Kreisel, S.I. (2016) De voorspellende waarde van familieanamnese voor ziekteprogressie bij patiënten met Autosomaal Dominante Polycysteuze Nierziekte. thesis, Medicine.
Full text available on request.Abstract
SI Kreisel, 25 februari 2016 5 Samenvatting (Engels) Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease caused by a PKD1 or PKD2 gene mutation and has a prevalence of 3-4 to 10.000. Eventually 70% of the patients will reach end-stage renal disease (ESRD), with a median age of 58, where the only treatment option is renal replacement therapy (RRT). Furthermore there is evidence for more vascular malformations in patients with ADPKD, resulting in CVA’s and MI’s. Recently the European Medical Agency (EMA) accepted tolvaptan, the first medicament that inhibits disease progression, as a treatment especially for patients with a high likelihood of rapid disease progression. Therefore it has become important to predict disease progression in individual patients. There are a couple of known predictors for disease progression, such as sex, PKD mutation, estimated GFR (eGFR) and total kidney volume (TKV). However, these methods are not sensitive, are invasive or involve costly and labor-intensive methods. There is evidence that family history is predictive for the disease progression of a patient, which is a lot less expansive and easier method. Therefore, the aim of this study is to investigate the predictive value of family history on disease progression. Primary research questions: 1- What is the predictive value of the family history on the rate of disease progression in patients with ADPKD? 2- How well does family history predict the rate of disease progression compared to other prognostic parameters? Secondary research questions: 3- Is a CVA/MI more common in people with ADPKD compared to people without ADPKD? 4- Is there a difference in age during these two events, CVA/MI, between people with and without ADPKD? 5- Is CVA/MI more often fatal in patients with ADPKD compared to people without ADPKD? Materials and Methods: Family history from patients from the UMCG was taken via a questionnaire and blood was taken for DNA analysis. Both at baseline and follow-up kidney function was estimated (eGFR) and measured (mGFR) and an MRI was done to determine TKV. Disease progression was expressed in annual change in eGFR, mGFR and lTNV. Family history was expressed as ‘familie leeftijd ESNF’ (mean age of ESRD in the family) or ‘familiescore’ (all family members who reached ESRD <58 years, divided by all family members ≥58 years with ADPKD times 100%) for the statistical tests. Linear regression was used to examine whether ’familie leeftijd ESNF’ was associated with the above mentioned continuous outcome variables. Patients were divided into fast and slow progressors and differences were assessed for ‘familie leeftijd ESNF’ and ‘familiescore’ between the two groups using t-tests or Mann-Whitney U tests. Finally, we tested via ANOVA or Kruskal-Wallis test for differences in ‘familie leeftijd ESNF’ and ‘familiescore’ for different risk classes from an existing prediction model. A chi-square test was used to answer the secondary research questions. Results: ‘Familie leeftijd ESNF’ was not associated with the annual change in eGFR, mGFR or lTNV (st.β=0.15 p=0.27, st.β=-0.07 p=0.71, st.β=-0.002 p=1.0 resp.). There was also no difference between fast and slow progressors for ‘familie leeftijd ESNF’ and ‘familiescore’ based on annual change in eGFR (p=0.733 and p=0.742 resp.) and based on annual change in lTNV (p=0.957 en p=0.611 resp.). There was no difference in ‘familie leeftijd ESNF’ and ‘familiescore’ between different risk classes of an existing prediction model (p=0.315 and p=0.664 resp.) CVA and MI were more common in people with ADPKD compared to people without ADPKD (8.9% vs. 3.6% p<0.001 and 7.2% vs.6.4% p<0.001) and people with ADPKD were younger during the event (48.3 ± 11.7 vs. 66.9 ± 15.1 p<0.001 en 53.1 ± 10.1 vs. 62.1 ± 11.4 p=0.003). A CVA or MI was not more often fatal in people with ADPKD compared to people without ADPKD (43% vs. 38% p=0.871). Conclusion: This study shows no association between family history and disease progression. Further research is recommended in which the study population will be enlarged and will be made more general and in which the methodology will be optimized.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Facultair begeleider and Gansevoort, Prof. dr. R.T. and Dagelijkse begeleider and Messchendorp, Drs A.L. and UMCG Interne geneeskunde afd.Nefrologie |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:01 |
| Last Modified: | 25 Jun 2020 11:01 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2094 |
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