Nierenfunktion und metabolisches Syndrom - Vereinigung Zuercher ...

Vereinigung Zürcher Internisten 3.3.2005
Nierenfunktion und
metabolisches Syndrom -
welche Zusammenhänge
gibt es
PD Dr. B. Hess, Chefarzt Med. Klinik

PA
Fall – 48jährige Frau
• Appendektomie mit 16 Jahren
• Hypertonie seit 40. LJ, Atenolol-Behandlung wegen
“kalten Fingern” abgebrochen, BD-Wert bei letzter Kontrolle
154 / 101 mmHg
• Seit 5 Jahren Typ 2-Diabetes, zuerst mit Diät behandelt,
jetzt mit Metformin 2 x 850 mg
FA
• Positiv für Typ 2 Diabetes
• Vater mit 67 Jahren an Hirnschlag gestorben
© B.Hess 2/2005

Status
Fall – 48jährige Frau (2)
• 159 cm, 78.5 kg, BMI 31.1 kg/m 2 , Bauchumfang 92 cm
• BD 162/104 mmHg, P. 88/Min, reg.
• Übriger Status unauffällig
EKG : LV-Hypertrophiezeichen
Sonographie Niere : Struktur normal, leicht vergrössert
24-h-BD-Messung :
• Tagsüber mittlerer BD 159/97 mmHg
• Nachts mittlerer BD 151/89 mmHg = “Non-Dipper”
© B.Hess 2/2005

Labor
Fall – 48jährige Frau (3)
• Hb 12.4 g%; Hkt. 37%; Lc 7.42x10 3 /mm 3 ; Thr 306x10 3 /mm 3
• BZ nü 6.38 mmol/l, HbA1c 5.9%
• Na 143 mM, K 4.5 mM, Hst. 9.6 mM, Krea 80 M, Harnsre.
375 M
• Cholesterin 6.18 mM, HDL-Chol 1.42 mM, LDL-Chol 3.82
mM, Triglyceride 2.21 mM
• Albumin/Crea im 2. Morgenurin (nüchtern) 2.71 mg/mmol
• Urinsediment unauffällig
© B.Hess 2/2005

Metabolic Syndrome - Definition
Adult Treatment Panel III (ATP III) 2001
> 3 of the following characteristics have to be present :
Clinical symptoms
• Hypertension:
BP > 130/85 mm Hg
• Abdominal Obesity
Waist circumference
> 88 cm (Women)
> 102 cm (Men)
Laboratory parameters
• Triglycerides > 1.7 mmol/l
• Low HDL-Cholesterol :
< 1.30 mmol/l (Women)
< 1.05 mmol/l (Men)
• Fasting blood glucose
> 6.1 mmol/l
© B.Hess 5/2004 (from JAMA 287: 356-359, 2002)

Metabolic Syndrome - Effects of
its components on renal function
• Hypertension Renal function
• Obesity Renal function
• High triglycerides Renal function
• Low HDL-Cholesterol Renal function
• fasting plasma glucose Renal function
© B.Hess 5/2004

Multivariate-adjusted OR for
chronic kidney disease
Metabolic syndrome (NHANES III)
Risk for C Crea < 60 ml/min./1.73 m 2 (n = 6217)
3
2.5
2
1.5
1
0.5
0
BP > 130/85
mmHg
Whole
syndrome
Low HDL-C
Abd.
Obesity
High TG plasma
glucose
© B.Hess 5/2004 (adapted from Chen J et al., Ann Intern Med 140: 167-174, 2004)

Metabolic Syndrome - Effects of
its components on renal function
• Hypertension Renal function
• Obesity Renal function
• High triglycerides Renal function
• Low HDL-Cholesterol Renal function
• fasting plasma glucose () Renal function
© B.Hess 5/2004

Cardiovascular Disease and Kidney
CV Disease
Kidney Disease
Kidney Disease
CV Disease
© B.Hess 5/2004

Labor
Fall – 48jährige Frau (4)
• Hb 12.4 g%; Hkt. 37%; Lc 7.42x10 3 /mm 3 ; Thr 306x10 3 /mm 3
• BZ nü 6.38 mmol/l, , HbA1c 5.9%
• Na 143 mM, K 4.5 mM, Hst. 9.6 mM, Krea 80 M, Harnsre.
375 M
• Cholesterin 6.18 mM, , HDL-Chol 1.42 mM, LDL-Chol
3.82
mM, Triglyceride 2.21 mM
• Albumin/Crea im 2. Morgenurin (nü) 2.71 mg/mmol
• Urinsediment unauffällig

Definition der Albuminurie
Kategorie S a m m e l u r i n S p o n t a n u r i n
mg/24h g/min mg/l mg/mmol
Creatinin
Normal < 30 < 20 < 20 < 2.0
Mikroalbuminurie 30 – 300 20 – 200 20 - 200 2 - 20
Makroalbuminurie > 300 > 200 > 200 > 20
© B.Hess 8/2004 (mod. nach Hess B, CARDIOVASC 1: 24-29, 2002)

Metabolic Syndrome - 2 nd Definition
WHO - Proposal 1998
Type 2 Diabetes or Impaired fasting glucose or Insulin resistance
plus > 2 of the following criteria have to be present :
Clinical criteria
• Hypertension :
BP > 160/90 mm Hg
• Abdominal Obesity
BMI > 30 kg/m 2 and / or
Waist-to-hip ratio
> 0.85 (Women)
> 0.90 (Men)
Laboratory criteria
• Dyslipidemia :
- Triglycerides > 1.7 mmol/l
and / or
- HDL-Cholesterol
< 1. 0 mmol/l (Women)
< 0.9 mmol/l (Men)
• MICROALBUMINURIA (> 20 g/min.)
© B.Hess 5/2004 (from Diabet Med 15: 539-553, 1998)

Metabolic syndrome (WHO) and ist com-
ponents - risk factors for CV mortality
(Botnia study, 3606 subjects, 35-70 years old, median follow-up 6.9 years)
Relative CV mortality risk
4
3
2
1
0
Metabolic
syndrome
© B.Hess, 5/2004 (adapted from Isomaa B et al.,
Diabetes Care 24: 683-689, 2001)
MAU Hypertension Insulin res. Obesity Dyslipidemia

Prevalences of microalbuminuria
(NHANES III, 5659 participants from U.S., age 20-80 years)
Prevalence of MAU (%)
15
10
5
0
Metabolic syndrome (ATP III)
Controls
Women
Men
© B.Hess, 5/04 (adapted from Palaniappan L et al., Am J Hypertens 16: 952-958, 2003)

Albuminuria and Risk of CV Events,
4
Heart Failure and Death
(HOPE study, 9043 subjects with MAU measurements, 38.7% with DM)
MI/Stroke/CV death All-cause mortality CHF hosp.
Relative Risk
3
2
1
0
Alb/Crea < 0.22 0.22-0.57 0.58-1.62 > 1.62
(mg/mmol)
(adjusted for age, sex, systolic/diastolic blood pressure, waist-hip ratio, diabetes or HbA1c)
© B.Hess, 9/01 (adapted from Gerstein HC et al., JAMA 286: 421-426, 2001)

Albumin/Creatinine
Creatinine-Ratio
(ACR) and CV
risk in hypertensive patients with LVH
3
2.5
(LIFE, 7143 non-diabetic hypertensives with LVH, follow-up 39122 patient- years)
CV mortality
Stroke
All-cause mortality
MI
Hazard ratio
2
1.5
1
0.5
0
(adjusted for LV mass (ECG), age, sex, smoking, serum creatinine, race, study treatment)
< 0.25 0.25-
0.40
0.41-
0.58
0.59-
0.81
0.82-
1.15
1.16-
1.66
1.67-
2.52
2.53-
4.31
© B.Hess, 2/04 (adapted from Wachtell K et al., Ann Intern Med 139: 901-906, 2003)
4.32-
9.42
9.43-

Albumin/Creatinine
Creatinine-Ratio
(ACR) and All-Cause
Mortality in the General Population
RR all-cause mortality
10
8
6
4
2
0
Alb/Crea > 0.76 > 1.10 > 1.64 > 2.5 mg/mmol
(Cut-off)
(2089 men & women, no hypertension, no diabetes mellitus, follow-up 4.4 ys.)
(adjusted for age, sex, smoking, systolic blood pressure, BMI, cancer, long-termillness, education)
© B.Hess, 10/03 (adapted from Romundstad S et al., Am J Kidney Dis, 42: 466-473, 2003)

© B.Hess 2/05
C Crea
& MAU
The Kidney - a window to vasculature
Renal dysfunction = strong predictor of CV risk !

Diagnostik bei Metabolischem Syndrom
S-Kreatinin
Berechnung von C Krea !
Mann :
C Krea =
(140
- Alter; Jahre) x (KG; kg)
0.82 x Serum-Krea
( mol/l)
Frau :
C Krea = C Krea Mann x 0.85
(from Cockroft DW & Gault MH, Nephron 16: 31-41, 1976)
© B.Hess, 5/2004

Mikroalbuminurie-Bestimmung
-
wann, wie oft und bei wem
Mindestens 1 x pro Jahr bei folgenden Patienten :
• Typ 1-Diabetiker > 12 Jahre ab 5 Jahren nach
Diagnosestellung
• Typ 2-Diabetiker ab Zeitpunkt der Diagnose
(Ausnahmen: sehr alte Patienten, kurze Lebenserwartung)
• Langjährige „essentielle“ Hypertoniker mit Zeichen
des metabolischen Syndroms
Pathologische Werte/Therapieumstellung: Kontrolle nach 3-6 Monaten
© B.Hess, 2/2005 (adaptiert nach Hess B, CARDIOVASC 1: 24-29, 2002)

Mikroalbuminurie - wie messen
Mikroalbuminurie - spezielle Teststreifen
Diagnostik
Konventionelle Teststreifen:
erfassen MAU nicht !
Pathophysiologie
Normal
MIKROALBUMINURIE
PROTEINURIE /
MAKROALBUMINURIE
< 20 mg/l / < 2 mg/mmol
< 30 mg A / 24h
20-200 mg/l = 2-20 mg/mmol
= 30 - 300 mg A / 24h
> 200 mg/l / > 20 mg/mmol
> 300 mg A / 24h
© B.Hess, 2/2005 (adaptiert nach Hess B, CARDIOVASC 1: 24-29, 2002)

CV Disease
Kidney Disease
= AMPLIFIER
© B.Hess 2/2005