Search Results (35)

The kidney and the brain share similarities in terms of structure and haemodynamic regime. The aim of the study was to assess a potential correlation of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sFlt-1), and placental growth factor (PlGF) with biomarkers of podocyte damage, proximal tubular (PT) dysfunction, and endothelial dysfunction, as well as with cerebral vessels haemodynamic indices in neurologic asymptomatic type 2 DM patients. A cohort of 212 patients diagnosed with type 2 DM and 49 age- and gender-matched healthy controls were enrolled in the study. Parameters studied were urinary albumin/creatinine ratio (UACR), biomarkers of podocyte damage (synaptopodin, podocalyxin), PT dysfunction (kidney injury molecule-1-KIM-1, N-acetyl-β-(D)-glucosaminidase-NAG), endothelial dysfunction (P-selectin), VEGF, sFlt-1, and PlGF. The cerebrovascular hemodynamic indices evaluated were intima–media thickness (IMT) in the common carotid arteries (CCAs), the pulsatility index (PI), and the resistivity index (RI) in the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs). Cerebrovascular reactivity (CVR) was assessed by the breath-holding index (BHI). In multivariable regression analysis, serum VEGF correlated directly with UACR, synaptopodin, NAG, serum P-selectin; serum sFlt-1 correlated directly with UACR, synaptopodin, podocalyxin, NAG, KIM-1; serum PlGF correlated negatively with eGFR and directly with UACR, synaptopodin, KIM-1. IMT-CCA correlated indirectly with eGFR and directly with UACR, serum P-selectin, and serum sFlt-1. The PI-ICAs correlated negatively with eGFR and positively with UACR, synaptopodin, serum P-selectin, and serum sFlt-1. The PI-MCAs correlated indirectly with eGFR and directly with synaptopodin, serum P-selectin, and serum sFlt-1. The RI-ICAs had a negative correlation with eGFR and a positive one with UACR, synaptopodin, NAG, KIM-1, urinary sFlt-1, and serum PlGF. The RI-MCAs displayed an indirect correlation with eGFR and a direct correlation with NAG, KIM-1, and serum sFlt-1. The BHT correlated directly with eGFR and negatively with serum P-selectin and serum PlGF. The study shows a significant association of VEGF, sFlt-1, and PlGF with biomarkers of podocyte injury, PT dysfunction, and endothelial dysfunction in early stages of DKD. These pro-angiogenic and anti-angiogenic factors correlated with cerebrovascular haemodynamic indices in neurologic asymptomatic type 2 DM, even in the normoalbuminuric stage of diabetic kidney disease. 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

Cancer metastasis, the spread of tumour cells from the primary site to distant organs, is responsible for over 90% of cancer deaths, yet effective treatments remain elusive due to incomplete understanding of the molecular drivers involved. Podocalyxin (PODXL), a protein overexpressed in many aggressive cancers, links the cell membrane to the internal skeleton through its interaction with Ezrin, an actin cytoskeleton cross-linker. Despite its therapeutic relevance, the PODXL–Ezrin interface remains structurally uncharacterised and pharmacologically intractable. Here, we employed an integrated computational approach combining protein–protein docking, molecular dynamics (MD) simulations, and virtual screening to investigate the structural basis of the PODXL–Ezrin interaction. Using AlphaFold-predicted structures, we modelled PODXL and Ezrin complexes, revealing that PODXL’s cytoplasmic domain stabilises upon Ezrin binding, with Arg495 mediating temporally distinct electrostatic interactions essential for initial complex assembly. Particularly, we characterised the R495W missense mutation in PODXL’s Ezrin-binding domain, demonstrating that substitution of arginine with bulky, hydrophobic tryptophan may allosterically destabilise Ezrin’s dormant conformation. This mutation slightly increases the intramolecular distance between the F3 subdomain and C-terminal domain from 2.59 Å to 3.40 Å, thus leading to potential partial unmasking of the Thr567 phosphorylation site that could plausibly prime Ezrin for activation. Molecular dynamics simulations in the WT state with a total simulation time of 100 ns revealed enhanced structural rigidity and reduced radius of gyration fluctuations in the mutant complex, consistent with a potential “locked,” activation-prone state that amplifies oncogenic signalling. Through virtual screening, we identified NSC305787 as a selective destabiliser of the R495W mutant complex by disrupting key Trp495–pre-C-terminal loop Ezrin interactions and causing steric hindrance to PIP2 recruitment. Our findings identified mutation-dependent changes in drug binding that can guide the development and repurposing of compounds for targeting PODXL-related cancers and improve patient outcomes in PODXL-altered malignancies. Full article

Introduction and Objectives: Persistent hepatic inflammation serves as a key driver of fibrogenesis in chronic hepatitis B. Fibrosis is a complex molecular and cellular process. Podocalyxin is a type I transmembrane sialomucin, and physiological expression of podocalyxin has been identified in the liver. Pentraxin 3 plays a crucial role in humoral innate immune responses. Isthmin-1 has been associated with metabolic regulation and immune response modulation. We aimed to evaluate the immunoreactivities of podocalyxin, Isthmin-1, and pentraxin-3 in the liver tissue of patients with chronic hepatitis B. Materials and Methods: Power analysis was performed (effect size (f = 0.5), (α) = 0.05 and statistical power of 0.80). Sample size was calculated to be a total of 63 samples, with 21 samples per group. Individuals with negative hepatitis serology and normal liver histopathology, from whom liver tissue was obtained for any reason, were designated as the control group. Liver specimens of chronic hepatitis B were categorized into F0–F2 (no or mild fibrosis) and ≥F3 (advanced fibrosis). Immunohistochemical staining was performed to assess the expression and immunoreactivity of Podocalyxin, Isthmin-1, and Pentraxin-3. A histoscore was created based on the prevalence of staining immunoreactivity (0.1: <25%, 0.4: 26–50%, 0.6: 51–75%, 0.9: 76–100%) and intensity (0: none, +0.5: very low, +1: low, +2: moderate, +3: severe). Results: A statistically significant increase in Podocalyxin, Pentraxin-3, and Isthmin-1 immunoreactivities was found in fibrotic liver tissue compared to normal liver tissue and mild fibrotic groups (p < 0.05). Conclusions: We concluded that our findings suggest these proteins may have an additional role in the progression of liver fibrosis in chronic hepatitis B. Full article

Background: Podocalyxin (PODXL) has been identified as a promising therapeutic target and a potential diagnostic biomarker in various tumors. Despite the therapeutic potential of anti-PODXL monoclonal antibodies (mAbs), their further development has been limited by concerns regarding potential on-target off-tumor toxicities. To minimize adverse effects on normal tissues, developing a cancer-specific mAb (CasMab) against PODXL is essential. Methods: Our group established a cancer-specific anti-PODXL mAb, PcMab-60 (IgM, κ), through the screening of over one hundred hybridoma clones. In this study, PcMab-60 was engineered into a humanized IgG₁-type mAb (humPcMab-60), and its antitumor activity was examined using mouse xenograft models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer. Results: HumPcMab-60 retains cancer-specific reactivity; humPcMab-60 reacted to PDAC cell lines (PK-45H and MIA PaCa-2) and the colorectal cancer cell line (Caco-2), but not to a normal lymphatic endothelial cell line in flow cytometry. Furthermore, humPcMab-60 exerted antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against PODXL-expressing cell lines and showed antitumor effects against the tumor xenografts. Conclusions: A humanized anti-PODXL CasMab, humPcMab-60, could be a promising mAb-based tumor therapy. Full article

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

Background/Objectives: Podocalyxin is a sialoprotein mainly expressed in the kidney cortex and lung tissue, which has been described as a component of the podocyte glycocalyx. This protein promotes the reorganization of the podocyte cytoskeleton, as well as the morphogenesis and differentiation of nascent podocytes, actively participating in glomerular filtration. Previous research has suggested that PODXL haploinsufficiency leads to podocytopathy with development of focal segmental glomerulosclerosis, a disorder that has been demonstrated in Podxl-deficient animal models and proposed as a primary cause in human families affected by this condition. However, only a few families have been reported, which limits the understanding about the spectrum of phenotype and prognosis of the disease. Methods: We performed high-throughput sequencing in a cohort of young adults with CKD, describing the clinical scenario of those who harbored truncating variants in the PODXL gene and testing the families for detected variants. Results: The PODXL gene exhibited a slight deviation in loss intolerance probability and moderate deviation in the observed/expected ratio of variation, which is typically observed in dominant genes with age-dependent incomplete penetrance or variable expression. We reported four novel truncating variants in the PODXL gene, along with a collection of previously published monoallelic truncating variants. Conclusions: These findings further support evidence about genetic defects in the PODXL gene associated with a new molecular entity of podocytopathy with adult onset. Additionally, the nucleotide sequence of PODXL contains particularities that require careful analysis to interpret the effect of the variants detected in this gene. Full article

Extracellular vesicles (EVs) have a key role in intercellular communication. We hypothesized that EVs are biomarkers of nephropathy or kidney allograft rejection. We screened patients with chronic kidney disease (CKD) and kidney transplant (KT) recipients. We measured the urine and plasma levels of total EVs overall and EV subpopulations (positive for podocalyxin, aquaporin-1, CD133, CD144, CD19, CD3, CD16, CD56, or CD41). We included 92 patients with CKD, 70 KT recipients, and 33 healthy volunteers. In CKD, the total urine EV concentration was correlated positively with the estimated glomerular filtration rate (eGFR), but none of the subpopulations was identified as a potential biomarker of nephropathy. Among the KT recipients, 30 had good allograft function and 40 had allograft disease (13 with antibody-mediated rejections (ABMR), 12 with T-cell-mediated rejection (TCMR), and 15 with allograft dysfunction). Patients with ABMR had low plasma levels of EVs derived from B-cells, T-cells, and endothelium (p = 0.003, 0.009, and 0.005, respectively). Patients with TCMR had a low urine level of EVs derived from endothelium (p = 0.05). EVs derived from B-cells, T-cells, and endothelium might be biomarkers of kidney allograft rejection. However, we did not identify biomarkers of nephropathy in CKD. Full article

Background/Objectives: Nephrotic syndrome, a glomerular disease caused by podocyte dysfunction, is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Current treatment relies on corticosteroids, which carry the risk of long-term side effects. Physalis angulata has potential as an adjunct therapy for immune-mediated kidney injury. This study aims to evaluate the effects of Physalis angulata extracts on anti-nephrin IgG, IL-4, and podocytopathy through BAFF inhibition in a doxorubicin-induced nephrotic syndrome rat model. Methods: This experimental study involved 36 Sprague–Dawley rats divided into control and treatment groups. The treatment groups received Physalis angulata extract at doses of 500 mg/kgBW, 1500 mg/kgBW, and 2500 mg/kgBW, or in combination with prednisone, alongside a group receiving prednisone monotherapy. Podocytopathy was assessed using proteinuria, nephrin, podocalyxin, and GLEPP-1. Proteinuria was measured using spectrophotometry. Serum BAFF levels, renal IL-4, urinary nephrin, and urinary podocalyxin were analyzed using ELISA. Renal nephrin, renal podocalyxin, GLEPP-1, and BAFF expression were evaluated by immunofluorescence microscopy. The data were analyzed using SPSS 25. Results: The results showed significant reductions in proteinuria, serum BAFF levels, renal BAFF expression, anti-nephrin IgG, IL-4, urinary nephrin, and urinary podocalyxin, along with significant increases in GLEPP-1, renal nephrin, and renal podocalyxin expression, in all treatment groups compared to the nephrotic syndrome control group. The combination of Physalis angulata at 2500 mg/kgBW with prednisone demonstrated the best effects. Conclusions: Physalis angulata shows promise as an adjuvant therapy for nephrotic syndrome by improving podocytopathy through BAFF inhibition. Further research is needed to evaluate its long-term safety, optimize dosing, and explore clinical applications in humans. Full article

Background/Objectives: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial. Because of its complications and reduced number of diagnostic biomarkers, it is important to explore new biomarkers with possible roles in the early diagnosis of DKD. Our study aims to investigate the pattern of previously identified metabolites and their association with biomarkers of endothelial dysfunction, proximal tubule (PT) dysfunction, and podocyte injury. Methods: A total of 110 participants, comprising 20 healthy individuals and 90 patients divided in three groups were enrolled in the study: normoalbuminuria, microalbuminuria, and macroalbuminuria. Untargeted and targeted metabolomic methods were employed to assess urinary and serum biomarkers, as well as indicators of endothelial dysfunction, podocyte damage, and PT dysfunction through ELISA techniques. Results: Our research uncovered specific metabolites that exhibit varying levels across different sub-groups. Notably, glycine serves as a distinguishing factor between group C and the normoalbuminuric group. Furthermore, glycine is correlated with endothelial markers, especially VCAM. We observed a gradual decrease in kynurenic acid levels from group C to group P3; this biomarker also demonstrates an inverse relationship with both p-selectin and VCAM. Additionally, tryptophan levels decline progressively from group C to group P3, accompanied by a negative correlation with p-selectin and VCAM. Urinary tiglylglycine also differentiates among the patient groups, with concentrations decreasing as the condition worsens. It shows a strong positive correlation with nephrin, podocalyxin, KIM1, and NAG. Conclusions: In conclusion, glycine, tiglylglycine, kynurenic acid and tryptophan may be considered putative biomarkers for early diagnosis of DKD and T2DM progression. Full article

Objectives: The downregulation of anti-adhesive regulatory proteins and upregulation of adhesive genes are critical for the receptive endometrium. This study was designed to determine whether switching between the anti-adhesive podocalyxin (PDX) and adhesive HOXA10 receptivity modulator occurs in the endometrium of women with recurrent implantation failure (RIF). Methods: Twenty-four patients with RIF who could not conceive for three or more cycles despite good-quality embryo transfer constituted the study group. Twenty-four patients with unexplained infertility (UEI) matched for age, BMI, and infertility duration were included in the control group. Twenty women scheduled to undergo intrauterine device (IUD) placement for birth control were included in the comparative group. Endometrial tissue was collected from patients with RIF and UEI during egg retrieval after ovarian stimulation using the GnRH antagonist protocol. In the fertile group, endometrial tissues were collected during IUD insertion. HOXA10 mRNA expression was analyzed by qRT-PCR and PDX protein expression was analyzed by ELISA. The relative expression of endometrial HOXA10 mRNA was calculated using the 2^−ΔΔCt equation. Results: The relative expression of HOXA10 mRNA in the RIF group was significantly lower than that in the UEI group (p < 0.001). HOXA10 mRNA expression in the fertile group was significantly higher than that in the RIF group and was similar to that in the UEI group. PDX expression in the RIF group was significantly higher than that in the UEI group (p < 0.001). PDX expression in the fertile group was significantly lower than in the RIF and UEI groups. A negative correlation was detected between the anti-adhesive PDX protein and adhesive HOXA10 (r = −0.797, p < 0.001). Although there was a positive correlation between endometrial thickness recorded on the day of hCG administration and HOXA10 (r = 0.590, p < 0.01), endometrial thickness was negatively correlated with PDX (r = −0.529, p < 0.01). Conclusions: The failed physiological downregulation of the anti-adhesive PDX protein in patients with RIF prevented the upregulation of adhesive HOXA10 mRNA. Full article

Patients carrying APOL1 risk alleles (G1 and G2) have a higher risk of developing Focal Segmental Glomerulosclerosis (FSGS); we hypothesized that escalated levels of miR193a contribute to kidney injury by activating renin–angiotensin system (RAS) in the APOL1 milieus. Differentiated podocytes (DPDs) stably expressing vector (V/DPD), G0 (G0/DPDs), G1 (G1/DPDs), and G2 (G2/DPDs) were evaluated for renin, Vitamin D receptor (VDR), and podocyte molecular markers (PDMMs, including WT1, Podocalyxin, Nephrin, and Cluster of Differentiation [CD]2 associated protein [AP]). G0/DPDs displayed attenuated renin but an enhanced expression of VDR and Wilms Tumor [WT]1, including other PDMMs; in contrast, G1/DPDs and G2/DPDs exhibited enhanced expression of renin but decreased expression of VDR and WT1, as well as other PDMMs (at both the protein and mRNA levels). G1/DPDs and G2/DPDs also showed increased mRNA expression for Angiotensinogen and Angiotensin II Type 1 (AT1R) and 2 (AT2R) receptors. Protein concentrations of Brain Acid-Soluble Protein [BASP]1, Enhancer of Zeste Homolog [EZH]2, Histone Deacetylase [HDAC]1, and Histone 3 Lysine27 trimethylated [H3K27me3] in WT1-IP (immunoprecipitated proteins with WT1 antibody) fractions were significantly higher in G0/DPDs vs. G1/DPD and G2/DPDs. Moreover, DPD-silenced BASP1 displayed an increased expression of renin. Notably, VDR agonist-treated DPDs showed escalated levels of VDR and a higher expression of PDMMs, but an attenuated expression of renin. Human Embryonic Kidney (HEK) cells transfected with increasing APOL1(G0) plasmid concentrations showed a corresponding reduction in renin mRNA expression. Bioinformatics studies predicted the miR193a target sites in the VDR 3′UTR (untranslated region), and the luciferase assay confirmed the predicted sites. As expected, podocytes transfected with miR193a plasmid displayed a reduced VDR and an enhanced expression of renin. Renal cortical section immunolabeling in miR193a transgenic (Tr) mice showed renin-expressing podocytes. Kidney tissue extracts from miR193aTr mice also showed reduced expression of VDR and PDMMs, but enhanced expression of Renin. Blood Ang II levels were higher in miR193aTr, APOLG1, and APOL1G1/G2 mice when compared to control mice. Based on these findings, miR193a regulates the activation of RAS and podocyte molecular markers through modulation of VDR and WT1 in the APOL1 milieu. Full article

Objectives: To compare the levels of podocyte damage markers nephrin and podocalyxin in urine samples taken at the time of gestational diabetes mellitus (GDM) diagnosis and at birth. Amniotic fluid podocalyxin (pdx) and nephrin levels were also analyzed to determine whether GDM had an impact on fetal glomeruli. Methods: A total of 50 patients, including 24 patients diagnosed with gestational diabetes and 26 healthy pregnant women whose gestational weeks were matched, were included in the study. GDM was diagnosed with a 75 g oral glucose tolerance test (OGTT). Fresh morning urine samples from patients diagnosed with GDM were collected. The second urine sample was collected with the help of a catheter during birth. Amniotic fluid samples were taken from patients who gave birth by cesarean section. The urinary podocalyxin and nephrin levels were measured via the quantitative sandwich enzyme immunoassay. Albumin–creatinine ratio (uACR) was also calculated in urine samples. Results: Urinary nephrin and pdx levels on the day of GDM diagnosis were similar in the GDM and control groups. Microalbuminuria was detected in only one patient from each group at the time of GDM diagnosis. In the urine samples taken from the time of birth, pdx and nephrin levels of the GDM group were significantly higher than the control group (p < 0.001 for each). While microalbuminuria was detected in five patients (20.8%) at the time of birth in the GDM group, it was detected in only two patients (7.7%) in the control group. In the GDM group, a significant increase was detected between the urine pdx and nephrin levels measured at diagnosis and those measured at birth. In the control group, measurements at baseline and at birth were similar. There was no significant difference between the GDM and control groups in terms of amniotic fluid pdx and nephrin levels. A positive and significant correlation was detected between urinary pdx, nephrin, SBP, and uACR. Conclusions: While GDM triggers podocyte damage in maternal glomeruli, it does not cause significant change in fetal glomeruli. Full article

Equine gastric ulcer syndrome (EGUS) is a common condition in horses. This study explores the use of liquid proteomics to identify new biomarkers in saliva and serum to monitor EGUS treatment. The proteomes of horses with EGUS before and after a successful treatment with omeprazole were analysed. In saliva, 503 proteins were identified, with 7 upregulated and 6 downregulated post-treatment. Among the proteins that changed, there was an increase in vimentin, linked to wound healing, and a decrease in podocalyxin, associated with tissue damage. In serum, 206 proteins were found, with significant changes in 5. Keratin type I increased, supporting epithelial integrity, whereas immunoglobulin lambda decreased, indicating a reduced immune response. Gene ontology analysis revealed a decrease in immune-related pathways after successful treatment. Overall, 13 proteins in saliva and 5 in serum showed significant changes after treatment, highlighting the differential responses of saliva and serum in EGUS. This report creates new avenues for discovering potential biomarkers to monitor EGUS treatment, which is of high importance for the management of this prevalent disease. Full article

Objective: To determine whether the urinary excretion of podocyte degradation products varies according to PCOS phenotype and metabolic syndrome (MetS). Methods: The concentrations of podocalyxin (PDX) and nephrin, chronic markers of podocyte damage, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute glomerular damage, were analyzed in the morning urine samples of 50 PCOS patients and 50 healthy controls matched by age and BMI. Albuminuria was assessed by calculating the urine albumin–creatinine ratio (uACR). Results: The PDX, nephrin and NGAL concentrations of PCOS participants were significantly higher than those of the control group. While PDX, nephrin and NGAL levels of classic phenotypes were similar, they were higher than ovulatory and non-hyperandrogenic phenotypes. Significant increases in urinary levels of each podocyte protein were detected in PCOS patients with MetS compared to patients without MetS. A positive significant correlation between podocyte proteins and BMI, systolic blood pressure, testosterone, glucose, HOMA-IR and uACR. After adjusting for age and BMI, podocyte proteins were an independent risk factor for microalbuminuria. The incidence of microalbuminuria in PCOS increased 6-fold compared to controls. The frequency of microalbuminuria was higher in classical phenotypes than in ovulatory phenotype. The frequency of microalbuminuria in PCOS patients with MetS was 6.5 times higher than in PCOS patients without MetS. Conclusions: In PCOS accompanied by hyperandrogenemia or metabolic syndrome, leakage of acute and chronic podocyte breakdown products into the urine becomes more pronounced. Full article