Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Erosional characteristic of cohesive fine grained sediments from lake Dabie

Jezioro Dąbie położone jest w obrębie ujściowego odcinka Dolnej Odry. Akwen ten ma ważne znaczenie dla żeglugi, gdyż przez jego czaszę przechodzi główny tor wodny pomiędzy portem Schwedt a Zatoką Pomorską. Zbiornik ten jest intensywnie zanoszony rumowiskiem polifrakcyjnym ze znaczną zawartością cząstek pylastych i ilastych oraz materii organicznej. Wysoka zawartość cząstek pyłów i iłów nadaje rumowisku cechy materiału częściowo spoistego względnie spoistego. Osadzające się rumowisko powoduje utrudnienia w eksploatacji zbiornika oraz istotne zmniejszenie jego pojemności. W ciągu 34 lat jego pojemność zmniejszyła się o 12,1 mln m3, a średni roczny przyrost objętości osadów oceniany jest na 356 000 m3. Autorzy przeprowadzili wstępną ocenę parametrów erozji osadów z jeziora Dąbie na podstawie jego cech fizycznych i reologicznych.The Lake Dąbie is located in Lower Odra estuary. That water region plays very important role for navigation, because through the Lake Dąbie the main seaway between Schwedt and Pomeranian Gulf is running. The Lake in strongly silted with polyfractional sediments with high clay and silt particles content and also with high organic matter content. That high clay and silt particles content causes that muds from the Lake have semi-cohesive or cohesive properties. Settled muds cause difficulties in seaway exploitation and significant decrease of its capacity. During 34 years the Lake Dąbie capacity decreased about 12,1 mln m3. The estimated mean year increase of sediments volume is equal about 356 000 m3. The authors performed the preliminary estimation of erosion parameters for sediments from Lake Dąbie on the base of theirs physical and rheological properties

Estimation of the degradation of the middle Odra river bed and programme of the restoration works

Degradacja koryta Odry jest obserwowana głównie poniżej ostatniego stopnia na skanalizowanym odcinku tej rzeki. Średni poziom dna obniża się o około 4–8 cm rocznie, powodując odpowiednie obniżenie tak zwierciadła wody w rzece, jak i poziomu wody gruntowej w przyległej dolinie. Ta degradacja powoduje poważne problemy tak dla żeglugi, jak i dla rolnictwa i środowiska przyrodniczego. Budowa kolejnego ostatniego stopnia we Wrocławiu (1897), Rędzina (1922) i Brzeg Dolny (1958) miała tylko okresowy pozytywny skutek. Poniżej każdego z tych stopni zasięg erozji dna wyniósł 50–60 km. W 1994 r. Parzonka zaproponował koncepcję „karmienia” Odry tuż poniżej nowego stopnia Malczyce (km 300,0), który będzie działał prawdopodobnie od 2012 r. Władze administracyjne zdecydowały w 2008 r., że stopień może wejść do eksploatacji pod warunkiem wykonania ważnych działań naprawczych, uwzględniających potrzeby środowiska przyrodniczego, żeglugi, rolnictwa i mieszkańców doliny Odry. Program tych działań naprawczych przewiduje dwa etapy: – odbudowę (podniesienie) poziomu dna Odry w poszczególnych przekrojach na odcinku objętym erozją liniową wywołaną oddziaływaniem stopnia Brzeg Dolny, do wysokości odpowiadającej co najmniej połowie różnicy między rzędną dna Odry z początku okresu eksploatacji stopnia Brzeg Dolny i rzędną aktualną, będącą skutkiem 50-letniego okresu erozji dna rzeki (Etap I), – trwałe utrzymanie tak uzyskanej rzędnej dna Odry w poszczególnych przekrojach poniżej stopnia Malczyce, poprzez tzw. „karmienie” rzeki (Etap II).The degradation of the Odra river bed is observed mainly below each last barrage of the channelized river sector Koźle – Wrocław. The mean river bed level is decreasing of some 4–8 cm yearly, causing the corresponding drop so of water surface in the river as of the ground water level in the valley. This degradation causes great problems so for navigation, as for agriculture and environment. The construction of successives last barrages Wrocław (1897), Rędzin (1922) and Brzeg Dolny (1958) had only a temporary effect. Below each of these barrages the river bed erosion continued, concerning a river reach of some 50-60 km. In 1994 Parzonka has proposed the conception of the “feeding” of the Odra just below the new barrage Malczyce (km 300,0), entering in action probably in 2012. The administration has decided in 2008, that this barrage can enter in work only after the accomplishment of important restoration works, taking in account the needs of environment, of navigation and agriculture and of the human population. The programme of restoration works provides two steps: – Step I: the elevation of the Odra bed level on the sector Malczyce–Ścinawa (km 300 – km 335) minimum by the half on the eroded height. – Step II: the feeding of the Odra just below the barrage Malczyce on the length of some 4–5 km, after each flood causing local river bed erosion

The preliminary analysis of silting conditions of the storage reservoir Otmuchow localised in upland region

Autorzy przeprowadzili wstępną analizę warunków zamulania zbiornika Otmuchów. Specyfiką tego zbiornika jest jego położenie geograficzne w zlewni oraz pełnione funkcje. Kaskada zbiorników Nysa-Otmuchów położona jest w środkowym odcinku doliny rzeki Nysy Kłodzkiej w południowo-zachodnim, podgórskim rejonie województwa opolskiego. Przeanalizowano ogólną charakterystykę ilości rumowiska dostarczanego do zbiornika i cechy fizyczne osadów z różnych stref tego zbiornika. Przeanalizowano również warunki zamulania zbiornika i zmiany jego pojemności w czasie.The authors performed the preliminary analysis of the silting conditions of the reservoir Otmuchów. The specific of this reservoir is it’s geographic localization in catchment and hydrotechnic functions. The reservoir Otmuchów-Nysa cascade is localized in the middle sector of the Nysa Kłodzka river in south-west, upland region of the Opole District. The main characteristic of the amount of sediments settled in the reservoir, the physical sediment properties for different reservoir zones are presented. The authors have also analyzed the silting conditions in this reservoir, and the changes of the reservoir capacit

Preliminary estimation of dynamic features of muds from lake Dabie

Namuły zalegające w jeziorze Dąbie mają cechy plastyczno-lepkie. Zawierają one dużą ilość materii organicznej oraz są zanieczyszczone przez ścieki komunalne i przemysłowe. Obecność tych substancji zmienia w istotny sposób cechy dynamiczne rumowiska drobnoziarnistego oraz warunki sedymentacji i resuspensji cząstek stałych. Przez jezioro Dąbie przechodzi ważny tor wodny o długości 14,5 km, szerokości 150 m i o głębokości gwarantowanej 3,2 m. Jest on okresowo pogłębiany za pomocą refulerów. Autorzy przeprowadzili wstępną ocenę własności fizycznych i reologicznych próbek pobranych z dna jeziora Dąbie w rejonie toru wodnego. Miąższość warstwy namułów wynosi od 3 do 5 m. Mają one konsystencję płynną, a ich wilgotność wynosi od 300–500%. Nominalna średnica ziarn d50 waha się od 12–15 μm na powierzchni do 44–95 μm przy dnie, a zawartość części organicznych zmienia się od 10–30%. Badania cech reologicznych namułów organicznych wykazały, że zachowują się one jak ciecze nienewtonowskie. Ich cechy można opisać za pomocą dwuparametrowego modelu Binghama.The muds settled in the Lake Dąbie have visco-plastic properties. They contain many organic matter and are polluted by sewage from communities and industry. The presence of this substances changes clearly the dynamic properties of the fine grained material, as well the conditions of sedimentation and resuspension of solid particles. An important navigation way is located in the lake Dąbie with following parameters: length 14.5 km, width 150 m and guaranteed depth 3.2 m. This way is periodically deepened by dredgers. The authors have performed a preliminary estimation of the physical and rheological features of mud samples from the Lake Dąbie in the region of the navigation way. The thickness of the mud layer is equal 3–5 m. The fine grined sediments have a liquid consistency, and their water content is equal to some 300- 500%. The nominal granulometric size d50 changes between 12–15 μm for superficial muds and between 44-95 μm for bottom muds, and the organic matter content varies between 10 – 30%. The studies on rheological features of organic sediments proved that they behave as non-newtonian liquids. Their behaviour can be described by the twoparameter rheological model of Bingham

Measurement of local concentrations of fine-grained particles by optical sensors.

C

Reological characteristics of sedimentation process and erosion of river sediments

Autorzy przeprowadzili ocenę dynamiki zmian koryt rzecznych spowodowanych przez procesy sedymentacyjne i erozyjne. Zbadano cechy fizyczne i reologiczne wybranych osadów spoistych i częściowo spoistych. Próbki osadów pochodziły z nizinnych odcinków rzeki Odra (Polska) i rzeki Warnow (Niemcy). Charakterystyki reologiczne zbadano za pomocą wiskozymetrów rotacyjnych. Badane namuły miały cechy typowe dla cieczy nienewtonowskich. Charakterystyki erozyjne wyznaczono na podstawie metodyki Migniota. Sprawdzono je w skali naturalnej po przejściu fali powodziowej przez stopień Brzeg Dolny, która spowodowała częściowe wymycie osadów z górnego stanowiska jazu.The authors performed an estimation of the dynamic of the river bed changes caused by sedimentation and erosion processes. The physical and rheological parameters for chosen cohesive and semi-cohesive sediments were investigated. Mud samples were taken from 3 different localisation on Middle Odra (Poland) and from 2 localisations on Warnow river (Germany). Rheological characteristics were studied with use of the rotative viscometer. Erosion characteristics of the mud’s were studied accordingly to methodology of Migniot [1968]. Results for Middle Odra were verified in the natural scale during the passage of the catastrophic flood through barrage Brzeg Dolny in 1997. This flood caused partly erosion of mud’s from the upstream part of this barrage

Predicting Kidney Failure, Cardiovascular Disease and Death in Advanced CKD Patients

Introduction: Predicting the timing and occurrence of kidney replacement therapy (KRT), cardiovascular events, and death among patients with advanced chronic kidney disease (CKD) is clinically useful and relevant. We aimed to externally validate a recently developed CKD G4+ risk calculator for these outcomes and to assess its potential clinical impact in guiding vascular access placement. Methods: We included 1517 patients from the European Quality (EQUAL) study, a European multicentre prospective cohort study of nephrology-referred advanced CKD patients aged ≥65 years. Model performance was assessed based on discrimination and calibration. Potential clinical utility for timing of referral for vascular access placement was studied with diagnostic measures and decision curve analysis (DCA). Results: The model showed a good discrimination for KRT and “death after KRT,” with 2-year concordance (C) statistics of 0.74 and 0.76, respectively. Discrimination for cardiovascular events (2-year C-statistic: 0.70) and overall death (2-year C-statistic: 0.61) was poorer. Calibration was fairly accurate. Decision curves illustrated that using the model to guide vascular access referral would generally lead to less unused arteriovenous fistulas (AVFs) than following estimated glomerular filtration rate (eGFR) thresholds. Conclusion: This study shows moderate to good predictive performance of the model in an older cohort of nephrology-referred patients with advanced CKD. Using the model to guide referral for vascular access placement has potential in combating unnecessary vascular surgeries

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: Results of the EQUAL study

Background: Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods: CKD patients (≥65 years; estimated glomerular filtration rate ≤20 mL/min/1.73 m2) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off ≤70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results: Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m2/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions: There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men