Investigation on lysosomal accumulation by a quantitative analysis of 2D phase-maps in digital holography microscopy.

Lysosomes are the terminal end of catabolic pathways in the cell, as well as signaling centers performing important functions such as the recycling of macromolecules, organelles, and nutrient adaptation. The importance of lysosomes in human health is supported by the fact that the deficiency of most lysosomal genes causes monogenic diseases called as a group Lysosomal Storage Diseases (LSDs). A common phenotypic hallmark of LSDs is the expansion of the lysosomal compartment that can be detected by using conventional imaging methods based on immunofluorescence protocols or overexpression of tagged lysosomal proteins. These methods require the alteration of the cellular architecture (i.e., due to fixation methods), can alter the behavior of cells (i.e., by the overexpression of proteins), and require sample preparation and the accurate selection of compatible fluorescent markers in relation to the type of analysis, therefore limiting the possibility of characterizing cellular status with simplicity. Therefore, a quantitative and label-free methodology, such as Quantitative Phase Imaging through Digital Holographic (QPI-DH), for the microscopic imaging of lysosomes in health and disease conditions may represent an important advance to study and effectively diagnose the presence of lysosomal storage in human disease. Here we proof the effectiveness of the QPI-DH method in accomplishing the detection of the lysosomal compartment using mouse embryonic fibroblasts (MEFs) derived from a Mucopolysaccharidosis type III-A (MSP-IIIA) mouse model, and comparing them with wild-type (WT) MEFs. We found that it is possible to identify label-free biomarkers able to supply a first pre-screening of the two populations, thus showing that QPI-DH can be a suitable candidate to surpass fluorescent drawbacks in the detection of lysosomes dysfunction. An appropriate numerical procedure was developed for detecting and evaluate such cellular substructures from in vitro cells cultures. Results reported in this study are encouraging about the further development of the proposed QPI-DH approach for such type of investigations about LSDs.

Predictive models in chronic kidney disease: essential tools in clinical practice.

PURPOSE OF REVIEW: The integration of risk prediction in managing chronic kidney disease (CKD) is universally considered a key point of routine clinical practice to guide time-sensitive choices, such as dialysis access planning or counseling on kidney transplant options. Several prognostic models have been developed and validated to provide individualized evaluation of kidney failure risk in CKD patients. This review aims to analyze the current evidence on existing predictive models and evaluate the different advantages and disadvantages of these tools. RECENT FINDINGS: Since Tangri et al. introduced the Kidney Failure Risk Equation in 2011, the nephrological scientific community focused its interest in enhancing available algorithms and finding new prognostic equations. Although current models can predict kidney failure with high discrimination, different questions remain unsolved. Thus, this field is open to new possibilities and discoveries. SUMMARY: Accurately informing patients of their prognoses can result in tailored therapy with important clinical and psychological implications. Over the last 5 years, the number of disease-modifying therapeutic options has considerably increased, providing possibilities to not only prevent the kidney failure onset in patients with advanced CKD but also delay progression from early stages in at-risk individuals.

24-Hour Urinary Chemistries and Kidney Stone Risk.

RATIONALE & OBJECTIVE: Most previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible "all-or-nothing" effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses' Health Studies I and II. EXPOSURE: Urine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium. OUTCOME: Incident symptomatic kidney stones. ANALYTICAL APPROACH: Multivariable logistic regression analysis incorporating restricted cubic splines to explore potentially nonlinear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor, and dominance analysis was performed to establish the relative importance of each urinary factor. RESULTS: Each urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. By contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified 3 categories of factors' relative importance: higher (calcium, volume, and citrate), intermediate (oxalate, potassium, and magnesium), and lower (uric acid, phosphorus, and sodium). LIMITATIONS: Predominantly White participants, lack of information on stone composition. CONCLUSIONS: Urine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation. PLAIN-LANGUAGE SUMMARY: Kidney stones are common and likely to recur. Certain urinary factors play a role in the development of stones, but their independent roles, relative importance, and shapes of association with stone formation are not well-characterized. We analyzed 24-hour urine collections from individuals with and without kidney stones. Stones were less likely in those with higher urine volume, citrate, potassium, magnesium, and uric acid and were more likely in those with higher calcium, oxalate, phosphorus, and sodium. The acidity of the urine was not related to stones. The urinary parameters showed different degrees of relative importance, with calcium, volume, and citrate being greatest. All parameters exhibited a linear or close-to-linear shape of association with stone formation.

Erythrocyte membrane fluidity: A novel biomarker of residual cardiovascular risk in type 2 diabetes.

AIMS: Improving the composition of circulating fatty acids (FA) leads to a reduction in cardiovascular diseases (CVD) in high-risk individuals. The membrane fluidity of red blood cells (RBC), which reflects circulating FA status, may be a valid biomarker of cardiovascular (CV) risk in type 2 diabetes (T2D). METHODS: Red blood cell membrane fluidity, quantified as general polarization (GP), was assessed in 234 subjects with T2D, 86 with prior major CVD. Based on GP distribution, a cut-off of .445 was used to divide the study cohort into two groups: the first with higher GP, called GEL, and the second, defined as lower GP (LGP). Lipidomic analysis was performed to evaluate FA composition of RBC membranes. RESULTS: Although with comparable CV risk factors, the LGP group had a greater percentage of patients with major CVD than the GEL group (40% vs 24%, respectively, p < .05). Moreover, in a logistic regression analysis, a lower GP value was independently associated with the presence of macrovascular complications. Lipidomic analysis showed a clear shift of LGP membranes towards a pro-inflammatory condition due to higher content of arachidonic acid and increased omega 6/omega 3 index. CONCLUSIONS: Increased membrane fluidity is associated with a higher CV risk in subjects with T2D. If confirmed in prospective studies, membrane fluidity could be a new biomarker for residual CV risk assessment in T2D.

Long-Term Bone Mineral Density Changes in Kidney Transplant Recipients Treated with Denosumab: A Retrospective Study with Nonequivalent Control Group.

Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60 mg/6 months for 4 years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4 years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.

Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. METHODS: We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. RESULTS: The study included 49 558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women). CONCLUSIONS: Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

Time trends in preemptive kidney transplantation in Europe: an era registry study.

BACKGROUND: Preemptive kidney transplantation has better outcomes when compared to transplantation after dialysis. We aimed to examine trends in preemptive kidney transplantation between 2000 and 2019 in Europe and to provide an overview of associated policies, barriers and initiatives. METHODS: Adult patients from 12 European countries who received a preemptive kidney transplant were included. The representatives of the registries providing these data were questioned on the policies, barriers and initiatives around preemptive kidney transplantation. RESULTS: Between 2000 and 2019, 20 251 adults underwent preemptive kidney transplantation (11 169 from living donors, 8937 from deceased donors). The proportion of first kidney transplantations that were preemptive more than doubled from 7% in 2000 to 18% in 2019, reflecting a similar relative increase for living donor kidney recipients (from 21% to 43%) and deceased donor kidney recipients (from 4% to 11%). Large international differences were found. The increase in preemptive kidney transplantation was observed across all age, sex and primary renal disease groups. Countries had similar criteria for preemptive waitlisting. Barriers mentioned included donor shortage, late referral to the transplant center and long donor or recipient work-up. Suggested initiatives included raising awareness on the possibility of preemptive kidney transplantation, earlier start and shorter work-up time for recipient and living donor. CONCLUSIONS: Over the last two decades the proportion of patients receiving a first kidney transplant preemptively has more than doubled, reflecting a similar relative increase for living and deceased donor kidney recipients.

Epidemiological and biological associations between cardiovascular disease and kidney stone formation: A systematic review and meta-analysis.

AIMS: Previous studies find kidney stone formers (KSF) are at greater risk of developing cardiovascular disease (CVD). The underlying mechanisms are poorly understood, and many clinicians are unaware of this connection. We will: DATA SYNTHESIS: Our systematic review is registered with PROSPERO (ID CRD42021251477). We searched epidemiological and biological data. The epidemiological search generated 669 papers, narrowed down to 15. There were 4,259,869 participants (230,720 KSFs). KSF was associated with 25% higher risk of coronary artery disease (CAD) (95% confidence interval (CI): 15, 35%), 17% higher risk of stroke/transient ischemic attacks (TIA) (CI:10, 25%) and 39% higher risk of arterial disease (AD) (CI: 17 65%). Significant heterogeneity was found. Female-identifying KSFs had a higher risk of stroke (ratio = 1.10) and CAD (1.20). The biological search generated 125 papers, narrowed down to 14. Potential underlying mechanisms were extracted and discussed, including intimal/medial vascular calcification, oxidative stress via osteopontin (OPN), cholesterol-induced pathology, and endothelial dysfunction. CONCLUSIONS: There is a significant association between KSF and CVD, supporting the consideration of KSF as a systemic, calcium-mediated disease. Clinicians will benefit from being aware of this connection.

Digital Holography and 3D Imaging: introduction to the joint feature issue in Applied Optics and Journal of the Optical Society of America A.

The Optica Topical Meeting on Digital Holography and 3D Imaging (DH) was held 14-17 August 2023 in Boston, Massachusetts. The meeting was organized co-jointly with the Optica Imaging Congress. Feature issues based on the DH meeting series have been released by Applied Optics (AO) since 2007. Since 2017, AO and the Journal of the Optical Society of America A (JOSA A) have presented a feature issue in each journal. This feature issues includes 17 papers in AO and 9 in JOSA A. Together they cover a large range of topics, reflecting the rapidly expanding techniques and applications of digital holography and 3D imaging. The upcoming DH Conference (DH 2024) will be held from 3 to 6 June in Paestum, Italy.

Digital Holography and 3D Imaging 2023: introduction to the joint feature issue in Applied Optics and Journal of the Optical Society of America A.

The Optica Topical Meeting on Digital Holography and 3D Imaging (DH) was held 14-17 August 2023 in Boston, Massachusetts. The meeting was organized co-jointly with the Optica Imaging Congress. Feature issues based on the DH meeting series have been released by Applied Optics (AO) since 2007. Since 2017, AO and the Journal of the Optical Society of America A (JOSA A) have presented a feature issue in each journal. This feature issues includes 17 papers in AO and 9 in JOSA A. Together they cover a large range of topics, reflecting the rapidly expanding techniques and applications of digital holography and 3D imaging. The upcoming DH Conference (DH 2024) will be held from 3 to 6 June in Paestum, Italy.

Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes.

AIMS/HYPOTHESIS: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. METHODS: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. RESULTS: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. CONCLUSIONS/INTERPRETATION: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity.

On monocytes and lymphocytes biolens clustering by in flow holographic microscopy.

Live cells act as biological lenses and can be employed as real-world optical components in bio-hybrid systems. Imaging at nanoscale, optical tweezers, lithography and also photonic waveguiding are some of the already proven functionalities, boosted by the advantage that cells are fully biocompatible for intra-body applications. So far, various cell types have been studied for this purpose, such as red blood cells, bacterial cells, stem cells and yeast cells. White Blood Cells (WBCs) play a very important role in the regulation of the human body activities and are usually monitored for assessing its health. WBCs can be considered bio-lenses but, to the best of our knowledge, characterization of their optical properties have not been investigated yet. Here, we report for the first time an accurate study of two model classes of WBCs (i.e., monocytes and lymphocytes) by means of a digital holographic microscope coupled with a microfluidic system, assuming WBCs bio-lens characteristics. Thus, quantitative phase maps for many WBCs have been retrieved in flow-cytometry (FC) by achieving a significant statistical analysis to prove the enhancement in differentiation among sphere-like bio-lenses according to their sizes (i.e., diameter d) exploiting intensity parameters of the modulated light in proximity of the cell optical axis. We show that the measure of the low intensity area (S: I z < I th z ) in a fixed plane, is a feasible parameter for cell clustering, while achieving robustness against experimental misalignments and allowing to adjust the measurement sensitivity in post-processing. 2D scatterplots of the identified parameters (d-S) show better differentiation respect to the 1D case. The results show that the optical focusing properties of WBCs allow the clustering of the two populations by means of a mere morphological analysis, thus leading to the new concept of cell-optical-fingerprint avoiding fluorescent dyes. This perspective can open new routes in biomedical sciences, such as the chance to find optical-biomarkers at single cell level for label-free diagnosis.

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.

OBJECTIVE: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Oscillation Dynamics of Dielectric Polymer Droplets during Electrohydrodynamic Jetting in a Wide Range of Viscosities.

The electrohydrodynamic (EHD) jetting of fluids is used for several applications such as inkjet printing, atomization of analyte in mass spectrometry, liquid metal alloy ion sources, and electrospinning of polymer fibers. Historically, the bulk of research has focused on nonviscous, highly conductive fluids which are most suitable for EHD spray and printing, while there is relatively little experimental work on EHD jetting of highly viscous liquid dielectrics. We studied the dynamics of oscillation and pulsating jetting from a suspended drop of polydimethylsiloxane (PDMS) polymers in an electric field, with particular attention to the viscosity dependence of the oscillation period and meniscus elongation and contraction time over a wide viscosity range (102-105 cSt). The reported results could help the appropriate design of EHD processes and may open new possibilities for the rheological characterization of liquid polymers using small volumes at the scale of nanoliters.

Factors associated with sex differences in the risk of kidney stones.

BACKGROUND: Men are at higher risk of developing stones compared with women; however, recent data suggest a changing epidemiology, with women being relatively more affected than before. METHODS: To estimate the proportion of excess risk among men, we analysed data from large cohorts (Health Professionals Follow-up Study and Nurses' Health Study I and II). Kidney stone incidence rates were computed and hazard ratios (HRs) and 95% confidence intervals (CIs) generated with age-adjusted Cox proportional regression models. Mediation analysis estimated the excess risk for men explained by risk factors, including waist circumference, high blood pressure, diabetes, use of thiazides and dietary intake. The 24-h urine composition was also examined. RESULTS: The analysis included 268 553 participants, contributing 5 872 249 person-years of follow-up. A total of 10 302 incident stones were confirmed and the overall incidence rate was 271 and 159 per 100 000 person-years for men and women, respectively. The age-adjusted HR was 2.32 (95% CI 2.20, 2.45) and the risk of stones was consistently higher across categories of age (HRs ranging from 2.02 to 2.76) for men compared with women. The risk remained higher among men, but tended to decrease over time (48.1%), while it increased among women. Urine supersaturations for calcium oxalate and uric acid were higher among men, primarily because of higher oxalate (26.3%), uric acid (16.3%), phosphate (23.5%) and lower pH. CONCLUSIONS: The risk of kidney stones is higher among men and this difference is only partly explained by lifestyle risk factors; differences in urine chemistries explain a substantial fraction of the excess risk.

Tolvaptan treatment is associated with altered mineral metabolism parameters and increased bone mineral density in ADPKD patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a unique bone and mineral phenotype. The impact of tolvaptan treatment on mineral metabolism and bone mineral density (BMD) is unknown. METHODS: We conducted an analysis in the Bern ADPKD Registry, a prospective observational cohort study. Mineral metabolism parameters were measured at baseline and every 12 months thereafter. BMD was determined by dual-energy X-ray absorptiometry at baseline and after 3 years. Multivariable mixed-effects regression models were applied to assess changes in mineral metabolism parameters and BMD associated with tolvaptan treatment. RESULTS: A total of 189 participants (122 without and 67 with subsequent tolvaptan treatment) were included in the analysis. During follow-up, tolvaptan treatment was associated with increased BMD at the femoral neck {ß = 0.092 [95% confidence interval (CI) 0.001-0.183], P = .047}. In addition, tolvaptan treatment was associated with higher plasma magnesium [ß = 0.019 (95% CI 0.001-0.037), P = .037], bicarbonate [ß = 0.972 (95% CI 0.242-1.702), P = .009] and urine pH [ß = 0.214 (95% CI 0.056-0.372), P = .008] and lower parathyroid hormone [ß = -0.191 (95% CI -0.328 to -0.053), P = .006], 1,25(OH)D3 [ß = -0.126 (95% CI -0.235 to -0.164), P = .024] and fractional urinary magnesium excretion [ß = -0.473 (95% CI -0.622 to -0.324), P < .001]. CONCLUSIONS: Chronic tolvaptan treatment is associated with increased femoral BMD and significant changes in both mineral metabolism and acid-base parameters in ADPKD patients.

Increasing numbers and improved overall survival of patients on kidney replacement therapy over the last decade in Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017. METHODS: Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis. RESULTS: The standardized incidence of KRT was stable [annual percentage change (APC): -1.48 (-3.15; 0.21)] from 2008 (146.0 pmp) to 2011 (141.6 pmp), followed by a slight increase [APC: 1.01 (0.43; 1.60)] to 148.0 pmp in 2017, although trends in incidence varied across countries. This increase was primarily due to a rise in the incidence of KRT in men older than 65 years. Moreover, as a cause of kidney failure, diabetes mellitus is increasing. The standardized prevalence increased from 2008 (990.0 pmp) to 2017 (1166.8 pmp) [APC: 1.82 (1.75; 1.89)]. Patient survival on KRT improved in the time period 2011-13 compared with 2008-[adjusted HR: 0.94 (0.93; 0.95)]. CONCLUSION: This study showed an overall increase in the incidence and prevalence of KRT for ESKD as well as an increase in the KRT patient survival over the last decade in Europe.

Inflammation and kidney stones: cause and effect?

PURPOSE OF REVIEW: This short review is intended to highlight the potential role of inflammation as a key pathological driver, rather than a mere consequence, of nephrolithiasis. Although there is clearly a strong likelihood that the relationship is bidirectional, and that kidney stone-triggered inflammation can establish a vicious cycle of tissue injury and stone formation. RECENT FINDINGS: These consist of data from both recent preclinical and clinical studies demonstrating the importance of inflammation in models of stone disease and in kidney tissue from patients with nephrolithiasis, and as a potential driver of disease recurrence and a suitable treatment target. In particular, the role of immune cells and their relationship to the NLRP3 inflammasome is becoming clearer, as well as the potential contribution to tissue injury and stone formation of the pro-inflammatory cytokines interleukin-1ß and interleukin-18. SUMMARY: This concept is not new and raises the possibility that targeting inflammation directly may prove to be a novel and suitable means of treatment for at least some types of kidney stone, and in certain clinical settings, both acutely and as prevention, especially in those patients experiencing recurrent stone episodes and/or who have a well defined metabolic cause such as uric acid or calcium oxalate stones.

Digital Holography and 3D Imaging: introduction to the joint feature issue in Applied Optics and Journal of the Optical Society of America A.

This feature issue is a continuation of a tradition to follow the conclusion of the Optica Topical Meeting on Digital Holography and 3D Imaging (DH+3D). It addresses current research topics in digital holography and 3D imaging that are also in line with the topics of Applied Optics and Journal of the Optical Society of America A.