Search Results (452)

Background: Clinical tools to structure kidney transplant waitlist management at the time of listing are limited. We evaluated a simple, donor-independent clinical grading applied at waitlist registration to stratify patients according to post-transplant risk. Methods: We retrospectively analyzed 465 adult kidney transplant recipients from two German centers (2018–2023). Patients were assigned to three clinical grading groups based on age and comorbidities, and to three immunologic groups based on pre-immunization. One-year outcomes included mortality, graft loss, eGFR, albuminuria, and rejection. Results: Higher clinical grades were associated with worse one-year outcomes, including lower eGFR and higher rates of death or graft loss, whereas immunologic grading was associated with waiting time but not short-term post-transplant outcomes. These associations appeared robust to donor characteristics in sensitivity analyses. Conclusions: A simple, listing-time clinical grading may support structured waitlist management before donor information is available. External validation is required. Full article

Background: Renal dysfunction is common in patients hospitalized with acute decompensated heart failure (ADHF) and represents a key component of cardiorenal syndrome. However, the relationships between renal impairment, cardiorenal biomarkers, and echocardiographic markers of myocardial function remain incompletely characterized in ADHF populations. Methods: We conducted a cross-sectional analysis of 144 consecutive patients hospitalized with ADHF. Renal dysfunction was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Clinical, laboratory, and echocardiographic parameters were compared according to renal function. Correlation analyses, multivariable logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to evaluate associations between renal dysfunction, cardiorenal biomarkers, and myocardial functional indices. Results: Patients with renal dysfunction were older (p = 0.002) and more frequently had diabetes mellitus (p = 0.006). Echocardiographic evaluation demonstrated significantly lower systolic mitral annular velocity (S′) (p < 0.001) and higher E/e′ ratios (p < 0.001) in patients with renal dysfunction, whereas left ventricular ejection fraction (p = 0.133) and global longitudinal strain (GLS) (p = 0.121) were similar between groups. Log-transformed NT-proBNP and albuminuria were significantly correlated with S′, GLS, and E/e′ (all p < 0.001). In multivariable analysis adjusted for clinically relevant confounders, chronic kidney disease (OR 8.16, 95% CI 2.13–31.34; p = 0.002) and the E/e′ ratio (OR 2.01, 95% CI 1.52–2.66; p < 0.001) remained independently associated with renal dysfunction. ROC analysis showed that E/e′ had the strongest ability to distinguish between patients with and without renal dysfunction (AUC 0.887, 95% CI 0.834–0.941; p < 0.001). Conclusions: Renal dysfunction in ADHF is associated with echocardiographic markers reflecting impaired longitudinal myocardial function and elevated filling pressure, with E/e′ emerging as the strongest echocardiographic correlate. The integration of echocardiographic parameters with cardiorenal biomarkers may improve the characterization of the cardiorenal profile in patients hospitalized with ADHF. Full article

Hypertension and chronic kidney disease (CKD) are closely linked conditions and represent common global health problems. Hypertension is a leading risk factor for cardiovascular disease, which is the main cause of mortality in CKD. Endothelial injury underlies the etiopathogenesis of both hypertension and CKD. The endothelial glycocalyx (eGC) is a dynamic, negatively charged, carbohydrate-rich layer that covers the luminal surface of endothelial cells. Its primary physiological function is to protect the endothelium, including the regulation of vascular permeability and homeostasis. Damage to the eGC, known as “shedding”, is an early predictor of endothelial dysfunction and is driven by oxidative stress and low-grade inflammation. In hypertension, loss of eGC integrity—often impaired by a high-salt diet—can reduce the bioavailability of nitric oxide (NO) and increase arterial stiffness. Similarly, in CKD, uremic toxicity, hypertension, and inflammation damage the eGC, resulting in increased permeability, albuminuria, and higher cardiovascular risk. This review summarizes current evidence and underscores the potential of eGC shedding markers, especially syndecan 1 (SDC-1) and hyaluronic acid (HA), as early predictors of vascular risk and disease progression in hypertension and CKD. Full article

Background: Diabetic nephropathy (DN), also referred to as diabetic kidney disease, represents one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and remains a leading cause of end-stage renal disease worldwide. Conventional clinical markers, including albuminuria and estimated glomerular filtration rate (eGFR), are widely used for diagnosis and staging but may have limited sensitivity for detecting early renal injury and predicting disease progression. In recent years, circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers that reflect underlying molecular mechanisms of diabetic nephropathy and may complement traditional clinical indicators. Objective: The present study aimed to evaluate serum and urinary levels of hsa-miRNA-770-5p across different stages of diabetic nephropathy and to assess its potential diagnostic value in relation to established indicators of renal function. Methods: A total of 257 participants were included and divided into four groups: healthy controls, patients with T2DM without nephropathy, patients with T2DM and DN in CKD stages I–II, and patients with DN undergoing maintenance hemodialysis (MHD). Serum and urinary levels of miRNA-770-5p were measured using quantitative real-time polymerase chain reaction (qPCR) and analyzed using the 2^−ΔΔCt method. Statistical analyses included comparisons between groups using ANOVA, correlation analyses with renal function parameters such as eGFR and proteinuria/albuminuria, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance. Results: Serum levels of miRNA-770-5p were significantly elevated in patients with DN and in patients undergoing maintenance hemodialysis compared with healthy controls and patients with T2DM without nephropathy. In contrast, urinary levels of miRNA-770-5p were markedly reduced in patients with DN. Serum levels in patients with T2DM without nephropathy were slightly lower than those observed in healthy controls. Significant correlations were identified between miRNA-770-5p levels and renal function parameters, including eGFR and proteinuria/albuminuria, supporting the biological relevance of this microRNA in renal injury. ROC curve analysis demonstrated good discriminatory ability for differentiating DN from T2DM without nephropathy (serum AUC = 0.82; urine AUC = 0.79). Conclusions: hsa-miRNA-770-5p demonstrates distinct and opposite patterns in serum and urine that correlate with the severity of diabetic nephropathy. The complementary changes observed in circulating and urinary levels support the potential of miRNA-770-5p as a non-invasive biomarker that may complement conventional clinical markers and provide additional insight into the molecular mechanisms involved in the development and progression of diabetic nephropathy. Full article

Background: Albuminuria reflects systemic endothelial dysfunction and cardiorenal interaction in heart failure (HF), yet its short-term prognostic value in acute decompensated HF (ADHF) remains incompletely characterized. Methods: We conducted a prospective observational cohort study including 144 patients with complete follow-up hospitalized for ADHF. Urinary albumin-to-creatinine ratio (ACR), NT-proBNP, and estimated glomerular filtration rate (eGFR) were measured within 24 h of admission. Prior HF hospitalization within 12 months was recorded. The primary endpoint was a 90-day post-discharge composite of all-cause mortality or HF rehospitalization. Associations were examined using logistic regression, and discrimination was assessed using ROC curves with AUC comparisons. Results: Twenty-six patients (18.1%) experienced the 90-day composite endpoint. In univariable analysis, log₁₀-transformed ACR was strongly associated with events (OR 3.90, 95% CI 1.92–7.91; p < 0.001). In multivariable analysis, ACR remained independently associated with the endpoint in Model 1 (ACR + prior HF hospitalization: OR 4.21, 95% CI 1.93–9.17; p < 0.001) and Model 2 (additional adjustment for log₁₀ NT-proBNP: OR 3.49, 95% CI 1.54–7.91; p = 0.003). NT-proBNP was not independently associated with outcome in the fully adjusted model (p = 0.080). Discrimination improved from AUC 0.724 for ACR alone to 0.821 for Model 1 and 0.836 for Model 2; the AUC difference between Model 1 and Model 2 was not statistically significant (p = 0.404). Conclusions: Urinary ACR independently predicts 90-day adverse outcomes after ADHF hospitalization and improves discrimination when combined with recent HF hospitalization history; NT-proBNP did not provide significant incremental discrimination beyond this model. Full article

Background/Objectives: Cardiorenal syndrome type 2 (CRS-2) is characterized by progressive renal dysfunction caused by chronic heart failure (HF) and is associated with increased morbidity and mortality. However, the prognostic value of renal biomarkers in patients with CRS-2 hospitalized for decompensated HF remains unclear. Methods: This prospective observational cohort study included 200 consecutive patients hospitalized for decompensated HF in the Intensive Care Unit of the Clinic for Internal Medicine at the University Clinical Centre Tuzla between April and October 2025. CRS-2 was defined as chronic HF with chronic kidney disease persisting for ≥3 months before admission according to KDIGO criteria. Patients were followed for three months. The primary composite outcome was all-cause mortality or initiation of renal replacement therapy. Results: CRS-2 was identified in 130 patients (65.0%) and was associated with higher in-hospital mortality (32.3% vs. 11.4%, p = 0.002) and three-month mortality (44.6% vs. 21.4%, p = 0.002). Within the CRS-2 subgroup, patients who experienced the primary composite outcome had higher admission levels of cystatin C and urinary albumin-to-creatinine ratio (UACR) and lower estimated glomerular filtration rate (eGFR). ROC analysis demonstrated moderate discriminative ability of cystatin C (AUC 0.739) and UACR (AUC 0.733). In Cox regression analysis, cystatin C (HR 1.534, 95% CI 1.263–1.863, p < 0.001) and UACR (HR 1.003, 95% CI 1.001–1.006, p = 0.001) were significantly associated with the primary composite outcome. Conclusions: Renal dysfunction markers, particularly cystatin C and albuminuria, are associated with early adverse outcomes in CRS-2 patients hospitalized for decompensated HF. Routine assessment of these biomarkers may provide additional prognostic information and support risk assessment in this high-risk population. Full article

Diabetic kidney disease (DKD) affects a substantial proportion of individuals with diabetes mellitus and represents the leading cause of end-stage renal disease worldwide. Familial aggregation studies consistently demonstrate that genetic factors contribute significantly to DKD susceptibility beyond metabolic and hemodynamic determinants. The carnosine dipeptidase 1 (CNDP1) gene on chromosome 18q22.3 has emerged as a compelling susceptibility locus, with a trinucleotide (CTG) repeat polymorphism in exon 2 that encodes the Mannheim variant, which has demonstrated protective associations in selected populations. Individuals homozygous for the shorter (CTG)₅ allele exhibit reduced serum carnosinase-1 concentrations and activity, resulting in elevated tissue carnosine levels. Carnosine exerts multiple renoprotective effects, including antioxidant activity, inhibition of advanced glycation end-product formation, and attenuation of profibrotic signaling. Experimental models demonstrate that genetic or pharmacological reduction in carnosinase activity attenuates diabetic kidney injury. Early clinical studies of carnosine supplementation report improvements in albuminuria and oxidative stress markers, though available trials are limited in size, duration, and population scope. Therapeutic targeting of CNDP1 via carnosinase inhibition, therefore, represents a biologically grounded yet still emerging pharmacological strategy. This review synthesizes genetic, molecular, and translational evidence supporting CNDP1 as a model for genetics-informed therapeutic development in DKD, while highlighting important population-specific variation in allele frequencies that constrain universal clinical applicability. Full article

Diabetic kidney disease (DKD) persists as the leading cause of chronic kidney disease (CKD) and often leads to end-stage renal disease (ESRD). Worldwide, 30–50% of patients with diabetes are affected by DKD, while DKD contributes to about half of ESRD. Previously, DKD had been defined based on overt proteinuria—that is, a urine albumin-to-creatinine ratio (UACR) above 300 mg/g—after a stage of microalbuminuria (UACR 30–300 mg/g). However, emerging data suggest that a significant number of patients develop renal functional decline without albuminuria, suggesting that DKD can occur in the absence of protein excretion. This phenotype of normoalbuminuric or non-proteinuric DKD (NA-DKD or NP-DKD) is emerging as an important clinical entity. It is characterized by a gradual decline in renal function, commonly with an annual reduction in estimated glomerular filtration rate (eGFR) > 3 mL/min/1.73 m² or an eGFR < 60 mL/min/1.73 m², while the UACR remains < 30 mg/g. Growing rates of NP-DKD expose limitations inherent in traditional models of DKD pathogenesis and underscore the need for diagnostic and therapeutic paradigms that are not reliant on albuminuria-only criteria. Here, we present a comprehensive review of the NP-DKD to guide a more inclusive model of DKD pathogenesis, its diagnosis, and therapy. Full article

Podocyte injury is an early hallmark of chronic kidney disease (CKD) and can be influenced by SGLT2 inhibitors (SGLT2i). Early effects of SGLT2i include transient estimated glomerular filtration rate (eGFR) dip and reduced proteinuria; however, the latter may be subtle in patients with normal or moderately increased albuminuria. In such cases, urinary podocyte-derived biomarkers may provide sensitive early indicators of SGLT2i effect. This study prospectively assessed short-term changes in urinary podocyte biomarkers (nephrin, podocin, podocalyxin) following SGLT2i initiation in diabetic and non-diabetic CKD patients. Our cohort had a low urinary albumin to creatinine ratio (UACR) of 19.09 mg/g (6.28; 164.93) and preserved eGFR 45 mL/min/1.73 m² (36.85; 53.15). At baseline, podocyte biomarkers were mutually correlated, whereas only podocalyxin was associated with UACR. Baseline podocalyxin independently predicted transient eGFR dip and UACR reduction. Early decreases in both podocin and podocalyxin were associated with eGFR decline and lower UACR at 3 months. ROC analyses identified cutoff values for all three biomarkers that predicted short-term eGFR decline, with baseline podocalyxin demonstrating the highest discriminative accuracy. These findings support pleiotropic nephroprotective effects of SGLT2 inhibitors and identify urinary podocyte biomarkers—particularly podocalyxin, and to a lesser extent podocin—as a sensitive indicator of early renal response. Full article

Background/Objectives: Kidney injury is a frequent complication of multiple myeloma (MM) and monoclonal gammopathies. Podocyte stress markers, such as urinary nephrin and podocin, have been studied in other renal diseases but their utility in paraprotein-related kidney disease remains unclear. This pilot study investigated the association of urinary nephrin and podocin levels with albuminuria and biopsy-proven podocytopathy in patients with paraprotein-related diseases. Methods: We retrospectively analyzed 75 patients with plasma cell dyscrasias, including MM and MGRS, along with 11 healthy controls. Urinary podocin and nephrin mRNA levels were measured using qPCR, and urinary podocin protein levels were quantified via ELISA. Associations were assessed between these biomarkers and urinary protein-to-creatinine ratio (uPCR), albumin-to-creatinine ratio (uACR), and histologically confirmed podocytopathia. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analysis. Results: Higher urinary podocin protein levels were significantly associated with lower uACR (p = 0.007) and uPCR (p = 0.026). Neither podocin nor nephrin mRNA showed significant associations with proteinuria metrics. ROC analysis indicated that podocin ELISA (AUC = 0.350) and podocin mRNA (AUC = 0.510) lacked diagnostic accuracy for predicting renal involvement. The presence of urinary tract infection (UTI) was a significant confounder, leading to increased levels of podocin and nephrin mRNA. Conclusions: Urinary podocin shows a trend toward elevation in MM/MGRS patients with histological podocyte injury. The study revealed an unexpected inverse association between urinary podocin and albuminuria, suggesting complex release kinetics or stage mismatches in this population. Given the confounding effect of UTIs, and the pilot nature of this study, further research is required to validate these podocyte proteins as biomarkers in paraprotein-related kidney disease. Full article

Background: Early vascular aging (EVA) reflects accelerated arterial stiffening and is closely linked to cardiovascular and renal target organ damage. The Early Vascular Aging Ambulatory score (EVAAs) estimates EVA using ambulatory blood pressure monitoring (ABPM) and routinely available clinical parameters. We aim to investigate the association between EVAAs-defined early vascular aging and markers of kidney involvement—particularly albumin-to-creatinine ratio (ACR)—in a hypertensive population. Methods: Fifty treated hypertensive adults undergoing 24 h ABPM were enrolled. All participants underwent laboratory evaluation, including serum electrolytes and 24 h urine collection for albumin, creatinine, sodium, and potassium. EVAAs was calculated using ABPM-derived parameters and established cardiovascular risk factors. Results: EVAAs was positively correlated with ACR (r = 0.276, p = 0.049). In addition, inverse correlations were observed between EVAAs and serum potassium (r = −0.290, p = 0.038) and serum sodium (r = −0.284, p = 0.046). Participants with moderately increased albuminuria tended to exhibit higher EVAAs values, although this difference did not reach statistical significance. Conclusions: EVAAs is associated with early markers of renal involvement in hypertensive patients, supporting its potential role as a non-invasive indicator of subclinical target organ damage. Larger studies are warranted to confirm these findings and to further validate EVAAs as a clinically useful marker of EVA. Full article

Diabetic nephropathy (DN) is a serious complication in diabetic patients, leading to kidney dysfunction and ultimately end-stage renal disease. Although several pharmacological agents have been developed, treating DN remains challenging due to its complex and multifaceted pathogenesis. Endoplasmic reticulum (ER) stress plays a crucial role in DN pathology; however, the molecular mechanisms underlying reduced ER stress remain poorly understood. This study investigated the protective effects of 4-phenylbutyrate (4-PBA), an ER stress inhibitor, on DN and the related regulatory molecules through gene expression network analysis. A C57BL/6 mouse model of DN was used in combination with a high-fat diet and streptozotocin after unilateral nephrectomy and treated with 4-PBA by intraperitoneal injection for 6 weeks. The 4-PBA treatment effectively improves DN-induced renal structural and functional abnormalities by reducing albuminuria, podocyte loss, glomerular and tubular injury, and renal inflammation and cell death. These changes induced by 4-PBA were associated with decreased expression of ER stress markers and increased autophagy activities in diabetic kidneys. Importantly, 4-PBA reduced components of the complement C1q pathway, the NADPH oxidase complex, and chemokines, thereby attenuating chronic renal dysfunction. Conclusively, inhibition of ER stress is a promising pharmacological target for treating patients with DN. Full article

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. During the last few years, remarkable advances have been made in the treatment of DN. Sodium–glucose cotransporter type 2 inhibitors (SGLT2i) consistently prevent or delay albuminuria and renal failure in patients with DN. Prior research from our group highlights the Janus kinase/signal transducers and activators of transcription axis as a critical target in DN. Specifically, the administration of suppression of cytokine signaling 1 (SOCS1) mimetic peptides (MiS1) modulates aberrant signaling, resulting in profound beneficial effects on renal function and structural integrity in experimental DN. The aim of this study was to evaluate the effect of empagliflozin and MiS1 on kidney damage and its associated inflammatory, oxidative stress and lipotoxic mechanisms in an advanced type 2 DN mouse model BTBR ob/ob. Mice were treated for 7 weeks with empagliflozin and MiS1, alone or in combination, and monitored for glycemia, body weight, albuminuria, histopathological damage, podocyte loss, and gene expression related to inflammation, redox balance, and lipid metabolism. Empagliflozin or MiS1 monotherapies significantly reduced albuminuria and structural renal injury, preserved podocyte number, and downregulated genes involved in inflammatory, oxidative, and mitochondrial–lipid metabolic dysregulation, with empagliflozin additionally improving metabolic parameters. Notably, the combined therapy achieved the greatest reduction in albuminuria and histological damage with enhanced suppression of pathogenic inflammatory and metabolic pathways, resulting in superior renoprotection compared with monotherapy. These findings suggested that add-on therapy with SOCS1 peptidomimetics and SGLT2i may help mitigate residual albuminuria and renal damage in type 2 DN. Full article

Background/Objectives: Chronic kidney disease (CKD) is a global public health concern, posing significant diagnostic and management challenges in primary care. Estimated glomerular filtration rate (eGFR) is central to CKD staging, yet different estimating equations may yield substantially different stage classifications when applied to the same population. This study aims to compare the eGFR-based CKD stage classification and stage distribution obtained using the Chronic Kidney Disease: Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations in a large primary care cohort, and to explore the implications of these classification differences for routine use in primary healthcare (PHC). Methods: A cross-sectional analysis was conducted using standardized electronic health records from 117,055 PHC patients in the Matosinhos Health Unit, Portugal, spanning 22 years (2000–2022). CKD staging followed KDIGO guidelines and focused on stages G3–G5, based on the most recent available serum creatinine value. CKD-EPI and MDRD equations were compared overall and across age strata, BMI categories, albuminuria categories (when available), and major comorbidity subgroups, including heart failure, diabetes, and hypertension. Results: Using CKD-EPI, a higher proportion of individuals were classified as CKD stages G3–G5 (9042; 7.73%) compared with MDRD (7686; 6.57%). Classification differences were most pronounced in advanced stages (relative increase with CKD-EPI: G3b +29.4%, G4 +23.6% and G5 +34.4%). Among individuals aged ≥80 years, equation-related classification differences were particularly marked in advanced stages (G5). Similarly, CKD-EPI was associated with higher CKD stage classification rates in high-risk subgroups, including patients with heart failure. Conclusions: Compared with MDRD, CKD-EPI yields a higher proportion of individuals classified into CKD stages, particularly advanced stages and among older adults and high-risk comorbidity subgroups. These findings highlight the substantial impact of equation choice on CKD stage classification in primary care and support the use of CKD-EPI for standardized eGFR reporting, while emphasizing that observed differences reflect classification rather than confirmed CKD diagnosis. Full article

The increasing global burden of chronic kidney disease (CKD) magnifies an urgent need to find treatable targets. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine secreted by kidney tubular epithelia in response to a variety of stimuli. To better understand the effects of tubular MCP-1 in response to kidney injury, we generated tubular epithelia-specific MCP-1 knockout mice (KO; Pax8-Mcp-1^fl/fl). We then exposed these mice and their control littermates to Adriamycin (Adr; 18 mg/kg, IV bolus). Thirty-two days after Adr injection, Mcp-1 transcript and protein levels were suppressed in the KO mice compared to their wild-type (WT) littermates. The KO mice exhibited no effect on survival, change in body weight, albuminuria, kidney function, glomerular or tubular injury, or tubulointerstitial fibrosis compared to WT. Overall, the results suggest that tubule-secreted MCP-1 is not necessary for progression of Adr-induced injury. These findings contribute to our understanding of the role of MCP-1 in kidney injury. Full article