLINICO
Serv. de Nefrologa. Hosp. Privado-Centro Mdico
de Crdoba
Carrera de Posgrado en Nefrologa
Univ. Catlica de Crdoba. Argentina
SITUACION CLINICA AL MOMENTO DE DERIVACION AL

NEFROLOGO
CRITERIOS DE INCLUSION
Primera visita al nefrlogo.
TFG (Cockorff) < 60 ml/min.
Caracteristicas basales al momento de la derivacin

n
63
Edad (aos)
57,7 17,3
Sexo (M / F)
45 /18
LUGAR DE LA 1 CONSULTA AL NEFRLOGO

N Ptes
20
18
16
52,9 %
47,1 %
14
12
10
8
6
4
2
0
CONSULTORIO
EXTERNO
INTERNADO
FACTORES COMORBIDOS
DIABETES
NO-DBT
(60,3%)
DBT
(39,7%)
FACTORES COMORBIDOS
MEDICAMENTOS ANTI- HTA EN DIABETES
IECA - ARA
DIURETICOS
80
70
60
50
40
30
20
10
0
SI
NO
SI
NO
FACTORES COMORBIDOS
Patologa
N (%)
Anemia
14 (37,8)
Dislipemia
17 (70,8)
IAM / ATC
14 (37,8)
ACV
8 (26,6)
ICC
2 (6,9)
E. Hepticas
1 (3,7)
Vascular perifrica
6 (21,4)
Tabaquismo
9 (32,1)
DATOS BIOQUIMICOS
X DS
Rango
Creatinina, mg/dl
2,9 2,1
0,9 11,7
Urea, mg/dl
100 53,4
20 242
Ac Urico, mg/dl
6,8 2,0
3,9 10,7
HTO, %
37,3 6,3
28,9 51,0
HB, g/dl
12,1 1,8
8,3 15,4
DATOS BIOQUIMICOS
NIVELES DE CREATININA
%
50
45
40
35
30
25
20
15
10
5
0
< 1,5
1,5 - 3,0
> 3,0
Creat, mg/dl
DATOS BIOQUIMICOS
NIVELES DE CREATININA SEGN ETIOLOGIA
5
4,5
4
3,5
3
2,5
2
1,5
1
0,5
0
GMN
DBT
PKD
NTI
NAE
OTROS
% Pacientes afectados
Complicaciones de la
Insuficiencia Renal Crnica
HTA
Hiperparat.
Anemia
Hiperfosfatemia
Inactividad
Hipoalbuminem.
Estadios de Enfermedad Renal

NHANES III: J Am Soc Nephrol 13: 504510, 2002
Calcificaciones coronarias en
Diabticos
90
80
70
60
50
40
30
20
10
0
CAC < 10
CAC 10-100
CAC 101-400
CAC > 400
No
IRC
IRC
1-2
IRC
3-5
Kramer H et al, J Am Soc Nephrol 2005
CASO CLINICO
Varn, 66 aos
Diabtico tipo 2 (20 aos de diagnstico)
IAM a los 50 aos
Fumador 30 cig/da desde los 18 aos
BMI: 28
Retinopata diabtica proliferativa (laser bilateral)
Control previo hace 1 ao
PA: 165/105
Edema MMII ++
Creatinina: 3.5 mg/dl (previa 2.8 mg/dl)
Indice Protenas/Creatinina urinaria: 2.7 g/g
K: 4.8 mEq/l
Hb glicosilada: 8.5%
LDL: 145 mg/dl
HDL: 48 mg/dl
Triglicridos: 290 mg/dl
Orina completa: Prot +++, Gluc ++, Hemoglobina +
Medicacin: Losartn 100 mg/da, Hidroclorotiazida 25 mg/da,
Atenolol 50 mg/da, Atorvastatina 20 mg/da, AAS 100 mg/da, Insulinoterapia
Cul sera el esquema hipotensor a utilizar ?

Es de utilidad usar IECAs o ARA II ante esta funcin renal?
Cul es superior entre ambas categorias?
La asociacin de IECAs con ARA II es til?
Existen otros tratamientos que aporten beneficio?
Es posible pensar en el Trasplante renal en un paciente
diabtico?

diabtico?
The risk of macrovascular and microvascular

complications in type 2 diabetes is strongly
associated with blood pressure
UKPDS (36): BMJ 2000;321:412-419
Rate of major cardiovascular events

according to Diastolic Blood Pressure
DBP Goal
< 90
Rate/1000 person/year
25
< 85
25
< 80
20
15
20
P <0.5
for trend
15
10
10
All patients
n: 18790
P <0.005
for trend
Diabetic
HOT Study: Lancet 1998
n: 1501
Modification of Diet in Renal Disease study

840 patients with non-diabetic proteinuric nephropathies
Mean glomerular filtration rate (GFR) decline and
achieved follow-up blood pressure
Peterson JC et al. Ann Intern Med, 1995
Relative risk for kidney disease progression based on

current level of SBP and current proteinuria
11 randomized, controlled trials comparing the efficacy of antihypertensive regimens
with or without ACE inhibitors
n = 1860 patients
Jafar TH et. Ann Intern Med, 2003
The decrease in risk for each 10 mm Hg reduction of

SBP for macro and microvascular complications
UKPDS (36): BMJ 2000;321:412-419
ACE inhibitors versus dihydropyridine

calcium channel blockers in diabetic patients
12
Nisoldipine
12
% 6
% 8
Enalapril
Amlodipine
16
Fosinopril
4
0
ABCD trial
FACET trial
470 Hipertensive patients

5 years follow up
MI: secondary end point
380 Hipertensive patients

3.5 years follow up
Combined End Point:
MI, stroke, angina
CAPPP study: ACE inhibitor therapy associated with

reduction in endpoints : Diabetic vs Total population
Hansson L , et al. Lancet 1999
EFFECTS ON RAMIPRIL ON CARDIOVASCULAR

AND MICROVASCULAR OUTCOMES IN 3.577
PATIENTS WITH TYPE 2 DIABETES ENROLLED
IN THE HOPE STUDY
THE MICRO-HOPE STUDY
- age > 55 years
- no clinical proteinuria
- previous cardiovascular event or at least
one other cardiovascular risk factor
HOPE Study Investigators, Lancet, 2002
THE MICROHOPE STUDY

Clinical outcomes for Ramipril and placebo group
Relative Risk (95% CI)
Primary outcomes
Combined
Myocardial infarction
Stroke
Cardiovascular death
Secondary outcomes
Total mortality
Revascularization
Overt nephropathy
- 50%
- 25%
25%
HOPE Study Investigators, Lancet, 2002
ATENOLOL AND CAPTOPRIL IN REDUCING RISK OF MACRO

AND MICROVASCULAR COMPLICATIONS: UKPDS 39
- 1148 hypertensive type 2 diabetic patients
Myocardial infarction, sudden death,

stroke, peripheral vascular disease
and renal failure
-Less tight BP control: 154/87

-Captopril: 144/83
-Atenolol: 143/81
UKPDS (39) BMJ, 1998
Cardiovascular morbidity and mortality in patients with

diabetes in the Losartan Intervention For Endpoint reduction
in hypertension study (LIFE):
Inclusion criteria
- Diabetes (both types)

- Hypertension
SBP: 160 - 200 mmHg and/or
DBP: 95 - 115 mmHg
- Left ventricular hypertrophy
Design
- Randomized, double blind
Treatment
- Losartan (50 - 100 mg/day) n = 586

- Atenolol (50 - 100 mg/day) n = 609
Follow-up
- 4.7 1.1 years
Main end point
- Combined cardiovascular mortality, stroke,

miocardial infarction
Lindholm et al., Lancet, 2002
Blood pressure and

metabolic control
were comparable
in the two treatment
groups throughout
the whole study period
Lingholm et al., Lancet, 2002
Average Drugs Needed to Achieve

Blood Pressure Goal
MAP (mmHg)
0
95
98
101
104
107
113
116
119
r = 0.69; p < 0.05
-2
GFR (ml/min/year)
110
-4
-6
-8
-10
-12
-14
130/85
140/90
Diabetes
Parving et al., Br Med J, 1989
Viberti et al., JAMA, 1993
Hebert et al., Kidney Int, 1994
Lebovitz et al., Kidney Int, 1994
Bakris et al., Kidney Int, 1996
Bakris et al., Hypertension, 1997
Untreated HTN
Non-diabetes
Klahr et al., N Engl J Med, 1993
Maschio et al., N Engl J Med, 1996
GISEN Group, Lancet, 1997
Bakris et al., Am J Kidney Dis, 2000

diabtico?
EFECTOS DEL CAPTOPRIL EN LA PROGRESIN

HACIA LA INSUFICIENCIA RENAL
EN DIABTICOS TIPO 1 PROTEINRICOS
0
% con duplicacin
de la creatinina
Captopril
Tratamiento convencional
25
50
75
Creatinina basal > 1.5 mg/dl
100
-2
4
- 40
Reduccin
de la MAP - 2
(mm Hg)
P <.001
- 20
% Reduccin 0
de la
Proteinuria - 20
-4
-6
-8
- 40
NS
- 60
Lewis et al. N Engl J Med. 1993
RENAAL
Reduction of Endpoints in NIDDM with the AII Antagonist Losartan
ESRD
- 1513 type 2 diabetes
30
- Alb/Cr ratio >300 mg/g,

- S Creat 1.3-3.0 mg/dL,
% with event
- Age 31-70 years
20
Risk Reduction: 28%
p=0.002
10
0
0
NNT: 32
12
24
Months
36
48
RENAAL
ESRD by Baseline Level of Serum
Creatinine
sCr < 2.0 mg/dL 2.0 mg/dL
RR:
31%
26%
p=
0.045
0.029
% with event
60
sCr2.0 mg/dL
40
P
20
sCr < 2.0 mg/dL

L
P
L
12
24
Months
36
48
463/252
468/246
424/186
429/196
254/93
269/106
33/9
51/18
sCr (mg/dL) <2.0/2.0
P (+CT) 482/280
L (+CT) 482/269

La asociacin de IECAs con ARA II es til en Nefropata DBT?
diabtico?
IECAs o ARAII en Nefropata Diabtica:

DETAIL study
- 250 type 2 diabetic patients

- Mild-moderate hypertensive
- Albuminuria < 1000 /min
- 80% microalbuminuric
- S Creat. 1.01 mg/dl
Barnett et al., N Eng J Med, 2004

diabtico?
CANDESARTAN
AND
LISINOPRIL
MICROALBUMINURIA (CALM) STUDY
Adjusted risk reduction (at 24 weeks) in SBP, DBP, and urinary A/C
ratio in 197 type 2 diabetics with hypertension and microalbuminuria
DBP
SBP
urinary A/C ratio
(mmHg)
(mmHg)
(%)
mg/day
Candesartan 16
n = 66
Lisinopril
n = 64
20
Combination 16 + 20 n = 67
1
10 20 30 40 50
10 20 30 40 50
10 20 30 40 50 60
Mogensen et al., Br Med J, 2000
ADDITIVE EFFECT OF ACE INHIBITION AND

ANGIOTENSIN II RECEPTOR BLOCKADE
-Type 1 DM
100
-Overt nephropathy
mmHg
- Crossover study
150
50
-Treatment:
Placebo
Blood Pressure
0
Placebo
1000
mg/24 hs
Combination (full doses)
Valsartan
Combination
Albuminuria
Benazepril 20 mg/day
Valsartan 80 mg/day
Benazepril
500
0
Jacobsenet.al.JAmSocNephrol2003
Placebo
Benazepril
Valsartan
Combination

diabtico?
BENEFICIAL EFFECTS OF ADDING

SPIRONOLACTONE TO ANTIHIPERTENSIVE
TREATMENT IN TYPE 2 DIABETES NEPHROPATHY
-Crossover study: (8 weeks per

period)
Albuminuria
p < 0.001
- Spironolactone 25 mg/day vs.
-20 patients with type 2 DM

-Overt nephropathy
-Full doses of inhibition on RASS
(g/24 hours)
- Placebo
1.5
1.0
0.5
0
Placebo
Spironolactone
Rossing et. al. Diabetes Care 2005
EFFECT OF LIPID REDUCTION ON

PROGRESSION OF RENAL DISEASE: GFR
THE
Meta analysis of studies with statins, fibrates and probucol
Trials
N of patients
Smulders et al., 1997

Aranda et al.,
1994
Rayner et al.,
1996
Thomas et al., 1993
Nielsen et al., 1993
Tonolo et al.,
1993
Buemi et al.,
1999
Hommel et al., 1992
Scanferla et al., 1991
Lam et al.,
1995
Olbricht et al., 1999
Nishimuria et al.,1999
TOTAL
Difference in change of GFR (95% CI)
15
16
17
18
19
21
21
24
34
43
118
362
p = 0.008
Treatment worse
-5
Treatment better
-3
-1
1
3
Difference in GFR decline (ml/min/month)
Fried et al., Kidney Int, 2001
INTERACTION BETWEEN THE RENINANGIOTENSIN SYSTEM AND STATINS

ACE-inhibitors
ANG I
ACE
ANG II
AT2
AIIRA
Transcription factors
(rho, rac, rab...)
AT1
Other districts
NF-B
- Chemoattraction, adhesion, inflammation

- proliferation, differentiation, sclerosis
- increased ROS production
- endothelial dysfunction
STATINS
LDL, VLDL
sdLDL
Tonelli M, et al. J Am Soc Nephrol 16: 37483754, 2005.
Riesgo* de Insuficiencia Renal Crnica Terminal

en Diabeticos segn cuartilos de Hemoglobina
R.R. (95 % C.I.)
< 11.3
11.3 12.5
12.5 13.8
13.8
0.5
1.25
1.5
2.0
2.5
Incremento del riesgo

Ajustado segn edad, sexo, raza, BMI, tabaquismo, funcin renal, albuminuria, perfil lipdico,
calcio, fsforo y PA.
RENAAL Study: Kidney International Vol. 66, 2004
REMISSION CLINIC
Targets:
Blood pressure
Proteinuria
LDL
LDL + VLDL
HbA1c
< 120/80 mmHg

< 0.3 g/24 h
< 100 mg/dl
< 130 mg/dl
< 7.5 % (diabetics)
Ruggenenti et al., Lancet, 2001

Cules son los resultados del Trasplante renal en un diabtico?
SOBREVIDA DEL INJERTO
Supervivencia Acumulada
1
,8
,6
Logrank: p= 0.6
No DBT
DBT
,4
,2
0
No DBT
DBT
10
20
30
40
50
60
488
35
375
24
306
21
258
13
209
11
171
9
138
8
Tiempo (meses)
Supervivencia acumulada
SOBREVIDA DEL PACIENTE
1
,8
,6
Logrank: p= 0.9
,4
No DBT
DBT
,2
0
No DBT
DBT
10
20
488
35
377
24
307
21
30
40
50
60
258
13
210
11
173
9
141
8
Tiempo (meses)

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Nefropata Diabtica

Servicio de Nefrologa y Programa de Trasplantes Renales

Mortalidad anual segn los

Adler et al. Kidney Int. 2003;63:225-232.

DIABETES COMO CAUSA DE INSUFICIENCIA RENAL

Logrank: p < 0,0001

Hospital Privado-Centro Mdico de Crdoba: perodo 1997-2003

Medir la creatinina srica

Tiene esta paciente cada de la funcin renal?

Tiene esta paciente cada de la funcin renal?

Estimacin del Clearance de Creatinina:

Desarrollada en 249 hombres

Sobrestimacin del ClCr en:

Datos de 176 pacientes estudiados en el

Levey et al., Ann Int Med, 1999

Ecuacin MDRD: Rendimiento

Levey et al., Ann Int Med, 1999

Ecuacin MDRD: Limitaciones

Relacionadas a la calibracin de la creatinina

Subestimacin del FG con MDRD en

Clearance Plasmtico de Iohexol (ml/min/1.73m2)

Estimacin del FG en Diabticos

Rigellau V et al. Diabetes Care 2006

Tiene esta paciente cada de la funcin renal?

GUIDELINE 5. ASSESSMENT OF PROTEINURIA

An alternative method for quantitative evaluation of proteinuria is

American Journal of Kidney Diseases,Vol 39, No 2, Suppl 1 (February), 2002

Por qu es necesario conocer

Ritmo circadiano de la proteinuria:

Koopman N, et al .Nephrol Dial Transplant 1989

Indice P/C como indicador de Proteinuria de 24 hs:

Robdy R, et al. Am J Kidney Dis, 1995

Indice A/C como indicador de Albuminuria de 24 hs:

Incerti et al.Nephrol Dial Transplant 2005

Tiene esta paciente cada de la funcin renal?

INDICATIONS FOR INITIAL TREATMENT AND GOALS

American Diabetes Association, Diabetes Care 2004

Tiene esta paciente cada de la funcin renal?

WITHDRAWAL FROM CLINICAL TRIALS ON RAS

EL BLOQUEO DEL SRAA SE ASOCIA CON MENOR

Parving et al., N Engl J Med, 2001

Tiene esta paciente cada de la funcin renal?

Reversin de la ND con el Tx de Pancreas

Fioretto P, et al. N Eng J Med 1998

INCIDENCIA DE MICRO Y MACROALBUMINURIA

DCCT Research Group N Eng J Med 1993

CONTROL METABLICO INTENSIVO Y EVENTOS

Relative Risk (95% CI)

ADVANCE Collaborative Group. N Eng J Med 2008

Tiene esta paciente cada de la funcin renal?

THE BENEDICT TRIAL

1,204 subjects with type 2 diabetes,

* ADA guidelines, Diabetes Care 1998

Ruggenenti et al., N Eng J Med, 2004

Arterial Blood Pressure (mmHg)

Blood pressure according to treatment group

Ruggenenti et al., N Eng J Med, 2004

A.F. (95 % C.I.) = 0.39 (0.19 - 0.80) p = 0.01

Ruggenenti et al., N Eng J Med, 2004

A.F. (95 % C.I.) = 0.47 (0.26 - 0.83) p = 0.01

Ruggenenti et al., N Eng J Med, 2004

Ruggenenti et al., N Eng J Med, 2004

EFFECTS OF ENALAPRIL (10 mg/day) IN NON-OBESE SUBJECTS WITH