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.
- Klíčová slova
- SGLT2 inhibitor, chronic kidney disease, dapagliflozin, empagliflozin, renal protection, type 2 diabetes,
- MeSH
- benzhydrylové sloučeniny terapeutické užití MeSH
- časná diagnóza * MeSH
- chronická renální insuficience * farmakoterapie diagnóza MeSH
- diabetes mellitus 2. typu * farmakoterapie komplikace MeSH
- diabetické nefropatie * diagnóza prevence a kontrola farmakoterapie MeSH
- glifloziny * terapeutické užití MeSH
- glukosidy terapeutické užití MeSH
- hodnoty glomerulární filtrace účinky léků MeSH
- lidé MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- empagliflozin MeSH Prohlížeč
- glifloziny * MeSH
- glukosidy MeSH
AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis. RESULTS: A total of 1777 participants from 15 centres were included, with 12.3% of these having a high-risk proteomic pattern. Participants in the high-risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low-risk group (n=1559, P<0.02). Numerical differences were small and univariate regression analyses showed weak associations (R2 < 0.04) of CKD273 with each baseline variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin-angiotensin system-blocking agents remained significant determinants of the CKD273 high-risk group: area under the curve 0.72 (95% CI 0.68-0.75; P<0.01). CONCLUSIONS: In this population of individuals with Type 2 diabetes and normoalbuminuria, traditional diabetic kidney disease risk factors differed slightly between participants at high risk and those at low risk of diabetic kidney disease, based on CKD273. These data suggest that CKD273 may provide additional prognostic information over and above the variables routinely available in the clinic. Testing the added value will be subject to our ongoing study. (European Union Clinical Trials Register: EudraCT 2012-000452-34 and Clinicaltrials.gov: NCT02040441).
- MeSH
- analýza moči metody MeSH
- antagonisté mineralokortikoidních receptorů terapeutické užití MeSH
- diabetes mellitus 2. typu komplikace farmakoterapie metabolismus moč MeSH
- diabetické nefropatie diagnóza metabolismus prevence a kontrola moč MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- hypoglykemika terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prognóza MeSH
- proteom analýza metabolismus MeSH
- proteomika metody MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- antagonisté mineralokortikoidních receptorů MeSH
- hypoglykemika MeSH
- proteom MeSH
The number of type 2 diabetic patients is increasing world-wide and a prediction of prevalence of chronic kidney disease up to 2025 in European diabetic population is alarming. Albuminuria and estimated glomerular filtration rate are cardinal biochemical parameters in diagnostics of diabetic nephropathy. Following diagnostic methods are also used: renal ultrasonography, ophthalmoscopy and in not clarified cases renal biopsy. Long-term optimal glycemic control, efficient antihypertensive treatment by angiotensin converting enzyme inhibitor, or angiotensin receptor blocker and recommended protein intake is a cornerstone of therapy. The research is presently focused on new pathophysiological mechanisms, as analysis of genome, microRNA, kidney injury biomarkers and proteomes.Key words: chronic kidney disease - type 2 diabetes mellitus.
- MeSH
- albuminurie diagnóza farmakoterapie etiologie genetika MeSH
- antagonisté receptorů pro angiotenzin terapeutické užití MeSH
- antihypertenziva terapeutické užití MeSH
- biopsie MeSH
- chronická renální insuficience diagnóza farmakoterapie etiologie genetika MeSH
- diabetes mellitus 2. typu komplikace diagnóza farmakoterapie MeSH
- diabetické nefropatie diagnóza farmakoterapie etiologie genetika MeSH
- genomika MeSH
- hodnoty glomerulární filtrace MeSH
- inhibitory ACE terapeutické užití MeSH
- ledviny diagnostické zobrazování patologie MeSH
- lidé MeSH
- mikro RNA MeSH
- oftalmoskopie MeSH
- proteomika MeSH
- ultrasonografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antagonisté receptorů pro angiotenzin MeSH
- antihypertenziva MeSH
- inhibitory ACE MeSH
- mikro RNA MeSH
BACKGROUND: Additional urinary biomarkers for diabetic nephropathy (DN) are needed, providing early and reliable diagnosis and new insights into its mechanisms. Rigorous selection criteria and homogeneous study population may improve reproducibility of the proteomic approach. METHODS: Long-term type 1 diabetes patients without metabolic comorbidities were included, 11 with sustained microalbuminuria (MA) and 14 without MA (nMA). Morning urine proteins were precipitated and resolved by 2D electrophoresis. Principal component analysis (PCA) and Projection to latent structures discriminatory analysis (PLS-DA) were adopted to assess general data validity, to pick protein fractions for identification with mass spectrometry (MS), and to test predictive value of the resulting model. RESULTS: Proteins (n = 113) detected in more than 90% patients were considered representative. Unsupervised PCA showed excellent natural data clustering without outliers. Protein spots reaching Variable Importance in Projection score above 1 in PLS (n = 42) were subjected to MS, yielding 33 positive identifications. The PLS model rebuilt with these proteins achieved accurate classification of all patients (R2X = 0.553, R2Y = 0.953, Q2 = 0.947). Thus, multiple earlier recognized biomarkers of DN were confirmed and several putative new biomarkers suggested. Among them, the highest significance was met in kininogen-1. Its activation products detected in nMA patients exceeded by an order of magnitude the amount found in MA patients. CONCLUSIONS: Reducing metabolic complexity of the diseased and control groups by meticulous patients' selection allows to focus the biomarker search in DN. Suggested new biomarkers, particularly kininogen fragments, exhibit the highest degree of correlation with MA and substantiate validation in larger and more varied cohorts.
- Klíčová slova
- Diabetes, Kallikrein-kinin system, Nephropathy, Proteomics,
- MeSH
- albuminurie diagnóza moč MeSH
- biologické markery moč MeSH
- časná diagnóza MeSH
- diabetické nefropatie diagnóza moč MeSH
- dospělí MeSH
- kalikrein-kininový systém * MeSH
- lidé MeSH
- nefrony metabolismus MeSH
- proteiny metabolismus MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Názvy látek
- biologické markery MeSH
- proteiny MeSH
BACKGROUND: The utility of renal biopsy in patients with diabetes is highly debated. Diabetics with rapidly worsening renal disease are often 'clinically' labelled as having diabetic nephropathy (DN), whereas, in many cases, they are rather developing a non-diabetic renal disease (NDRD) or mixed forms (DN + NDRD). METHODS: We performed a systematic search for studies on patients with diabetes with data on the frequency of DN, NDRD and mixed forms, and assessed the positive predictive values (PPVs) and odds ratios (ORs) for such diagnoses by meta-analysing single-study prevalence. Possible factors explaining heterogeneity among the different diagnoses were explored by meta-regression. RESULTS: In the 48 included studies ( n = 4876), the prevalence of DN, NDRD and mixed forms ranged from 6.5 to 94%, 3 to 82.9% and 4 to 45.5% of the overall diagnoses, respectively. IgA nephropathy was the most common NDRD (3-59%). PPVs for DN, NDRD and mixed forms were 50.1% [95% confidence interval (CI): 44.7-55.2], 36.9% (95% CI: 32.3-41.8) and 19.7% (95% CI: 16.3-23.6), respectively. The PPV when combining NDRD and mixed forms was 49.2% (95% CI: 43.8-54.5). Meta-regression identified systolic pressure, HbA1c, diabetes duration and retinopathy as factors explaining heterogeneity for NDRD, creatinine and glomerular filtration rate for mixed forms and only serum creatinine for DN. ORs of DN versus NDRD and mixed forms were 1.71 (95% CI: 1.54-1.91) and 4.1 (95% CI: 3.43-4.80), respectively. CONCLUSIONS: NDRD are highly prevalent in patients with diabetes. Clinical judgment alone can lead to wrong diagnoses and delay the establishment of adequate therapies. Risk stratification according to individual factors is needed for selecting patients who might benefit from biopsy.
- Klíčová slova
- diabetes, diabetic nephropathy, meta-analysis, non-diabetic nephropathy, renal biopsy,
- MeSH
- biopsie MeSH
- diabetes mellitus 2. typu komplikace chirurgie MeSH
- diabetické nefropatie diagnóza etiologie MeSH
- diferenciální diagnóza MeSH
- hodnoty glomerulární filtrace MeSH
- lidé MeSH
- nemoci ledvin diagnóza etiologie MeSH
- vyšetření funkce ledvin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Elevated resting heart rate (RHR) has been associated with increased risk of mortality and cardiovascular events. Limited data are available so far in type 2 diabetic (T2DM) subjects with no study focusing on progressive renal decline specifically. Aims of our study were to verify RHR as a simple and reliable predictor of adverse disease outcomes in T2DM patients. A total of 421 T2DM patients with variable baseline stage of diabetic kidney disease (DKD) were prospectively followed. A history of the cardiovascular disease was present in 81 (19.2%) patients at baseline, and DKD (glomerular filtration rate < 60 mL/min or proteinuria) was present in 328 (77.9%) at baseline. Progressive renal decline was defined as a continuous rate of glomerular filtration rate loss ≥ 3.3% per year. Resting heart rate was not significantly higher in subjects with cardiovascular disease or DKD at baseline compared to those without. Using time-to-event analyses, significant differences in the cumulative incidence of the studied outcomes, that is, progression of DKD (and specifically progressive renal decline), major advanced cardiovascular event, and all-cause mortality, between RHR
- MeSH
- časové faktory MeSH
- diabetes mellitus 2. typu komplikace diagnóza mortalita patofyziologie MeSH
- diabetické nefropatie diagnóza etiologie mortalita patofyziologie MeSH
- hodnoty glomerulární filtrace MeSH
- Kaplanův-Meierův odhad MeSH
- kardiovaskulární nemoci diagnóza etiologie mortalita patofyziologie MeSH
- ledviny patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- srdeční frekvence * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Diabetes mellitus is the most common cause of end stage kidney disease in the developed countries. Chronic kidney disease-mineral and bone disorder (CKD-MBD) develops with deteriorating of the renal functions. Diabetic patients on hemodialysis are characterized by low bone turnover, higher prevalence of severe and progressive vascular calcification with increased cardiovascular morbidity and mortality. The main factor which causes vascular calcification in patients with diabetic kidney disease (DKD) is poor glycemic control. The recent trial findings describe an inverse correlation between intact parathyroid hormone (iPTH) serum levels and glycemic control in a group of diabetic patients on hemodialysis. AIM: The objective of the proposed project is to access the difference of the laboratory markers MBD in the group of patients with 3rd stage DKD depending on glycemic control. We focused on the relationship between the glycemic compensation of diabetes (HbA1c) and iPTH serum level. PATIENTS AND METHOD: Ninety one patients with 3rd stage DKD were investigated. There were 46 women (50.5 %) and 45 men (49.5 %), average age of patients was 71.2 ± 7.0 years, with creatinine level 128 ± 30 μmol/l and estimated glomerular filtration (eGF, MDRD) 0.82 ± 0.16 ml/s. There were 60 patients with better glycemic control of diabetes (HbA1c < 7 %) vs 29 patients with poorly controlled diabetes (HbA1c > 7 %). MBD markers were compared in both groups. Patients were further stratified into subgroups based on the serum level of iPTH (iPTH < 35 pg/ml vs iPTH > 35 pg/ml) and MBD markers compared. Statistical analysis was performed using and Mann-Whitney test. RESULTS: We have found the statistical significance in the serum phosphate and proteinuria levels in between groups with HbA1c < 7 % vs patients with HbA1c > 7 %. Diabetics with better glycemic control had significant reduction in serum phosphate level (1.14 ± 0.20 vs 1.23 ± 0.18 mmol/l, p = 0.038) and in 24 hrs proteinuria level (0.56 ± 1.35 vs 1.30 ± 1.61 g/day, p = 0.007). In the group of presumed low bone turnover (iPTH < 35 pg/ml) we have found the trend towards increased serum calcium level (2.49 ± 0.12 vs 2.43 ± 0.10 mmol/l, p = 0.063) and increased HbA1c value (7.5 ± 1.8 vs 6.4 ± 1.6 %, p = 0.023). CONCLUSION: Our results suggest the closer relationship between glycemic control of diabetes and mineral-bone disorder in earlier stages of DKD. KEY WORDS: diabetes mellitus type 2 (DM2T) - chronic kidney disease (CKD) - mineral and bone disorder (MBD).
- MeSH
- biologické markery analýza MeSH
- chronické selhání ledvin diagnóza MeSH
- diabetes mellitus 2. typu komplikace MeSH
- diabetické nefropatie krev diagnóza MeSH
- krevní glukóza metabolismus MeSH
- lidé MeSH
- minerálová a kostní nemoc při chronickém onemocnění ledvin krev diagnóza MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- krevní glukóza MeSH
Epidemiological studies show increasing prevalence of diabetic nephropathy. Diabetic patients with chronic kidney disease are the biggest group from among patients on renal replacement therapy. Renal Pathology Society developed pathological classification of diabetic nephropathy. The cardinal biochemical diagnostic parameters are albuminuria and estimated glomerular filtration rate. European Renal Best Practice work group developed Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher.
BACKGROUND/AIMS: Calcium-Sensing Receptor (CaSR) significantly affects calcium-phosphate metabolism in kidneys, and it is implicated in the pathogenesis of diabetes mellitus (DM) due to its expression in pancreatic β-cells. The role of CaSR as one of the players in pathogenesis of chronic kidney disease (CKD) has been speculated. METHODS: 158 Type 2 diabetic patients divided into three groups according to occurrence and type of kidney complications, 66 nondiabetic patients CKD, and 93 healthy subjects were enrolled into the study to analyze the role of two CaSR polymorphisms (in the codon 990 and in the intron 4) in ethiopathogenesis of DM and CKD. The Type 2 diabetic groups consisted of 48 patients without any kidney abnormalities, 58 patients with diabetic nephropathy (DN), and 52 patients with nondiabetic renal disease (NDRD). The distribution of genotype and allele frequencies was studied using PCR with the TaqMan Discrimination Assay or followed by the Restriction Fragment Length Polymorphism method, respectively. RESULTS: We have found that the intron 4 polymorphism is a risk factor for the development of DM and CKD, except DN, while the codon 990 does not show any disease association. CONCLUSION: We conclude that CaSR is a general factor in pancreas and kidney pathologies.
- MeSH
- chronická nemoc MeSH
- diabetes mellitus 2. typu diagnóza genetika MeSH
- diabetické nefropatie diagnóza genetika MeSH
- dospělí MeSH
- introny genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- komplikace diabetu diagnóza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci ledvin diagnóza genetika MeSH
- receptory "calcium-sensing" genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- CASR protein, human MeSH Prohlížeč
- receptory "calcium-sensing" MeSH
BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273). METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier. RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found. CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.
- Klíčová slova
- biomarkers, chronic kidney disease, diabetic nephropathy, diagnosis, urine proteomics,
- MeSH
- diabetes mellitus 2. typu komplikace diagnóza moč MeSH
- diabetické nefropatie diagnóza etiologie moč MeSH
- diferenciální diagnóza MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- peptidomimetika moč MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- proteomika metody MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- validační studie MeSH
- Názvy látek
- peptidomimetika MeSH
