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Diabetic cardiovascular complications are associated with up to 50% mortality, and current therapies are not effective enough. Renin–angiotensin–aldosterone system inhibitors (RAASis) are the standard of care for diabetic patients with hypertension and albuminuria. Based on our previous studies reporting the renoprotective effects of low-dose RAASis, here, we hypothesized that low-dose RAASi treatment has cardioprotective and antifibrotic benefits in type 1 diabetes mellitus (T1DM). After five weeks of T1DM, adult male Wistar rats received low doses of ramipril, losartan, or eplerenone for two weeks. Heart rate, blood pressure, and pulse wave velocity (PWV) were recorded. Aortic intima–media thickness (IMT), collagen accumulation, and myocardial fibrosis were assessed. All RAASis reduced PWV elevation, prevented the progression of myocardial fibrosis, and normalized B-type natriuretic peptide, troponin I, and fibroblast growth factor 23 levels without affecting blood pressure. Interestingly, only eplerenone reversed the decline in Klotho levels and reduced IMT and fibrosis in the media of the aorta. Our comparative analysis suggests that mineralocorticoid receptor antagonists, particularly eplerenone, may offer superior efficacy in halting both the arterial and the myocardial injuries in T1DM compared to angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.

Angiotensin converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are the standard clinical therapy of diabetic nephropathy (DN), while aldosterone antagonists are only used as adjuncts. Previously in experimental DN we showed that Na/K ATPase (NKA) is mislocated and angiotensin II leads to superimposed renal progression. Here we investigated the monotherapeutic effect of aldosterone blockers on the progression of DN and renal NKA alteration in comparison to ACEi and ARBs. Streptozotocin-diabetic rats developing DN were treated with aldosterone antagonists; ACEi and ARB. Renal function, morphology, protein level and tubular localization of NKA were analyzed. To evaluate the effect of high glucose per se; HK-2 proximal tubular cells were cultured in normal or high concentration of glucose and treated with the same agents. Aldosterone antagonists were the most effective in ameliorating functional and structural kidney damage and they normalized diabetes induced bradycardia and weight loss. Aldosterone blockers also prevented hyperglycemia and diabetes induced increase in NKA protein level and enzyme mislocation. A monotherapy with aldosterone antagonists might be as, or more effective than ACEi or ARBs in the prevention of STZ-induced DN. Furthermore the alteration of the NKA could represent a novel pathophysiological feature of DN and might serve as an additional target of aldosterone blockers.

Objectives: Recognition of chronic kidney disease (CKD) is crucial in type 2 diabetes mellitus (T2DM). We conducted a nationwide epidemiological study to evaluate T2DM-associated CKD in Hungary between 2016 and 2020.Methods: Annual incidence and prevalence rates of registered CKD amongst all pharmacologically treated T2DM patients were analyzed in different age-groups by the central database of the Hungarian Health Insurance Fund Management. Statistical methods included Poisson regression, Bonferroni test, Chi-square test.Results: We found 499,029 T2DM patients and 48,902 CKD patients in 2016, and 586,075 T2DM patients and 38,347 CKD patients in 2020. The majority of all prevalent T2DM and CKD patients were older (aged 60–69 years: 34.1% and 25.8%; ≥70 years: 36.1% and 64.4%, respectively). The annual incidence of T2DM and incidence rates of CKD in T2DM decreased in 2017–2020 (p < 0.001). The annual prevalence of T2DM increased (p < 0.01), the prevalence rates of CKD in T2DM were low and decreased from 9.8% to 6.5% in 2016–2020 (p < 0.001).Conclusion: Incidence and prevalence of T2DM-associated CKD decreased significantly in Hungary in 2016–2020. Lower prevalence rates of CKD may suggest under-recognition and/or under-reporting.

Background: Patients with phenylketonuria (PKU) must maintain a lifelong natural protein-restricted diet to prevent neuro-cognitive damage. Early diagnosis is established with newborn screening, with diet subsequently controlled by regular phenylalanine (Phe) monitoring. During the COVID-19 pandemic, significant lockdown measures were introduced that may have influenced the above. Aim of our study: To establish whether the diagnosis was delayed in neonates during the pandemic. In addition, metabolic control was further assessed during the COVID-19 pandemic era (CE) compared to the same period a year prior (non-COVID-19 era, NCE). The lockdown periods (LD) were also compared with unrestricted periods (URP). Patients, methods: Six neonates born during the CE and eight neonates born during NCE were included in the newborn screening analysis. Seventy-two classical PKU patients aged 2–18 years and categorized as children (2–12 years; 51 patients) and adolescents (>13 years; 21 patients) were included in the metabolic control analysis. The frequency of dried blood spot (DBS) sampling and Phe levels were assessed according to the different periods. Results: There was no diagnostic or therapeutic delay in reaching the recommended Phe range in neonates born during CE compared to those born in NCE (median [interquartile range, IQR]: 23.5 [22.5–24] vs. 22 [18.0–27] days, p = NS). The cumulative DBS sampling frequency in children increased by 9.9% in the CE while no change was noted in the adolescent group. The median Phe level increased significantly in both age groups in the CE, but remained within the recommended target range. During CE, changes in Phe levels differed in the two age groups: children had the highest median Phe in the second lockdown period (LD2), while the adolescents had an increased Phe in URP.There were significant negative correlations between DBS sampling frequencies and Phe levels in both age groups in NCE (children: r − 0.43, p = 0.002; adolescents r = −0.37, p = 0.012), and in adolescents in CE (r = −0.62, p = 0.006). Conclusion: The pandemic did not impact newborn metabolic screening. The increased frequency of DBS sampling in CE and good target Phe levels suggest a better compliance in a very sensitive period. Since many factors may impact metabolic control in the different age groups, further studies are needed to analyse their respective role.

Background: In clinical practice, the possible diagnosis of tuberous sclerosis or polycystic kidney disease is primarily based on clinical criteria, which can later be verified by genetic testing. But in the case of TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1-CGS), the renal appearance of the disease is more serious. Therefore, early genetic analysis is recommended. Methods: Herein we present the report of four children with TSC2/PKD1-CGS, one involving the NTHL1 gene. We aim to emphasize the importance of genetic testing in this rare syndrome. Results: During the follow-up of tuberous sclerosis and polycystic kidney disease patients, it is essential to reappraise the diagnosis if the clinical symptoms’ appearance or onset time is unusual. Targeted genetic testing is recommended. However, early tumor formation necessitates the extension of genetic analysis. Conclusions: An appropriate evaluation of the phenotype is the cornerstone of diagnosing the rare TSC2/PKD1-CGS with the help of genetic results. In addition, malignant tumors could draw attention to an infrequent large deletion.

Background: Phenylketonuria (PKU) is an inherited error of metabolism, screened at 48–72 h of life since 1975 in Hungary. The patients have to keep a strict lifelong protein-restricted diet, resulting in PKU and its treatment can lead to social and financial burdens. The current study aimed to evaluate the health-related quality of life (HRQoL) of children living with PKU. Patients and methods: A single-centre, cross-sectional, observational study was conducted at the Center of Newborn Screening and Inherited Metabolic Disorders of Budapest, Hungary, using the PKU-quality of life (PKU-QoL) questionnaire. Responses of 59 parents and 11 teenagers were collected. Numerous aspects regarding HRQoL were analysed according to clinical compliance and severity. The patients were classified into groups with good or suboptimal adherence based on regular phenylalanine (Phe) values. The online officially translated versions of the adolescent or parental PKU-QoL questionnaire were used and analysed anonymously. Differences in HRQoL were compared - PKU vs. Hyperphenylalaninaemia (HPA) and good vs. suboptimal adherence. Results: Twenty-five of 32 examined parameters had no or little impact on HRQoL. The most frequently reported symptom was irritability. Food enjoyment was the most impacted domain, with a major severity score in the adolescent group (median 62,5, IQR: 25–75). The emotional impact was scored at moderate severity by both the adolescents and parents. Classical PKU patients with good metabolic control were more frequently tired than HPA patients (0,0027). The group with poor metabolic adherence showed more frequent tiredness (p = 0,03), slow thinking (p = 0,018) and anxiety (p = 0,015). Conclusion: Overall, our patients showed an excellent HRQoL; most domains (29/36) were reported as little/no impacted. Worse QoL was found in patients with suboptimal metabolic control. Particular attention should be paid to the emotional health of PKU patients.

Background/Aims: Congenital obstructive nephropathy (CON) is the main cause of pediatric chronic kidney diseases leading to renal fibrosis. High morbidity and limited treatment opportunities of CON urge the better understanding of the underlying molecular mechanisms. Methods: To identify the differentially expressed genes, microarray analysis was performed on the kidney samples of neonatal rats underwent unilateral ureteral obstruction (UUO). Microarray results were then validated by real-time RT-PCR and bioinformatics analysis was carried out to identify the relevant genes, functional groups and pathways involved in the pathomechanism of CON. Renal expression of matrix metalloproteinase (MMP)-12 and interleukin (IL)-24 were evaluated by real-time RT-PCR, flow cytometry and immunohistochemical analysis. Effect of the main profibrotic factors on the expression of MMP-12 and IL-24 was investigated on HK-2 and HEK-293 cell lines. Finally, the effect of IL-24 treatment on the expression of pro-inflammatory cytokines and MMPs were tested in vitro. Results: Microarray analysis revealed 880 transcripts showing >2.0-fold change following UUO, enriched mainly in immune response related processes. The most up-regulated genes were MMPs and members of IL-20 cytokine subfamily, including MMP-3, MMP-7, MMP-12, IL-19 and IL-24. We found that while TGF-β treatment inhibits the expression of MMP-12 and IL-24, H2O2 or PDGF-B treatment induce the epithelial expression of MMP-12. We demonstrated that IL-24 treatment decreases the expression of IL-6 and MMP-3 in the renal epithelial cells. Conclusions: This study provides an extensive view of UUO induced changes in the gene expression profile of the developing kidney and describes novel molecules, which may play significant role in the pathomechanism of CON.