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13 pages, 1971 KiB  
Article
Clinical Outcomes of Iron Supplement Therapy in Non-Anemic Female CKD Stage 3 Patients with Low Serum Ferritin Level: A Multi-Institutional TriNetX Analysis
by Hsi-Chih Chen, Min-Tser Liao, Joshua Wang, Kuo-Wang Tsai, Chia-Chao Wu and Kuo-Cheng Lu
J. Clin. Med. 2025, 14(15), 5575; https://doi.org/10.3390/jcm14155575 - 7 Aug 2025
Abstract
Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes [...] Read more.
Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m2), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article
(This article belongs to the Section Nephrology & Urology)
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26 pages, 6880 KiB  
Article
IgA Nephropathy in Native Kidneys: Oxford and Banff Classifications Reveal Distinct Profiles and Predict Outcomes in Pediatric and Adult Patients
by Danijel Milivojević, Gorana Nikolić, Björn Tampe, Maja Pecić, Snežana Babac, Dušan Paripović, Gordana Miloševski Lomić, Voin Brković, Marko Baralić, Aleksandar Janković, Petar Đurić, Nataša Stajić, Jovana Putnik, Sanja Radojević Škodrić and Maja Životić
Life 2025, 15(8), 1231; https://doi.org/10.3390/life15081231 - 3 Aug 2025
Viewed by 226
Abstract
IgA nephropathy is the most common primary glomerulonephritis, with pathohistological changes described by the Oxford classification, while the Banff classification is used in transplant pathology. This study included 253 patients with IgA nephropathy in native kidneys, divided into the pediatric (n = [...] Read more.
IgA nephropathy is the most common primary glomerulonephritis, with pathohistological changes described by the Oxford classification, while the Banff classification is used in transplant pathology. This study included 253 patients with IgA nephropathy in native kidneys, divided into the pediatric (n = 105) and adult (n = 148) groups. It aimed to examine clinical, and Oxford and Banff morphological parameters in relation to age, correlations of clinical data with pathohistological parameters, and predictors of the disease outcome. Pediatric patients more frequently presented with macroscopic hematuria, while adults showed higher urea and creatinine levels, and lower eGFR. Examining Oxford classification parameters, chronic glomerular and tubulointerstitial lesions were more common in adults. Banff parameters revealed more frequent chronically active glomerular, inflammatory, chronic tubulointerstitial, and vascular lesions in adults. All inflammatory, chronic tubulointerstitial, and vascular parameters correlated with serum urea levels, eGFR and CKD stage in adults, while less frequent in pediatric patients. Tubulointerstitial Oxford and Banff parameters were strong predictors of CKD and proteinuria progression in children, while such predictors were fewer in adults; segmental glomerulosclerosis predicted hematuria progression in adults. Banff parameters (cg, t, ti, i, i-IFTA, ptc, cv), not in Oxford classification, significantly predict outcomes and are recommended for incorporation into IgA nephropathy reports. Full article
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12 pages, 552 KiB  
Article
Impact of Kidney Function on the Survival of Patients with Chagas Cardiomyopathy and Implantable Cardioverter Defibrillators
by Fernanda Pinheiro Martin Tapioca, Luiz Carlos Santana Passos, Caio Cafezeiro, Willian Carvalho, Paulo Novis Rocha and Maria Gabriela Guimarães
J. Clin. Med. 2025, 14(14), 4862; https://doi.org/10.3390/jcm14144862 - 9 Jul 2025
Viewed by 373
Abstract
Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients [...] Read more.
Background/Objectives: Impaired kidney function significantly increases mortality in recipients of implantable cardioverter defibrillators (ICDs). However, in the landmark studies evaluating ICDs and cardiac resynchronization therapy with a defibrillator (CRT-D) for the treatment of heart failure (HF) with a reduced ejection fraction (HFrEF), patients with Chagas cardiomyopathy (CC) have been underrepresented. This study aimed to determine whether kidney dysfunction has the same negative impacts on patients with ICDs or CRT-Ds and CC. Methods: We prospectively followed patients with CC and left ventricular ejection fractions (LVEFs) of ≤40% who underwent ICD or CRT-D implantation and had at least one prior creatinine measurement. The primary outcome was the survival rate during follow-up. Variables with a p of <0.10 from the univariate analysis were selected for inclusion in the Cox regression model. Results: A total of 343 patients were enrolled, with a median follow-up duration of 777 days. The mean age was 60.2 (±11.2) years. Fifty percent of patients were observed to have a New York Heart Association (NYHA) functional class of III, and the median left ventricular ejection fraction (LVEF) was 27% (22–32). Overall mortality events occurred in 113 (32.9%) participants during follow-up. Although the estimated glomerular filtration rate (eGFR) was significantly associated with survival in the univariate analysis [HR 0.98 (CI 95% 0.98–0.99), p = 0.007], it did not retain significance in the multivariate model [HR 0.99 (0.98–1.00), p = 0.138], which was adjusted for age, gender, atrial fibrillation (AF), body mass index (BMI), and the use of digoxin, furosemide, anticoagulants, and LVEF. Conclusions: Unlike other cardiomyopathies, impaired eGFR was not an independent predictor of mortality in this cohort of CC patients undergoing ICD or CRT-D implantation, possibly due to the distinctive pathophysiological mechanisms of the disease. These findings suggest that clinicians should not be discouraged from recommending CIEDs in patients with CC and moderately impaired kidney function, although further studies are warranted to assess outcomes in those with advanced CKD. Full article
(This article belongs to the Section Nephrology & Urology)
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20 pages, 1474 KiB  
Review
Protocol Biopsies in Kidney Transplant Recipients: Current Practice After Much Discussion
by Christina Lazarou, Eleni Moysidou, Michalis Christodoulou, Stamatia Stai, Georgios Lioulios, Efstratios Kasimatis, Asimina Fylaktou and Maria Stangou
Biomedicines 2025, 13(7), 1660; https://doi.org/10.3390/biomedicines13071660 - 7 Jul 2025
Viewed by 490
Abstract
Protocol biopsies are a fundamental component in the management of kidney transplant recipients, offering critical insights into graft health by detecting subclinical pathological changes undetectable through routine clinical and laboratory assessments. Conducted at predetermined intervals, these biopsies enable early identification of subclinical rejection, [...] Read more.
Protocol biopsies are a fundamental component in the management of kidney transplant recipients, offering critical insights into graft health by detecting subclinical pathological changes undetectable through routine clinical and laboratory assessments. Conducted at predetermined intervals, these biopsies enable early identification of subclinical rejection, chronic allograft nephropathy, drug-induced toxicities, viral infections such as BK polyomavirus nephropathy, and recurrence of primary glomerular diseases. Early detection facilitates timely therapeutic interventions, including immunosuppressive regimen adjustments, which are pivotal in preserving graft function and improving long-term outcomes. While the optimal timing and frequency of protocol biopsies vary, early post-transplant biopsies within the first year are widely advocated. High-risk groups, including ABO- and HLA-incompatible recipients and those with recurrent primary nephropathies, particularly benefit from surveillance biopsies. Despite the invasive nature and associated risks of biopsy procedures, most experts agree that the benefits outweigh the risks in selected populations. However, the role of routine protocol biopsies in low-risk patients remains debated due to unclear long-term outcome improvements and resource considerations. Retrospective observational studies have demonstrated the ability of protocol biopsies to detect subclinical pathological changes such as rejection, drug toxicity, viral infections, and recurrent diseases before clinical or laboratory abnormalities appear. These studies also highlight the impact of biopsy-guided interventions on graft survival and management in high-risk groups (e.g., HLA- and ABO-incompatible recipients, and patients at risk for disease recurrence). Furthermore, randomized controlled trials provide higher-level evidence showing that protocol biopsy-guided interventions improve graft function, reflected by better serum creatinine levels and glomerular filtration rates, compared to indicated biopsies alone. They also emphasize the importance of both early and late surveillance biopsies for predicting long-term outcomes. Expert opinion and consensus acknowledge the benefits of protocol biopsies for early detection and tailored management but also highlight ongoing debates regarding their routine use in low-risk patients due to risks, costs, and resource considerations. Overall, protocol biopsies represent a valuable tool for personalized graft monitoring and management, aiding in early detection of complications, guiding immunosuppressive therapy, and enhancing graft longevity. Further multicenter randomized trials are needed to refine guidelines and optimize their clinical utility. Full article
(This article belongs to the Special Issue Pharmaceutical Treatments for Typical CKD Comorbidities)
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15 pages, 946 KiB  
Review
Focal and Segmental Glomerulosclerosis: A Comprehensive State-of-the-Art Review
by Dearbhail Ni Cathain, Donnchadh Reidy, Serena Bagnasco and Sam Kant
Sclerosis 2025, 3(3), 24; https://doi.org/10.3390/sclerosis3030024 - 1 Jul 2025
Viewed by 512
Abstract
Focal and segmental glomerulosclerosis (FSGS) describes a histological pattern of injury seen by light microscopy in kidney biopsy specimens and is the end result of various injuries to the podocyte. Our understanding of this disease entity has evolved greatly since it was first [...] Read more.
Focal and segmental glomerulosclerosis (FSGS) describes a histological pattern of injury seen by light microscopy in kidney biopsy specimens and is the end result of various injuries to the podocyte. Our understanding of this disease entity has evolved greatly since it was first described, with particular focus on changes in the classification of FSGS as a disease entity and expansion in our understanding of the underlying pathophysiology. The incidence and prevalence of FSGS and FSGS-associated end-stage kidney disease (ESKD) have increased globally, particularly in the United States; it is now the most common primary glomerular disorder in those with ESKD. APOL-1 is likely responsible for this epidemiological trend in kidney disease in the US and is an important focus of clinical trials and potential targeted therapies. Currently, the goal of treatment in FSGS is to achieve remission of proteinuria and to prevent progression to ESKD. Remission is achieved by using immunosuppressive therapies in primary FSGS, but treatment in secondary and genetic FSGS is largely supportive. Recurrent FSGS (rFSGS) post-transplantation remains a significant clinical challenge to nephrologists; current monitoring and treatment strategies are based on retrospective meta-analysis and observational studies with no clear consensus as to the optimum approach. Emerging therapies are focused on developing more targeted interventions in genetic and secondary FSGS. This review article aims to comprehensively explore this multifaceted disease entity. Full article
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15 pages, 864 KiB  
Systematic Review
Targeting the Roots of Kidney Disease: Systematic Review of the Therapies Targeting the Complement System
by Maja Roman and Michał Nowicki
Medicina 2025, 61(7), 1205; https://doi.org/10.3390/medicina61071205 - 1 Jul 2025
Viewed by 820
Abstract
Background/Objectives: The field of nephrology is increasingly embracing advanced treatments and clinical trials that focus on inhibiting specific components of the complement cascade, a key driver in complement-mediated kidney diseases. Materials and Methods: This review aims to summarize innovative therapies targeting [...] Read more.
Background/Objectives: The field of nephrology is increasingly embracing advanced treatments and clinical trials that focus on inhibiting specific components of the complement cascade, a key driver in complement-mediated kidney diseases. Materials and Methods: This review aims to summarize innovative therapies targeting various pathways, including the inhibition of the terminal part of the complement pathway (mainly C5), the alternative pathway (factor B inhibitors), and the lectin pathway (MASP inhibitors. C5 inhibitors play a critical role in preventing the formation of the membrane attack complex (MAC), offering effective solutions for conditions like atypical hemolytic uremic syndrome (aHUS) and paroxysmal nocturnal hemoglobinuria (PNH). Meanwhile, avacopan, a C5a receptor antagonist, addresses ANCA-associated vasculitis (AAV) by mitigating inflammation and enabling reduced reliance on corticosteroids. Similarly, narsoplimab, which inhibits MASP-2, targets the lectin pathway implicated in conditions such as aHUS. Iptacopan, a factor B inhibitor, focuses on the alternative pathway and demonstrates efficacy in managing C3 glomerulopathy (C3G). Results: A systematic review of complement-targeted therapies was conducted, analysing studies from 2013 to 2023 that address unmet medical needs in primary and secondary glomerular diseases. Conclusions: Our systematic review of complement-targeted therapies shows that these tailored and innovative treatments may specifically address unmet medical needs in primary and secondary glomerular diseases. Full article
(This article belongs to the Section Urology & Nephrology)
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12 pages, 302 KiB  
Article
The Impact of a 10-Month Synbiotic Intake on eGFR, Uremic Toxins, Oxidative Stress, and Inflammatory Markers in Non-Dialysis Chronic Kidney Disease Patients: A Prospective, Non-Randomized, Placebo-Controlled Study
by Teodor Kuskunov, Eduard Tilkiyan, Irina Zdravkova, Siyana Valova, Krasimir Boyanov and Anelia Bivolarska
Medicina 2025, 61(7), 1199; https://doi.org/10.3390/medicina61071199 - 30 Jun 2025
Viewed by 354
Abstract
Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic [...] Read more.
Background and Objectives: The worldwide prevalence of chronic kidney disease (CKD) continues to increase, representing a major concern for public health systems. CKD is associated with gut microbiota dysbiosis, which may exacerbate disease progression by increasing the levels of uremic toxins, systemic inflammation, and oxidative stress. Modulation of the gut microbiota through biotic supplementation has been proposed as a potential therapeutic strategy to slow CKD progression and mitigate its complications. This study aimed to evaluate the effect of 10-month synbiotic supplementation on estimated glomerular filtration rate (eGFR), circulating concentrations of indoxyl sulfate (IS), p-cresyl sulfate (p-CS), interleukin-6 (IL-6), and malondialdehyde (MDA) in patients with stage IV–V CKD not receiving dialysis, in comparison to placebo. Materials and Methods: Fifty non-dialysis CKD IV–V patients were assigned (n = 25 each) via matched, non-randomized allocation (age, sex, and primary disease) to synbiotic or placebo. This single-blind, placebo-controlled trial blinded participants and laboratory personnel. The synbiotic group received daily capsules containing Lactobacillus acidophilus La-14 (2 × 1011 CFU/g) + fructooligosaccharides; controls received identical placebo. Adherence was monitored monthly (pill counts, diaries), with < 80% over two visits resulting in withdrawal. The eGFR, IS, p-CS, IL-6, and MDA were measured at baseline and month 10. Results: Forty-two patients (21/arm) completed the study; eight withdrew (4 per arm). At 10 months, the change in eGFR was −1.2 ± 2.5 mL/min/1.73 m2 (synbiotic) vs. −3.5 ± 3.0 mL/min/1.73 m2 (placebo); between-group difference in change was 2.3 mL/min/1.73 m2 (95% CI: 0.5–4.1; p = 0.014; adjusted p = 0.07). IS decreased by −15.4 ± 8.2 ng/L vs. −3.1 ± 6.5 ng/L; between-group difference in change was −12.3 ng/L (95% CI: −17.8 to −6.8; p < 0.001; adjusted p = 0.005). No significant differences were observed for p-CS, IL-6, or MDA after correction. Conclusions: Synbiotic supplementation over a 10-month period resulted in a trend toward decreased serum IS levels in patients with advanced CKD, suggesting potential benefits of microbiota-targeted therapies. However, no significant effects were observed on renal function, inflammatory, or oxidative stress markers. Further large-scale studies are warranted to confirm these findings and explore the long-term impact of synbiotics in CKD management. Full article
(This article belongs to the Section Urology & Nephrology)
18 pages, 545 KiB  
Article
Biopsy-Proven Glomerulopathies in Romania: A 10-Year Nationwide Study
by Andreea Covic, Mihai Onofriescu, Flaviu R. Bob, Cristina Căpușă, Irina-Draga Căruntu, Otilia Ciurea, Adrian Covic, Simona Giusca, Ina Kacso, Adelina Mihăescu, Andreea Niculescu, Bogdan Obrișcă, Dacian Tirinescu, Adalbert Schiller, Alexandra Vrabie, Yuriy Maslyennikov and Gener Ismail
Life 2025, 15(6), 938; https://doi.org/10.3390/life15060938 - 11 Jun 2025
Viewed by 1006
Abstract
Glomerular diseases are a major cause of chronic kidney disease worldwide, yet epidemiological data from Eastern Europe, and Romania in particular, remain scarce. This study aimed to characterize the spectrum of biopsy-proven glomerulopathies in Romania through a multicenter national registry over a 10-year [...] Read more.
Glomerular diseases are a major cause of chronic kidney disease worldwide, yet epidemiological data from Eastern Europe, and Romania in particular, remain scarce. This study aimed to characterize the spectrum of biopsy-proven glomerulopathies in Romania through a multicenter national registry over a 10-year period. We retrospectively analyzed 4047 native kidney biopsies performed between 2014 and 2023 across four national nephrology reference centers. Patient demographics, clinical presentation, and histopathological diagnoses were collected and categorized into primary and secondary glomerular diseases, glomerulosclerosis, tubulointerstitial nephropathies, hereditary nephropathies, and vascular nephropathies. The mean patient age was 48 years, 54.8% were male, and 51.4% presented with nephrotic-range proteinuria. The most common primary glomerulopathies were membranous nephropathy (16.7%), immunoglobulin A nephropathy (15.6%), focal segmental glomerulosclerosis (8.8%), and membranoproliferative glomerulonephritis (10%). Among secondary glomerular diseases, lupus nephritis (9.3%), diabetic nephropathy (8.5%), and vasculitis (7.7%) were most frequent. Marked inter-center variability was observed, with a notably high prevalence of membranous nephropathy in Iași (31.1%). Over the study period, the incidence of focal segmental glomerulosclerosis increased while immunoglobulin A nephropathy declined. This study provides the first nationwide epidemiological assessment of biopsy-proven glomerular disease in Romania, revealing both similarities and distinctive differences compared to patterns reported in other European countries. Full article
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15 pages, 2402 KiB  
Systematic Review
Copeptin as a Biomarker in Chronic Kidney Disease—A Systematic Review and Meta-Analysis
by Gabi Gazi, Robert Cristian Cruciat, Daniel-Corneliu Leucuta, Nahlah Al Srouji, Stefan-Lucian Popa, Mohamed Ismaiel, Dinu Iuliu Dumitrascu and Abdulrahman Ismaiel
Biomolecules 2025, 15(6), 845; https://doi.org/10.3390/biom15060845 - 10 Jun 2025
Viewed by 528
Abstract
Background: Numerous studies have explored the potential of the biomarker copeptin (CPP) in diagnosing and assessing the severity of chronic kidney disease (CKD). Despite these efforts, findings have been inconsistent. Consequently, this study aimed to examine the association between CPP and CKD, [...] Read more.
Background: Numerous studies have explored the potential of the biomarker copeptin (CPP) in diagnosing and assessing the severity of chronic kidney disease (CKD). Despite these efforts, findings have been inconsistent. Consequently, this study aimed to examine the association between CPP and CKD, specifically evaluating its diagnostic value and correlation with CKD severity as classified by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Methods: A systematic search of PubMed, EMBASE, and Scopus was conducted using a predefined search string to identify relevant studies. Eligible studies included those involving CKD patients classified by glomerular filtration rate (GFR) according to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines or by the estimated GFR (eGFR) calculated using the MDRD formula, provided they met predefined inclusion criteria. Study quality was assessed using the Newcastle–Ottawa Scale (NOS). The primary outcome measured was the mean difference (MD) in serum CPP levels across the various stages of CKD. Results: A total of seven studies, comprising 2769 participants, met the inclusion criteria and were incorporated into our systematic review and meta-analysis. Notable differences in CPP levels were identified across various comparisons. Specifically, CPP levels were significantly elevated in CKD patients compared to healthy controls, with a mean difference (MD) of 12.975 (95% CI 6.572, 19.379). Additional significant MDs were observed in comparisons including controls versus CKD stages 1–2/2 (−1.600 [95% CI −3.179, −0.020]), controls versus CKD stage 3 (−9.598 [95% CI −12.959,−6.237]), controls versus CKD stages 4–5 (−28.776 [95% CI −42.925, −14.628]), and CKD stages 1–2 versus stages 4–5 (−30.475 [95% CI −46.790, −14.160]). Conclusions: Comparison between the CKD patients and healthy controls revealed significantly elevated CPP levels, suggesting a possible role in renal pathology. Furthermore, the distinct differences in CPP concentrations across various CKD stages highlight its potential as a biomarker for assessing disease severity and progression. Full article
(This article belongs to the Special Issue The Biomarkers in Renal Diseases)
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18 pages, 3203 KiB  
Article
Adjunct Therapy with Ipragliflozin Exerts Limited Effects on Kidney Protection in Type 1 Diabetes: A Retrospective Study Conducted at 25 Centers in Japan (IPRA-CKD)
by Yuta Nakamura, Ichiro Horie, Hiroshi Yano, Hiroshi Nomoto, Tomoyasu Fukui, Yoshihiko Yuyama, Tomoyuki Kawamura, Mariko Ueda, Akane Yamamoto, Yushi Hirota, Yoshiki Kusunoki, Kenro Nishida, Dan Sekiguchi, Yasutaka Maeda, Masae Minami, Ayako Nagayama, Shimpei Iwata, Hitomi Minagawa, Shinya Furukawa, Teruki Miyake, Hiroaki Ueno, Rei Chinen, Yoshiro Nakayama, Hiroaki Masuzaki, Yasutaka Miyachi, Yosuke Okada, Mitsuhiro Okamoto, Kaoru Ono, Ken-ichi Tanaka, Akira Kurozumi, Takenori Sakai, Hironori Yamasaki, Jun-ichi Yasui, Ayako Ito, Atsushi Kawakami and Norio Abiruadd Show full author list remove Hide full author list
Biomedicines 2025, 13(6), 1287; https://doi.org/10.3390/biomedicines13061287 - 23 May 2025
Viewed by 1142
Abstract
Background/Objectives: While sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor [...] Read more.
Background/Objectives: While sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated additional non-glycemic benefits for renal protection in individuals with type 2 diabetes, less evidence is available for those with type 1 diabetes (T1D). To determine whether the adjunctive use of the SGLT2 inhibitor ipragliflozin confers kidney protection in individuals with T1D, we retrospectively analyzed data from a real-world cohort examined at 25 centers in Japan. Methods: We enrolled 359 subjects aged 20–74 years with T1D (IPRA group: 159 ipragliflozin users; control [CTRL] group: 200 non-users). The primary outcome was changes in the estimated glomerular filtration rate (eGFR) from baseline to 24 months after the initiation of ipragliflozin. The secondary outcomes were all other changes, including the urinary albumin–creatinine ratio (UACR) and urinary protein–creatinine ratio (UPCR). Results: The IPRA group’s eGFR decline slopes were 0.79 mL/min/1.73 m2/year milder than the CTRL group’s after propensity score matching, but this difference was not significant. The subjects complicated by chronic kidney disease (CKD) defined as UACR ≥ 30 mg/g and/or UPCR ≥ 0.5 g/g and/or eGFR < 60 mL/min/1.73 m2 showed changes in UPCR (g/g) from baseline to 24 months that were significantly lower in the IPRA group (−0.27 ± 1.63) versus the CTRL group (0.18 ± 0.36) (p = 0.016). No significant increase in adverse events (including severe hypoglycemia and hospitalization due to ketosis/ketoacidosis or cardiovascular diseases) was observed in the IPRA group. Conclusions: Adjunctive treatment with ipragliflozin exerted potential renal benefits by decreasing proteinuria in T1D subjects with CKD. Further investigations are required to determine whether its additional benefits exceed the increased risk of ketoacidosis. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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16 pages, 396 KiB  
Article
Determinants of Health-Related Quality of Life in Patients with Chronic Kidney Disease: A Cross-Sectional Study
by Geetha Kandasamy, Thangamani Subramani, Mona Almanasef, Khalid Orayj, Eman Shorog, Asma M. Alshahrani, Tahani S. Alanazi and Sangeetha Balasubramanian
Healthcare 2025, 13(10), 1167; https://doi.org/10.3390/healthcare13101167 - 16 May 2025
Viewed by 792
Abstract
Background: Chronic kidney disease (CKD) significantly affects health-related quality of life (HRQoL), impacting physical and mental well-being. This study aimed to identify the key determinants influencing HRQoL among patients with CKD. Methods: A cross-sectional observational study was conducted from July 2022 to March [...] Read more.
Background: Chronic kidney disease (CKD) significantly affects health-related quality of life (HRQoL), impacting physical and mental well-being. This study aimed to identify the key determinants influencing HRQoL among patients with CKD. Methods: A cross-sectional observational study was conducted from July 2022 to March 2023 at the Rajiv Gandhi Cooperative Multi-Specialty Hospital, Palakkad, Kerala, South India, including 154 patients diagnosed with CKD stages 3 to 5. Eligible participants were required to be at least 18 years of age and have a confirmed diagnosis of CKD, specifically stages 3 to 5, with prior treatment. CKD stages were defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines, based on estimated glomerular filtration rate (eGFR) thresholds as follows: Stage 3 (eGFR 30–59 mL/min/1.73 m2), Stage 4 (eGFR 15–29 mL/min/1.73 m2), and Stage 5 (eGFR < 15 mL/min/1.73 m2). Participants were classified into stages based on their most recent stable eGFR value at the time of recruitment. HRQoL was assessed using the European Quality of Life-5 Dimensions-3 Levels (EQ-5D-3L) questionnaire. Chi-square, ANOVA, and multivariate regression were used to analyze associations with EQ-5D-3L domains. Results: Out of 154 participants, 68.8% were male, 91.6% were aged over 50 years, and 63.6% were from rural areas. Most had primary education (55.2%) and were unemployed, retired, or housewives (66.2%). As CKD progressed, comorbidities, particularly diabetes mellitus and coronary artery disease (CAD), increased, with Stage 5 showing the highest prevalence. Clinical markers showed significant declines in the glomerular filtration rate (GFR) (Stage 3: 49.16 ± 7.59, Stage 4: 22.37 ± 3.88, Stage 5: 8.79 ± 1.68) and hemoglobin (Stage 3: 10.45 ± 0.84, Stage 4: 8.88 ± 0.60, Stage 5: 7.12 ± 0.53) and an increase in serum creatinine (Stage 3: 1.72 ± 0.40, Stage 4: 3.21 ± 0.44, Stage 5: 7.05 ± 1.46). HRQoL assessments showed significant declines in mobility, self-care, usual activities, pain, and anxiety/depression with advancing CKD. Mobility issues increased from 61.2% in Stage 3 to 62.0% in Stage 5, with greater difficulties in self-care and usual activities at Stage 5. Pain and anxiety/depression worsened across stages. Multivariate analysis identified female gender, older age (≥50 years), lower education, unemployment, multiple comorbidities, smoking, lack of social support, and advanced CKD stages as significant factors linked to impaired HRQoL. CKD stage 5 (GFR < 29 mL/min/1.73 m2) and high serum creatinine (>1.2 mg/dL) were associated with significantly higher odds of impairment in all HRQoL domains. Conclusions: This study highlights that factors such as female gender, older age, lower education, unemployment, multiple comorbidities, smoking, advanced CKD stages, and high serum creatinine levels are associated with reduced quality of life in CKD patients. Conversely, social support acts as a protective factor. The findings emphasize the need for targeted interventions that address both medical care and psychosocial aspects, including lifestyle changes, patient education, mental health support, and community involvement, to improve CKD patients’ well-being. Full article
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16 pages, 1253 KiB  
Review
Recurrence of Primary Glomerular Diseases After Kidney Transplantation: Incidence, Predictors, Characteristics and Treatment
by Maurizio Salvadori and Giuseppina Rosso
Transplantology 2025, 6(2), 14; https://doi.org/10.3390/transplantology6020014 - 15 May 2025
Viewed by 1036
Abstract
Recurrent primary glomerulonephritis is a frequent and severe disease that represents the second or third leading cause of graft loss. The purpose of this study is to address the rates of recurrence for all types of glomerulonephritis, detailing their characteristics and the treatments [...] Read more.
Recurrent primary glomerulonephritis is a frequent and severe disease that represents the second or third leading cause of graft loss. The purpose of this study is to address the rates of recurrence for all types of glomerulonephritis, detailing their characteristics and the treatments adopted. The authors collected the main studies and meta-analyses published on PubMed. In addition, the main clinical trials ongoing on the topic were collected. The results highlighted the different frequency of recurrence in relation to the glomerulone-phritis considered, assessing the different characteristics and the different treatments adopted. In conclusion, this review confirms the severity of this disease. The treatment possibilities differ among glomerulonephritis variants. Frequently, a pre-transplant period should be distinguished from a peri-transplant period and a post-transplant period. Fi-nally, new drugs are being discovered to treat recurrent glomerulonephritis and several ongoing trials are also discussed. Some of them have shown important results already. Full article
(This article belongs to the Section Solid Organ Transplantation)
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17 pages, 528 KiB  
Review
Pediatric Chronic Kidney Disease: Mind the Gap Between Reality and Expectations
by Chien-Ning Hsu, Pei-Chen Lu, Wei-Ting Liao and You-Lin Tain
Children 2025, 12(5), 614; https://doi.org/10.3390/children12050614 - 8 May 2025
Viewed by 1747
Abstract
Pediatric chronic kidney disease (CKD) is a growing concern that often originates early in life, yet significant challenges remain in translating clinical guidelines into real-world practice. World Kidney Day 2025 highlights the importance of early detection, but the three levels of preventive strategies [...] Read more.
Pediatric chronic kidney disease (CKD) is a growing concern that often originates early in life, yet significant challenges remain in translating clinical guidelines into real-world practice. World Kidney Day 2025 highlights the importance of early detection, but the three levels of preventive strategies commonly recommended for adults may not be directly applicable to children. Unlike adult CKD, primary prevention in pediatrics should focus on prenatal, neonatal, and early-life factors such as congenital anomalies of the kidney and urinary tract (CAKUT), preterm birth, maternal health, and environmental exposures. Secondary prevention, involving early detection through screening, is crucial, yet the effectiveness of mass urinary screening in children remains a subject of global debate. Several key challenges persist, including the accurate estimation of glomerular filtration rate (eGFR), consistent definition and diagnosis of pediatric hypertension, identification of reliable biomarkers, and targeted screening in specific pediatric populations. Although clear guidelines exist to manage CKD progression and enhance quality of life, a critical gap remains between what is known and what is practiced. Closing this gap requires robust evidence to inform best practices, improve health-related quality of life, and advance pediatric kidney replacement therapies. To protect and improve kidney health for every child worldwide, these challenges must be acknowledged, and sustainable, evidence-based solutions must be developed and implemented without further delay. Full article
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20 pages, 1660 KiB  
Article
Phenotypes and the Importance of Genetic Analysis in Adult Patients with Nephrolithiasis and/or Nephrocalcinosis: A Single-Center Experience
by Elena Emanuela Rusu, Bogdan Marian Sorohan, Robert Pandele, Andreea Popescu, Raluca Bobeica, Sonia Balanica, Diana Silvia Zilisteanu, Alexandru Iordache, Adrian Lungu and Gener Ismail
Genes 2025, 16(5), 501; https://doi.org/10.3390/genes16050501 - 27 Apr 2025
Cited by 1 | Viewed by 786
Abstract
Background: Molecular analysis in patients with nephrolithiasis (NL) and/or nephrocalcinosis (NC) enables more accurate evaluation of underlying etiologies. The existing clinical evidence regarding genetic testing in adults with NL comprises only a few cohort studies. Materials and Methods: We retrospectively analyzed 49 adult [...] Read more.
Background: Molecular analysis in patients with nephrolithiasis (NL) and/or nephrocalcinosis (NC) enables more accurate evaluation of underlying etiologies. The existing clinical evidence regarding genetic testing in adults with NL comprises only a few cohort studies. Materials and Methods: We retrospectively analyzed 49 adult patients diagnosed with NL and/or NC from a single center, on whom we performed a genetic test using a nephrolithiasis panel. We reviewed the phenotype of the patients and compared the cases with positive and negative molecular diagnosis. Results: In total, 49 adult patients with NL and/or NC underwent genetic testing. Of the tested patients, 29 (59.2%) patients had 24 abnormal variants in 14 genes. Mendelian diseases were diagnosed in 14 (28.6%) cases: cystinuria (SLC3A1, SLC7A9; n = 4), hereditary distal renal tubular acidosis (SLC4A1; n = 3), Dent disease (CLCN5; n = 2), familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (CLDN16; n = 1), infantile hypercalcemia type 1 (CYP24A1; n = 1), primary hyperoxaluria type 1 (AGXT; n = 1), Bartter syndrome type 2 (KCNJ1; n = 1), and autosomal dominant tubulointerstitial kidney disease (UMOD; n = 1). Eight (16.3%) patients had pathogenic or likely pathogenic monoallelic variants as predisposing factors for NL and/or NC, and seven (14.3%) had biallelic or monoallelic variants of uncertain significance. Patients with positive genetic tests had a lower estimated glomerular filtration rate (p = 0.03) and more frequent NL associated with NC (p = 0.007) and were unlikely to have arterial hypertension (p = 0.03) when compared with patients with negative tests. Conclusions: Our study shows an increased effectiveness of molecular diagnosis and highlights the benefits of genetic testing. NL associated with NC and the presence of chronic kidney disease are the characteristics that should prompt the clinician to suspect an inherited form of NL and/or NC. Full article
(This article belongs to the Special Issue Genes and Gene Therapies in Chronic Renal Disease)
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9 pages, 567 KiB  
Review
Prognostic Factors of Proteinuria Remission in Primary Membranous Nephropathy
by Kornelia Krakowska-Jura, Anna Natalia Kler, Weronika Wajerowska, Andrzej Konieczny and Mirosław Banasik
J. Clin. Med. 2025, 14(9), 2880; https://doi.org/10.3390/jcm14092880 - 22 Apr 2025
Viewed by 969
Abstract
Primary membranous nephropathy is a leading cause of nephrotic syndrome in adults, characterized by immune complex deposition in the glomerular basement membrane. Predicting proteinuria remission is essential for guiding treatment decisions, optimizing immunosuppressive therapy, and improving renal outcomes. Traditional prognostic markers, such as [...] Read more.
Primary membranous nephropathy is a leading cause of nephrotic syndrome in adults, characterized by immune complex deposition in the glomerular basement membrane. Predicting proteinuria remission is essential for guiding treatment decisions, optimizing immunosuppressive therapy, and improving renal outcomes. Traditional prognostic markers, such as anti-PLA2R antibody status and baseline proteinuria levels, offer valuable insights into disease progression. However, recent research has identified additional biomarkers that may enhance risk stratification and refine individualized treatment strategies. Serum-based markers, such as uric acid and inflammatory indices, may indicate systemic changes that impact disease progression. Urinary biomarkers, including microhematuria, α1-microglobulin, and CXCL13, have been proposed as potential predictors of disease activity and remission likelihood. Furthermore, histopathological features, such as glomerular basement membrane thickness, tubulointerstitial injury, and acute kidney injury, provide structural correlates that may inform prognosis. This review explores both established and emerging prognostic indicators across various biological domains. Understanding these predictors can aid in developing personalized therapeutic strategies, optimizing disease management, and improving patient outcomes in primary membranous nephropathy. Full article
(This article belongs to the Special Issue Chronic Kidney Disease: Global Dimension and Perspectives)
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