Search Results (175)

Gender medicine represents a key paradigm for advancing equitable and effective healthcare by systematically integrating sex- and gender-related differences into medical research and clinical practice. Despite regulatory efforts and international guidelines, significant gaps persist in the consideration of sex and gender across medical disciplines, including nephrology. Biological factors—including genetic, hormonal, and metabolic differences—interact with social, cultural, and environmental determinants to influence chronic kidney disease (CKD) susceptibility, clinical presentation, progression, and response to therapy. Insufficient consideration of sex and gender contributes to persistent disparities in CKD progression, cardiovascular outcomes, access to kidney transplantation, adverse drug reactions, dialysis outcomes, and pregnancy-related kidney complications. This narrative review outlines the historical development of gender medicine and critically appraises its relevance and unresolved challenges in kidney disease, with a focus on sex-specific differences in selected conditions, including autosomal dominant polycystic kidney disease, glomerular diseases, acute kidney injury, and pregnancy-associated kidney disorders. Integrating sex- and gender-informed approaches into nephrology is not merely an ethical requirement but a scientific necessity to improve risk stratification, personalize therapeutic strategies, and promote truly equitable and effective kidney care. Full article

Lithium remains endorsed as first-line treatment for bipolar disorders across major clinical guidelines, yet robust evidence demonstrates its progressive decline in use in psychiatric practice across numerous countries. To justify this decline, concerns regarding lithium’s efficacy, safety profile, and monitoring requirements are frequently cited. Yet these apprehensions largely stem from an insufficient understanding of lithium’s clinical uses. In fact, when patients are selected for lithium stabilization according to a characteristic clinical profile and not just a bipolar verdict, lithium continues demonstrating good efficacy compared to all other psychiatric medications currently available. Moreover, after sufficient clinician and patient education regarding lithium stabilization principles, monitoring requirements stop being burdensome. Furthermore, among lithium-responsive patients, adverse effects are typically mild and clinically manageable, except for glomerular filtration rate decline, which tends to develop after decades of continuous administration. Thus, it might be possible to reverse this unfortunate decline in lithium’s use by teaching clinicians to identify the patient profile responsive to lithium stabilization and by implementing educational programs regarding optimal lithium utilization for psychiatrists, patients, and their families. Furthermore, it is worth investigating intermittent lithium administration to mitigate renal complications. Full article

Steroid-resistant nephrotic syndrome (SRNS) in childhood frequently reflects monogenic podocytopathies in which immunosuppression is ineffective. Biallelic variants in MYO1E, encoding the class I myosin Myo1E, cause a distinctive form of focal segmental glomerulosclerosis (FSGS) often accompanied by “Alport-like” multilamination of the glomerular basement membrane (GBM). Early recognition has therapeutic and prognostic implications. A previously healthy 4-year-old boy presented with generalized edema and nephrotic-range proteinuria. Glucocorticoids induced no remission; sequential calcineurin inhibition (cyclosporine, then tacrolimus) and a single dose of ofatumumab yielded only transient, partial reductions in proteinuria. A first biopsy elsewhere showed FSGS with nonspecific IgM/C3 trapping; electron microscopy (EM) was not performed. At age 10, repeat biopsy with EM revealed ~30% segmental foot-process effacement, focal GBM thickening (to 1740 nm), irregular lamina densa multilamination, and lamellar duplications without immune-complex deposits—features highly suggestive of hereditary GBM disease. Targeted sequencing identified compound-heterozygous MYO1E variants segregating in trans: a canonical splice-donor change (c.2785+1G>A) and a frameshift (c.3094_3097del; p.Thr1032Profs*73). Each parent was an unaffected heterozygous carrier; the sibling was negative. Supportive therapy with ramipril was continued. At last follow-up (January 2025), renal function was normal (serum creatinine 0.5 mg/dL; creatinine clearance 122 mL/min) with stable sub-nephrotic proteinuria (0.52 g/day; 16 mg/m² per hour) and normotension. This case broadens clinicopathologic recognition of MYO1E-associated nephropathy and highlights the teaching point that Alport-like GBM changes are not pathognomonic for type IV collagen disorders but may signal defects in podocyte cytoskeletal anchoring. Full article

Background: Inherited kidney diseases represent a genetically and clinically heterogeneous group of disorders affecting both pediatric and adult populations. Advances in next-generation sequencing (NGS) have improved diagnostic precision; however, genotype–phenotype correlations and diagnostic yield vary substantially across disease entities. Methods:We retrospectively evaluated 165 patients referred for genetic testing due to suspected inherited kidney disease. Patients were classified into three clinical groups: polycystic kidney disease, Alport syndrome, and other syndromic patients with inherited kidney diseases. Genetic analysis was performed using NGS with Human Phenotype Ontology–based gene filtering and included evaluation of both single-nucleotide variants and copy number variations. Results: Overall diagnostic yield differed markedly between groups. A molecular diagnosis was achieved in 71.4% of Alport patients, 41.0% of PKD patients, and 70.2% of patients in the Other syndromic group. In the Alport group, variants were identified exclusively in COL4A3, COL4A4, and COL4A5, with pathogenicity and gene involvement correlating with disease severity and the presence of extrarenal manifestations. The PKD group showed predominant involvement of PKD1, followed by PKHD1 and PKD2, while a substantial proportion of patients remained genetically negative, reflecting technical and biological complexity. The Other group exhibited pronounced genetic heterogeneity, with variants distributed across multiple genes involved in tubular, glomerular, metabolic, and ciliopathy-related pathways. Computational assessments demonstrated that several variants of uncertain significance (VUS) were located in functionally critical domains and were predicted to disrupt protein stability, intermolecular interactions, or conserved structural motifs, thereby supporting the biological plausibility of their potential pathogenic impact. Conclusions: Phenotype-driven NGS enables effective molecular diagnosis across diverse inherited kidney diseases while revealing disease-specific differences in diagnostic yield and genotype–phenotype correlations. Systematic inclusion of variants of uncertain significance and careful integration of genetic and clinical data are essential for accurate interpretation and long-term patient management. Collectively, this study enhances understanding of inherited kidney diseases and underscores the value of integrating comprehensive genomic and computational approaches into routine nephrogenetic practice. Full article

Background/Objectives: Psoriasis is a chronic, recurrent inflammatory skin disorder with a steadily rising prevalence worldwide. Current therapeutic strategies include topical and systemic treatments selected based on disease severity and associated comorbidities; however, no therapy provided a definitive cure. Topical therapy is associated with a lower risk of systemic adverse effects, although the altered skin barrier observed in psoriasis may significantly reduce the bioavailability of active pharmaceutical ingredients. The aim of this study was to develop and evaluate the efficacy of a topical formulation containing triterpenoid acids derived from lavender extract (Lavandula angustifolia Mill.) as a potential adjunctive approach for symptom management in patients with psoriasis and chronic kidney disease (CKD). Methods: Following removal of the volatile oil, oleanolic, ursolic, pomolic, and rosmarinic acids were identified and quantified. The preparation was analyzed in terms of organoleptic properties, colloidal stability, pH determination, and rheological characteristics. The clinical study included 18 patients (both sexes) aged 28 to 71 years, with psoriasis and CKD of varying etiologies. Urinary albumin/creatinine ratio (uACR) and estimated glomerular filtration rate (eGFR) were used as renal biomarkers, while high-sensitive C-reactive protein (hs-CRP), hs-CRP/albumin, and neutrophil–lymphocyte ratio (NLR) were selected as inflammatory biomarkers. Laboratory assessments were performed at baseline and after 60 days of topical treatment with the lavender extract-based formulation. Clinical outcomes were evaluated using validated measures of psoriasis severity and patient impact, including the Psoriasis Area and Severity Index (PASI), the Investigator Global Assessment (IGA), and the Dermatology Life Quality Index (DLQI). Results: The formulation contained 1.4% rosmarinic acid and up to 8% ursolic acid (extract mass) and demonstrated good stability, a pH of 5.5, favorable local tolerability, antiproliferative activity, reduction in pruritus, and no treatment-related adverse effects. Efficacy and tolerability scores showed statistically significant improvements at 60 days (T2) after topical terpenoid administration compared with baseline (T0): PASI (0.722 ± 0.714 vs. 2.044 ± 0.690 at T0, p < 0.001), DLQI (3.889 ± 1.997 vs. 13.333 ± 3.361 at T0, p < 0.001), and IGA (0.556 ± 0.616 at T2 vs. 2.167 ± 0.618, p < 0.001). uACR decreased significantly over the study period (308.714 ± 240.782 after 60 days vs. 379.78 ± 308.81 at T0, p < 0.001), while eGFR values remained similar at baseline and follow-up. All evaluated inflammatory biomarkers showed significant reductions: hs-CRP (4.33 ± 2.127 at T2 vs. 9.7 ± 10.045 at T0, p < 0.009), hs-CRP/albumin ratio (0.105 ± 0.052 at T2 vs. 0.241 ± 0.225, p < 0.011), and NLR (2.154 ± 2.171 vs. 2.253 ± 0.256 at baseline, p = 0.027). Linear regression analysis identified no predictors of responsiveness to topical triterpenoid therapy in patients with psoriasis and CKD. Conclusions: This topical lavender extract-based formulation showed promising clinical and anti-inflammatory effects and favorable local tolerability in this pilot cohort of psoriasis patients with CKD. However, these findings should be considered preliminary and require confirmation in larger randomized controlled studies. Full article

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent systemic inflammation, which contributes to progressive multi-organ dysfunction, particularly in metabolically active tissues such as the liver and kidneys. Bee bread (Perga), a fermented bee pollen product rich in bioactive compounds, has been reported to exert anti-inflammatory and organ-protective effects; however, its tissue-specific influence on inflammatory responses under diabetic conditions remains incompletely defined. Thirty-two male Wistar Albino rats were randomly assigned to four groups: Control, DM, DM + Perga, and Perga. Diabetes was induced by streptozotocin (STZ; 55 mg/kg, i.p.). Perga was administered orally at a dose of 0.5 g/kg/day for 28 days. Pro-inflammatory cytokine levels (CRP, TNF-α, IL-1β, and IL-6) were quantified in liver and kidney tissues using ELISA. Histopathological alterations were evaluated by hematoxylin and eosin staining. DM significantly increased the IL-1β, IL-6, and CRP levels in hepatic tissue and elevated TNF-α, IL-1β, IL-6, and CRP levels in renal tissue. Perga administration attenuated these inflammatory responses, particularly reducing IL-1β and IL-6 levels in the liver and all measured cytokines in the kidney. Histopathological analyses revealed hepatocyte degeneration and necrosis, sinusoidal dilatation, tubular epithelial degeneration, and glomerular damage in diabetic rats, whereas Perga treatment partially improved hepatic alterations and improved renal structural integrity. These findings indicate that Perga exerts tissue-specific anti-inflammatory and protective effects in experimental diabetes, with a more pronounced impact on renal inflammation than on hepatic responses. Although its effects on hepatic TNF-α and CRP levels were limited, Perga may act as a natural modulator of cytokine-mediated inflammatory processes. Further studies are warranted to elucidate the underlying molecular mechanisms. Full article

Background: Cardiorenometabolic syndrome (CRMS) reflects the interaction between heart failure (HF), chronic kidney disease, and metabolic disorders. Its prognostic impact during the acute phase of HF remains poorly defined. The primary objective of this study was to assess whether severe CRMS (sCRMS: estimated glomerular filtration rate <45 mL/min/1.73 m² associated with type 2 diabetes mellitus and/or obesity) predicts worse clinical outcomes. Methods: This was a retrospective observational study of a prospective cohort including 2228 patients admitted for acute HF between 2015 and 2025. Clinical characteristics and outcomes (mortality, HF readmission, and the composite endpoint) were compared between patients with and without sCRMS. Results: sCRMS was present in 486 patients (21.8%) who were older, had worse functional class, and a higher burden of cardiovascular comorbidities. They presented more frequently with systemic congestion and less often with de novo HF. During follow-up, sCRMS was associated with higher mortality (29.4% vs. 18.4%), HF readmissions (56.2% vs. 33.5%), and the composite endpoint (85.6% vs. 51.9%) (all p < 0.001). In multivariable analysis, sCRMS remained an independent predictor of mortality (HR 1.25), readmissions (HR 1.24), and overall morbidity and mortality (HR 1.20). Conclusions: In patients hospitalized for acute HF, sCRMS consistently identified a clinically vulnerable phenotype with an unfavorable prognosis. These findings support the value of sCRMS as a simple and reproducible prognostic marker and highlight the need for integrated cardiorenometabolic strategies during post-discharge follow-up. Full article

Background: Susception to cardio–reno–metabolic disorders increases markedly with age; however, the dominant contributors to risk may differ across the adult life course. While metabolic abnormalities often predominate at younger ages, vascular and renal alterations become more prominent in older populations. Understanding how these risk components reconfigure with aging may inform age-tailored prevention strategies. Methods: This cross-sectional observational study included 287 adults undergoing clinical and biochemical evaluation for cardio–metabolic risk. Participants were stratified into three age categories: <65 years (n = 175), 65–75 years (n = 84), and >75 years (n = 28). Anthropometric measurements, blood pressure, metabolic parameters, liver enzymes, inflammatory markers, and renal function indices were assessed. Insulin resistance was estimated using the triglyceride–glucose (TyG) index, and renal function was evaluated by estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). Comparisons across age groups were performed using one-way analysis of variance (ANOVA). Results: Younger participants (<65 years) exhibited a predominantly metabolic risk profile, characterized by higher body mass index, waist circumference, fasting plasma glucose, triglycerides, and TyG index (all p < 0.05). In contrast, advancing age was associated with a progressive vascular–renal phenotype, including higher systolic blood pressure, lower diastolic blood pressure, and a marked decline in eGFR (p < 0.001). Liver enzymes decreased with age, while the FIB-4 index increased. UACR and C-reactive protein levels did not differ significantly between age groups. Despite these differences in individual risk markers, the composite risk category score was similar across age strata. Conclusions: Cardio–reno–metabolic risk profiles show distinct age-stratified patterns in dominant risk markers, with metabolic predominance more evident at younger ages and vascular–renal vulnerability more prominent in older adults. These findings support a life-course perspective on risk assessment and highlight the potential importance of early detection of vascular and microvascular risk in metabolically burdened younger individuals, prior to the development of overt renal dysfunction and advanced vascular aging. Full article

Hypertension has traditionally been viewed as a hemodynamic disorder leading to cardiac and renal injury; however, growing evidence suggests that, in many individuals, elevated blood pressure is instead the earliest clinical expression of subtle cardiorenal dysfunction. Early abnormalities—such as low-grade albuminuria, increased renal resistive index, arterial stiffness, and masked or nocturnal hypertension—can appear before estimated glomerular filtration rate decline or elevated office blood pressure, indicating early impairment of pressure–natriuresis, heightened tissue renin–angiotensin–aldosterone system (RAAS) activity, and increased renal microvascular impedance. The aim of this review is to summarize mechanistic, clinical, and phenotypic evidence supporting the concept that hypertension functions as an early biomarker along the cardiorenal continuum. Incorporating vascular and renal biomarkers, ambulatory blood pressure phenotyping, and targeted laboratory indices into routine assessment may identify individuals transitioning from functional disturbances to structural organ damage. These abnormalities reflect a mechanistic triad of arterial stiffening, salt-sensitive RAAS activation, and circadian blood pressure disruption, collectively defining the early cardiorenal–hypertensive phenotype. Viewing hypertension through a cardiorenal lens underscores a critical opportunity for earlier detection and mechanism-oriented intervention, which may modify disease trajectory and prevent progression to overt chronic kidney disease and heart failure. Full article

Introduction: Diabetes mellitus (DM) is a prevalent metabolic disorder frequently leading to serious renal complications, particularly diabetic nephropathy. This retrospective case–control study investigated the levels and associations of commonly used enzymatic (serum creatinine and urea) and physiological (glomerular filtration rate [GFR]) markers of kidney function in diabetic patients compared to non-diabetic controls. Methodology: A total of 237 participants were enrolled, comprising 81 diabetic cases and 156 non-diabetic controls. Creatinine and urea levels were determined using enzymatic methods, measuring optical density, whereas GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, based on creatinine, age, and sex. Statistical comparisons include p-value, Pearson correlation, etc. Results: The diabetic group exhibited significantly higher mean levels of serum creatinine (2.08 ± 2.26 mg/dL) and urea (57.71 ± 38.75 mg/dL) and a significantly lower mean GFR (59.59 ± 34.16 mL/min/1.73 m²) compared to the non-diabetic control group (0.95 ± 0.69 mg/dL, 31.79 ± 20.49 mg/dL, and 96.72 ± 23.77 mL/min/1.73 m², respectively; all comparisons with p < 0.005). Correlation analysis revealed a more scattered positive association between creatinine and urea, and a pronounced inverse correlation between GFR and both creatinine and urea in the diabetic cases, suggesting a compromised renal function profile. Conclusions: Our findings demonstrate a significant association between diabetes and impaired renal function, as evidenced by elevated creatinine and urea levels and reduced GFR. These readily available biomarkers are crucial prognostic indicators for the early detection and effective management of diabetic nephropathy, emphasizing the importance of rigorous metabolic and blood pressure control to mitigate disease progression. Full article

Plasma cell disorders often have urinary excretion of monoclonal immunoglobulins and renal injury that are evaluated using total protein assays and electrophoresis. Proteinuria was evaluated for 100 patients with plasma cell disorders and 24 h collections. A turbidimetric method on the Abbott Alinity quantified protein. Electrophoresis used agarose gels. Most specimens (66%) had protein concentrations below the manufacturer’s limit of quantitation (LOQ), 6.8 mg/dL (68 mg/L). After validating an LOQ of 3 mg/dL (30 mg/L), 34% of urine specimens still were below the LOQ. After excluding 40 patients with other causes of increased protein excretion (decreased estimated glomerular filtration rate (eGFR), diabetes mellitus, or overflow proteinuria), almost all patients had protein excretion below an upper reference limit of 150 mg/d. Median total protein excretion for these 60 patients was 75 mg/d; only one patient excreted >132 mg/d. However, 32% of these patients without increased total protein excretion had albumin excretion ≥ 30 mg/d, suggestive of kidney injury. Electrophoretic patterns included glomerular, tubular, and overflow proteinuria; 32 specimens contained monoclonal immunoglobulins. Protein concentrations of urine are often below LOQs of total protein assays, raising questions about whether LOQs should be improved. Urine albumin measurements and electrophoretic patterns may serve as more sensitive indicators of kidney injury in patients with plasma cell disorder than measurements of total protein excretion or increased serum creatinine. Full article

Kidney cells are exposed to a wide range of physiological and pathological stresses, including hormonal changes, mechanical forces, hypoxia, hyperglycemia, and inflammation. These insults can trigger adaptive responses, but when they persist, they can lead to organelle stress. Organelles such as mitochondria, the endoplasmic reticulum, and primary cilia sustain cellular metabolism and tissue homeostasis. When organelle stress occurs, it disrupts cellular processes and organelle communication, leading to metabolic dysfunction, inflammation, fibrosis, and progression of kidney disease. Sex and hormonal factors play a significant role in the development of renal disorders. Many glomerular diseases show distinct differences between the sexes. Chronic Kidney Disease is more common in women, while men often experience a faster decline in kidney function, partly due to the influence of androgens. Additionally, the loss of female hormonal protection after menopause highlights the importance of sex as a factor in renal susceptibility. This narrative review synthesizes preclinical evidence on how sexual dimorphism and sex hormones affect organelle stress in mitochondria, the endoplasmic reticulum, and primary cilia, from 33 studies identified through a non-systematic literature search of the PubMed database, to provide an overview of how these mechanisms contribute to sex-specific differences in kidney disease pathophysiology. Full article

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder marked by progressive kidney enlargement and cyst formation, often resulting in end-stage renal disease (ESRD). Oxidative stress (OxS) significantly contributes to renal damage in chronic kidney disease (CKD) and ADPKD. While the Mediterranean diet (Med-diet) is known for its antioxidative and anti-inflammatory effects, its impact on OxS in ADPKD remains unclear. This study aimed to assess the relationship between adherence to the Med-diet, OxS levels, and renal function in ADPKD patients. We enrolled 63 ADPKD patients aged 18–70 years with CKD stages G2–G4. Adherence to the Med-diet was evaluated using the PREDIMED questionnaire. OxS markers (NOX2-derived peptide [sNOX2-dp] and hydrogen peroxide [H₂O₂]) were measured via ELISA. Correlations between these markers, Med-diet adherence, serum creatinine, and estimated glomerular filtration rate (eGFR) were analyzed. Higher adherence to the Med-diet was associated with significantly lower OxS markers (sNOX2, p < 0.001; H₂O₂, p = 0.04). Reduced NOX2 and H₂O₂ levels correlated with lower creatinine and higher eGFR (NOX2, p < 0.001; H₂O₂, p < 0.001), suggesting an inverse relationship between OxS and renal function. In conclusion, adherence to the Mediterranean diet appears to be associated with lower levels of oxidative stress and may slow the progression of chronic kidney disease. These findings suggest that dietary interventions could mitigate disease progression by modulating OxS. Further studies are needed to confirm these results and explore the long-term effects of the Med-diet on disease progression. Full article

Fabry disease (FD) is an X-linked lysosomal disorder caused by GLA mutations, typically associated with glycosphingolipid accumulation and a wide phenotypic spectrum. The p.R112H variant is generally linked to a non-classic predominantly renal phenotype with mild biochemical abnormalities and slow progression. We report the case of a young woman carrying the R112H mutation who exhibited early-onset kidney involvement and unusually rapid progression to end-stage renal disease. Clinical history, serial evaluations, and kidney biopsy findings initially supported a diagnosis of Fabry nephropathy; however, re-evaluation of the native kidney biopsy revealed marked remodeling and multilamellation of the glomerular basement membrane, suggesting Alport-like lesions. Subsequent genetic testing confirmed a heterozygous pathogenic COL4A4 variant (G912R), indicating coexistence of Fabry disease and autosomal dominant Alport syndrome. This dual genetic condition likely accounted for the accelerated decline in kidney function, in contrast with the typically mild phenotype associated with R112H. Our literature review indicates that coexistence of these two inherited nephropathies has not previously been confirmed either histologically or genetically. This case underscores the importance of integrating genetic and ultrastructural assessment in patients with atypical or rapidly progressive renal disease Full article

Neurodegenerative synucleinopathies—including Parkinson’s disease, multiple system atrophy, pure autonomic failure, and dementia with Lewy bodies—often feature cardiovascular autonomic dysfunction. Neurogenic orthostatic hypotension (nOH) is common and symptomatic, while neurogenic supine hypertension (nSH) is less frequent but may carry long-term cardiovascular risks. Lifestyle measures are first-line for managing nSH, yet persistent hypertension unresponsive to nonpharmacological strategies presents a treatment dilemma. Limited trial data and unclear guidelines make it difficult to determine when antihypertensive therapy is appropriate. Evidence from studies on hypertension-mediated organ damage (HMOD)—assessed through markers such as carotid intima-media thickness, pulse wave velocity, left ventricular hypertrophy, estimated glomerular filtration rate, and white matter hyperintensities—suggests that nSH, rather than the underlying neurodegenerative disorder, drives vascular, cardiac, renal, and cerebral injury. Therefore, treatment decisions should be individualized. While antihypertensive therapy may help prevent subclinical organ damage, clinicians must balance this benefit against the risk of worsening nOH and further compromising overall prognosis. Full article