Diagnosis and risk factors for intracranial aneurysms in autosomal polycystic kidney disease: a cross-sectional study from the Genkyst cohort.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyse the risk factors associated with the occurrence of IAs in ADPKD patients. METHODS: A cross-sectional study was performed in 26 nephrology centres from the western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes. RESULTS: Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9%, 6.2% and 8.1% at 50, 60 and 70 years, respectively. While this risk appeared to be similar in male and female individuals <50 years, after that age, the risk continued to increase more markedly in female patients, reaching 10.8% versus 5.4% at 70 years. The diagnosis rate of IAs was >2-fold higher in PKD1 compared with PKD2, with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension <35 years, smoking and PKD1 genotype were associated with an increased risk for diagnosis of IAs. CONCLUSIONS: This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of oestrogen.

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease.

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0-3 points), intermediate risk (4-6 points), and high risk (7-9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.

Type of PKD1 mutation influences renal outcome in ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is heterogeneous with regard to genic and allelic heterogeneity, as well as phenotypic variability. The genotype-phenotype relationship in ADPKD is not completely understood. Here, we studied 741 patients with ADPKD from 519 pedigrees in the Genkyst cohort and confirmed that renal survival associated with PKD2 mutations was approximately 20 years longer than that associated with PKD1 mutations. The median age at onset of ESRD was 58 years for PKD1 carriers and 79 years for PKD2 carriers. Regarding the allelic effect on phenotype, in contrast to previous studies, we found that the type of PKD1 mutation, but not its position, correlated strongly with renal survival. The median age at onset of ESRD was 55 years for carriers of a truncating mutation and 67 years for carriers of a nontruncating mutation. This observation allows the integration of genic and allelic effects into a single scheme, which may have prognostic value.

[ANCA-vasculitis with renal impairment treated by intravenous versus oral cyclophosphamide: Multicentric analysis of relapse free survival (VaReCyS)]. / Vascularites associées aux ANCA avec atteinte rénale recevant un traitement d'induction par cyclophosphamide oral versus intraveineux : étude rétrospective multicentrique de la survie sans rechute (VaReCyS).

INTRODUCTION: ANCA-vasculitis are associated with high morbidity and mortality. Large use of cyclophosphamide as induction immunosuppressive therapy is limited by its side effects. All recent literature trends in decreasing cumulative dose while optimizing maintenance therapy. METHODS: This retrospective multicentric analysis included ANCA-vasculitis patients with renal impairment and de novo diagnose followed in Rennes and Vannes hospitals for 2 years minimum. The primary endpoint was to analyze relapse free survival comparing oral and intravenous administration of cyclophosphamide. RESULTS: From 01/01/2003 to 01/03/2016, 91 patients were included (45 oral and 46 intravenous group). Patients in oral group were 10 years younger (P<0,001), with higher maintenance therapy (P<0,001) and steroids (P<0,001) duration. With a Cox model adjusted on age, steroid and maintenance therapy duration, oral cyclophosphamide showed no benefice in decreasing relapse free survival (OR 0,80; 95%IC 0,38-1,66; P=0,55). No difference was observed on either mortality or renal survival. Oral group at 1-year trends to achieve more leucopenia (40 vs 24%) and infection (30 vs 22%) episodes, but less hospitalization (40 vs 65%), without reaching statistical significance. CONCLUSION: In this retrospective multicentric analysis, oral cyclophosphamide induction was not associated with better relapse free survival after adjustment with age, steroid and maintenance therapy duration. Maintenance therapy duration is believed to better prevent ANCA-vasculitis relapse.