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Journal of Clinical Medicine Jun 2024Granulomatous tubulointerstitial nephritis (GTIN) attributed to early onset sarcoidosis is an ultrarare finding in an allograft kidney biopsy. We present the case of a... (Review)
Review
Granulomatous tubulointerstitial nephritis (GTIN) attributed to early onset sarcoidosis is an ultrarare finding in an allograft kidney biopsy. We present the case of a young man with allograft dysfunction who had GTIN upon biopsy. We performed a thorough case review based on recovered records from early childhood and reassessed genetic testing results. We revised his underlying diagnosis from cryopyrin-associated periodic syndrome to early-onset sarcoidosis with wild-type and established a rationale to use the interleukin-6 (IL-6) receptor blocker tocilizumab (TCZ). This suppressed his inflammatory disease and stabilised kidney function. We performed a literature review related to the emerging role of IL-6 pathway blockade in kidney transplantation. We identified 18 reports with 417 unique patients treated with TCZ for indications including HLA-desensitisation, transplant immunosuppression induction, treatment of chronic antibody-mediated rejection, and treatment of subclinical rejection. Both TCZ and the direct IL-6 inhibitor clazakizumab are being studied in ongoing randomised control trials.
PubMed: 38929956
DOI: 10.3390/jcm13123427 -
Journal of Clinical Medicine Jun 2024This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve...
This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve decongestion in the context of patients hospitalized for acute heart failure (HF). However, data in terms of safety are lacking. We conducted a monocentric observational prospective study from November 2023 to February 2024 in a 12-bed cardiology department, recording adverse events (hypotension, severe metabolic acidosis, severe hypokalemia and renal events) during in-hospital HF treatment. All patients hospitalized for acute HF during the study period treated with ACZ (500 mg IV daily for 3 days) on top of IV furosemide ( = 28, 48.3%) were compared with patients who have been treated with IV furosemide alone ( = 30, 51.7%). The patients treated with ACZ were younger than those without (median age 78 (range 67-86) vs. 85 (79-90) years, respectively, = 0.01) and had less frequent chronic kidney disease (median estimated glomerular fraction rate (60 (35-65) vs. 38 (26-63) mL/min, = 0.02). As concerned adverse events during HF treatment, there were no differences in the occurrences of hypotension (three patients [10.7%] in the ACZ group vs. four [13.3%], = 0.8), renal events (four patients [14.3%] in the ACZ group vs. five [16.7%], = 1) and severe hypokalemia (two [7.1%] in the ACZ group vs. three [10%], = 1). No severe metabolic acidosis occurred in either group. Although the clinical characteristics differed at baseline, with younger age and better renal function in patients receiving ACZ, the tolerance profile did not significantly differ from patients receiving furosemide alone. Additional observational data are needed to further assess the safety of ACZ-furosemide combination in the in-hospital management of HF, especially in older, frail populations.
PubMed: 38929950
DOI: 10.3390/jcm13123421 -
Journal of Clinical Medicine Jun 2024: Sex differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity...
: Sex differences characterize the prevalence and attitudes toward weight management. Despite limited evidence suggesting greater weight loss in women with anti-obesity pharmacotherapy, sex-specific analysis remains underexplored. This retrospective study aimed to evaluate the sex-specific response to liraglutide 3.0 mg treatment in people with obesity without type 2 diabetes (T2D). : Data were collected from 47 patients (31 women, 16 men) with age > 18 years; BMI ≥ 30 kg/m; absence of T2D; and exclusion of prior anti-obesity treatment, comorbidities, or bariatric surgery. Only patients who maintained the liraglutide 3.0 mg dose for at least 6 months were included. : Both sexes showed significant reductions in weight and BMI at 3 and 6 months. Men achieved greater weight loss (WL), BMI reduction, %WL, WL > 5%, and >10% than women, and they also showed more significant improvements in metabolic parameters (total and LDL cholesterol, Fibrosis-4 Index FIB-4). No significant sex differences were observed in glucose metabolism or renal function. : This study showed a greater therapeutic effect of liraglutide 3.0 mg in men. Given men's higher risk of cardiovascular disease (CVD), and underrepresentation in clinical weight loss programs, these findings may increase male engagement and improve their CVD risk.
PubMed: 38929898
DOI: 10.3390/jcm13123369 -
Life (Basel, Switzerland) Jun 2024Although lysophosphatidic acid (LPA) is known to have multiple pathophysiological roles, its contributions to ocular tissues, especially conjunctival fibrogenesis,...
BACKGROUND
Although lysophosphatidic acid (LPA) is known to have multiple pathophysiological roles, its contributions to ocular tissues, especially conjunctival fibrogenesis, remain to be elucidated.
METHODS
To study this issue, the effects of LPA on transforming growth factor-β2 (TGF-β2)-induced fibrogenesis of two-dimensional (2D) and three-dimensional (3D) cultures of human conjunctival fibroblasts (HconF) were examined by the following analyses: (1) planar proliferation determined by transepithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran permeability measurements, (2) real-time metabolic analyses, (3) measurements of the size and stiffness of 3D spheroids, and (4) mRNA expression of extracellular matrix (ECM) molecules and their modulators.
RESULTS
LPA had no effect on TGF-β2-induced increase in the planar proliferation of HconF cells. LPA induced a more quiescent metabolic state in 2D HconF cells, but this metabolic suppression by LPA was partially blunted in the presence of TGF-β2. In contrast, LPA caused a substantial decrease in the hardness of 3D HconF spheroids independently of TGF-β2. In agreement with these different LPA-induced effects between 2D and 3D cultured HconF cells, mRNA expressions of ECM and their modulators were differently modulated.
CONCLUSION
The findings that LPA induced the inhibition of both TGF-β2-related and -unrelated subepithelial proliferation of HconF cells may be clinically applicable.
PubMed: 38929752
DOI: 10.3390/life14060770 -
Life (Basel, Switzerland) May 2024Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity....
BACKGROUND
Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited.
METHODS
Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide.
RESULTS
A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5-20) prior to the initiation of afamelanotide and 120 min (IQR, 60-240) after treatment ( < 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment.
CONCLUSIONS
This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.
PubMed: 38929673
DOI: 10.3390/life14060689 -
Medicina (Kaunas, Lithuania) Jun 2024: Interatrial block (IAB) is defined as a conduction delay between the right and left atria. No data are available about the prevalence of both partial IAB and advanced...
: Interatrial block (IAB) is defined as a conduction delay between the right and left atria. No data are available about the prevalence of both partial IAB and advanced IAB among the different stages of chronic kidney disease. The aim of this study was to describe the prevalence and type of advanced IAB across the spectrum of renal function, including patients on dialysis and the clinical characteristics associated with advanced IAB. : Retrospective, single-center study of 151 patients consecutively admitted to the Nephrology and Ophthalmology Unit for 3 months. The study population was divided into three groups according to stages of chronic kidney disease. We evaluated the prevalence and pattern of IAB among the groups and the clinical characteristics associated with advanced IAB. : The prevalence of partial IAB was significantly lower in end-stage kidney disease (ESKD) group compared to control group (36.7% vs. 59.6%; = 0.02); in contrast the prevalence of advanced IAB was significantly higher in both chronic kidney disease (CKD) (17.8% vs. 5.3%, = 0.04) and ESKD group (24.5% vs. 5.3%, = 0.005) compared to control group. The atypical pattern of advanced IAB was more frequent in both the ESKD and CKD group than in the control group (100% and 75% vs. 33.3%; = 0.02). Overall, among patients that showed advanced IAB, 17 (73.9%) showed an atypical pattern by morphology and 2 (8.7%) showed an atypical pattern by duration of advanced IAB. The ESKD group was younger than the control group (65.7 12.3 years vs. 71.3 ± 9.9 years; = 0.01) and showed a higher prevalence of beta blockers (42.9% vs. 19.3%; = 0.009), as in the CKD group (37.8% vs. 19.3%; = 0.04). The progressive worsening of renal function was associated with an increasing prevalence of advanced IAB. Advanced IAB may be a sign of uremic cardiomyopathy and may suggest further evaluation with long-term follow-up to investigate its prognostic significance in chronic kidney disease.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Aged; Interatrial Block; Prevalence; Renal Insufficiency, Chronic; Kidney Failure, Chronic; Aged, 80 and over; Renal Dialysis
PubMed: 38929618
DOI: 10.3390/medicina60061001 -
Medicina (Kaunas, Lithuania) Jun 2024This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Baseline characteristics and...
This study aimed to assess the prevalence, predictors, and outcomes of pulmonary hypertension (PH) in patients with lupus nephritis (LN). Baseline characteristics and clinical outcomes of 387 patients with LN were retrospectively collected from 2007 to 2017. PH was defined as pulmonary artery systolic pressure ≥40 mmHg assessed by resting transthoracic echocardiography. The primary endpoint was all-cause mortality. The secondary endpoint was renal events, defined as the doubling of baseline serum creatinine or end-stage renal disease. Associations between PH and outcomes were analyzed by Cox regression models. A total of 15.3% (59/387) of patients with LN were diagnosed with PH, and the prevalence of PH was higher for patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m compared to those with an eGFR ≥ 30 mL/min/1.73 m (31.5% vs. 12.6%). Higher mean arterial pressure, lower hemoglobin, and lower triglyceride levels were associated with greater odds of having PH. After adjusting for relevant confounding variables, PH was independently associated with a higher risk for death (HR: 2.01; 95% CI: 1.01-4.00; = 0.047) and renal events (HR: 2.07; 95% CI: 1.04-4.12; = 0.039). PH is an independent risk factor for all-cause mortality and adverse renal outcomes in patients with LN.
Topics: Humans; Female; Male; Hypertension, Pulmonary; Lupus Nephritis; Adult; Retrospective Studies; Prevalence; Middle Aged; Glomerular Filtration Rate; Risk Factors; Proportional Hazards Models
PubMed: 38929605
DOI: 10.3390/medicina60060988 -
Serum Endocan Is a Risk Factor for Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis.Medicina (Kaunas, Lithuania) Jun 2024: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and...
: Endocan, secreted from the activated endothelium, is a key player in inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and angiogenesis. We aimed to investigate the link between endocan and aortic stiffness in maintenance hemodialysis (HD) patients. : After recruiting HD patients from a medical center, their baseline characteristics, blood sample, and anthropometry were assessed and recorded. The serum endocan level was determined using an enzyme immunoassay kit, and carotid-femoral pulse wave velocity (cfPWV) measurement was used to evaluate aortic stiffness. : A total of 122 HD patients were enrolled. Aortic stiffness was diagnosed in 53 patients (43.4%), who were found to be older ( = 0.007) and have a higher prevalence of diabetes ( < 0.001) and hypertension ( = 0.030), higher systolic blood pressure ( = 0.011), and higher endocan levels ( < 0.001), when compared with their counterparts. On the multivariate logistic regression model, the development of aortic stiffness in patients on chronic HD was found to be associated with endocan [odds ratio (OR): 1.566, 95% confidence interval (CI): 1.224-2.002, < 0.001], age (OR: 1.040, 95% CI: 1.001-1.080, = 0.045), and diabetes (OR: 4.067, 95% CI: 1.532-10.798, = 0.005), after proper adjustment for confounders (adopting diabetes, hypertension, age, systolic blood pressure, and endocan). The area under the receiver operating characteristic curve was 0.713 (95% CI: 0.620-0.806, < 0.001) for predicting aortic stiffness by the serum endocan level, at an optimal cutoff value of 2.68 ng/mL (64.15% sensitivity, 69.57% specificity). Upon multivariate linear regression analysis, logarithmically transformed endocan was proven as an independent predictor of cfPWV (β = 0.405, adjusted R change = 0.152; < 0.001). : The serum endocan level positively correlated with cfPWV and was an independent predictor of aortic stiffness in chronic HD patients.
Topics: Humans; Vascular Stiffness; Male; Proteoglycans; Female; Middle Aged; Renal Dialysis; Risk Factors; Neoplasm Proteins; Aged; Adult; Pulse Wave Analysis; ROC Curve; Biomarkers; Logistic Models; Cross-Sectional Studies
PubMed: 38929601
DOI: 10.3390/medicina60060984 -
Medicina (Kaunas, Lithuania) May 2024Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial... (Review)
Review
Chronic kidney disease (CKD) is characterized by persistent kidney dysfunction, ultimately resulting in end-stage renal disease (ESRD). Renal fibrosis is a crucial pathological feature of CKD and ESRD. However, there is no effective treatment for this condition. Despite the complex molecular mechanisms involved in renal fibrosis, increasing evidence highlights the crucial role of histone modification in its regulation. The reversibility of histone modifications offers promising avenues for therapeutic strategies to block or reverse renal fibrosis. Therefore, a comprehensive understanding of the regulatory implications of histone modifications in fibrosis may provide novel insights into more effective and safer therapeutic approaches. This review highlights the regulatory mechanisms and recent advances in histone modifications in renal fibrosis, particularly histone methylation and histone acetylation. The aim is to explore the potential of histone modifications as targets for treating renal fibrosis.
Topics: Humans; Fibrosis; Histones; Renal Insufficiency, Chronic; Kidney; Acetylation; Methylation; Protein Processing, Post-Translational; Histone Code
PubMed: 38929505
DOI: 10.3390/medicina60060888 -
Medicina (Kaunas, Lithuania) May 2024: The configuration of the aortic arch, particularly a Gothic arch shape, in individuals with corrected coarctation of the aorta (CoA) has been associated with a...
: The configuration of the aortic arch, particularly a Gothic arch shape, in individuals with corrected coarctation of the aorta (CoA) has been associated with a decreased systolic wave amplitude across the arch, which could potentially impair renal perfusion and elevate the risk of arterial hypertension. This study aims to explore the relationship between the morphological characteristics of the aortic arch and their impact on renal perfusion in patients with CoA. : Seventy-one subjects with corrected CoA underwent continuous 24 h ambulatory blood pressure monitoring, computed tomography to assess the aortic arch, and renal perfusion scanning. Subjects were stratified into three groups based on the height-to-width (H/W) ratio of their aortic arch: Group 1 with a H/W ratio of <0.65, Group 2 with a H/W ratio between 0.65 and 0.85, and Group 3 with a H/W ratio of >0.85. : Groups 1 and 2 (53,78% and 62.63%) presented with a higher hypertension prevalence of elevated blood pressure than Group 3 (38.89%). Notable variations were observed among the subjects in the time to peak perfusion (Tmax) in the left kidney across the groups. Group 1 showed a median T at 0.27, Group 2 at 0.13, and Group 3 at -0.38 (-value = 0.079). The differences in T for the right kidney followed a similar trend but were not statistically significant (Group 1 at 0.61, Group 2 at 0.22, and Group 3 at 0.11; -value = 0.229). : This study suggests that variations in the aortic arch morphology might not significantly influence renal perfusion in CoA patients. This indicates the potential adaptability of the renal blood flow, which appears to compensate for reduced perfusion, thus minimizing adverse effects on the kidney function. This adaptability suggests an inherent physiological resilience, emphasizing the need for further targeted research to understand the specific interactions and impacts on treatment strategies for CoA.
Topics: Humans; Aortic Coarctation; Female; Male; Adult; Aorta, Thoracic; Hypertension; Kidney; Tomography, X-Ray Computed; Blood Pressure Monitoring, Ambulatory; Middle Aged; Adolescent
PubMed: 38929503
DOI: 10.3390/medicina60060886