Diagnostikk av akutt og

kronisk nyresvikt sett fra

klinisk synsvinkel på St Olav

Cecilia Montgomery Øien

St Olavs Hospital

10.10.12

AKUTT NYRESVIKT

Definitions – Acute kidney injury

• 0-7 days, often spontanous recovery

• Non-renal causes

– Acute kidney disease

• 7-180 days, can be treatable

• Acute glomerulonephritis, acute interstitial nephritis,

vasculitis, intoxication

– Chronic kidney disease

• 180 days +, difficult to reverse

• Chronic glomerulonephritis, diabetes, HT,

atherosclerosis, hereditary diseases (ADPCKD), …

INTENSIVE CARE UNIT CLASSIFICATION

Akpesso. Intens Care

Med 2000; 400

•Obstruktiv (postrenal)

22 %

•Prerenal 24 %

•Renal 54 %

Differensialdiagnoser

Epidemiology

2 per 1000 admissions

needed dialysis

Other studies: Only 1 of 4 are registered, correct frequency are 80 per 1000 admissions

Prognosis: mortality

Patients with severe AKI requiring dialysis

Adjusted regression analysis of mortality risk RR 8 after adjusting for age, sex, race

RR 4 after adjusteing also for comorbidity & other hospital problems

Study (n) In-hospital mortality 1 year mortality

Schiffl (425) 47% 35%

Lins (293) 51% 22%

Basgshaw (240) 61% 64%

Prognosis: kidney function

• Patients with severe AKI requiring dialysis

AKI in patients without previous CKD can expect full recovery

Acute on chronic kidney disease can result in ESRD

Study (n) Previous CKD RRT at discharge RRT at 1 year

Schiffl (425) None 0 % 0.5%

Lins (293) None 5% 5%

Basgshaw (240) Some 33% 22%

(2/3 with pre CKD)

Acute kidney injury

Fluid

overload

Electrolyte/acid–base

abnormalities

Impaired innate

immunity

Chronic kidney

disease

Figure 2 | Acute kidney injury (AKI) can have both immediately recognizable consequences as well as less noticeable or delayed

consequences. Fluid overload and electrolyte/acid–base abnormalities represent well known, easily recognized consequences of

AKI.

Contrary, impaired innate immunity and chronic kidney disease do not manifest themselves immediately

Causes of acute kidney injury

Nephrotoxic agents N

ephro

toxic

agents

Bare kreatinin og

urinmengde?

Figure 1. Origin of acute kidney injury biomarkers within

a single nephron. GST, glutathione S-transferase; GT, glutamyl

transpeptidase; KIM, kidney injury molecule; L-FABP, liver-type fatty

acid-binding protein; NAG, N-acetyl-β-D-glucosaminidase; NGAL,

neutrophil gelatinase-associated lipocalin; RBP, retinol binding

protein.

Ostermann et al. Critical Care 2012, 16:233

NEW MARKERS

Unanswered questions

The new biomarkers of AKI have enhanced our understanding

of some of the biological and biochemical

processes during AKI; however, to date their clinical

utility remains unclear. It is not known whether any of

the new biomarkers add anything beyond clinical evaluation

and traditional renal function tests and whether

they can guide clinical management and ultimately alter

the outcome of patients with AKI. There is also concern

that a single biomarker may not be able to fulfil all criteria

as outlined in Table 1, and that it is more realistic to

search for a panel of different biomarkers that, in combination,

may provide the necessary data to manage patients with AKI.

Ostermann et al. Critical Care 2012, 16:233

MARKERS OF INTEREST

Kreatinin, karbamid, K, St bikarbonat, urinmengde, urinmicro

KLINIKK

Ultralyd:

Ekkorike nyrer dag 2,

Kreatinin 437

Urinmikroskopi:

Sigarformede

kalsiumoksalatkrystaller

- monohydratform

ETYLENGLYCOL

KRONISK NYRESVIKT

KDOQI CKD klassifikasjon

2002

≈ PROTEINURIA

CKD in Norway vs USA

1000 : 1 need for

better risk classification

Problemer med CKD

klassifiseringen • Svært få av CKD pasienter progredierer til

ESRD

• Spesiellt stort misforhold for eldre og

kvinner

Hallan et al. BMJ 2006; 333: 1047-1053

ESRD

fre

esu

rviv

al

Time (yrs)

GFR N ESRD

> 60 62 066 0.0%

45-59 2 389 0.4%

30-44 548 1.3%

15-29 120 18.3%

Hallan et al. BMJ 2006; 333: 1047-1053

ESRD

fre

esu

rviv

al

Time (yrs)

GFR N ESRD

> 60 62 066 0.0%

45-59 2 389 0.4%

30-44 548 1.3%

15-29 120 18.3%

ESRD INCIDENCE

Norwegian Nephrology Register Annual Reports

Okinawa study

100 x

Iseki et al. Am J Kidney Dis 2004; 44: 806-814

Rates of ESRD (n=95 000, observed for 7 years)

1000 x

Fordeler med CKD klassifiseringen

• Økt søkelys på tidlige stadier av nyresykdom

med muligheter for bedre forebygging av ESRD

• Muliggjør internasjonale sammenligninger

• Gir også mulighet for forbedret CV

risikostratifisering

Astor et al. Am J Epidemiol 2008; 167.

NHANES III

Summay 1: CKD classification

4 146 (1 187 - 14 482) 2 036 (594.3 - 6 973) 641.1 (143.6 - 2 862) 196.3 (27.6 - 1 397)

6 957 (2 286 - 21 165) 3 167 (1066 - 9 403) 1 108 (285.8 - 4 297) 306.6 (50.3 - 1 871)

Macroalbuminuria

2 202 (632.5 - 7 669) 448.9 (133.7 - 1 508) 146.5 (42.7 - 502.7) 27.3 (8.8 - 84.5)

3 833 (1 265 - 11 611) 740.6 (246.7 - 2 222) 227.4 (72.8 - 710.2) 33.9 (11.2 - 102.6)

Microalbuminuria

368.7 (69.2 - 1 964) 51.9 (11.5 - 233.5) 23.4 (6.7 - 82.1) 1.0

583.1 (120.5 - 2 822) 76.0 (18.5 - 313.2) 30.8 (9.30 - 102.2) 1.0

Normal ACR

eGFR 15 - 29 eGFR 30 - 44 eGFR 45 - 59 eGFR ? 60

HIGH RISK

Macroalbuminuria

RISK MODERATE

Microalbuminuria

LOW RISK

Normal ACR

eGFR 15 - 29 eGFR 30 - 44 eGFR 45 - 59 eGFR 60

• Lifetime risk of ESRD.

• Turin TC, Tonelli M, Manns BJ, Ahmed SB, Ravani P, James M, Hemmelgarn BR.

• Source

• Division of Nephrology, Foothills Medical Centre, 1403 29th Street NW, Calgary, AB, Canada T2N

2T9. Brenda.hemmelgarn@albertahealthservices.ca.

• Abstract

• Lifetime risk is the cumulative risk of experiencing an outcome between a disease-free index age

and death. The lifetime risk of ESRD for a middle-aged individual is a relevant and easy to

communicate measure of disease burden. We estimated lifetime risk of ESRD in a cohort of

2,895,521 adults without ESRD from 1997 to 2008. To estimate lifetime risk of ESRD by level of

baseline kidney function, we analyzed a cohort of participants who had a serum creatinine

measurement. We also estimated the sex- and index age-specific lifetime risk of incident ESRD

and accounted for the competing risk of death. Among those individuals without ESRD at age 40

years, the lifetime risk of ESRD was 2.66% for men and 1.76% for women. The risk was higher in

persons with reduced kidney function: for eGFR=44-59 ml/min per 1.73 m(2), the lifetime risk of

ESRD was 7.51% for men and 3.21% for women, whereas men and women with relatively

preserved kidney function (eGFR=60-89 ml/min per 1.73 m(2)) had lifetime risks of ESRD of

1.01% and 0.63%, respectively. The lifetime risk of ESRD was consistently higher for men at all

ages and eGFR strata compared with women. In conclusion, approximately 1 in 40 men and 1 in

60 women of middle age will develop ESRD during their lifetimes (living into their 90s). These

population-based estimates may assist individuals who make decisions regarding public health

policy.

whether the associations of eGFR and albuminuria

with all-cause mortality, cardiovascular mortality and

ESRD differ between men and women.

Objective

To assess • • •

CKD Prognosis Consortium (CKD-PC): Established in 2009

Compiles and meta-analyzes the best available data to provide

comprehensive evaluation of the impact of CKD on prognosis

46 cohorts (~2 million participants,

54% women) with data on serum

creatinine (eGFR) and albuminuria

o General population (GP) (n=1,861,052)

o At high risk (HR) for cardio-

vascular disease (n=151,494)

o CKD cohorts (n=38,612)

Methods-Study population

(Lancet 2010, KI 2011)

12

48

16

Adju

ste

d H

R

10 30 100 300 1000 3000

ACR

Female

Male

Adjusted for traditional risk factors and eGFR spline

Reference at ACR=100

End Stage Renal Disease in CKD Cohorts

12

48

16

Adju

ste

d H

R

10 30 100 300 1000 3000

ACR

Female

Male

Adjusted for traditional risk factors and eGFR spline

Reference at ACR=100

End Stage Renal Disease in CKD Cohorts

12

48

16

32

Adju

ste

d H

R

15 30 45 60

eGFR, ml/min/1.73m2

Female

Male

Adjusted for traditional risk factors and logACR/PCR or dipstick

Reference at eGFR=50

End Stage Renal Disease in CKD Cohorts

12

48

16

32

Adju

ste

d H

R

15 30 45 60

eGFR, ml/min/1.73m2

Female

Male

Adjusted for traditional risk factors and logACR/PCR or dipstick

Reference at eGFR=50

End Stage Renal Disease in CKD Cohorts

A B

C D

Results: ESRD according to eGFR (A & B) and ACR (C & D) in

CKD cohorts. (male: red, female: blue)

Conclusion

Low eGFR and/or albuminuria are at least as potent risk factors for all-cause mortality, cardiovascular mortality and ESRD in women as they are in men.

Future CKD classification

NICE / NHS Clinical guideline no 73: National clinical guideline for the management of adults with chronic kidney disease in primary and secondary care. Sept. 24. 2008

ACR >30mg/mmol (macroalbuminuria)

Albuminuri eller Proteinuri?

Why has ACR been

recomended?

• Greater sensitivity and improved precision for

the detection of lower but clinically significant

levels of proteinuria compared to total protein.

• Albumin is the predominant protein in the vast

majority of proteinuric kidney disease.

• There is no constant numerical relationship

between albumin and totalprotein. At normal

levels of protein loss albumin is a minor

component

NICE

MARKERS OF INTEREST

Kreatinin, eGFR

K, fosfat,st bikarbonat, karbamid,Hb calcium

Urin stix, albumin/kreatinin ratio

(protein/kreatinin ratio)

KLINIKK

OPPSUMMERING

• Ved akutt nyresvikt: kreatinin, karbamid, elektrolytter, st bikarbonat og urinmengde

• Ved kronisk nyresvikt: kreatinin, eGFR, elektrolytter, karbamid, st bikarbonat, urin stix, alb/kreatinin ratio

•KLINIKK

www.edren.org

• SUMMARY

• of regular monitoring for low-risk patients with < 1g

protein/d (PRC=100, ACR=70)

• Every 6 months, extending to 12-24 months if all is

unchanged, check: Blood pressure Quantitate

proteinuria (PCR or ACR) Serum creatinine

Vanlige årsaker til normotensiv

iskemisk nyresvikt

Abuelo. N Engl J Med 2007;357:797-805

Behandling av akutt nyresvikt etter

ACEI eller Ang II receptor blokker

• Seponering

• ”Motgiften” er NaCl

• Hyperkalemi kan være livstruende

• Dialyse sjelden nødvendig (<10%)

• Ultralyd/Doppler nyrer og nyrearterier

• Angiografiberedskap

• Gjenoppta behandling?

Frostvæskeforgiftning

• Livstruende tilstand (100 ml)

• Diagnostikk forsinkes ofte

• Tidlig behandling, evt. på

mistanke

• Lab. diagnostikk

• Urinfunn og ultralyd

Frostvæskeforgiftning Behandling

• Akutt dialyse

• Korrigere acidose

• Blokkere metabolisme – Etanol 1-2 o/oo

– Fomepizol

• Dialyse evt. flere uker

Effective RAS blockade should be obtained by using sufficient high ACEi doses (often higher than standard recommendations)

or by adding an ARB so that a substantial reduction in proteinuria is achieved.

Test for s-creatinine and s-K increase after 1 and 3 weeks