Empagliflozin Changes Urine Supersaturation by Decreasing pH and Increasing Citrate.

Clinical Trial registry name and registration number: Empagliflozin and Renal Oxygenation in Healthy Volunteers (EMPA-REIN), NCT03093103.

[Diabetic nephropathy: Interprofessional support of medication adherence]. / Néphropathie diabétique : soutenir l'adhésion médicamenteuse de façon interprofessionnelle.

Medication non-adherence in patients with diabetic kidney disease (DKD) is endemic. The PANDIA-IRIS study, implemented at the community pharmacy of Unisanté, illustrates the support of medication adherence in patients with DKD by pharmacists, through an interprofessional program (IMAP) based on a behavioral science theoretical framework. Implementing behavioural support programmes such as PANDIA-IRIS on a large scale in Switzerland is both a necessity and a challenge. These programmes should be an integral part of standard patient care. The transition of care towards interprofessional collaborations and a clarification of roles in supporting adherence, including the patient as a partner, will contribute to fully considering adherence in therapeutic decision making and support to enable better achievement of long-term clinical goals.

La non-adhésion médicamenteuse chez les patient-es avec une néphropathie diabétique (ND) est endémique. L'étude PANDIA-IRIS, implémentée à la pharmacie communautaire d'Unisanté, illustre le soutien de l'adhésion des patient-es avec ND par des pharmacien-nes, au travers d'un programme interprofessionnel (IMAP) fondé sur un cadre théorique des sciences du comportement. Mettre en place des programmes d'accompagnement comportemental comme PANDIA-IRIS à large échelle en Suisse est à la fois une nécessité et un défi. Ces programmes devraient faire partie intégrante des soins standards des patient-es. La transition des soins vers des collaborations interprofessionnelles et une clarification des rôles dans le soutien de l'adhésion, incluant le-la patient-e comme partenaire, contribueront à considérer pleinement l'adhésion dans la prise de décisions thérapeutiques et dans son accompagnement pour permettre une meilleure atteinte des objectifs cliniques à long terme.

Translation of the Diabetes Knowledge Questionnaire into French and its validation / Traduction et validation en langue française de l'instrument « Diabetes Knowledge Questionnaire ¼

Introduction: Improving patients' knowledge of diabetes would support adherence to treatment, prevent complications, and promote shared decision-making. Healthcare professionals need to assess patients' knowledge using a validated questionnaire in the local language. Objective: The aim of the study was to translate the Diabetes Knowledge Questionnaire from English to French and assess the psychometric properties of the translated version. Methods: A cross-sectional method was used. Individuals with diabetes were recruited from diabetes clinics, as well as dialysis units, since approximately 30 percent of dialysis patients have diabetes. Participants with type 1 or type 2 diabetes completed the translated questionnaire. The questionnaire targeted both groups, with additional questions for those with type 1 diabetes. Reliability and validity were assessed according to COSMIN approach. Results: Analysis of the translated questionnaire (n=102) showed good internal consistency (α=0.77), similar to the original questionnaire. The removal of an item on the self-monitoring of blood glucose increased the α Cronbach coefficient by 0.03. Discussion: Despite its validation, the questionnaire should be updated according to new clinical and medical recommendations to ensure consistency between the desired knowledge and the intended goals of care. Conclusion: The French version of the Diabetes Knowledge Questionnaire demonstrated good validity and reliability. It can be used in practice and research, after deleting item 9.

Introduction: L'amélioration des connaissances des patients sur le diabète pourrait soutenir leur adhésion au traitement, prévenir les complications et favoriser la prise de décision partagée. Les professionnels de la santé ont besoin d'évaluer les connaissances des patients à l'aide d'un questionnaire validé dans la langue locale. Objectif: L'étude avait pour but de traduire le Diabetes Knowledge Questionnaire en français et d'évaluer les qualités psychométriques de la version traduite. Méthodes: Dans cette étude transversale, les personnes diabétiques ont été recrutées dans les services de diabétologie, ainsi que dans les services de dialyse, car environ 30 % des patients dialysés sont diabétiques. Les participants diabétiques de type 1 ou 2 ont répondu au questionnaire traduit, le questionnaire s'adressant aux deux populations, avec des questions supplémentaires pour les diabétiques de type 1. La fidélité et la validité ont été évaluées selon la démarche COSMIN. Résultats: L'analyse du questionnaire traduit (n = 102) a montré une bonne cohérence interne (α = 0,77), similaire au questionnaire d'origine. La suppression d'un item portant sur les autocontrôles de glycémie a augmenté le coefficient α Cronbach de 0,03. Discussion: Malgré sa validation, le questionnaire mériterait une mise à jour selon les nouvelles pratiques et recommandations médicales, pour garantir une cohérence entre les connaissances souhaitées et les objectifs de soins visés. Conclusion: La version française du Diabetes Knowledge Questionnaire a démontré une bonne validité et fidélité, et peut être utilisée dans la pratique et la recherche, après la suppression de l'item n° 9.

Metformin versus SGLT-2 inhibitors: how low can we go?

The progression of chronic kidney disease is difficult to stop once established. Metformin and sodium-glucose cotransporter 2 inhibitors show promise, but clinical trials with a head-to-head comparison in patients with more advanced (stage 3b-4) chronic kidney disease are largely lacking, partly for safety reasons. In this issue, Corremans et al. compare the effects of metformin and canagliflozin in rats with adenine-induced moderate (stage 2-4) chronic kidney disease. Metformin halted progression, whereas canagliflozin did not. This commentary puts the results in a wider clinical context.

[How is the management of diabetic hypertensive patients different?] / En quoi la prise en charge de l'hypertendu diabétique est-elle différente?

High blood pressure (HBP) is common in diabetic patients and significantly increases complications of diabetes and cardiovascular risk. It is therefore particularly important to routinely screen and treat HBP in these patients. Blood pressure targets in this population (<130/80mmHg) should be adapted to age and comorbidities. The therapeutic strategy has expanded beyond renin-angiotensin-aldosterone system inhibitors in the diabetic population, with treatments which decrease cardiovascular and renal risk, such as SGLT2 inhibitors, GLP-1 receptor agonists, and soon finerenone.

L'hypertension artérielle (HTA) est fréquente chez les patients diabétiques et augmente de manière considérable les complications du diabète et le risque cardiovasculaire. Il est donc particulièrement important de dépister de manière systématique et de traiter l'HTA chez ces patients. Les cibles tensionnelles dans cette population (< 130/80 mmHg) doivent être adaptées à l'âge et aux comorbidités. Dans la population diabétique, l'arsenal thérapeutique s'est élargi au-delà des inhibiteurs du système rénine-angiotensine-aldostérone, avec des traitements qui influencent le pronostic cardiovasculaire et rénal, comme c'est le cas pour les inhibiteurs du SGLT2, les agonistes des récepteurs du GLP-1 et, bientôt, la finérénone.

[SGLT2 inhibitors in diabetic and non-diabetic nephropathies]. / Inhibiteurs du SGLT2 dans les néphropathies diabétiques et non diabétiques.

SGLT2 inhibitors (SGLT2i) will change the clinical practice of nephrology with their therapeutic cardiorenal and antidiabetic properties. By inhibiting proximal tubular sodium and glucose reabsorption, these new drugs decrease intraglomerular pressures. Over the last 5 years several breakthrough studies have demonstrated the SGLT2i protective effects on outcomes such as cardiovascular mortality, hospital admission for heart failure, sustained decreases in eGFR in patients with diabetic nephropathy and the development of ESKD. With the new DAPA-CKD study revealing protective effects of SGLT2i in CKD patients without diabetes, therapeutic recommendations will now have to evolve towards including these drugs in the chronic management of all most proteinuric CKD patients.

Les inhibiteurs du cotransporteur du sodium-glucose de type 2 (iSGLT2) révolutionnent la pratique clinique en néphrologie par le biais de leurs effets antidiabétique, cardio et néphroprotecteur. Ces molécules inhibent la réabsorption du glucose et du sodium au niveau du tubule proximal, ce qui résulte en une baisse de la pression intraglomérulaire. Plusieurs grandes études ont démontré l'effet protecteur des iSGLT2 sur la mortalité cardiovasculaire, le taux d'hospitalisation pour une insuffisance cardiaque et le ralentissement de la progression de la néphropathie diabétique. La sortie de DAPA-CKD va certainement modifier les recommandations thérapeutiques pour la prise en charge de l'insuffisance rénale chronique (IRC) non diabétique, en démontrant un effet néphroprotecteur majeur chez les IRC protéinuriques d'origine non diabétique également.

[Diabetes and COVID-19 infection]. / Diabète et infection à COVID-19.

Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.

D'après les données épidémiologiques actuellement disponibles, le diabète ne semble pas être un facteur de risque d'infection par le SARS-CoV-2. Il est cependant associé à une maladie plus sévère principalement en raison de sa haute prévalence chez les personnes âgées et polymorbides dont l'évolution est plus souvent défavorable. Comme lors de n'importe quelle autre infection, un diabète préexistant, surtout s'il est mal contrôlé, peut favoriser les surinfections et entraîner des complications aiguës liées à l'hyperglycémie, elle-même majorée par l'infection. Il est important de recommander aux patients d'avoir suffisamment de matériel à domicile, d'effectuer des automesures régulières de la glycémie, ainsi que de contacter un soignant immédiatement en cas de déséquilibre glycémique ou d'infection. Le traitement antidiabétique doit être adapté comme habituellement en cas d'infection. Une insulinothérapie doit être envisagée en cas d'hyperglycémie persistante chez tout patient hospitalisé pour une infection aiguë.

[Medication adherence and physician-pharmacist collaboration. Focus on the patient with diabetic nephropathy]. / Adhésion thérapeutique et collaboration médecin-pharmacien. L'exemple du patient avec néphropathie diabétique.

Polypharmacy is common in patients with a chronic disease. It is appropriate when both the patient and the physician discuss the goal of each prescribed medication with a motivated patient capable of managing his/her medication. It can however be inappropriate when treatment becomes too complex for the frail patient. The risk is non-adherence to therapy, which often results in an intensification of treatment due to unmet therapeutic goals. Collaboration between physicians and pharmacists is therefore essential for the educational support of patients with polypharmacy. In this article, we review the studies examining the impact of a physician-pharmacist collaboration on the medication adherence of diabetic patients with renal impairment.

La polypharmacie concerne de nombreux patients avec une maladie chronique. Elle est appropriée lorsque chaque médicament a été prescrit dans un but thérapeutique spécifique discuté avec un patient motivé et capable de gérer ses médicaments. Elle peut cependant être inappropriée lorsque le traitement devient trop complexe pour une personne fragile. Le risque est une non-adhésion au traitement, dont découle souvent une intensification de la thérapie en raison d'objectifs thérapeutiques non atteints. La collaboration médecin-pharmacien est donc primordiale pour l'accompagnement éducatif du patient complexe dans la gestion de ses médicaments. Dans cet article, nous revoyons les études examinant l'adhésion thérapeutique chez le patient diabétique avec une atteinte rénale lors d'une collaboration médecin-pharmacien.

[Post-transplantation diabetes in kidney transplant: from the diabetologist point of view]. / Diabète post-transplantation rénale: le point de vue du diabétologue.

Post-transplantation diabetes (PTDM) exposes to increased morbidity (cardiovascular or infectious complications, early graft dysfunction) and to a risk of premature death. Recognition of risk factors is essential for early and individualized care. The management of a PTDM requires the use of oral antidiabetic treatments (metformin or DPP4 inhibitors) or GLP1 receptor agonists for their favorable effects on weight and kidney that seem ideal in this context. Corticosteroid-induced diabetes or the rare occurrence of diabetic ketoacidosis require insulin therapy. In the long term, the main objective remains to integrate PTDM treatment in a more comprehensive management, targeting the reduction of cardiovascular risk of vulnerable transplant patients.

Le diabète post-transplantation (PTDM) expose le patient à une morbidité accrue (cardiovasculaire, infectieuse ou dysfonction précoce du greffon), ainsi qu'à un risque de décès prématuré. La reconnaissance des facteurs de risque est primordiale pour une prise en charge précoce et individualisée. La prise en charge d'un PTDM d'apparition progressive recourt à l'utilisation d'antidiabétiques oraux (metformine ou inhibiteurs de la dipeptidyl peptidase 4) ou aux agonistes du récepteur du glucagon-like peptide-1 dont l'effet pondéral et néphroprotecteur semble idéal dans ce contexte. Un diabète cortico-induit ou, plus rare, une acidocétose aiguë seront traités par une insulinothérapie précoce. À long terme, l'objectif reste d'intégrer le traitement du PTDM dans une prise en charge plus globale ciblant la réduction du risque cardiovasculaire de ces patients transplantés fragiles.

[Challenges in managing diabetes in chronic hemodialysis]. / Défis dans la prise en charge du diabète en hémodialyse chronique.

Hemodialysis (HD) centers are facing an increasing number of patients with diabetes. These cases require an intensive multidisciplinary approach of the consequences of renal failure, glycemic control and nutrition and the management of frequent co-morbidities, in particular the diabetic foot. A major challenge is to decrease glycemic variability and the risk of hypoglycemia. Because of increased risk of hypoglycemia-associated mortality, the HbA1C target is loosened in the majority of HD patients. Continuous glucose monitoring technology has identified important glycemic fluctuations during and after dialysis. However, their reliability in HD needs to be improved. New therapeutic pathways that decrease glucose excursions and hypoglycemia, such as GLP1 receptor agonists and sensor-coupled insulin pumps, have yet to be validated in HD.

Les centres d'hémodialyse (HD) sont confrontés à un nombre croissant de patients diabétiques. Leur prise en charge multidisciplinaire tient compte de l'insuffisance rénale, du contrôle glycémique, de la nutrition et des comorbidités fréquentes, en particulier le pied diabétique. La réduction de la variabilité glycémique et des hypoglycémies qui sont associées à une mortalité accrue reste un défi. La cible de l'HbA1C est assouplie chez la majorité des patients. L'usage du contrôle en continu de la glycémie permet d'identifier les fluctuations glycémiques per et interdialytiques importantes. Sa fiabilité doit cependant être améliorée en HD. Les nouvelles voies thérapeutiques qui diminuent les excursions glycémiques et le risque d'hypoglycémie comme les GLP1 agonistes et les pompes à insuline couplées aux sensors restent à valider en HD.

The impact of a multidisciplinary self-care management program on quality of life, self-care, adherence to anti-hypertensive therapy, glycemic control, and renal function in diabetic kidney disease: A Cross-over Study Protocol.

BACKGROUND: Diabetic kidney disease, a global health issue, remains associated with high morbidity and mortality. Previous research has shown that multidisciplinary management of chronic disease can improve patient outcomes. The effect of multidisciplinary self-care management on quality of life and renal function of patients with diabetic kidney disease has not yet been well established. METHOD/DESIGN: The aim of this study is to evaluate the impact of a multidisciplinary self-care management program on quality of life, self-care behavior, adherence to anti-hypertensive treatment, glycemic control, and renal function of adults with diabetic kidney disease. A uniform balanced cross-over design is used, with the objective to recruit 40 adult participants with diabetic kidney disease, from public and private out-patient settings in French speaking Switzerland. Participants are randomized in equal number into four study arms. Each participant receives usual care alternating with the multidisciplinary self- care management program. Each treatment period lasts three months and is repeated twice at different time intervals over 12 months depending on the cross-over arm. The multidisciplinary self-care management program is led by an advanced practice nurse and adds nursing and dietary consultations and follow-ups, to the habitual management provided by the general practitioner, the nephrologist and the diabetologist. Data is collected every three months for 12 months. Quality of life is measured using the Audit of Diabetes-Dependent Quality of Life scale, patient self-care behavior is assessed using the Revised Summary of Diabetes Self-Care Activities, and adherence to anti-hypertensive therapy is evaluated using the Medication Events Monitoring System. Blood glucose control is measured by the glycated hemoglobin levels and renal function by serum creatinine, estimated glomerular filtration rate and urinary albumin/creatinine ratio. Data will be analyzed using STATA version 14. DISCUSSION: The cross-over design will elucidate the responses of individual participant to each treatment, and will allow us to better evaluate the use of such a design in clinical settings and behavioral studies. This study also explores the impact of a theory-based nursing practice and its implementation into a multidisciplinary context. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01967901 , registered on the 18th of October 2013.

Effects of empagliflozin on reproductive system in men without diabetes.

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for the treatment of type 2 diabetes, renal disease and chronic heart failure. The protein SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2), which is highly expressed in renal cortex, but also in the testes where glucose uptake may be essential for spermatogenesis and androgen synthesis. We postulated that in healthy males, SGLT2 inhibitor therapy may affect gonadal function. We examined the impact on gonadal and steroid hormones in a post-hoc analysis of a double-blind, randomized, placebo-controlled research including 26 healthy males who were given either placebo or empagliflozin 10 mg once daily for four weeks. After one month of empagliflozin, there were no discernible changes in androgen, pituitary gonadotropin hormones, or inhibin B. Regardless of BMI category, the administration of empagliflozin, a highly selective SGLT2 inhibitor, did not alter serum androgen levels in men without diabetes. While SGLT2 is present in the testes, its inhibition does not seem to affect testosterone production in Leydig cells nor inhibin B secretion by the Sertoli cells.

The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.

Background: Mutations in the GCK gene cause Maturity Onset Diabetes of the Young (GCK-MODY) by impairing glucose-sensing in pancreatic beta cells. During pregnancy, managing this type of diabetes varies based on fetal genotype. Fetuses carrying a GCK mutation can derive benefit from moderate maternal hyperglycemia, stimulating insulin secretion in fetal islets, whereas this may cause macrosomia in wild-type fetuses. Modulating maternal glycemia can thus be viewed as a form of personalized prenatal therapy, highly beneficial but not justifying the risk of invasive testing. We therefore developed a monogenic non-invasive prenatal diagnostic (NIPD-M) test to reliably detect the transmission of a known maternal GCK mutation to the fetus. Methods: A small amount of fetal circulating cell-free DNA is present in maternal plasma but cannot be distinguished from maternal cell-free DNA. Determining transmission of a maternal mutation to the fetus thus implies sequencing adjacent polymorphisms to determine the balance of maternal haplotypes, the transmitted haplotype being over-represented in maternal plasma. Results: Here we present a series of such tests in which fetal genotype was successfully determined and show that it can be used to guide therapeutic decisions during pregnancy and improve the outcome for the offspring. We discuss several potential hurdles inherent to the technique, and strategies to overcome these. Conclusion: Our NIPD-M test allows reliable determination of the presence of a maternal GCK mutation in the fetus, thereby allowing personalized in utero therapy by modulating maternal glycemia, without incurring the risk of miscarriage inherent to invasive testing.

Diabetic kidney disease in type 2 diabetes: a consensus statement from the Swiss Societies of Diabetes and Nephrology.

Diabetic kidney disease is highly prevalent in patients with type 2 diabetes and is a major cause of end-stage renal disease in Switzerland. Patients with diabetic kidney disease are among the most complex patients in diabetes care. They require a multifactorial and multidisciplinary approach with the goal to slow the decline in glomerular filtration rate (GFR) and cardiovascular morbidity. With this consensus we propose an evidence-based guidance to health care providers involved in the care of type 2 diabetic patients with diabetic kidney disease.First, there is a need to increase physician awareness and improve screening for diabetic kidney disease as early intervention may improve clinical outcomes and the financial burden. Evaluation of estimated GFR (eGFR) and spot urine albumin/creatinine ratio is recommended at least annually. Once it is diagnosed, glucose control and optimisation of blood pressure control with renin-angiotensin system blockers have been recommended as mainstay management of diabetic kidney disease for more than 20 years. Recent, high quality randomised controlled trials have shown that sodium-glucose cotransporter-2 (SGLT2) inhibition slows eGFR decline and cardiovascular events beyond glucose control. Likewise, mineralocorticoid receptor antagonism with finerenone has cardiorenal protective effects in diabetic kidney disease. Glucagon-like peptide-1 (GLP1) receptor agonists improve weight loss if needed, and decrease albuminuria and cardiovascular morbidity. Lipid control is also important to decrease cardiovascular events. All these therapies are included in the treatment algorithms proposed in this consensus. With advancing kidney failure, other challenges may rise, such as hyperkalaemia, anaemia and metabolic acidosis, as well as chronic kidney disease-mineral and bone disorder. These different topics and treatment strategies are discussed in this consensus. Finally, an update on diabetes management in renal replacement therapy such as haemodialysis, peritoneal dialysis and renal transplantation is provided. With the recent developments of efficient therapies for diabetic kidney disease, it has become evident that a consensus document is necessary. We are optimistic that it will significantly contribute to a high-quality care for patients with diabetic kidney disease in Switzerland in the future.

Blood pressure and vascular determinants of glomerular filtration rate decline in diabetic kidney disease.

Objective: In patients with type 2 diabetes and diabetic kidney disease (DKD), explore the relationship between estimated glomerular filtration rate decline (eGFR-d) and simultaneously assessed vascular risk markers including office, ambulatory or central blood pressure, pulse pressure, carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT) and renal resistive indexes (RRI). Research design and methods: At baseline, vascular risk markers were measured in addition to the routine clinical workup. The eGFR-d was based on 2000-2019 creatinine values. Parameters were compared by eGFR-d quartiles. Regression models of eGFR-d and vascular markers were assessed. Results: In total, 135 patients were included. Mean age was 63.8 ± 10.8y, baseline eGFR 60.2 ± 26.4 ml/min/1.73 m2 and urine albumin-creatinine ratio (ACR) 49 ± 108 mg/mmol. Mean eGFR-d was based on 43 ± 39 creatinine values within a time span of 7.0 ± 1.9y. The average yearly eGFR decline was -1.8 ± 3.0 ml/min/1.73 m2 ranging from -5.8 ± 2.3 in the first quartile to +1.4 ± 1.7 in the fourth quartile. Mean 24 h systolic (SBP) and diastolic (DBP) blood pressure were 126 ± 17 and 74 ± 9 mmHg. Mean PWV was 11.8 ± 2.8 m/s, RRI 0.76 ± 0.07 and IMT 0.77 ± 0.21 mm. SBP and pulse pressure correlated with eGFR-d but not DBP. 24 h SBP stood out as a stronger predictor of eGFR-d than office or central SBP. PWV and RRI correlated with eGFR decline in univariate, but not multivariate regression models including 24 SBP and ACR. Conclusions: In this study, eGFR decline was highly variable in patients with type 2 diabetes and DKD. Twenty-four hour SBP provided an added value to the routine measurement of ACR in predicting eGFR decline, whereas PWV and RRI did not.

Twenty-Four Hour Blood Pressure Response to Empagliflozin and Its Determinants in Normotensive Non-diabetic Subjects.

Background: Sodium-glucose co-transport 2 inhibitors (SGLT2i) lower blood pressure (BP) in normotensive subjects and in hypertensive and normotensive diabetic and non-diabetic patients. However, the mechanisms of these BP changes are not fully understood. Therefore, we examined the clinical and biochemical determinants of the BP response to empagliflozin based on 24-h ambulatory BP monitoring. Methods: In this post-hoc analysis of a double-blind, randomized, placebo-controlled study examining the renal effects of empagliflozin 10 mg vs. placebo in untreated normotensive non-diabetic subjects, the 1-month changes in 24 h ambulatory BP were analyzed in 39 subjects (13 placebo/26 empagliflozin) in regard to changes in biochemical and hormonal parameters. Results: At 1 month, empagliflozin 10 mg decreased 24-h systolic (SBP) and diastolic (DBP) BP significantly by -5 ± 7 mmHg (p < 0.001) and -2 ± 6 mmHg (p = 0.03). The effect on SBP and DBP was more pronounced during nighttime (resp. -6 ± 11 mmHg, p = 0.004; -4 ± 7 mmHg, p = 0.007). The main determinants of daytime and nighttime SBP and DBP responses were baseline BP levels (for daytime SBP: coefficient -0.5; adj. R2: 0.36; p = 0.0007; for night-time SBP: coefficient -0.6; adj. R2: 0.33; p = 0.001). Although empaglifozin induced significant biochemical changes, none correlated with blood pressure changes including urinary sodium, lithium, glucose and urate excretion and free water clearance. Plasma renin activity and plasma aldosterone levels increased significantly at 1 month suggesting plasma volume contraction, while plasma metanephrine and copeptin levels remained the same. Renal resistive indexes did not change with empagliflozin. Conclusion: SGLT2 inhibition lowers daytime and nighttime ambulatory systolic and diastolic BP in normotensive non-diabetic subjects. Twenty-four jour changes are pronounced and comparable to those described in diabetic or hypertensive subjects. Baseline ambulatory BP was the only identified determinant of systolic and diastolic BP response. This suggests that still other factors than sustained glycosuria or proximal sodium excretion may contribute to the resetting to lower blood pressure levels with SGLT2 inhibition. Clinical Trial Registration: [https://www.clinicaltrials.gov], identifier [NCT03093103].