Se zvyšujícím se počtem diabetiků v populaci dochází také ke zvýšení mikrovaskulárních a makrovaskulárních komplikací. Poškození ledvin představuje jednu z hlavních příčin mortality u pacientů s diabetem. Klasifikace diabetické nefropatie je založena na hodnotě glomerulární filtrace a stupni albuminurie a rozděluje pacienty do tříd podle mortalitního rizika. Léčba pacientů je založena na datech z velkých multicentrických studií, které prokázaly kardiovaskulární benefit zejména při používání gliflozinů. Proto glifloziny a statiny společně s metforminem patří mezi léky první volby u pacientů s diabetem mellitem 2. typu a renálním postižením. Komplexní péče o tyto nemocné by současně měla zahrnovat pravidelné dieto- logické konzultace, fyzickou aktivitu a psychologickou podporu. Odlišná situace je zatím u pacientů s diabetem mellitem 1. typu. Glifloziny se u těchto nemocných nedoporučují používat. Zde základem farmakoterapie zůstávají ACEi nebo sar- tany a současně dostatečná kompenzace diabetu. V pokročilých stadiích je důležité odesílat pacienty včas ke specialistům k posouzení transplantační léčby.

With the increasing number of diabetics in the population, there is also a rise in both microvascular and macrovascular complications. Kidney damage represents one of the leading causes of mortality in patients with diabetes. The classification of diabetic nephropathy is based on the glomerular filtration rate and the degree of albuminuria, categorizing patients into risk groups according to their mortality risk. The treatment of these patients is based on data from large multicenter studies, which have demonstrated cardiovascular benefits, particularly with the use of gliflozins. Therefore, gliflozins and statins, together with metformin, are among the first-line treatment options for patients with type 2 diabetes mellitus and renal impairment. Comprehensive care for these patients should also include regular dietary consultations, physical activity, and psychological support. The situation is different for patients with type 1 diabetes mellitus, where the use of gliflozins is not recommended. In this group, the cornerstone of pharmacotherapy remains ACE inhibitors or sartans, along with adequate diabetes management. In advanced stages of the disease, it is crucial to refer patients to specialists in a timely manner for the evaluation of transplantation therapy.

• MeSH
• Angiotensin II Type 1 Receptor Blockers administration & dosage   pharmacology   therapeutic use   MeSH
• Diabetes Mellitus * diagnosis   therapy   MeSH
• Diabetic Nephropathies diagnosis   drug therapy   prevention & control   MeSH
• Sodium-Glucose Transporter 2 Inhibitors administration & dosage   pharmacology   therapeutic use   MeSH
• Diabetes Complications prevention & control   therapy   MeSH
• Humans MeSH
• Kidney Transplantation MeSH
• Pancreas Transplantation MeSH
• Check Tag
• Humans MeSH

BACKGROUND: Hyperkalemia (HK) is associated with suboptimal renin-angiotensin system (RAS) inhibitor and mineralocorticoid receptor antagonist (MRA) use in heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: This study sought to assess characteristics and RAS inhibitor/MRA use in patients receiving patiromer during the DIAMOND (Patiromer for the Management of Hyperkalemia in Subjects Receiving RAASi Medications for the Treatment of Heart Failure) run-in phase. METHODS: Patients with HFrEF and HK or past HK entered a run-in phase of ≤12 weeks with patiromer-facilitated RAS inhibitor/MRA optimization to achieve ≥50% recommended RAS inhibitor dose, 50 mg/d MRA, and normokalemia. Patients achieving these criteria (randomized group) were compared with the run-in failure group (patients not meeting the randomization criteria). RESULTS: Of 1,038 patients completing the run-in, 878 (84.6%) were randomized and 160 (15.4%) were run-in failures. Overall, 422 (40.7%) had HK entering run-in with a similar frequency in the randomized and run-in failure groups (40.3% vs 42.5%; P = 0.605). From start to the end of run-in, in the randomized group, an increase was observed in target RAS inhibitor and MRA use in patients with HK (RAS inhibitor: 76.8% to 98.6%; MRA: 35.9% to 98.6%) and past HK (RAS inhibitor: 60.5% to 98.1%; MRA: 15.6% to 98.7%). Despite not meeting the randomization criteria, an increase after run-in was observed in the run-in failure group in target RAS inhibitor (52.5% to 70.6%) and MRA use (15.0% to 48.1%). This increase was observed in patients with HK (RAS inhibitor: 51.5% to 64.7%; MRA: 19.1% to 39.7%) and past HK (RAS inhibitor: 53.3% to 75.0%; MRA: 12.0% to 54.3%). CONCLUSIONS: In patients with HFrEF and HK or past HK receiving suboptimal RAS inhibitor/MRA therapy, RAS inhibitor/MRA optimization increased during patiromer-facilitated run-in.

• MeSH
• Mineralocorticoid Receptor Antagonists * therapeutic use   MeSH
• Angiotensin Receptor Antagonists therapeutic use   MeSH
• Hyperkalemia * drug therapy   blood   MeSH
• Angiotensin-Converting Enzyme Inhibitors therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Polymers * therapeutic use   MeSH
• Renin-Angiotensin System drug effects   MeSH
• Aged MeSH
• Heart Failure * drug therapy   MeSH
• Stroke Volume drug effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

• MeSH
• Angiotensin Receptor Antagonists classification   therapeutic use   MeSH
• Diabetes Mellitus drug therapy   MeSH
• Diabetes Complications drug therapy   classification   MeSH
• Congresses as Topic MeSH
• Neprilysin antagonists & inhibitors   MeSH
• Heart Failure drug therapy   MeSH
• Publication type
• News MeSH

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

• MeSH
• Angiotensin Receptor Antagonists therapeutic use   MeSH
• Antihypertensive Agents therapeutic use   MeSH
• Calcium Channel Blockers therapeutic use   MeSH
• Renal Insufficiency, Chronic * complications   drug therapy   MeSH
• Hypertension * drug therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Surveys and Questionnaires MeSH
• Societies, Medical MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Geographicals
• Europe MeSH

• MeSH
• Medication Adherence MeSH
• Antihypertensive Agents administration & dosage   therapeutic use   MeSH
• Calcium Channel Blockers administration & dosage   pharmacology   therapeutic use   MeSH
• Angiotensin II Type 1 Receptor Blockers administration & dosage   pharmacology   therapeutic use   MeSH
• Drug Combinations MeSH
• Hypertension * diagnosis   drug therapy   prevention & control   MeSH
• Angiotensin-Converting Enzyme Inhibitors administration & dosage   pharmacology   therapeutic use   MeSH
• Humans MeSH
• Secondary Prevention MeSH
• Check Tag
• Humans MeSH

BACKGROUND AND AIMS: There are limited data on real clinical practice in heart failure patients in the Czech Republic. We analysed the clinical parameters from the Moravian Midlands Registry (MMR) and compared them to LCZ696 patients in the Paradigm-HF trial. The Moravian Midlands Registry is a retrospective patient database from two outpatient cardiology centres in the Czech Republic. The Paradigm-HF is a large-scale prospective randomized multicentre trial with more than 8000 individuals with stabilized chronic heart failure. METHODS: A retrospective analysis of heart failure with reduced ejection fraction patients from two outpatient cardiology centres in the Czech Republic from October 2016 to December 2019. RESULTS: Patients in the MMR were younger (60.5 ± 10.7 vs 63.8 ± 11.5 years, P<0.05), had a higher body mass index (30.3 ± 5.0 vs 28.1 ± 5.5, P<0.05) and higher serum creatinine level (101.9 ± 36.0 vs 99.9 ± 26.5 μmol/L, P<0.05). MMR patients had lower left ventricular ejection fraction (27.8 ± 6.9 vs 29.6 ± 6.1%, P<0.05). The serum N-terminal pro-B-type natriuretic peptide, [2563.5 (377-3536) vs 1631 (885-3154), was non significantly higher P=0.07]. Pharmacotherapy use differed for mineralocorticoid antagonist (91.4% in MMR vs 54.2% in Paradigm-HF), and digoxin (13.5% vs 29.2%). Beta-blocker use was similar (96.2% vs 93.1%) as was angiotensin-converting enzyme (ACE) inhibitors - (71.2% vs 78.0%) and angiotensin-receptor blockers - ARB (27.9% vs 22.2%). Dosages of the commonly used ACE inhibitors at the screening visit (Paradigm-HF) / before angiotensin receptor-neprilysin inhibitor administration (MMR) differed significantly only for ramipril (7.0 ± 3.1 mg vs 4.8 ± 2.9 mg, P<0.05), dosages of ARB were - losartan (67.1 ± 30.2 vs 39.6 ± 32.0 mg, P=0.09) and valsartan (181.5 ± 71.1 vs 130.9 ± 82.2 mg, P=0.07). There was a substantial difference in device-based therapy (ICD in 60.6%, CRT 25.9% in MMR vs 14.9% and 7.0% in Paradigm-HF). CONCLUSION: The differences between the groups for the majority of clinical parameters compared were minimal, except for younger age, higher body mass index and serum creatinine level and lower left ventricular ejection fraction and substantially lower dosage of administered ramipril prior to commencing sacubitril/valsartan therapy. There was a higher prevalence of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) in the MMR group.

• MeSH
• Aminobutyrates * therapeutic use   MeSH
• Angiotensin Receptor Antagonists * therapeutic use   MeSH
• Biphenyl Compounds * therapeutic use   MeSH
• Drug Combinations * MeSH
• Middle Aged MeSH
• Humans MeSH
• Natriuretic Peptide, Brain blood   MeSH
• Registries * MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Heart Failure * drug therapy   physiopathology   MeSH
• Stroke Volume * physiology   MeSH
• Tetrazoles therapeutic use   MeSH
• Valsartan * therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH
• Geographicals
• Czech Republic MeSH

Srdeční selhání je závažným zdravotním a také socioekonomickým problémem. Terapie srdečního selhání v poslední době doznala řady změn. U srdečního selhání s redukovanou ejekční frakcí je kromě β-blokátorů, antagonistů mineralokortikoidního receptoru a inhibitorů SGLT2 nedílnou součástí základní terapie také sakubitril/valsartan, který díky svému duálnímu účinku působí na řadu mechanismů v patofyziologii srdečního selhání. Kromě zahájení farmakoterapie je také velmi důležitá další titrace jednotlivých léčiv do maximálně snášených dávek. Díky optimální farmakoterapii můžeme ovlivnit nejenom kvalitu života pacientů, ale také jejich prognózu.

Heart failure is a serious health as well as socio-economic problem. Heart failure therapy has recently undergone a number of changes. In heart failure with a reduced ejection fraction, in addition to beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors, sacubitril/ valsartan is also an integral part of basic therapy, which, thanks to its dual effect, acts on a number of mechanisms in the pathophysiology of heart failure. In addition to starting drug therapy, further titration of individual drugs to the maximum tolerated doses is also very important. Thanks to optimal pharmacotherapy, we can influence not only the quality of life of patients, but also their prognosis.

• Keywords
• sakubitril/valsartan,
• MeSH
• Aminobutyrates pharmacology   therapeutic use   MeSH
• Angiotensin Receptor Antagonists pharmacology   therapeutic use   MeSH
• Biphenyl Compounds pharmacology   therapeutic use   MeSH
• Drug Combinations MeSH
• Middle Aged MeSH
• Humans MeSH
• Heart Failure * drug therapy   MeSH
• Valsartan pharmacology   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

Kazuistika je věnovaná zkušenosti s využitím inhibitoru neprilysinu a angiotenzinového receptoru II (sakubitril/valsartanu) v léčbě srdečního selhání se zachovanou systolickou funkcí levé komory (HFpEF), ale s progredující systolickou dysfunkcí pravé komory a trikuspidální regurgitací při dilataci anulu. Doplnění léčby diuretikem a β-blokátorem o sakubitril/valsartan namísto inhibitoru angiotenzin konvertujícího enzymu vedlo ke zmírnění převážně pravostranného srdečního selhání a umožnilo odložení potřebné operace trikuspidální chlopně do doby zvládnutí průvodní hematologické problematiky. Přes příznivý dopad plastiky trikuspidální chlopně zůstal sakubitril/valsartan v nižší dávce potřebnou a přínosnou součástí léčby i v následujícím období. V článku jsou dále diskutovány současné možnosti farmakoterapie HFpEF.

The case report describes the experience with the use of an neprilysin and angiotensin II receptor blocker (sacubitril/valsartan) in the treatment of heart failure with preserved left ventricular systolic function (HFpEF) but with progressive right ventricular systolic dysfunction and tricuspid regurgitation in tricuspid annular dilation. Adding a diuretic and a β-blocker to sacubitril/valsartan instead of an angiotensin-converting enzyme inhibitor resulted in amelioration of the predominantly right-sided heart failure and allowed deferral of the necessary tricuspid valve surgery until the accompanying hematologic issues were managed. Despite the beneficial impact of tricuspid valve surgery, lower-dose of sacubitril/valsartan remained a necessary and beneficial part of treatment in the subsequent period. Current options for pharmacotherapy of HFpEF are also discussed.

• Keywords
• sakubitril/valsartan,
• MeSH
• Aminobutyrates pharmacology   therapeutic use   MeSH
• Angiotensin Receptor Antagonists pharmacology   therapeutic use   MeSH
• Biphenyl Compounds pharmacology   therapeutic use   MeSH
• Drug Combinations MeSH
• Humans MeSH
• Aged MeSH
• Heart Failure * drug therapy   MeSH
• Valsartan pharmacology   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports MeSH

BACKGROUND: Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. METHODS: PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin-angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. FINDINGS: Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6-110) was -2·7 mL/min per 1·73 m2 per year versus -3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1-week 110) was -2·9 mL/min per 1·73 m2 per year versus -3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI -0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (-42·8%, 95% CI -49·8 to -35·0, with sparsentan versus -4·4%, -15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. INTERPRETATION: Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function. FUNDING: Travere Therapeutics.

• MeSH
• Angiotensin Receptor Antagonists adverse effects   MeSH
• Kidney Failure, Chronic * MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Glomerulonephritis, IGA * drug therapy   MeSH
• Irbesartan adverse effects   MeSH
• Humans MeSH
• Proteinuria drug therapy   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Randomized Controlled Trial MeSH

Výskyt arteriální hypertenze je u diabetiků 2. typu dvakrát častější než v běžné populaci a stoupá v závislosti na věku a délce trvání diabetu. Dobrá kontrola hypertenze u diabetiků je zásadní pro snížení kardiovaskulárního rizika a také mikrovaskulárních komplikací. Základem léčby hypertenze u diabetiků je blokáda renin-angiotenzin-aldosteronového systému. V současných postupech se doporučuje preference kombinační antihypertenzní léčby a snaha o rychlou normalizaci krevního tlaku. Nová antidiabetika (inhibitory sodíko-glukózového kotransportéru 2 [sodium-glucose co-transporter 2, SGLT2] a agonisté glukagonu podobného peptidu 1 [glucagon-like peptide-1, GLP-1]) mají nezanedbatelný antihypertenzní účinek a představují novou příležitost k optimalizaci současné léčby hypertenze u diabetických pacientů. Agonisté GLP-1 mají i významný vliv na redukci tělesné hmotnosti. Tento článek shrnuje současné poznatky a doporučení v léčbě hypertenze u obézních diabetiků 2. typu.

The incidence of arterial hypertension is twice as common in type 2 diabetics as in the general population and increases with age and duration of diabetes. Good control of hypertension in diabetics is essential to reduce cardiovascular risk as well as microvascular complications. The basis of the treatment of hypertension in diabetics is the blockade of the renin-angiotensin-aldosterone system. In current procedures, preference for combination antihypertensive therapy and efforts to rapidly normalize blood pressure are recommended. The new antidiabetics (sodium-glucose co-transporter 2 [SGLT2] inhibitors and glucagon-like peptide-1 [GLP-1] agonists) have a significant antihypertensive effect and represent a new opportunity to optimize the current treatment of hypertension in diabetic patients. Glucagon-like peptide-1 agonists also have a significant effect on reducing body weight. This article summarizes current knowledge and recommendations in the treatment of hypertension in obese type 2 diabetics.

• MeSH
• Antihypertensive Agents pharmacology   classification   therapeutic use   MeSH
• Bariatric Surgery methods   MeSH
• Angiotensin II Type 1 Receptor Blockers pharmacology   classification   therapeutic use   MeSH
• Diabetes Mellitus, Type 2 * diagnosis   drug therapy   MeSH
• Sodium-Glucose Transporter 2 Inhibitors pharmacology   therapeutic use   MeSH
• Hypertension * diagnosis   etiology   drug therapy   MeSH
• Angiotensin-Converting Enzyme Inhibitors pharmacology   classification   therapeutic use   MeSH
• Humans MeSH
• Obesity diagnosis   drug therapy   MeSH
• Glucagon-Like Peptide-1 Receptor therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH