Search Results (153)

Membranous nephropathy (MN) is the most prevalent cause of nephrotic syndrome (NS) in adults, and it can be primary (idiopathic) with an unknown cause or secondary due to a variety of conditions (lupus, infections, malignancies, medications, etc.). It progresses to chronic kidney disease (CKD) in up to 60% of patients, and 10 to 30% develop end-stage kidney disease (ESKD). This retrospective study examines the importance of specific factors, including baseline demographic and clinical data, kidney biopsy PH findings, and selected biochemical parameters, influencing MN outcomes after 10 years of follow-up. The cohort included 94 individuals in whom a diagnosis of MN was established by percutaneous biopsy of the left kidney’s lower pole at the University Clinical Center of Serbia (UCCS) between 2008 and 2013. According to the outcomes, patients were divided into three groups: the recovery (Rec) group, with complete remission, including normal serum creatinine (Scr) and proteinuria (Prt), the group with development of chronic kidney disease (CKD), and the group with development of end-stage kidney disease (ESKD). Nephropathologists graded pathohistological (PH) results from I to III based on the observed PH findings. During the follow-up period, 33 patients were in the Rec group, CKD developed in 53 patients, and ESKD developed in 8 patients. Baseline creatinine clearance levels (Ccr), Scr, and uric acid (urate) were found to be significantly associated with the outcomes (p < 0.001). The lowest values of baseline Scr and urate were observed in the Rec group. The presence of acute kidney injury (AKI) or CKD at the time of kidney biopsy was associated with the more frequent development of ESKD (p = 0.02). Lower Ccr was associated with a higher likelihood of progressing to CKD (B = −0.021, p = 0.014), whereas older age independently predicted progression to ESKD (B = 0.02, p = 0.032). Based on this study, it was concluded that the most important biochemical and clinical factors that are associated with the outcomes of this disease are the values of Scr, Ccr, and urate and the existence of CKD at the time of kidney biopsy. Unlike most previous studies, the presence of HTN had no statistical significance in the outcome of the disease. Full article

Ascorbic acid (AA) plays a multidimensional role in human physiological and pathological processes, and the detection of its urinary concentration facilitates the diagnosis of metabolic or kidney diseases. Visual detection exhibits minimal reliance on instrumentation and is suitable for on-site analysis in routine settings. Current visual colorimetric detection methods typically rely on enzymatic or nanozyme-based catalysis. Organic neutral radicals bearing unpaired electrons represent a class of materials exhibiting intrinsic responsiveness to redox stimuli. The tris (2,4,6-trichlorophenyl) methyl (TTM) radical has attracted widespread attention for its adjustable optical properties and sensitive response to external redox stimuli. We synthesized a novel radical TTM-DMODPA and applied it for non-catalytic colorimetric detection of AA. It not only enables quantitative AA measurement via UV-vis spectroscopy (linear range: 1.25–75 μmol/L, LOD: 0.288 μmol/L) but also facilitates instrument-free visual detection using smartphone cameras (linear range: 0–65 μmol/L, LOD: 1.46 μmol/L). This method demonstrated satisfactory performance in the measurement of AA in actual urine samples. Recovery rates ranged from 97.8% to 104.1%. Consequently, this work provides a portable and effective method for assessing AA levels in actual urine samples. Full article

Background: The management of end-stage renal disease (ESRD) is undergoing a paradigm shift, with increasing emphasis on kidney transplantation as a preferred treatment modality for elderly patients (≥65 years), who constitute a substantial portion of new ESRD cases. Transplantation offers markedly superior survival and quality of life (QoL) advantages compared to dialysis for this demographic. Nevertheless, key determinants such as frailty, physical functionality, and cognitive function have emerged as critical predictors of post-transplant success. Despite their relevance, standardized methodologies for evaluating these parameters in transplantation candidacy remain absent. This systematic review examines the influence of frailty, physical functionality, and cognitive function on outcomes in elderly kidney transplant recipients. Methods: Adhering to PRISMA guidelines, a rigorous literature search was conducted across PubMed, CINAHL, Embase, PsycINFO, and the Web of Science for studies published up to October 31, 2024. Relevant studies focused on elderly transplant candidates and examined correlations between frailty, physical functionality, or cognitive function and post-transplant outcomes. The Newcastle–Ottawa Scale was employed to evaluate studies quality. Results: Seven studies met the inclusion criteria. Five explored physical functionality, demonstrating that better pre-transplant physical performance predicts enhanced survival. Two studies addressed frailty, utilizing the Fried frailty phenotype, and linked frailty to elevated mortality and diminished QoL recovery. Notably, no studies explored cognitive function in elderly kidney transplant candidates or recipients and its association with post-transplant outcomes, exposing a salient gap in the literature. The included studies’ varied methodologies, reliance on single time-point assessments, and exclusive focus on kidney transplant recipients restrict both comparability among studies and the generalizability of findings to the broader end-stage renal disease (ESRD) population. Conclusions: These findings underscore the profound impact of physical functionality and frailty on transplant outcomes in the growing elderly kidney transplant population, illuminating the necessity for standardized assessment protocols and targeted pre-transplant interventions. The critical gap in cognitive function research underscores a vital direction for future investigation. This research received no external funding. This review is registered with PROSPERO under registration ID CRD42025645838. Full article

Backgrounds and Objectives: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but potentially severe complication of SARS-CoV-2 infection, with increasingly reported renal manifestations. Materials and Methods: The aim of this retrospective study was to compare clinical and laboratory characteristics across age categories, with special emphasis on renal function. We analysed data from 64 patients with MIS-C treated between July 2020 and December 2023. Results: In children under 3 years of age, there was a higher prevalence of leucocytosis, elevated platelet counts, and anaemia, along with a lower frequency of complications. The 3–6-year age group was characterized by the presence of rash, hypoalbuminemia, and elevated transaminases. The 7–12-year age group showed the highest rate of organ dysfunction. In adolescents (13–18 years), neurological symptoms, the highest BMI values, the greatest prevalence of comorbidities, leukopenia, lymphopenia, and elevated GGT levels were observed. The incidence of acute kidney injury (AKI) was 6.3% (n = 4/64). Following treatment, the majority of patients achieved full recovery (n = 61/64; 95.2%). Conclusions: There are pronounced age-related differences in the clinical presentation of MIS-C, with distinct immune and clinical patterns suggesting developmental influences on disease expression and outcomes. Older children showed a higher prevalence of comorbidities and organ dysfunction compared to younger patients. Notably, this study found a markedly lower incidence of acute kidney injury (6.3%) compared to previously reported rates (20–30%), indicating potential regional or age-related protective factors. These findings highlight the importance of age-specific evaluation in MIS-C and underscore the need for further multicentre research to refine therapeutic protocols. Full article

Patients with chronic kidney disease (CKD) face an increased risk of early vascular aging, progressive vascular calcification, and premature death. With increasing age, mitochondrial function and mitochondrial DNA copy number (mtDNA-cn) decline. This has been identified as an independent predictor of frailty and mortality in cardiovascular diseases (CVDs) and cancer. However, the relationship between mtDNA-cn and vascular calcification in the context of a uremic milieu remains ambiguous. We hypothesize that a lower mtDNA-cn is associated with medial calcification, as both are linked to impaired vascular health and accelerated aging. mtDNA-cn was analyzed in 211 CKD5 patients undergoing renal transplantation (RTx) and 196 healthy controls using quantitative PCR (qPCR) for three mtDNA genes (mtND1, mtND4, and mtCOX1) and single-locus nuclear gene hemoglobin beta (HbB). In 32 patients, mtDNA-cn was also quantified one year after RTx. The association between mtDNA-cn and vascular calcification scores, circulatory cell-free (ccf) mtDNA in plasma, and the surrogate marker of biological aging (skin autofluorescence) and CVD risk was assessed. mtDNA-cn was significantly lower in CKD5 patients than in controls and correlated with biological age, vascular calcification, and CVD risk. One year after RTx there was a significant recovery of mtDNA-cn in male patients compared to baseline levels. mtDNA-cn and ccf-mtDNA were inversely correlated. This prospective study provides novel insights into the link between low mtDNA-cn and vascular aging. It demonstrates that RTx restores mtDNA levels and may improve oxidative phosphorylation capacity in CKD. Further investigation is warranted to evaluate mtDNA as a biologically relevant biomarker and a potential therapeutic target for early vascular aging in the uremic environment. Full article

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease that affects various organs, including the kidneys. Despite recent advancements, effective treatment options for renal involvement in SLE remain limited. Rebamipide, originally developed as a gastroprotective agent, has been reported to exert immunomodulatory effects in rheumatic diseases. Here, we aimed to evaluate the therapeutic potential of rebamipide in SLE using an animal model and to elucidate its mechanisms of action. We administered rebamipide or vehicle control to lupus-prone MRL/lpr mice and evaluated its efficacy on lupus-like phenotypes, including renal manifestations and immune cell profiles. Additionally, we investigated potential therapeutic mechanisms through in vitro treatment of murine immune cells and podocytes with rebamipide. Oral administration of rebamipide in lupus-prone mice significantly reduced kidney size, weight, and histopathological inflammation. Among circulating immune cell subsets, only regulatory T cells were significantly increased by rebamipide. In vivo treatment with rebamipide enhanced the expression of podocyte structural proteins, such as Synaptopodin, in kidney tissues, accompanied by the recovery of antioxidative factors, including nuclear factor erythroid 2-related factor 2 (Nrf2). Similarly, in vitro treatment of murine immune cells and podocytes with rebamipide replicated its immunoregulatory and antioxidative effects. Rebamipide is proposed as a potential therapeutic candidate for managing renal involvement in SLE through its antioxidative effects on podocytes. Full article

Arsenic, in the form of inorganic arsenite, is toxic to the kidney and can cause acute kidney injury, manifesting as destruction of proximal tubule cells. Nephron repair is possible through the proliferation of resident tubular progenitor cells expressing CD133 and CD24 surface markers. We simulated regenerative repair in the continued presence of i-As (III) using a cell culture model of a renal progenitor cell line expressing CD133 (PROM1) and CD24. Continued exposure and subculturing of progenitor cells to i-As (III) led to a reduction in the expression of PROM1 and CD24, as well as a decrease in the ability to differentiate into tubule-like structures. Cessation of i-As (III) and recovery for up to three passages resulted in continued repression of PROM1 and reduced ability to differentiate. Chronically exposed cells exhibited an ability to form colonies in soft agar, suggesting neoplastic transformation. Chronically exposed cells also exhibited an induction of CD44, a cell surface marker commonly found in renal cell carcinoma, as well as in tubular repair in chronic renal injury such as chronic kidney disease. These results demonstrate potential adverse outcomes of renal progenitor cells chronically exposed to a nephrotoxicant, as well as in environmental exposure to arsenic. Full article

Acute kidney injury (AKI) causes damage to the renal epithelium, initiating a reparative process intended to restore renal function. Although effective repair can result in the complete recovery of kidney function, this process is frequently incomplete. In instances where repair is unsuccessful, the kidney experiences maladaptive alterations that may progressively result in chronic kidney disease (CKD), a phenomenon referred to as failed repair. This condition is precipitated by hypotensive, septic, or toxic insults, which initiate a series of pathophysiological processes, including microcirculatory dysfunction, the activation of inflammatory responses, and the death of tubular epithelial cells. These events collectively compromise renal function and trigger a complex repair response. This review provides a comprehensive examination of the multifactorial mechanisms underlying the initiation and progression of AKI, the regenerative pathways facilitating structural recovery in severely damaged kidneys, and the critical transition from adaptive repair to maladaptive remodeling. Central to this transition are mechanisms such as epigenetic reprogramming, G2/M cell-cycle arrest, cellular senescence, mitochondrial dysfunction, metabolism reprogramming, and cell death, which collectively drive the progression of CKD. These mechanistic insights offer a robust foundation for the development of targeted therapeutic strategies aimed at enhancing adaptive renal repair. Full article

Rhabdomyolysis is one of the leading causes of acute kidney injury (AKI) and is infrequently associated with chronic kidney disease (CKD). CKD appears in diabetes mellitus and arterial hypertension, as a result of other systemic diseases and glomerulonephritis. In this study, we present two cases (one with CKD and one with AKI) that are caused by a genetic defect. A genetic examination was performed in both patients, proving that the patient with CKD has a genetic defect in the RYR1 gene, which is observed in patients with malignant hyperthermia. Meanwhile, the patient with AKI has a homozygous pathogenic variant in SLC2A9, which is associated with urinary urate wasting and is characterized by asymptomatic hypouricemia and AKI after exercise. The first case is chronic rhabdomyolysis, as the patient is an athlete and performs heavy daily exercise. The second case is AKI without prior kidney damage or symptoms. Both patients did not undergo a kidney biopsy. In the first case, changes in daily routine without extreme physical exercise led to the recovery of normal kidney function. The second patient recovered from AKI without sequelae. These two cases are an example of “thinking outside the box” with respect to how genetic diseases and defects can cause kidney damage, both chronic and acute. Full article

Kidney transplantation significantly improves outcomes in patients with end-stage renal disease; however, postoperative complications remain a substantial concern. This review summarizes the incidence, risk factors, and management strategies for common complications after kidney transplantation. Reported incidence varies widely due to differences in definitions, diagnostic methods, and study designs. Ureteral stenosis occurs in 2.8–18.0% of recipients, vesicoureteral reflux in 0.5–86%, and urinary leakage in 1.1–7.2%. Lymphatic complications, including lymphocele and lymphorrhea, range from 0.6% to 35.2%, with one-third of complications requiring intervention. The incidence of urinary tract infections ranges from 20 to 43%, while asymptomatic bacteriuria is reported in up to 53% of recipients. Surgical site infections have a median incidence of 3.7%, and incisional hernias develop in 2.5–10% of cases, depending on follow-up duration. Vascular complications affect approximately 10% of recipients, with renal artery stenosis and thrombosis being the most prevalent. Neurologic complications, such as femoral nerve palsy and immunosuppression-related neurotoxicity, though less frequent, can impair recovery. Management strategies vary depending on severity, ranging from observation to surgical intervention. Preventive measures—including optimized ureteral stenting protocols, early catheter removal, careful immunosuppression, and appropriate antimicrobial use—play a crucial role in reducing complication risk. Despite advances in transplantation techniques and perioperative care, these complications continue to affect graft survival and patient outcomes. Further research is needed to standardize definitions and establish evidence-based protocols. Full article

Background/Objectives: Peptide Receptor Radionuclide Therapy (PRRT) is approved for patients with inoperable, progressive and/or metastatic well-differentiated NETs. Before the approval of Lutathera^®, locally manufactured ¹⁷⁷Lu-HA-DOTATATE was used on a regular basis in clinical routine. The aim of this study was (1) to compare the hematotoxicity of locally manufactured ¹⁷⁷Lu-HA-DOTATATE with Lutathera^® in GEP-NET patients and (2) to compare the recommended treatment interval of 8 weeks between each cycle to a prolonged scheme of up to 11 weeks for both ¹⁷⁷Lu-HA-DOTATATE and Lutathera^®. Methods: The included patients with GEP NETs (n = 46) received four cycles of PRRT, either ¹⁷⁷Lu-HA-DOTATATE or Lutathera^®, and were divided into four subgroups. The subgroups were treated with either locally manufactured ¹⁷⁷Lu-HA-DOTATATE or Lutathera^® and were stratified into a mean application interval of 8 (HA_8weeks, n = 10/Lutathera_8weeks, n = 16) or 11 weeks (HA_adapted, n = 10/Lutathera_adapted, n = 10). To evaluate therapy associated hemato- and nephrotoxicity, patients underwent two laboratory follow-up examinations (follow-up 1—between 2./3. therapy cycle; follow-up 2—after the termination of the 4. therapy cycle) and were then compared to pre-PRRT laboratory results. To assess hematological and renal recovery trends, blood values and parameters of kidney function were collected up to 58.9 weeks after PRRT completion. Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) were used for grading hematological parameters. Results: The occurrence of high-grade adverse events (CTCAE grade 3/4) after PRRT was moderate, with 1/10 (10%) grade 4 lymphocytopenia in the Lutathera_adapted group, while overall, 20/46 (43.5%) patients had grade 3 lymphocytopenia. Grade 3 thrombocytopenia occurred in 1/10 (10%) patients of the HA_adapted group. Absolute and percentage changes in the kidney function (creatinine, TER) remained constant during PRRT in all subgroups. All four subgroups showed a significant decrease in absolute blood value changes for PLT counts, WBC counts, neutrophil granulocytes and lymphocytes between, prior to and after PRRT (p < 0.05, each). Regarding percentage changes in laboratory parameters, only the HA_adapted and the HA_8weeks groups had significant decreases in WBC (p < 0.03, each) and PLT counts (p < 0.04, each) while there was no significant degradation of any other hematological parameter in any of the subgroups. Only patients with longer treatment intervals under ¹⁷⁷Lu-HA-DOTATATE therapy showed a statistically significant correlation in the long-term recovery analysis concerning the PLT counts (r = 0.6, p < 0.0001). Other blood and kidney values showed no significant correlation in the long-term analysis in the other subgroups. Conclusion: Comparing the hematotoxicity in patients that were treated with locally manufactured ¹⁷⁷Lu-HA-DOTATATE with patients that were treated with Lutathera^® and assessing different treatment intervals in both groups (8 vs. 11 weeks), revealed that there is overall a low to moderate incidence of significant changes in hematological and renal parameters directly after PRRT. Recovery trends of hematological and renal parameters after 1 year suggest that patients treated with locally manufactured ¹⁷⁷Lu-HA-DOTATATE might benefit from a longer treatment interval of 11 weeks regarding their PLT counts. Given the risk of developing hematological diseases such as therapy-related myeloid neoplasms years after PRRT, longer observational periods after PRRT will be crucial. Full article

The relationship between telomere shortening and patients with chronic kidney disease (CKD) has recently been investigated. Although most patients respond adequately to erythropoiesis-stimulating agents (ESAs), approximately 10% do not, and this is referred to as ESA resistance. The aim of our study was to investigate the relationship between telomere shortening and erythropoietin resistance in patients with CKD on hemodialysis. This cross-sectional, comparative, analytical, and observational study was conducted in patients of both sexes over 18 years of age diagnosed with CKD. Two groups of patients were identified. The first group consisted of 40 patients receiving erythropoiesis-stimulating agents with erythropoietin resistance. The second group consisted of 40 patients with the same characteristics but without erythropoietin resistance. Telomere length was measured by real-time PCR. Eighty patients were included in the study. Mean hemoglobin levels were lower in the erythropoietin resistance group (8.8 ± 1.67 vs. 11.95 ± 1.81, p = 0.001). Differences were observed in hematocrit and albumin levels, which were lower in patients with erythropoietin resistance, while PTH levels were higher in this group (788 ± 538.47 vs. 535.65 ± 603.06, p = 0.001). A significant difference in telomere length (T/S) was observed between the two groups, with shorter telomere length in the erythropoietin resistance group (0.45 ± 0.04 vs. 0.56 ± 0.03, p = 0.01). Telomere shortening may be associated with anemia and erythropoietin resistance in patients with CKD undergoing hemodialysis. This relationship suggests the need to explore whether telomere length recovery improves the response to ESAs. Full article

Heart failure and diabetes mellitus are major contributors to global morbidity and mortality, with their prevalence continuously rising, primarily due to aging populations and improvements in healthcare. These conditions often coexist or develop sequentially, leading to complex interactions that significantly influence the progression and management of both diseases. Furthermore, heart failure and diabetes are commonly associated with coronary artery disease, which presents a unique challenge in clinical management, particularly in the context of myocardial revascularization. The presence of diabetes exacerbates atherosclerotic progression and impairs endothelial function, while heart failure complicates the perfusion and recovery of myocardial tissue post-intervention. This narrative review delves into the underlying mechanisms contributing to revascularization failure in patients with heart failure and diabetes, emphasizing the importance of understanding these interactions for optimal treatment. The review also summarizes key findings from randomized controlled trials, examining evidence both in the general population and in specific subgroups, including the elderly and patients with left main coronary artery disease, chronic kidney disease, peripheral artery disease, and chronic obstructive pulmonary disease. Understanding these complexities is critical for improving patient outcomes. Full article

Background and Clinical Significance: Takotsubo cardiomyopathy (TCM), an acute stress-induced left ventricular dysfunction, stems from catecholaminergic surges leading to transient myocyte stunning, calcium overload, and microvascular dysregulation. Although most cases resolve spontaneously, roughly 10% deteriorate into fulminant cardiogenic shock, warranting mechanical circulatory support (MCS). Impella^® provides direct transvalvular LV unloading but carries elevated risks of hemolysis, vascular compromise, and thrombogenicity. Conversely, the intra-aortic balloon pump (IABP) enhances diastolic coronary perfusion and marginally reduces afterload via counterpulsation, albeit with less potent LV decompression. Optimal MCS selection in TCM-associated shock therefore hinges on balancing hemodynamic benefits against procedural morbidity. Case Presentation: A 72-year-old female with coronary artery disease, paroxysmal atrial fibrillation (status post–left atrial appendage occlusion), and stage 3 chronic kidney disease presented with anterior ST-segment elevations (V2–V4) and troponin I >1000 ng/L, progressing rapidly to cardiogenic shock and respiratory failure. Coronary angiography revealed mild luminal irregularities, while echocardiography demonstrated severely reduced ejection fraction (5–10%) with characteristic apical ballooning. Refractory elevations in pulmonary capillary wedge pressure, despite escalating inotropes and vasopressors, prompted IABP insertion for partial LV offloading. Over one week, her ejection fraction improved to 35%, facilitating weaning from pressor support, extubation, and discharge on guideline-directed medical therapy. Conclusions: In TCM complicated by shock, meticulous MCS selection is paramount. Although Impella confers more robust unloading, heightened device-related complications may be unjustified in a largely reversible disease. IABP can sufficiently stabilize hemodynamics, enable myocardial recovery, and mitigate morbidity, underscoring the importance of individualized decision-making in TCM-related shock. Importantly, no trial has shown that MCS confers a proven long-term mortality benefit beyond initial hemodynamic rescue. Full article

Due to the sudden emergence and burnout nature of Marburg virus (MARV) outbreaks, little is known about MARV’s pathogenicity and immunogenicity. These gaps in knowledge are limiting our understanding of the disease and the implementation of cost-effective prevention and control measures including case management through safe and effective therapeutic modalities. Therefore, this review aims to synthesize and summarize evidence about pathogenicity, immunogenicity, and virulence in humans towards MARV. Upon infection, MARV rapidly disseminates throughout various tissues, provoking severe cellular injury, particularly in lymphatic organs, the liver, kidneys, and the gastrointestinal tract. The virus takes advantage of host cells by avoiding immune responses, mainly by disrupting the function of dendritic cells and blocking the signaling pathways for interferon. As a result, patients experience profound immune dysregulation characterized by early lymphocyte depletion and a shift towards pro-inflammatory cytokine release, resulting in a cytokine storm that can lead to hemorrhagic septic shock. Additionally, adaptive immune responses, including antibody production, are impaired, further complicating recovery and increasing susceptibility to severe disease outcomes. Understanding these intricate host–pathogen interactions is critical for developing effective therapeutic strategies and vaccines against MARV. Continuing research is essential to explain the mechanisms of immune evasion and to identify potential intervention points for improving patient outcomes. Full article