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.

Phenotypes influencing low physical activity in maintenance dialysis.

OBJECTIVE: The "Pas à Pas" initiative aimed at evaluating the weekly physical activity (PA) and its determinants in a large cohort of dialysis patients. SETTING: Physical inactivity is a risk factor for mortality in maintenance dialysis patients and is still poorly documented in this population. DESIGN: A prospective national epidemiological study was performed. SUBJECTS: A total of 1,163 patients on maintenance dialysis (hemodialysis and peritoneal dialysis) were included. INTERVENTION AND MAIN OUTCOME MEASURE: PA was recorded during seven consecutive days using a pedometer to measure daily step numbers. RESULTS: Median age was 63 years (Q1 51-Q3 75). Sixty-three percent were sedentary (<5000 steps/day) with a median of 3,688 steps/day (1,866-6,271)]. PA level was similar between hemodialysis patients and those on peritoneal dialysis (3,693 steps [1,896-6,307] vs. 3,320 [1,478-5,926], P = .33). In hemodialysis patients, PA was lower on dialysis days compared with nondialysis days (2,912 [1,439-5,232] vs. 4,054 [2,136-7,108], respectively, P < .01). PA gradually decreased with age, 57% being sedentary between 50 and 65 years and 83% of patients after 80 years. Beyond this age effect, we identified, for the first time, specific phenotypes of patients with lower PA, such as inflammation, cardiovascular disease, protein energy wasting, obesity, and diabetes. By contrast, previous kidney transplantation and a higher muscle mass were associated with higher PA. CONCLUSIONS: Dialysis patients present a very low level of PA with high sedentary. Acting on patient's modifiable phenotypes may help to increase PA to improve morbidity, mortality, and quality of life.

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.

Fish oil attenuates adrenergic overactivity without altering glucose metabolism during an oral glucose load in haemodialysis patients.

Haemodialysis patients display an increased cardiac mortality, which may be partly related to increased sympathoadrenal activity and insulin resistance. Fish oil decreases adrenal activation induced by mental stress and has an insulin sensitizing effect in healthy subjects. Whole-body glucose metabolism after oral glucose was studied in eight haemodialysis patients before and after a 3-week oral fish oil supplementation (i.e. EPA + DHA at 1.8 g/d). Plasma glucose fluxes were traced by using [6,6- (2)H2]glucose infusion. Substrate oxidation was determined by using indirect calorimetry. Each patient was studied in the basal state and over the 6 h following absorption of a 1 g/kg glucose load. Energy expenditure in response to glucose re-increased over the last 2 h of the experiment (P < 0.05), which coincided with an increase in plasma catecholamines, especially epinephrine (P < 0.05), strongly suggesting a sympathoadrenal overactivity. Fish oil supplementation blunted both re-increase in thermogenic response and concomitant increase in plasma epinephrine, but not in plasma norepinephrine, over the last 2 h of the experiment. Fish oil did not alter either whole-body glucose metabolism or substrate oxidation. These data show that in haemodialysis patients, fish oil attenuates adrenal overactivity induced by oral glucose but does not modulate whole-body glucose metabolism and insulin sensitivity.