ADPKD.

Præsentationer af emnet: "ADPKD."— Præsentationens transcript:

1 ADPKD

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5 ADPKD Autosomal dominant arvegang Prævalens ca. 0,1%
Udvikling af cyster i: nyrer lever pancreas gld. Thyreoidea, testes & flere

6 ADPKD Uræmi i 40-60 års alderen
Patienterne udgør % af alle i behandling for nyresvigt Overdødelighed af intrakranielle arterielle aneurismer (3 %)

7 ADPKD 80% af patienterne lider af hypertension
Hypertensionen optræder ofte tidligt i sygdomsforløbet før tab af nyrefunktion Hypertension øger hastigheden af nyrefunktionstabet ved cystenyresygdom

8 Behandling af ADPKD Tidlig opsporing og behandling af hypertension
Behandling af andre kardiovaskulære risikofaktorer Behandling af renale komplikationer Blødning/smerter/infektion/sten Håndtering af ekstrarenale manifestationer Behandling af CKD Renal erstatningsterapi

9 ADPKD i danmark Dalgaard, O. (1957). Bilateral polycystic disease of the kidneys, a follow-up of two hundred and eigty-four patients and their families (From the Municipal Hospital, Copenhagen, 3. dept., the Municipal Hospital Copenhagen, radiological dept. and the University Institute for Human Genetics). Cph.

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18 Genetik ved ADPKD Mutationen er unik for familien
8 -10 % af patienter med ADPKD har negativ mutationsscreening Mutationsscreening kan ikke bruges til at afkræfte en usikker ADPKD diagnose Hvis familiens mutation kendes er mutationsundersøgelse hos familemedlemmer sikker Hvad med præimplantations diagnostik?

19 Diagnose ved ADPKD Pei’s Kriterier:
15-39 år: Mindst 3 cyster, uni- eller bilateralt 40-59 år: Mindst 2 cyster i hver nyre 60 år: Mindst 4 cyster i hver nyre Gælder kun ved kendt ADPKD I familien

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22 Hildebrandt 2009

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25 Hildebrandt 2009

26 Ciliopatier

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28 Torres & Harris 2006

29 Torres & Harris 2006

30 Torres & Harris 2006

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32 CRISP (Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease)
Dannet af NIDDK 1999 Emory University The Mayo Clinic University of Kansas University of Alabama at Birmingham University of Pittsburgh (billed analyse) Develop imaging methods that reliably assess changes in kidney structure in a well-characterized cohort of patients with PKD, and evaluate whether changes in kidney structure are useful.  Establish and maintain a database of uniformly and accurately collected information including renal functional parameters and other selected markers of disease progression identified by both the data-coordinating and imaging-analysis center and the participating clinical centers Correlate parenchymal involvement with renal functional changes in PKD patients with various rates of progression Maintain and make available such data to facilitate the planning and implementation of future interventional studies of PKD.

33 CRISP MRI renal blood flow as a marker of disease severity in ADPKD.

PKD1 is more severe because more cysts develop earlier, not because they grow faster, implicating the disease gene in cyst initiation but not expansion.

There was significantly more urinary albumin in PKD1 cases. Kidney and cyst volumes consistently increased in both the PKD1 and PKD2.

Increases in cyst volume can be detected within 6 months.

The most relevant result was the evidence that MRI is the best procedure for estimating changes in cystic and renal volume in this disease over short follow-up periods.

The decline in renal function and disease progression in human ADPKD appears to be closely linked with the decline in renal blood flow.

34 Tolvaptan "TEMPO 3/4 Trial" Tolvaptan Efficacy and Safety in Management of Polycystic Kidney Disease and Its Outcomes (TEMPO3/4) Multicenter (130 centre), dobbelt blindet RCT, Tolvaptan vs. placebo 18-50 år, eGFR > 60ml/min./1,73 m2, totalt nyrevolumen > 750 ml (MR) Start jan 2007, slut maj 2012 Effektmål Totalt nyrevolumen (MR) GFR Hypertension Albuminuri

35 TEMPO 3:4

36 Everolimus Walz G, Budde K, Mannaa M, et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2010;363:830-40 Dobbelt blindet RCT, multicenter (24), 24 mdr., 433 pt. eGFR ml/min./1,73 m2 eller eGFR > 90 ml/min./1,73 m2 + nyrevolumen > 1000 ml Everolimus, start 2,5 mg x 2, C μg/l Effektmål Nyrevolumen (MR) eGFR + crea ESRD Død

37 Walz 2010

38 Walz 2010

39 Sirolimus Serra AL, Poster D, Kistler AD, et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med 2010;363:820-9. Open label RCT, 18 mdr., 100 pt. 18-40 år, eGFR > 70 ml/min./1,73 m2 Sirolimus, startdosis 2 mg x 1, C μg/l Effektmål Nyrevolumen (MR) eGFR Urin albumin/creatinin

40 Serra 2010

41 Lanreotid Hogan MC, Masyuk TV, Page LJ, Kubly VJ, Bergstralh EJ, Li X, Kim B, King BF, Glockner J, Holmes DR, Rossetti S, Harris PC, LaRusso NF, Torres VE. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney and liver disease. J Am Soc Nephrol 21: 1052–1061, 2010 Lanreotid (40 mg im. Pr. md.) vs. Placebo, 2:1 randomisering Levervolumen > 4 l (MR) 12 md. Levervol. (MR), nyrevol. (MR), GFR (Iothalamat), QOL

42 Hogan 2010

43 Hogan 2010

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