Real-life use of tolvaptan in ADPKD: a retrospective analysis of a large Canadian cohort.

Tolvaptan is the first disease-modifying drug proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers from the patient perspective to its use in real-life settings have not been systemically examined in a large cohort. This was a single-center, retrospective study of 523 existing or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario, between January 1, 2016 to December 31, 2018. All patients underwent clinical assessment including total kidney volume measurements and Mayo Clinic Imaging Class (MCIC). Those who were deemed to be at high risk were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded. Overall, 315/523 (60%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at their last follow-up. Among these high-risk patients, those not treated versus treated with tolvaptan were more likely to have a higher eGFR (82 ± 26 vs. 61 ± 27 ml/min/1.73 m2), CKD stages 1-2 (79% vs. 41%), and MCIC 1C (63% vs. 31%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥ 60 (12%), and pregnancy/family planning (6%). In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had early stages of CKD with well-preserved eGFR and as such, were prime targets for tolvaptan therapy to slow disease progression. Given that the most common reason for tolvaptan refusal was the concern for intolerability of the aquaretic side-effect, strategies to mitigate this may help to reduce this barrier to tolvaptan therapy.

[ADPKD treatment: Tolvaptan and Octreotide].

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent monogenic hereditary disease as well as the most studied inherited kidney disease. Two drugs have recently been authorized that can slow down the progression of the disease: Tolvaptan (vasopressin receptor antagonist) and Octreotide-LAR (long-acting somatostatin analogue); they both are able to reduce the activity of cyclic adenosine monophosphate (cAMP) and therefore have anti-proliferative and anti-secretory effects. This review analyzes the main trials published to date demonstrating the effects on disease progression in patients with ADPKD and illustrates the indications for identifying subjects eligible for therapy.

Deterioration in Clinical Status Is Not Enough to Suspend Eculizumab: A Genetic Complement-Mediated Atypical Hemolytic Uremic Syndrome Case Report.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Mutations in CFI gene coding for complement regulation factors and in THBD gene coding for endothelial cell receptor thrombomodulin could predispose to the disease and hypertension can trigger the onset. CASE PRESENTATION: A 51-year-old female patient who had received kidney transplant eighteen years ago presented with hypertensive peak and hemolysis pattern. Normal ADAMTS13 levels as well as negative culture and serology for Shiga-toxin excluded, respectively, thrombotic thrombocytopenic purpura (TTP) and typical HUS caused by Shiga toxin-producing Escherichia coli (STEC-HUS). In suspicion of aHUS, we administered eculizumab and hemodialysis sessions were started as the patient showed severe renal failure. After an initial response, the patient developed cerebral hemorrhage. After last eculizumab administration, according to hematological parameters, an unsatisfactory response was observed: given the worsening clinical scenario, we withdrew eculizumab. Pathogenic mutations in CFI and THBD genes were found. After eculizumab reinitiation, looking at hemolysis indexes, we observed a suboptimal response as well as an otherwise adequate renal one: renal graft function was recovered despite persistence of hemolysis signs, after 6 months on regular dialysis. CONCLUSION: For the first time, we report an aHUS case in which a peculiar combination of mutations in CFI and THBD is found. We describe the importance of continuing eculizumab despite deterioration of patient's clinical conditions.

Sodium Fluctuations and Mortality in a General Hospitalized Population.

BACKGROUND/AIMS: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. METHODS: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. RESULTS: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend <0.001) irrespective of severity of dysnatremia (HR 2.34, 95% CI 1.55, 3.54, p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). CONCLUSIONS: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.

Utility of serum procalcitonin and C-reactive protein in severity assessment of community-acquired pneumonia in children.

OBJECTIVES: Although the importance of serum Procalcitonin (PCT) levels at diagnosis is well established in adult Community-Acquired Pneumonia (CAP), its use remains controversial in pediatric CAP. The aim of our study is to investigate the role of PCT and C-Reactive Protein (CRP) in the assessment of pediatric CAP severity defined by the extent of consolidation on chest X-rays and the presence of pleural effusion. In this particular setting, no clinical severity score is available at present and chest X-ray, although important for diagnosis confirmation, is not recommended as routine test. DESIGN AND METHODS: The study involved 119 children admitted to the Department of Pediatric Infectious Disease for radiographically documented CAP aged 1 year to 14 years, without chronic diseases. Baseline PCT, CRP and routine laboratory tests were performed on admission. RESULTS: The median PCT (µg/L) and CRP (mg/L) were 0.11 (0.05­0.58) and 21.3 (4.2­48.1), respectively. PCT showed a good correlation with CRP, neutrophils and WBC (r = 0.538, P < 0.001; r = 0.377, P < 0.001; r = 0.285, P0.002, respectively). CRP, but not PCT, was associated with lobar consolidation (P = 0.007) and pleural effusion (P = 0.002). Logistic regression analysis revealed that only CRP was a predictor of lobar consolidation (OR: 1.078; 95% CI: 1.017­1.143; P = 0.011) and pleural effusion (OR: 1.076; 95% CI: 1.005­1.153; P = 0.036). CONCLUSION: Our findings revealed that PCT is correlated to the main inflammatory markers in children with CAP. CRP, unlike PCT, is able to predict the extent of chest X-ray infiltration and ultimately the severity of the disease confirming its usefulness in the management of pneumonia