Marina López-Martínez

Background/Objectives: Repeat kidney biopsy in lupus nephritis is increasingly used to resolve discrepancies between clinical, serological and histological findings, but its diagnostic yield in real-world practice remains incompletely defined. This study aimed to describe the indications, safety, histological transitions, clinically relevant findings, treatment changes and clinical course of patients with lupus nephritis undergoing repeat native kidney biopsy. Methods: We conducted a retrospective single-centre study including adults with biopsy-proven lupus nephritis attended between 2003 and 2025 who underwent at least one repeat native kidney biopsy. Analyses were performed at patient level, comparing the index and last biopsy, and at episode level, evaluating consecutive biopsy transitions. Results: Nineteen patients and 45 native kidney biopsies were included. The most frequent indication for repeat biopsy was serological and/or proteinuric worsening. Comparing the index and last biopsy, histological or diagnostic change was observed in 14/19 patients (73.7%), including diagnoses not compatible with active lupus nephritis in 3/19 (15.8%). Sequential analysis identified 26 transitions; 17/26 (65.4%) showed lupus nephritis class change, 4/26 (15.4%) incident membranous component and 3/26 (11.5%) a diagnosis that was not compatible with active lupus nephritis. Two biopsy-related hematomas occurred and three patients required kidney replacement therapy during follow-up. Conclusions: In this real-world cohort, repeat kidney biopsy provided clinically relevant and potentially actionable diagnostic information, particularly through sequential analysis of consecutive biopsies.

Key Points: Treatment with semaglutide compared with placebo for 24 weeks reduced lean body mass and fat mass in adults with CKD and overweight or obesity. Changes in lean body mass or fat mass during semaglutide treatment did not correlate with changes in creatinine or cystatin C‑eGFR or measured GFR. Semaglutide significantly reduced extracellular water and BP, and changes in BP correlated with extracellular water. Background: The glucagon-like peptide-1 receptor agonist semaglutide reduces hemoglobin A1c, body weight, BP, and GFR decline. Semaglutide may influence serum creatinine and cystatin C levels by nonkidney-related mechanisms and thereby affect eGFR. We studied the relationship between changes in body composition, eGFR and measured GFR (mGFR), and BP during semaglutide treatment. Methods: We performed a prespecified analysis of a randomized placebo-controlled double-blind clinical trial in 101 adults with CKD with overweight status or obesity and without type 2 diabetes. Participants were randomized to 24 weeks of semaglutide 2.4 mg/wk subcutaneously or matched placebo treatment. We measured GFR with iohexol clearance, estimated GFR with creatinine and cystatin C, and used bioimpedance spectroscopy to determine lean body mass, fat mass, and extracellular water. Results: After 24 weeks of treatment, semaglutide compared with placebo changed total body weight, lean body mass, and fat mass by −9.1 (95% confidence interval [CI], −11.0 to −7.2), −2.5 (95% CI, −6.6 to 1.6), and −3.9 (95% CI, −7.8 to 0.0) kg, respectively. No correlations were present between changes in total body weight, lean body mass, and fat mass with changes in eGFR (creatinine or cystatin C) or mGFR during semaglutide treatment (all Spearman correlation coefficients P = 0.005). Conclusions: Semaglutide reduced lean body mass and fat mass in patients with CKD with overweight status or obesity. These changes did not correlate with changes in creatinine or cystatin C eGFR or mGFR, suggesting that body weight reductions of 10% with semaglutide do not influence GFR estimates. Clinical Trial registry name and registration number: ClinicalTrials.gov, NCT04889183.

Weight loss is central to treating obesity-related kidney disease, yet the renal effects of a low-fat diet (LFD) versus bariatric surgery (BS) remain incompletely understood. This study compared their impact on obesity-related glomerulopathy (ORG). Twenty-eight male Wistar rats were fed a high-fat diet (HFD) for 10 weeks to induce obesity. Eight rats were sacrificed (the HFD group), eight switched to LFD for 10 weeks, and twelve underwent sleeve gastrectomy. Body weight, albuminuria, renal histology, and transcriptomic profiles were analyzed. Weight loss was modest in the LFD group (−1.6%) but substantial after BS (−13.2%), occurring 2.1 times faster. Albuminuria decreased in both interventions compared to HFD (LFD: 7228 ± 514 ng/mL; BS: 6242 ± 418 ng/mL; HFD: 10,384 ± 1168 ng/mL; p < 0.01) and correlated strongly with weight loss (R² = 0.78). The glomerular area was reduced in both groups, but only BS achieved complete histological resolution of ORG. Tubular cells in BS-treated rats showed megamitochondria and cristae disruption, while LFD induced milder alterations. Transcriptomics revealed suppression of mitochondrial maintenance genes and upregulation of oxidative stress and immunometabolic pathways. Immune-related genes upregulated in BS clustered into pro-inflammatory/chemotactic and regulatory modules. To the best of our knowledge, this is the first piece of evidence that BS fully reverses ORG, highlighting renal effects beyond weight loss alone.

Patients with diabetes and chronic kidney disease (CKD-DM) often have residual albuminuria despite pharmacological treatment. Finerenone targets mineralocorticoid overactivation, but real-world evidence remains limited. This study evaluated the impact of finerenone in a cohort of patients with CKD-DM. This was a real-life study including patients with CKD-DM and an estimated glomerular filtration rate (eGFR) ≥ 20 mL/min/1.73 m², treated with finerenone, aged ≥ 18 years, and followed at the Nephrology Department of Vall d’Hebron Hospital. Clinical and laboratory data were collected at baseline and at 1, 3, and 6 months of treatment. Changes in albuminuria and eGFR were analyzed in patients who completed 6 months of follow-up. A total of 60 patients were included in the analysis; 39 (65%) were male, with a median age of 79 ± 10.12 years. Finerenone was initiated at 10 mg daily in 57 patients (95%), with 38.3% escalating to 20 mg after 1 month. After 6 months, the urinary albumin-to-creatinine ratio (UACR) decreased by 37.1% (p = 0.012, n = 34). Patients with an initial eGFR drop > 20% showed a greater UACR decrease of around 43% at 3 (p = 0.012) and 6 months (p = 0.013). A significant 9.5% decline in eGFR was observed at 1 month, followed by stabilization at 3 and 6 months. Finerenone was discontinued in 10% of the patients due to adverse events. Hyperkalemia occurred in 18.3% of the patients, but no hospitalizations for adverse events or heart failure were reported. In summary, finerenone induced a significant 37.1% reduction in albuminuria after 6 months of treatment. This reduction was more pronounced in patients who experienced an initial eGFR dip ≥ 20%. Finerenone was generally well tolerated and appears to be a promising therapeutic strategy for reducing albuminuria in this population.

Obesity represents a serious and growing disease worldwide. The pathophysiological changes secondary to chronic inflammation lead to the development of diseases that increase the morbidity and mortality of individuals. Chronic kidney disease (CKD) is a condition with deleterious effects that acts bidirectionally with obesity. From approximately 20% to 30% of individuals share phenotypes of CKD and obesity, increasing their cardiovascular risk and the risk of other complications. Obesity and CKD form a vicious cycle in which inflammation is the central axis of multiorgan damage. Despite increasing the risk of cardiac and renal mortality, CKD progresses in relation to body mass index and albuminuria. Nowadays, the implementation of the new medications aimed at mitigating the peak of inflammation is becoming a cornerstone of treatments for obesity, diabetes, cardiovascular diseases, and renal disease.

Obesity represents a serious and growing disease worldwide. The pathophysiological changes secondary to chronic inflammation led to the development of diseases that increase the morbidity and mortality of individuals. Chronic kidney disease (CKD) is a condition with deleterious effects that acts bidirectionally with obesity. Approximately 20% to 30% of individuals share phenotypes of CKD and obesity, increasing their cardiovascular risk and the risk of other complications. Obesity and CKD form a vicious cycle in which inflammation is the central axis of multiorgan damage. Despite increasing the risk of cardiac and renal mortality, CKD progresses in relation to body mass index and albuminuria. Nowadays, the implementation of the new medications aimed at mitigating the peak of inflammation are becoming as cornerstone treatments for obesity, diabetes, cardiovascular diseases, and renal disease.

Obesity increases the risk of cardiovascular disease, diabetes and chronic kidney disease. Obesity-related glomerulopathy (ORG) is a potentially reversible cause of kidney disease that often progresses silently until it reaches irreversible stages. However, we are still lacking a sensitive and specific biomarker to identify patients with obesity who are at risk of developing CKD. The role of microRNAs (miRNAs) has emerged as a promising area for diagnostic and therapeutic applications in kidney disease. Recent research has highlighted the specific roles of various miRNAs in renal function, showing that their dysregulation can contribute to the development of kidney diseases. This review will discuss the emerging role of miRNAs in the context of ORG, focusing on their potential as biomarkers and therapeutic targets for this increasingly prevalent disease.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.