3b Chronic Kidney Disease Research Articles

Anti-Müllerian hormone concentrations in women with chronic kidney disease

[This corrects the article DOI: 10.1093/ckj/sfz164.][This corrects the article DOI: 10.1093/ckj/sfz164.].

Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study.

ObjectiveCompare rates of lactic acidosis (LA) among metformin‐exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD).Research Design and MethodsRetrospective, nested case‐control study using data from national VA Corporate Data Warehouse. All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003‐13 were included. The outcome was LA hospitalization or serum lactate >5 mEq/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications.ResultsOverall, 320 882 patients were included, contributing a total of 1 331 784 person‐years of follow‐up. LA occurred in 2 665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93‐2.08) per 1000 person‐years. Metformin exposure in the prior 3 months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69‐2.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71‐1.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19‐4.35 in CKD 3a, HR 3.34, 95% CI 1.95‐5.72 in CKD 3b, HR 7.87, 95% CI 3.51‐17.61 in CKD stage 4&5.ConclusionMetformin was not associated with an elevated risk of LA in persons with stage 1‐2 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.

MO021GALECTIN 3 LEVEL IS REDUCED BY TREATMENT WITH SODIUM BICARBONATE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims Circulating cardiac biomarkers implicated in the pathogenesis of heart disease are a non-invasive platform to assess the cardiovascular disease (CVD) burden in individuals with chronic kidney disease (CKD). Galectin 3 is a 26 kDa β-galactoside-binding lectin that has a graded and positive association with CKD stages. In animal models, inhibition of galectin-3 prevents myocardial fibrosis. These pre-clinical findings have not been replicated in randomized controlled studies in humans. Metabolic acidosis of CKD has been shown to be associated with adverse CVD outcomes. We sought to examine whether correction of metabolic acidosis of CKD leads to lower circulating levels of Galectin 3, as an expression of myocardial fibrosis. Method A total of 95 participants with stages 3 and 4 CKD and a serum bicarbonate level between 21-25 mEq/L, were randomized to receive sodium bicarbonate at a dose of 0.4 mEq/kg/day once a day or placebo for two years at two clinical sites in US. Galectin 3, was measured at study baseline and after one year. Results Fifty participants were randomized to sodium bicarbonate and 45 to placebo. Mean age (SD) was 61.4 (10.2) years, 48% were women, 57% were non-Hispanic black, and 40% were non-Hispanic white, 61% had diabetes mellitus and 90% had hypertension at baseline. Mean baseline serum bicarbonate level was 23.5 (SD 1.7), mean (SD) baseline eGFR was 38.8 (11.2) ml/min/1.7m2 and mean (SD) baseline systolic BP was 130 (17) mmHg. There were no differences in baseline characteristics between treatment groups. Compared to the placebo group, participants randomized to sodium bicarbonate had statistically significant change in the levels of Galectin 3 after one year of treatment (-7.12% vs 7.76% and -1.25 vs 1.54 ng/ml, p=0.03 in the sodium bicarbonate vs. placebo group, respectively, Figure). In subgroup analyses by CKD stages, participants with stage 3A randomized to sodium bicarbonate observed the highest decrement in Galectin 3 levels (-19.2% vs 14.7%, p=0.01; -3.3% vs -4.8%, p=0.49; and -7.4% vs 29.1%, p=0.09; for CKD 3B, 3B and 4, respectively). Conclusion The level of Galectin 3 was reduced in patients with CKD 3 and 4 treated with sodium bicarbonate. This provides a framework for future therapeutic interventions aimed at reduction of myocardial fibrosis in patients with CKD and metabolic acidosis.

P0695ANALYSIS OF HOSPITALIZATION EVENTS IN NON-DIALYSIS CKD PATIENTS

Abstract Background and Aims Data are limited about rates and causes of hospitalization in patients with Chronic Kidney Disease (CKD) during maintenance period. In the present study, we investigate the amount, characteristics and trends of hospital admissions in a large cohort of pre-dialysis CKD patients followed within the Emilia-Romagna Region (Italy) PIRP project. Method Patients who were enrolled in the PIRP project in the period 1.4.2004-31.12.2018 constitute the study population. The PIRP database contains clinical and laboratory data collected at each follow-up visit. Hospitalization data regarding admissions occurred during patients’ follow-up in PIRP were obtained from the regional hospital discharges database through unique individual linkage. Day-hospital admissions and hospitalizations aimed at arteriovenous fistula creation and peritoneal catheter placement were excluded. Results In almost 15 years of observation, 27,886 patients were enrolled in PIRP, mostly males (65,3%) with baseline median age of 75 years and baseline median eGFR=32.3 mL/min/1.73m2. Among them, 19,288 (69.2%) generated 72,432 hospitalizations during their follow-up in the project. The number of hospitalizations per person/year was 1.06 overall, increasing from 0.38 for stage CKD 1 to 1.93 for stage CKD 5 (Fig.1). The median length of stay was 9 days. Overall, cardio-vascular diseases were the main cause of hospitalization (30.0% of admissions), with renal diseases, tumors and respiratory diseases each accounting for over 10% of admissions, although the distribution of causes of hospitalization varies according to CKD stage (Fig.2). About one fifth of patients had one or more hospitalizations for acute kidney injury. The trend analysis revealed a steadily decreasing hospitalization rate for patients that were on CKD stage 4 and 5 at baseline, a constant hospitalization trend over time for patients who began their follow-up in stages 1 to 3a, while hospitalization rate of patients in CKD 3b stage declined after 9 years (Fig 3). Conclusion The study broadens our knowledge on the hospitalizations “consumption” by the population with CKD in the non-dialysis phase. It confirms that patients with CKD represent a vulnerable population, needing about 1 hospitalization / year / patient. The trend towards a reduction in hospitalizations during the follow-up period could be traced back to the specific care model, which encourages a more frequent management of patients in the Nephrology clinics.

Plasma Oxalate as a Predictor of Kidney Function Decline in a Primary Hyperoxaluria Cohort.

This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8–115), 3a (HR 13.7, 95% CI 3.0–62), and 3b stages (HR 5.2, 95% CI 1.1–25), p < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1–Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.

Едаравон у профілактиці контраст-індукованого гострого ураження нирок

Мета роботи – оцінити ефективність едаравону в запобіганні розвитку контраст-індукованого гострого ураження нирок (КІГУН).Матеріали і методи. Проведено багатоцентрове відкрите проспективне рандомізоване контрольоване дослідження для оцінювання ефективності едаравону в профілактиці КІГУН у пацієнтів із хронічною хворобою нирок (ХХН) 3b–4 стадії. Було сформовано дві групи хворих віком 46–68 років (у середньому (55±3) роки) – основну і контрольну. Основну групу становили 16 пацієнтів з ХХН 3b або 4 стадії (розрахункова швидкість клубочкової фільтрації за формулою СКD-EPI (32±4) мл/хв), які отримували едаравон у дозі 30 мг шляхом внутрішньовенного інфузійного введення. До контрольної групи увійшло 20 пацієнтів із ХХН 3b або 4 стадії (розрахункова швидкість клубочкової фільтрації (33±3) мл/хв), у яких едаравон при проведенні коронароангіографії не застосовували. Пацієнти обох груп перед коронароангіографією отримували внутрішньовенну гідратацію 0,9 % натрію. Первинна кінцева точка: розвиток КІГУН протягом 48 год після введення контрастного засобу та необхідність проведення ниркової замісної терапії. Вторинна кінцева точка: рівень калію в сироватці крові понад 5,5 ммоль/л. Результати та обговорення. Розвиток КIГУН документовано у 4 пацієнтів основної групи та 12 пацієнтів контрольної групи (р≤0,05; RR 0,417; RRR 0,583; RD 0,350; NNT 2,857). Виявлено статистично значущу різницю між групами для обох кінцевих точок, що свідчить про перспективні можливості застосування едаравону для профілактики КІГУН у пацієнтів з ХХН 3b–4 стадії. Аналіз індивідуальних даних показує, що едаравон був ефективнішим у хворих із ХХН 3b стадії (три випадки КІГУН з 10) порівняно з ХХН 4 стадії (один із 2).Висновки. Едаравон може бути перспективним рішенням для профілактики КІГУН у пацієнтів із ХХН 3b–4 стадії, яким терміново виконують коронароангіографію.&#x0D;

SAT-185 Primary Adrenal Lymphoma Presenting with Symptomatic Hypercalcaemia

Introduction: Primary adrenal lymphoma (PAL) is a rare cause of adrenal enlargement with approximately 200 cases reported in the literature to date. It tends to affect elderly men and has a high incidence of bilateral involvement at diagnosis. We report the case of a 66 year old man, whose PAL manifested with symptomatic hypercalcaemia.A 66 year old male, originally from the Philippines, was referred to the emergency department with nausea, vomiting, weight loss and right flank pain. His past medical history was significant for hypertension, gout and stage 3b chronic kidney disease. His medications were amlodipine, losartan and febuxostat. His family history was significant for hypertension. On examination he was hypertensive (blood pressure, 160/100 mmHg) and hyperpigmented. His laboratory investigations revealed; corrected calcium of 3.79 mmol/l, undetectable PTH, vitamin D 49 nmol/l. He was treated with intravenous (IV) 0.9% saline and IV zoledronic acid and his calcium levels improved.To investigate causes of non-PTH mediated hypercalcaemia, computerised tomography of the thorax, abdomen and pelvis (CT TAP) as well as a positron emission tomography (PET) scan were performed. These demonstrated bilateral, large, metabolically active adrenal masses with no evidence of extra-adrenal disease. Differential diagnosis at this point included bilateral adrenal hyperplasia, metastases, lymphoma or adrenal TB. There were no radiological features of adrenocortical carcinoma (ACC) or phaeochromocytoma and subsequent biochemical investigations confirmed no evidence of cortisol, androgen or catecholamine excess. Adrenocorticotrophic hormone (ACTH) levels were elevated however, and a synacthen test revealed inadequate adrenal reserve (peak cortisol 214 nmol/l). The patient was commenced on maintenance steroids and with stress dose steroid cover, proceeded to adrenal biopsy. Histology confirmed diffuse large B cell non-Hodgkin’s lymphoma. Haematology became involved in his care and he commenced polychemotherapy in the form of R-CHOP, 1 week post confirmation of the diagnosis. His treatment is ongoing and he has tolerated it well with minimal side effects, except a flare of gout.Learning points: PAL should be considered in the differential diagnosis in patients with bilateral adrenal masses. Image guided adrenal biopsy is the gold standard for diagnosis, though caution must be exercised and an ACC or phaeochromocytoma should be excluded prior to biopsy. The prognosis of PAL is poor and therefore early diagnosis and prompt initiation of treatment are required to improve outcomes.

TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome: The TROUPER trial

Chronic kidney disease (CKD) is associated with an increased risk of acute coronary syndrome (ACS) and cardiovascular death. CKD patients suffering from ACS are exposed to an increased risk of thrombotic recurrences and a higher bleeding rate than patients with normal renal function. However, CKD patients are excluded or underrepresented in clinical trials. Therefore, determining the optimal antiplatelet strategy in this population is of utmost importance. We designed the TicagRelor Or Clopidogrel in severe or terminal chronic kidney patients Undergoing PERcutaneous coronary intervention for acute coronary syndrome (TROUPER) trial: a prospective, controlled, multicenter, randomized trial to investigate the optimal P2Y12 antagonist in CKD patients with ACS. Patients with stage ≥3b CKD are eligible if the diagnosis of ACS is made and invasive strategy scheduled. Patients are randomized 1:1 between a control group with a 600-mg loading dose of clopidogrel followed by a 75-mg/d maintenance dose for 1 year and an experimental group with a 180-mg loading dose of ticagrelor followed by a 90-mg twice daily maintenance dose for the same duration. The primary end point is defined by the rate of major adverse cardiovascular events, including death, myocardial infarction, urgent revascularization, and stroke at 1 year. Safety will be evaluated by the bleeding rate (Bleeding Academic Research Consortium). To demonstrate the superiority of ticagrelor on major adverse cardiovascular events, we calculated that 508 patients are required. The aim of the TROUPER trial is to compare the efficacy of ticagrelor and clopidogrel in stage >3b CKD patients presenting with ACS and scheduled for an invasive strategy. RCT# NCT03357874.

Advanced Chronic Kidney Disease in Lupus Nephritis: Is Dialysis Inevitable?

Advanced chronic kidney disease (CKD) carries an increased risk for progression to endstage renal disease (ESRD). We aimed to determine the rate of progression and the factors that drive the decline of renal function in lupus nephritis (LN). Patients with advanced LN-related CKD were identified from our longterm longitudinal cohort. Advanced CKD was defined as stage 3b [estimated glomerular filtration rate (eGFR) = 30-44 ml/min/1.73 m2] and stage 4 (eGFR = 15-29 ml/min/1.73 m2). All individuals were followed until progression to ESRD or the last visit and were divided into "progressors" and "non- progressors." Demographic, clinical, immunological, and therapeutic variables were compared at baseline. Multivariable Cox regression analysis (both time-dependent and independent) was performed to identify predictors for progression. One hundred eighteen patients (74 CKD 3b and 44 CKD 4) were included. Forty-five patients progressed (29 to ESRD and 16 from CKD 3b to CKD 4) after 6 years on average. No significant decline in the renal function was observed in 73 patients ("non-progressors") after 10 years on average. Active serology (high anti-dsDNA titers and low complements C3/C4) at the time of CKD diagnosis and any increase of the daily prednisone dose after baseline were strongly associated with progression. Treatment with renin angiotensin system (RAS) blockers was associated with less risk for progression. Dialysis is not inevitable in LN-related advanced CKD because 62% of our patients did not progress over 10 years of followup on average. Certain predictors were identified to affect progression to ESRD.

Factors Affecting Trough Plasma Dabigatran Concentrations in Patients with Atrial Fibrillation and Chronic Kidney Disease.

Dabigatran is effective and widely used to prevent ischemic stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). Chronic kidney disease (CKD) also has implications for choice of any medications, as it alters pharmacokinetic parameters of drugs. To evaluate trough plasma dabigatran concentration (DTPC) and to analyse potential factors affecting these values in patients with AF and CKD. Patients with AF and stage 3 CKD were treated with dabigatran 110mg or 150mg have been included in the study and allocated into D110 or D150 group. DTPC was evaluated with high-performance liquid chromatography. A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. Factors affecting the DTPC were investigated. A total of 60 patients, aged 51-89years, were evaluated. Compared with patients given 150mg twice a day, those given 110mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5mL/min/1.73m2, p = 0.015). During the median follow up of 9.5months there were 11 bleedings in 9 patients. The C/D ratio was higher in patients aged > 75years (p = 0.024) and was also affected by CrCl (CrCl < 50mL/min, p = 0.02). Individuals with CKD 3B had higher concentration of dabigatran were compared with those with 3A stage (488.7 vs 332pg/ml: mg/day, p = 0.02). However, there was also negative correlation between C/D and CrCl (r = - 0.4, p = 0.0015). Co-prescribed medications did not influence DTPC. In addition, patients with bleeding events were additionally evaluated for C/D and no significant differences were found. Patients on dabigatran treatment showed highly variable trough plasma concentrations. C/D values were significantly higher in patients with CKD 3B stage and were influenced by elder age and comorbidities.

Pharmacokinetic/Pharmacodynamic Properties and Clinical Use of SGLT2 Inhibitors in Non-Asian and Asian Patients with Type 2 Diabetes and Chronic Kidney Disease.

Chronic kidney disease is a prevalent complication of type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) have a unique mode of action targeting the kidney. As their glucose-lowering potency declines with the reduction in estimated glomerular filtration rate, their clinical use in patients with T2DM with chronic kidney disease has been submitted to restriction. However, recent observations demonstrated that SGLT2is reduce the progression of renal impairment in patients with mild-to-moderate chronic kidney disease, with or without albuminuria. Furthermore, SGLT2is reduce the incidence of cardiovascular events in patients with T2DM at high cardiovascular risk, independently of baseline estimated glomerular filtration rate. Thus, recent guidelines recommend the prescription of SGLT2is in patients with T2DM with mild-to-moderate chronic kidney disease defined by an estimated glomerular filtration rate between ≥ 30 and < 90mL/min/1.73m2 and/or albuminuria. The present comprehensive review describes the pharmacokinetic/pharmacodynamic properties of SGLT2is commercialised worldwide and in Japan in patients with T2DM with mild, moderate and severe chronic kidney disease. Drug exposure increases when the estimated glomerular filtration rate declines but without a clear-cut relationship with the severity of chronic kidney disease and in a rather moderate amplitude that most often does not require a dose reduction in the presence of mild-to-moderate chronic kidney disease. The urinary glucose excretion steadily declines with the reduction in estimated glomerular filtration rate. This may explain a lower effect on glucose control, yet the positive effects on body weight and blood pressure still remain. The efficacy and safety of these SGLT2is are analysed among patients with stages 3a and 3b chronic kidney disease in placebo-controlled randomised clinical trials, with almost similar results in Asian and non-Asian individuals with T2DM. In summary, there is no reason not to prescribe SGLT2is in patients with T2DM with mild-to-moderate chronic kidney disease, especially if the aim is to benefit from cardiovascular and/or renal protection.

PUVs are more common in boys with hypospadias

The association between posterior urethral valves (PUVs) and hypospadias has previously been reported in case reports. After the identification of this twin pathology in a number of patients, a national retrospective review of all patients with this dual diagnosis was performed. All patients were identified in each centre from surgical databases of prospectively collated information on all surgical procedures. The medical notes were reviewed to ascertain demographics, the type of hypospadias, the mode of presentation of the valves and the outcome. Twenty-eight patients who had the dual diagnosis of hypospadias and PUV between 2002 and 2017 in the four tertiary paediatric centres where specialist paediatric urology is undertaken in our country were identified. Most patients (n=24) had the valves diagnosed after hypospadias surgery. The median age at the time of hypospadias surgery was 1.4 years (range 1-4 years). There were 12 proximal and 16 mid or distal hypospadias. The commonest presentation was with problems voiding after surgery in 14 cases with a further seven boys who had urinary tract infections. Four patients had a urethro-cutaneous fistula after repair that initiated further assessment. Two boys had distal dehiscence of their repair. There was one boy presented with new onset daytime incontinence. The median time of follow-up after valve incision surgery was 4.9 years (range 0.1-12.3 years). Twenty-two patients (three pre toilet training) had no ongoing urinary symptoms. Twenty-one boys have normal renal function with one patient in stage 3b chronic kidney disease. The incidence of this dual diagnosis in Scotland is estimated at one in 100 cases of hypospadias in the paediatric population. The incidence of PUV in boys with hypospadias is estimated at 1%patients.

Prevalence of Advanced Chronic Kidney Disease in Patients with Nonvalvular Atrial Fibrillation Hospitalized in Cardiology Departments

To estimate the prevalence of chronic kidney disease (CKD) 3b- 5 stages and the newly diagnosed sustained reduction in glomerular filtration rate (GFR) &lt;30 ml / min / 1.73 m2 in patients with atrial fibrillation (AF) in real clinical practice, as well as the features of their anticoagulant therapy. Retrospectively, data of all discharge epicrisis from cardiological departments of five Moscow hospitals from June 1, 2016 to May 31, 2017 were analyzed. Patients over 18 years old with AF were enrolled. At the next stage, patients with CKD 3 b- 5 st and newly diagnosed sustained reduction in GFR &lt;30ml / min / 1.73 m2 (at least 2 measurements during hospitalization) were selected. Data of 9725 patients were analyzed, AF was diagnosed in 2983 (31 %) cases, of which a decreased GFR &lt;45 ml / min / 1.73 m2 was detected in 27 % (n = 794) cases. Among them, 349 (44 %) were diagnosed with CKD 3b st, 123 (15 %) with CKD 4 st, 44 (6 %) with CKD 5 st, 278 (35 %) had a newly diagnosed sustained reduction in GFR. In 63 % of patients with AF and GFR &lt;45 ml / min / 1.73 m2, anemia was diagnosed, 39 % of them had moderate and severe one. 711 (89 %) patients were prescribed anticoagulants, 53 % were assigned direct oral anticoagulants (DOACs). Patients with CKD 3 b st. more often rivaroxaban 15 mg (29 %) was prescribed, with CKD 4 and CKD 5- warfarin (48 % and 25 %, respectively), in patients with newly diagnosed sustained reduction in GFR &lt;30 ml / min / 1.73m2- apixaban 10 mg / day (16.2 %). A quarter of patients with AF revealed a decreased GFR &lt;45 ml / min / 1.73 m2, half of them were recommended DOACs. 42 % of patients with GFR &lt;30 ml / min / 1.72 m2 were prescribed DOACs, 27 %- warfarin. Patients with CKD 5 st DOACs were not assigned; in half of cases, none of the anticoagulants was recommended. Most often, the dose of the prescribed anticoagulant was not counted according toGFR in patients with newly diagnosed sustained reduction in GFR &lt;30 ml / min / 1.73 m2.

The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease.

Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD). We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted. All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73; P < 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77; P < 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276; P = 0.629). In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.

Aortic Calcification and Arterial Stiffness Burden in a Chronic Kidney Disease Cohort with High Cardiovascular Risk: Baseline Characteristics of the Impact of Phosphate Reduction On Vascular End-Points in Chronic Kidney Disease Trial

Chronic kidney disease (CKD) is associated with excess cardiovascular morbidity and mortality compared to the general population. Hyperphosphataemia, associated with vascular calcification and arterial stiffness, may play a key role in the pathogenesis of cardiovascular disease (CVD) associated with CKD, although phosphate reduction strategies have not consistently proven to beneficially affect clinically relevant outcomes. The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) study is an international, multi-centre, randomized, placebo-controlled trial investigating the effect of the phosphate binder lanthanum carbonate on intermediate cardiovascular markers in patients with stage 3b–4 CKD. The primary end-point is change in carotid-femoral pulse wave velocity (PWV, SphygmoCor) after 96 weeks. Secondary outcomes include change in abdominal aortic calcification (AAC, computed tomography), serum phosphate and fibroblast growth factor 23 (FGF-23). In total, 278 participants were recruited and randomized, mean age 63 ± 13 years, 69% male, 45% diabetes, 32% CVD, 33% stage 3b CKD and 67% stage 4 CKD. Mean estimated glomerular filtration rate and serum phosphate were 26.6 ± 8.3 mL/min/1.72 m² and 1.25 ± 0.20 mmol/L, respectively. Median (interquartile range) intact and c-terminal FGF-23 levels were 133.0 (89.1–202) pg/mL and 221.1 (154.3–334.1) RU/mL, respectively. Mean PWV was 10.8 ± 3.6 m/s and 81% had AAC (median Agatston score 1,535 [63–5,744] Hounsfield units). PWV ≥10 m/s was associated with older age, diabetes, CVD, presence of AAC, higher systolic blood pressure (BP), larger waist circumference and higher alkaline phosphatase. AAC was associated with older age, male sex, diabetes, CVD, higher diastolic BP, dyslipidaemia (and use of statins), smoking, larger waist circumference and increased PWV. In conclusion, IMPROVE-CKD participants had high baseline risk for cardiovascular events, as suggested by high baseline PWV and AAC values.

Safety of dabigatran in patients with atrial fibrillation and chronic kidney disease: pharmacokinetic and pharmacogenetic aspects

Background: despite well-studied safety profile of dabigatran its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). This study was aimed to evaluate relationships between CES1 and ABCB1 polymorphism, dabigatran trough plasma concentration (DTPC) and bleeding events in patients with AF and CKD.Methods: patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110mg or 150 mg have been included in the study. Real-time PCR was used to evaluate single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs1045642, rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.Results: a total of 60 patients, aged 51–89 years (median age 76 years) were evaluated. Compared with patients given 150 mg twice a day, those given 110 mg twice a day were older (79 vs 67.5, p &lt; 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5 mL/min/1.73 m2, p = 0.015). We found C/D values to have high interindividual variability (mean 365.9 ± 290.4 μg/ml: mg/day, range 23.64-1452.73). Individuals with CKD 3B had higher concentration of dabigatran compared with those with 3A stage (488.7 ± 232.3 vs 332 ± 297.8 μg/ml : mg/day, p = 0.02). Consequently, there also was negative correlation of C/D with CrCl (r = -0.4, p = 0.0015). Evaluated SNPs (rs1045642, rs4148738, and rs2244613) did not affect C/D values (H test p &gt; 0.05).Conclusions: C/D values were significantly higher in patients with CKD 3B stage and those treated with dabigatran 110 mg. There was no influence of aforementioned SNPs on dabigatran trough concentrations and clinical outcomes.

The impact of chronic kidney disease in women undergoing transcatheter aortic valve replacement: Analysis from the Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) registry.

The prevalence of both chronic kidney disease (CKD) and aortic stenosis (AS) increase with age. Although baseline CKD is frequent in patients undergoing transcatheter aortic valve replacement (TAVR), its significance among women is largely unknown. Women's INternational Transcatheter Aortic Valve Implantation (WIN-TAVI) is a multinational, prospective registry of women undergoing TAVR for severe AS. We included patients with available baseline estimated glomerular filtration rate (eGFR) and completed 1-year follow-up. Patients were categorized into three groups based on their eGFR: No CKD (normal kidney function to stage 2 CKD: eGFR ≥60 ml/min/1.73 m2 ); (b) mild CKD (stage 3a CKD: eGFR = 45-59 ml/min/1.73 m2 ); and (c) moderate/severe CKD (stage ≥3b CKD: eGFR <45 ml/min/1.73 m2 ). All events were adjudicated according to the Valve Academic Research Consortium (VARC)-2 criteria. Out of 852 women undergoing TAVR, 326 (38.3%) had no CKD, 225 (26.4%) had mild CKD, and 301 (35.3%) had moderate/severe CKD. Women with higher stage of CKD at baseline were more likely to have a history of hypertension, diabetes, atrial fibrillation, anemia, chronic lung disease, hemodialysis, prior percutaneous coronary intervention, and pacemaker implantation. After multivariate adjustment, moderate/severe CKD was associated with a greater risk of 1-year VARC-2 safety endpoints [hazard ratio (HR) 1.68, 95% confidence interval (CI): 1.10-2.60], all-cause death (HR 2.00, 95% CI: 1.03-3.90), and composite of death, myocardial infarction, stroke or life-threatening bleeding (HR 1.70, 95% CI: 1.04-2.76). There were no differences in 30-day and 1-year VARC-2 efficacy and 30-day VARC-2 safety outcomes. CKD is associated with substantial and independent risk for mortality and morbidity at 1-year follow-up in women undergoing TAVR.

Clinical Characteristics of and Risk Factors for Chronic Kidney Disease Among Adults and Children

Chronic kidney disease (CKD) is serious and common, yet recognition and public health responses are limited. To describe clinical features of, prevalence of, major risk factors for, and care for CKD among patients treated in 2 large US health care systems. This cohort study collected data from the Center for Kidney Disease Research, Education, and Hope (CURE-CKD) registry, an electronic health record-based registry jointly curated and sponsored by Providence St Joseph Health and the University of California, Los Angeles. Patients were adults and children with CKD (excluding end-stage kidney disease) and adults at risk of CKD (ie, with diabetes, hypertension, or prediabetes) identified by laboratory values, vital signs, prescriptions, and administrative codes. Data were collected from January 2006 through December 2017, with analyses performed from March 2019 through November 2019. Diabetes, hypertension, and prediabetes. Clinical and demographic characteristics, prevalence, and prescribed medications. Of 2 625 963 adults and children in the sample, 606 064 adults (23.1%) with CKD had a median (interquartile range [IQR]) age of 70 (59-81) years, with 338 785 women (55.9%) and 434 474 non-Latino white individuals (71.7%). A total of 12 591 children (0.4%) with CKD had a median (IQR) age of 6 (1-13) years, with 7079 girls (56.2%) and 6653 non-Latino white children (52.8%). Median (IQR) estimated glomerular filtration rate was 53 (41-61) mL/min/1.73 m2 among adults and 70 (50-95) mL/min/1.73 m2 in children. Prevalence rates for CKD in adults were 4.8% overall (606 064 of 12 669 700) with 1.6% (93 644 of 6 011 129) during 2006 to 2009, 5.7% (393 455 of 6 903 084) during 2010 to 2013, and 8.4% (683 574 of 8 179 860) during 2014 to 2017 (P < .001). A total of 226 693 patients (37.4%) had category 3a CKD; 100 239 (16.5%), category 3b CKD; 39 125 (6.5%), category 4 CKD; and 20 328 (3.4%), category 5 CKD. Among adults with CKD, albuminuria and proteinuria assessments were available in 52 551 (8.7%) and 25 035 (4.1%) patients, respectively. A renin-angiotensin system inhibitor was prescribed to 124 575 patients (20.6%), and 204 307 (33.7%) received nonsteroidal anti-inflammatory drugs or proton pump inhibitors. Of 1 973 258 adults (75.1%) at risk, one-quarter had diabetes or prediabetes (512 299 [26.0%]), nearly half had hypertension (955 812 [48.4%]), and one-quarter had both hypertension and diabetes or prediabetes (505 147 [25.6%]). This registry-based cohort study revealed a burgeoning number of patients with CKD and its major risk factors. Rates of identification and use of kidney protective agents were low, while potential nephrotoxin use was widespread, underscoring the pressing need for practice-based improvements in CKD prevention, recognition, and treatment.

Anti-Müllerian hormone concentrations in women with chronic kidney disease.

BackgroundSerum anti-Müllerian hormone (AMH) is a biomarker of ovarian reserve. There are limited data to guide the clinical interpretation of AMH in women with chronic kidney disease (CKD). The purpose of this study was to examine AMH concentrations in women with CKD compared with women without CKD.MethodsWe conducted a prospective cohort study of serum AMH concentrations in 163 non-pregnant women with CKD. Serum AMH concentrations were compared with age-specific AMH centiles from 887 healthy female controls.ResultsParticipants included 30 women with Stage 1 CKD, 37 women with Stage 2 CKD, 26 women with Stage 3a CKD, 31 women with Stage 3b CKD and 39 women with Stages 4 and 5 CKD. The median estimated glomerular filtration rate (eGFR) was 51 (interquartile range 31–80) mL/min/1.73 m2. Serum AMH concentrations were lower in all CKD stages compared with women without CKD. Women ages 20–24 years with CKD had comparable serum AMH concentrations (median 1.959 ng/mL) to women ages 35–39 years without CKD (median 1.995 ng/mL). There was no evidence that eGFR was an independent modifier of serum AMH concentrations. More than half of women with CKD (58%) were predicted to have a low response to gonadotrophin stimulation.ConclusionsWomen with CKD have a lower ovarian reserve and are predicted to have a lower ovarian response to gonadotrophin stimulation compared with women without CKD of a similar age. Women with CKD who fail to conceive within 6 months of regular unprotected intercourse should be considered for fertility assessment and intervention.

Use of Potentially Nephrotoxic Medications by U.S. Adults with Chronic Kidney Disease: NHANES, 2011-2016.

People with chronic kidney disease (CKD) are at risk for adverse events and/or CKD progression with use of renally eliminated or nephrotoxic medications. To examine the prevalence of potentially inappropriate medication (PIM) use by U.S. adults by CKD stage and self-reported CKD awareness. Cross-sectional analysis of National Health and Nutrition Examination Surveys, 2011-2016 PARTICIPANTS: Non-pregnant adults with stages 3a (eGFR 45-59 mL/min/1.73 m2), 3b (eGFR 30-44), or 4-5 (eGFR < 30) CKD, stratified as CKD-aware/unaware. PIMs were identified on the basis of KDIGO guidelines, label information, and literature review. We calculated proportions using any and individual PIMs, assessing for differences over CKD awareness within each CKD stage. Analyses were adjusted for age, sex, race/ethnicity, education, comorbidities, and insurance type. Adjusted proportions of U.S. adults taking any PIM(s) exceeded 50% for all CKD stages and awareness categories, and were highest among CKD-unaware patients with stages 4-5 CKD: 66.6% (95% CI, 55.5-77.8). Proton pump inhibitors, opioids, metformin, sulfonylureas, and non-steroidal anti-inflammatory drugs (NSAIDs) were all used frequently across CKD stages. NSAIDs were used less frequently when CKD-aware by patients with stage 3a CKD (2.2% [95% CI, - 0.3 to 4.7] vs. 10.7% [95% CI, 7.6 to 13.8]) and stages 4-5 CKD (0.8% [95% CI, - 0.9 to 2.5] vs. 16.5% [95% CI, 4.0 to 29.0]). Metformin was used less frequently when CKD-aware by patients with stage 3b CKD (8.1% [95% CI, 0.3-15.9] vs. 26.5% [95% CI, 17.4-35.7]) and stages 4-5 CKD (none vs. 20.8% [95% CI, 1.8-39.8]). The impact of CKD awareness was statistically significant after correction for multiple comparisons only for NSAIDs in stage 3a CKD. PIMs are frequently used by people with CKD, with some impact of CKD awareness on NSAID and metformin use. This may lead to adverse outcomes or hasten CKD progression, reinforcing the need for improved medication management among people with CKD.