Inhibítory sodíko-glukózového kotransportéra 2 (SGLT2i), resp. gliflozíny sú modernou skupinou antidiabetických liekov v liečbe pacientov s diabetes mellitus 2. typu (DM2T). Kanagliflozín okrem dobrej glykemickej kontroly, nízkeho rizika hypoglykémie a poklesu telesnej hmotnosti vykazuje signifikantný kardiovaskulárny a nefroprotektívny benefit v liečbe pacientov s DM2T porovnateľný s ostatnými gliflozínmi (empagliflozín, dapagliflozín). Liečba kanagliflozínom sa môže potenciálne spájať s nižším rizikom cievnej mozgovej príhody dôsledkom inhibície SGLT1. Výskyt nežiaducich účinkov, ako sú zvýšené riziko infekcie močových ciest, najmä vaginálne kandidózy u žien, euglykemická ketoacidóza a deplécia objemu spojená s hypotenziou, je porovnateľný v celej skupine gliflozínov.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors, gliflozins are a modern class of diabetic medications in the treatment of patients with type 2 diabetes mellitus (T2DM). Apart from good glycemic control, low risk of hypoglycemia and weight loss, canagliflozin has been shown to provide significant cardiovascular and nephroprotective benefit in patients with T2DM co-equal to other gliflozines (empagliflozin, dapagliflozin). Treatment with canagliflozin is potentially associated with lower risk of stroke due to inhibition of SGLT1. Incidence of adverse side effects such as increased risk of urinary infections, mainly vaginal candidosis in female, euglycemic ketoacidosis and volume depletion with hypotension is comparable in whole group of gliflozines.
- MeSH
- Canagliflozin * administration & dosage pharmacology therapeutic use MeSH
- Renal Insufficiency, Chronic drug therapy prevention & control MeSH
- Diabetes Mellitus, Type 2 drug therapy MeSH
- Diabetic Nephropathies drug therapy prevention & control MeSH
- Sodium-Glucose Transporter 2 Inhibitors pharmacology therapeutic use MeSH
- Cardiovascular Diseases drug therapy prevention & control MeSH
- Humans MeSH
- Kidney Diseases drug therapy prevention & control MeSH
- Check Tag
- Humans MeSH
- MeSH
- Kidney Diseases, Cystic diagnosis drug therapy classification MeSH
- Diabetic Nephropathies diagnosis drug therapy MeSH
- Glomerulonephritis diagnosis etiology drug therapy classification pathology MeSH
- Urinary Tract Infections diagnosis etiology drug therapy classification MeSH
- Nephritis, Interstitial diagnosis drug therapy classification MeSH
- Kidney Neoplasms diagnosis classification MeSH
- Renal Replacement Therapy classification methods MeSH
- Kidney Diseases * diagnosis etiology drug therapy classification MeSH
- Urolithiasis diagnosis etiology drug therapy MeSH
- Publication type
- Review MeSH
Chronic kidney disease (CKD) affects approximately 13% of people globally, including 20%-48% with type 2 diabetes (T2D), resulting in significant morbidity, mortality, and healthcare costs. There is an urgent need to increase early screening and intervention for CKD. We are experts in diabetology and nephrology in Central Europe and Israel. Herein, we review evidence supporting the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for kidney protection and discuss barriers to early CKD diagnosis and treatment, including in our respective countries. SGLT2 inhibitors exert cardiorenal protective effects, demonstrated in the renal outcomes trials (EMPA-KIDNEY, DAPA-CKD, CREDENCE) of empagliflozin, dapagliflozin, and canagliflozin in patients with CKD. EMPA-KIDNEY demonstrated cardiorenal efficacy across the broadest renal range, regardless of T2D status. Renoprotective evidence also comes from large real-world studies. International guidelines recommend first-line SGLT2 inhibitors for patients with T2D and estimated glomerular filtration rate (eGFR) ≥20 mL/min/1.73 m2, and that glucagon-like peptide-1 receptor agonists may also be administered if required for additional glucose control. Although these guidelines recommend at least annual eGFR and urine albumin-to-creatinine ratio screening for patients with T2D, observational studies suggest that only half are screened. Diagnosis is hampered by asymptomatic early CKD and under-recognition among patients with T2D and clinicians, including limited knowledge/use of guidelines and resources. Based on our experience and on the literature, we recommend robust screening programmes, potentially with albuminuria self-testing, and SGLT2 inhibitor reimbursement at general practitioner (GP) and specialist levels. High-tech tools (artificial intelligence, smartphone apps, etc.) are providing exciting opportunities to identify high-risk individuals, self-screen, detect abnormalities in images, and assist with prescribing and treatment adherence. Better education is also needed, alongside provision of concise guidelines, enabling GPs to identify who would benefit from early initiation of renoprotective therapy; although, regardless of current renal function, cardiorenal protection is provided by SGLT2 inhibitor therapy.
- MeSH
- Benzhydryl Compounds therapeutic use MeSH
- Early Diagnosis * MeSH
- Renal Insufficiency, Chronic * drug therapy diagnosis MeSH
- Diabetes Mellitus, Type 2 * drug therapy complications MeSH
- Diabetic Nephropathies * diagnosis prevention & control drug therapy MeSH
- Sodium-Glucose Transporter 2 Inhibitors * therapeutic use MeSH
- Glucosides therapeutic use MeSH
- Glomerular Filtration Rate drug effects MeSH
- Humans MeSH
- Practice Guidelines as Topic MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Chronická choroba obličiek sa rozvinie takmer u 20–40 % diabetikov. Diabetes mellitus je vedúcou z príčin chronickej choroby obličiek u dialyzovaných pacientov. Diabetológ má kľúčovú úlohu v diagnostike, ovplyvnení jej progresie a prechodu do štádia zlyhania obličiek. Pacient s potvrdenou diabetickou chorobou obličiek má veľmi vysoké kardiovaskulárne riziko a riziko náhleho úmrtia. Manažment liečby diabetika s rozvinutými obličkovými komplikáciami by mal byť preto komplexný s cieľom ovplyvniť jednotlivé kardiovaskulárne rizikové faktory. Holistický prístup preferuje aj konsenzus ADA (American Diabetes Association) a KDIGO (Kidney Disease: Improving Global Outcomes) z roku 2022. Úprava režimových opatrení, liečba artériovej hypertenzie, dyslipidémie a úprava glykemickej kompenzácie tvoria základné piliere manažmentu a sú v kompetencii diabetológa. Preferovanými skupinami v liečbe diabetes mellitus 2. typu sú SGLT2-inhibítory (SGLT2i), GLP1-receptorové agonisty (GLP1-RA) a metformín. Za doplnkové liečivá sú považované inhibítory dipeptidylpeptidázy 4, deriváty sulfonylurey a inzulín. V prípade diabetes mellitus 1. typu zostáva ako jediná terapeutická možnosť inzulínoterapia. Nové skupiny antidiabetík (SGLT2i, GLP1-RA) majú preukázaný nefroprotektívny benefit (spomalenie progresie choroby obličiek, redukcia mikroalbuminúrie). Včasná iniciácia nefroprotektívnej liečby vie výrazne ovplyvniť rizikovosť a mortalitu pacienta. Komplementárne vyskladanie liečby diabetológom a nefrológom je kľúčové v manažmente pacienta. Článok prezentuje možnosti manažmentu diabetickej choroby obličiek zo strany diabetológa, zdôrazňuje potrebu komplexného prístupu a úzku spoluprácu s ďalšími špecialistami.
Chronic kidney disease develops in almost 20–40 % of patients with diabetes. Diabetes mellitus is the leading cause of chronic kidney disease in dialysis patients. The diabetologist has a key role in diagnosis, influencing its progression and the transition to the stage of kidney failure. A patient with confirmed diabetic kidney disease has a very high cardiovascular and sudden death risk. The management of the treatment of a diabetic patient with developed renal complications should therefore be comprehensive in order to influence individual cardiovascular risk factors. A holistic approach is also preferred by the consensus of the ADA (American Diabetes Association) and KDIGO (Kidney Disease: Improving Global Outcomes) from 2022. Adjustment of lifestyle interventions, treatment of arterial hypertension, dyslipidemia and adjustment of glycemic compensation form the basic pillars of management and are the competence of the diabetologist. SGLT2-inhibitors (SGLT2i), GLP1-receptor agonists (GLP1-RA) and metformin are the preferred groups in the treatment of type 2 diabetes mellitus. Dipeptidyl peptidase 4 inhibitors, sulfonylurea derivatives and insulin therapy are considered as complementary drugs. In the case of type 1 diabetes mellitus, insulin therapy remains the only possible option. New groups of antidiabetics (SGLT2i, GLP1-RA) have a proven nephroprotective benefit (slowing down the progression of kidney disease, reducing microalbuminuria). Early initiation of nephroprotective treatment can significantly affect the patient’s risk and mortality. Complementary creating of the treatment by a diabetologist and a nephrologist is key in patient management. This article presents the possibilities of diabetic kidney disease management by a diabetologist, emphasizes the need for a comprehensive approach and close cooperation with other specialists.
- MeSH
- Albuminuria diagnosis drug therapy MeSH
- Renal Insufficiency, Chronic diagnosis complications therapy MeSH
- Diabetes Mellitus diagnosis therapy MeSH
- Diabetic Nephropathies * diagnosis drug therapy MeSH
- Sodium-Glucose Transporter 2 Inhibitors pharmacology therapeutic use MeSH
- Hyperlipidemias diagnosis drug therapy MeSH
- Hypertension drug therapy MeSH
- Diabetes Complications prevention & control therapy MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
Diabetes mellitus predstavuje najčastejšiu príčinu chronickej choroby obličiek (CKD), ktorá postupne vedie až k terminálnemu zlyhaniu s potrebou náhrady funkcie obličiek. Pacienti s ochorením diabetes mellitus 2. typu (DM2T) sú vo vyššom riziku vzniku kardiovaskulárnych príhod (infarkt myokardu, cievna mozgová príhoda, arytmie a srdcové zlyhanie] a progresie chronickej choroby obličiek. Cieľom je predchádzať týmto komplikáciám zmenou životného štýlu, pravidelným monitorovaním hladiny tlaku krvi a glykémií, ale aj užívaním kardioprotektívnych a nefroprotektívnych liečiv. Finerenón ako nesteroidný selektívny antagonista mineralokortikoidných receptorov, predstavuje spolu s inhibítormi angiotenzín-konvertujúceho enzýmu (ACEi) alebo blokátormi angiotenzín II receptorov (ARB) a inhibítormi sodíkovo-glukózového kotransportéru 2 (SGLT2i) základný pilier liečby u pacientov s DM2T a CKD na zabránenie progresie chronickej choroby obličiek a prevencie kardiovaskulárnych príhod. V tomto článku sa nachádzajú bližšie informácie o mechanizme účinku finerenónu, o výsledkoch štúdií zaoberajúcich sa finerenónom (FIDELIO-DKD a FIGARO-DKD) a o indikačných kritériách, ktoré platia na Slovensku a musia byť splnené pred pridaním finerenónu do liečby. Na záver predstavujeme krátku kazuistiku nášho pacienta s ukážkou efektu liečby finerenónom v praxi.
Diabetes mellitus is the most common cause of chronic kidney disease (CKD), which progressively leads to end-stage renal failure with the need for renal replacement. Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cardiovascular events (myocardial infarction, stroke, arrhythmias and heart failure] and progression to chronic kidney disease. The aim is to prevent these complications by lifestyle changes, regular monitoring of blood pressure and glycemic levels, as well as the use of cardioprotective and nephroprotective drugs. Finerenone, as a non-steroidal selective mineralocorticoid receptor antagonist, represents, together with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), the mainstay of treatment in patients with T2DM and CKD to prevent the progression of chronic kidney disease and prevent cardiovascular events. This article provides more information on the mechanism of action of finerenone, the results of the finerenone trials (FIDELIO-DKD and FIGARO-DKD), and the indication criteria that are valid in Slovakia and must be met before finerenone can be added to the treatment regimen. Finally, we present a short case report of our patient showing the effect of finerenone treatment in practice.
- Keywords
- finerenon,
- MeSH
- Mineralocorticoid Receptor Antagonists therapeutic use MeSH
- Renal Insufficiency, Chronic diagnosis drug therapy complications MeSH
- Diabetes Mellitus, Type 2 diagnosis drug therapy complications MeSH
- Diabetes Mellitus diagnosis drug therapy MeSH
- Diabetic Nephropathies * diagnosis epidemiology drug therapy MeSH
- Clinical Studies as Topic MeSH
- Diabetes Complications drug therapy prevention & control MeSH
- Middle Aged MeSH
- Humans MeSH
- Naphthyridines therapeutic use MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
Prezentována kazuistika běžného vývoje diabetických komplikací u pacienta s diabetes mel- litus 2. typu s nižší adherencí k léčbě se zdůrazněním pozitivního přínosu léčby dapagliflo- zinem na zlepšení parametrů CKD.
The case report presents the common development of diabetic complications in a patient with type 2 diabetes mellitus with lower adherence to treatment, emphasizing the positive benefit of dapagliflozin treatment in improving chronic kidney disease parameters.
- Keywords
- dapagliflozin,
- MeSH
- Diabetes Mellitus, Type 2 diagnosis drug therapy complications MeSH
- Diabetic Nephropathies * diagnosis drug therapy blood prevention & control MeSH
- Sodium-Glucose Transporter 2 Inhibitors * pharmacology therapeutic use MeSH
- Glomerular Filtration Rate drug effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Case Reports MeSH
- Keywords
- Finerenon, studie FIDELIO -DKD,
- MeSH
- Albuminuria urine MeSH
- Mineralocorticoid Receptor Antagonists * administration & dosage pharmacology therapeutic use MeSH
- Diabetic Nephropathies * diagnosis diet therapy drug therapy complications MeSH
- Glomerular Filtration Rate MeSH
- Humans MeSH
- Proteinuria urine MeSH
- Randomized Controlled Trials as Topic MeSH
- Renal Insufficiency diagnosis MeSH
- Check Tag
- Humans MeSH
V rozvinutých zemích je diabetes mellitus (DM) jednou z hlavních příčin konečného stadia onemocnění ledvin (end stage renal disease; ESRD). Rozvoj chronického onemocnění ledvin (chronic kidney disease, CKD) navíc dále zvyšuje již tak výrazně zvýšené kardiovaskulární (KV) riziko u pacientů s diabetem. Albuminurie i zhoršená funkce ledvin predikují mortalitu související s KV onemocněním. Multifaktoriální patogeneze CKD související s DM zahrnuje strukturální, fyziologické, hemodynamické a zánětlivé procesy. Namísto tzv. glukocentrického přístupu je podle současných poznatků zapotřebí multimodální - interdisciplinární koncepce léčby, která by rovněž zabránila další progresi CKD a snížila riziko kardiovaskulárních příhod. Kombinovaná antihypertenzní, antihyperglykemická a hypolipidemická terapie je základem komplexního přístupu, který brání progresi diabetického onemocnění ledvin. Podle recentních důkazů je dalším efektivním nástrojem ke zlepšení nefroprotekce u CKD přídatná léčba nesteroidním antagonistou mineralokortikoidních receptorů (MRA) finerenonem - vedle použití blokátoru ACE (angiotenzin konvertující enzym) nebo AT1 (angiotenzin II receptor podtyp 1) a inhibitoru SGLT2 (sodíko‐glukózový kotransportér-2). Cílem předkládaného sdělení je podat stručnou informaci o tomto perspektivním farmakoterapeutickém přístupu k terapii diabetického onemocnění ledvin.
In developed countries, diabetes mellitus (DM) is one of the main causes of end stage renal disease (ESRD). In addition, the development of chronic kidney disease (CKD) further increases the already significantly increased cardiovascular (CV) risk in patients with diabetes. Both albuminuria and impaired renal function predict CV disease-related morbidity. The multifactorial pathogenesis of DM-related CKD involves structural, physiological, hemodynamic, and inflammatory processes. Instead of a so-called glucocentric approach, current evidence suggests that a multimodal, interdisciplinary treatment approach is needed to also prevent further progression of CKD and reduce the risk of cardiovascular events. Combined antihypertensive, antihyperglycemic and hypolipidemic therapy is the basis of a comprehensive approach to prevent the progression of diabetic kidney disease. According to recent evidence, adjunctive therapy with the non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone - in addition to the use of an ACE (angiotensin converting enzyme) or AT1 (angiotensin II receptor subtype 1) blocker and an SGLT2 (sodium-glucose cotransporter-2) inhibitor - represents an effective therapeutic tool to improve nephroprotection in CKD. The aim of this review is to provide brief information on this promising pharmacotherapeutic approach to the treatment of diabetic kidney disease.
- Keywords
- finerenon,
- MeSH
- Mineralocorticoid Receptor Antagonists * administration & dosage pharmacology therapeutic use MeSH
- Renal Insufficiency, Chronic drug therapy complications physiopathology MeSH
- Diabetes Mellitus, Type 2 drug therapy physiopathology MeSH
- Diabetic Nephropathies drug therapy MeSH
- Cardiovascular Diseases drug therapy prevention & control MeSH
- Diabetes Complications drug therapy prevention & control MeSH
- Humans MeSH
- Naphthyridines administration & dosage pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Nefrotický syndrom (NS) je charakterizován velkou proteinurií (nad 3,5 g/24 h), hypalbuminemií, generalizovanými otoky, hyperlipidemií a poruchami koagulace. Vedle primárních glomerulonefritid se vyskytuje u sekundárních glomerulopatií při diabetu, amyloidóze, systémových zánětlivých chorobách, onkologických onemocněních, u poškození léky a drogami, při alergiích, závažných infekcích a u dětí jsou i formy vrozené. Nejčastější příčinou NS v dospělosti je diabetes mellitus (DM). V současnosti je DM příčinou 40 % selhání ledvin u nemocných na dialýze. Z hlediska prevence je proto věnována velká pozornost gliflozinům (SGLT2 inhibitory), které mají prokazatelně nefroprotektivní účinky. Glifloziny vedou k navození glyko- surie, doprovázené současně natriurézou a osmotickou diurézou. Účinnost gliflozinů na snížení glykemie je proporcionální k úrovni glomerulární filtrace, zatímco efekty vázané na natriurézu jsou zachovány ve všech stadiích renální insuficience.
Nephrotic syndrome (NS) is characterized by high proteinuria (over 3,5g/24 hrs), hypalbuminaemia, general edemas and hypercoagulation. Beside of primary glomerulonephritides this is found in secundary glomerulopaties eg. diabetes, systemic inflammatory diseases, oncology, damage by drugs and poisoning, by alergy, serious infections and in children from hereditary reasons. The most frequent reason for NS in adults patiens is diabetes and diabetes with nephropathy represents almost 40% of dialysed patiens. From this point of view, there is great interest focusing on gliflozins (SGLT2 inhibitors) with positive nephroprotecive effect. It leads do increasing of glycosuria with concomitant natriuresis and osmotic diuresis. The effect is proportional to glomerulal filtration, but the effect on natriuresis stay in all stages of renal insufficiency.
- MeSH
- Diabetes Mellitus MeSH
- Diabetic Nephropathies diagnosis drug therapy prevention & control MeSH
- Sodium-Glucose Transporter 2 Inhibitors administration & dosage therapeutic use MeSH
- Hypoproteinemia diagnosis etiology MeSH
- Humans MeSH
- Metabolism MeSH
- Multimorbidity MeSH
- Nephrotic Syndrome * diagnosis etiology therapy MeSH
- Proteinuria diagnosis etiology physiopathology MeSH
- Check Tag
- Humans MeSH
