Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by a genetic dysregulation of the alternative complement pathway, characterized by thrombocytopenia, hemolytic anemia, and acute kidney injury, and included in the group of thrombotic microangiopathies. With the introduction of humanized monoclonal antibodies that inhibit C5 activation, the natural history of aHUS completely changed, with a better prognosis, a quick recovery of renal function, and a significant reduction of end-stage renal disease incidence. Nowadays, there is an increasing interest in the molecular and genetic bases of this severe disease. The aim of this narrative review is to provide readers with a practical guide about different possible involved genes, elucidating the specific role of each transcribed protein in the pathogenesis of aHUS. Moreover, we analyzed the main current evidence about the relationship among genetic mutations, outcomes, and the risk of recurrence of this manifold disease.

Effect of water composition and timing of ingestion on urinary lithogenic profile in healthy volunteers: a randomized crossover trial.

Kidney stone disease is a common condition with a high recurrence rate and elevated costs. Despite the well-known positive effects of high fluid intake, there are little data about the roles of water composition and timing of ingestion during the day. This study examines the effect of two different waters [calcium-bicarbonate water (CBW) and oligomineral water (OW)] consumed at different times during the day on urine composition in a group of healthy volunteers. In a cross-over randomized trial, 12 healthy volunteers were assigned to a different sequence of four combined interventions (1 L of water consumed during fasting and 1 L of water consumed with meals): CBW/OW; OW/CBW; CBW/CBW; OW/OW. Participants were instructed to follow the same diet and to avoid smoking, caffeine and other beverages during the day of intervention, and to collect their urine every 2 h during the day, followed by a single overnight collection. The relative supersaturation for calcium oxalate was higher for CBW/CBW compared with all other interventions, while relative supersaturation for calcium phosphate was lower for the combination OW/CBW with meals. Urinary excretion of oxalate was lower in all interventions including CBW, while no significant differences were found for urinary calcium. Water composition and timing of ingestion have complex and interacting effects on lithogenic risk. Depending on individual characteristics, a strategy involving either OW or a mix of CBW during meals and OW outside of meals could be effective in modulating the lithogenic profile.Trial registered at clinicaltrial.gov: Protocol ID NCT03447847.

Urinary supersaturation on fractioned urine collections: which urine sample can explain better the variability observed on 24-h urine? A proof-of-concept study.

Due to the difficulty of collecting 24-h urines in the stone-forming patient, some authors have suggested other types of urine collection, but their usefulness is not yet well studied. The objective of this study is to evaluate the variation of urinary supersaturation (SS) throughout the day and to analyze whether timed urine collections offer accurate information. 48 urine samples were collected from 12 young adults. Each 24-h urine was collected on 7 2-h urine fractions and a 10-h overnight sample. Solute concentrations and SS for calcium oxalate (CaOx), calcium phosphate (CaP), and uric acid (UA) were determined. Linear regression and relative importance of predictors were used to determine the percentage of R2 attributed to each timed collection (individual SS). 43 24-h urine samples were included in the study. The highest SS values were: for CaOx, night period and first morning urine; for CaP, between 2 and 6 pm and at night; for UA, between 8 am and 12 pm. For CaOx, the SS from the samples between 8 pm and 8 am accounted for more than 40% of the R2; for CaP, the results were more equally distributed throughout the day, and for UA, the SS values from 12 to 4 pm accounted for more than 45% of the observed variability. In conclusion, urinary SS varies throughout the day, being higher for CaOx and CaP at night, and in the early morning for UA. For CaOx and UA, the overnight and 12-4 pm urine samples, respectively, contribute most to the variability observed in the SS of 24-h urine.

Effect of different drug classes on reverse remodeling of intramural coronary arterioles in the spontaneously hypertensive rat.

BACKGROUND: Symptoms and signs of myocardial ischemia in the absence of obstructive coronary disease are common in hypertensive patients. This can be explained by CMD due to adverse remodeling of coronary arterioles which have also been reported in the SHR. OBJECTIVE: The aim of this study was to compare the effects of ramipril, perindopril, candesartan, atenolol, amlodipine, indapamide, and HMR1766 on CMD in the SHR. METHODS: Eight groups of 24-wk-old SHR were treated for 8 wk. BP was measured invasively at the end of the treatment. After sacrifice, hearts were mounted on a Langendorff apparatus for the measurement of hyperemic CF. Hearts were then processed for histomorphometric analysis. RESULTS: All compounds, except HMR1766, induced a significant reduction in BP. Perindopril and candesartan increased hyperemic CF, whereas the other compounds had no significant effect. Perindopril, ramipril, atenolol, indapamide, and HMR1766 induced significant reverse arteriolar remodeling, whereas candesartan and amlodipine did not. CONCLUSIONS: The effect of antihypertensive treatment on CMD is not exclusively dependent on BP reduction. Compounds with comparable antihypertensive efficacy may exert different effects on CF and induce different degrees of reverse arteriolar remodeling.

Polyvinylidene Fluoride Mesh (PVDF, DynaMesh®-IPOM) in The Laparoscopic Treatment of Incisional Hernia: A Prospective Comparative Trial versus Gore® ePTFE DUALMESH® Plus.

BACKGROUND: Laparoscopic approach is now generally accepted for the treatment of incisional hernia. The ideal mesh is still to be found. The aim of this study is to compare the well-known Gore® DUALMESH® Plus (WL Gore & Associates, Flagstaff, AZ) to a new prosthesis, the DynaMesh®-IPOM (FEG Textiltechnik GmbH, Aachen, Germany), to clinically verify its potential benefits in the laparoscopic treatment of incisional hernia. MATERIALS AND METHODS: Comparing the results of the laparoscopic treatment of two groups of patients affected by incisional hernia using Gore® DUALMESH® Plus and DynaMesh®-IPOM. RESULTS: There were 45 females and 31 males, with age variable from 21 to 84 years of age. The two groups were well matched for age (median age 60 years for group A and 57.6 years for group B-p=0.44) and sex (28F and 17M group A and 13 F and 18 M group B-p=0.008), while median BMI resulted slightly higher in group B (26.12 group A and 29.74 group B-p=0.001). The median size of the defect was similar in the two groups (87.5 mm group A and 83.4 mm for group B-p=0.83), while the median operating time was slightly longer in group A (77 min group A and 67 min group B-p=0.44). No difference in the length of hospital stay was evidenced between the two groups (3.19 days for group A and 3 days for group B-p=0.74). Time to return to physical activity was similar between the two groups (13.46 days for group A and 12.7 days for group B-p=0.32). Minor complications occurred in 15 cases (19.7%): seromas (7 cases), prolonged ileus (6 cases), and hemoperitoneum (2 cases), without significant difference in the incidence of such complications in the two groups. Five recurrences (6.5% of cases) occurred. No differences in the recurrence rate was noted between the two groups (3 cases/7% for group A and 2 cases/6% for group B-p=00.7). CONCLUSIONS: DynaMesh®-IPOM proved to be a safe and effective mesh for the laparoscopic repair of incisional hernia even when compared to DUALMESH® Plus.