• Indeed, the degree of foot process effacement correlates with the amount of proteinuria 43,44 and original studies by Velosa, Donadio and Holley showed diffuse foot process in all nephrotic patients with FSGS, involving all glomeruli, whether or not morphologic alterations were noted on light microscopy. (renalandurologynews.com)
  • Hemorrhagic fever with renal syndrome (HFRS) caused by pathogenic hantaviruses in Europe and Asia is often characterized by acute kidney injury (AKI) with massive proteinuria. (biomedcentral.com)
  • Severe infections with hantaviruses HTNV, Dobrava-Belgrade virus (DOBV), or PUUV are characterized by AKI with massive proteinuria. (biomedcentral.com)
  • However, patients with primary podocytopathy-minimal change disease (MCD) and primary FSGS, which result from a generalized podocyte insult-are more likely to have massive proteinuria and develop nephrotic syndrome. (renalandurologynews.com)
  • Tubular proteinuria is a result of tubulointersitial disease affecting the proximal renal tubules and interstitium. (medscape.com)
  • Proteinuria stimulates tubular chemokine expression and activates complement pathway which result in inflammatory response and fibrosis in the interstitium that contributes to progression of CKD [ 3 ]. (karger.com)
  • 1 g/24h should serve as a clue that proteins other than albumin (i.e. light chains, tubular proteinuria) account for the proteinuria and further evaluation (urinary protein electrophoresis, retinol binding protein) is necessary to identify the cause of the FSGS lesion. (renalandurologynews.com)
  • In this review, we highlight new molecular insights aiding our understanding of the initiation and progression of DN, including glomerular insulin resistance, dysregulation of cellular substrate utilisation, podocyte-endothelial communication, and inhibition of tubular sodium coupled glucose reabsorption. (scite.ai)
  • When filtration cells (podocytes) in the kidney's glomeruli become damaged due to either immune complexes in the blood (called glomerulonephritis), or due to dense deposits of hard protein (amyloid), abnormal accumulation of which is called amyloidosis, degeneration of the kidney's tubular system occurs. (petmd.com)
  • Most cases of proteinuria can be classified as tubular, overflow, or glomerular. (medscape.com)
  • Tubular proteinuria occurs most commonly in disease processes affecting the tubulo-interstitial component of the kidney. (medscape.com)
  • A ) Representative Western blot and densitometric analysis of SGLT2 protein in renal proximal tubular cells (RPTECs), used as positive control, and podocytes exposed to medium alone (control) or albumin (10 mg/ml, 6 hours). (jci.org)
  • Amiloride, an epithelial sodium channel (ENaC) inhibitor, was reported to reduce proteinuria in animal studies and case reports independent of ENaC inhibition. (karger.com)
  • We hypothesized that amiloride not triamterene (an analog of amiloride) would reduce proteinuria in the patients with proteinuric kidney disease. (karger.com)
  • Tangshenning (TSN) has been shown to reduce proteinuria, protect renal function, and reduce podocyte damage. (hindawi.com)
  • TSN has been applied clinically for many years to reduce proteinuria and improve renal function in patients with DN, and its therapeutic effects have been confirmed in clinical trials [ 10 ]. (hindawi.com)
  • Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. (hindawi.com)
  • For example, paraprotein deposition can induce a glomerulopathy leading to the additional loss of albumin and more profound proteinuria. (medscape.com)
  • 50% of total proteinuria is due to albumin then the possibility of a tubulopathy or presence of light chains should be considered. (renalandurologynews.com)
  • The first efficacy evaluation index was remission rate (complete remission and partial remission), and the secondary efficacy evaluation indices included relapse rate, proteinuria, serum albumin and estimated glomerular filtration rate (eGFR). (biomedcentral.com)
  • Here, we have shown that dapagliflozin provided glomerular protection in mice with protein-overload proteinuria induced by bovine serum albumin (BSA), to a similar extent as an ACE inhibitor used as standard therapy for comparison. (jci.org)
  • Through in vitro studies with cultured podocytes loaded with albumin we have identified what we believe to be a novel mechanism of action for SGLT2 inhibitor that directly targets podocytes and relies on the maintenance of actin cytoskeleton architecture. (jci.org)
  • Human cultured podocytes express SGLT2 that is upregulated by albumin. (jci.org)
  • B ) SGLT2 mRNA expression evaluated by real-time qPCR analysis in podocytes exposed to medium alone (control) or albumin (10 mg/ml) for 3 and 6 hours. (jci.org)
  • Alport syndrome is a genetic disorder characterized by kidney disease with high levels of proteinuria, hearing loss and eye abnormalities caused by mutations in the genes (COL4A3, COL4A4, and COL4A5) needed for production of type 4 collagen. (ozarksfirst.com)
  • podocytes run the risk of detachment from the basement membrane due to a decrease in the adherence to the surrounding matrix after contraction, a process called foot processes effacement. (degruyter.com)
  • Although effacement is not observed in the absence of proteinuria, heavy proteinuria may occur with normal foot processes. (msdmanuals.com)
  • Mice lacking all three isoforms develop proteinuria, podocytopathy and die of renal failure. (jax.org)
  • Proteinuria is a major determinant of progression of chronic kidney disease (CKD), which is associated with more rapid worsening of renal function and earlier initiation of renal replacement therapy independent of estimated glomerular filtration rate (eGFR) [ 1 ]. (karger.com)
  • DN progression is associated with podocyte damage due to reduced autophagy caused by mTORC1 activation. (hindawi.com)
  • Podocytes are the last barrier of the glomerular filtration membrane, and podocyte dysfunction can cause proteinuria and glomerular sclerosis, exacerbating the progression of DN [ 3 ]. (hindawi.com)
  • Podocyte damage caused by weak autophagic activity is an essential mechanism underlying DN progression [ 5 ]. (hindawi.com)
  • mTORC1 activation inhibits autophagy, and it is considered to be a molecular marker of diabetic nephropathy [ 7 , 8 ], as the decrease in podocyte autophagic activity caused by mTORC1 activation plays a vital role in the progression of this disease [ 9 ]. (hindawi.com)
  • Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease. (hindawi.com)
  • Patients with idiopathic MGN may experience spontaneous remission, persistent proteinuria of variable degree, or progression to kidney failure. (medscape.com)
  • Discussion Podocyte dysfunction is a key element in understanding the progression of CKD resulting in proteinuria. (wits.ac.za)
  • Minimal change disease causes abrupt onset of edema and heavy proteinuria, mostly in children. (msdmanuals.com)
  • Rather, it is a clinical state that TNF- plays a pathogenic role in the characterized by heavy proteinuria and induction and/or maintenance of glomeru- hypoalbuminaemia, often associated with lar barrier dysfunction [ 8 ]. (who.int)
  • Focal segmental glomerulosclerosis (FSGS) is a frequent glomerular kidney disease that is revealed by proteinuria or even nephrotic syndrome. (nephcure.org)
  • We hypothesized that podocytes are susceptible to filtered plasma components, including hormones and growth factors that stimulate signaling pathways leading to glomerulosclerosis. (medscape.com)
  • Herein, we report that genetic activation of Gα12 in podocytes leads to time-dependent increases in proteinuria and glomerulosclerosis. (medscape.com)
  • Proteinuria increased with age, and by 12-14 months, many demonstrated glomerulosclerosis with ultrastructural changes, including foot process fusion and both mesangial and subendothelial deposits. (medscape.com)
  • We tested whether Myh9 podocyte deletion predisposed mice to glomerulopathy in response to injury by doxorubicin hydrochloride (Adriamycin), and we found that Myh9 podocyte-deleted mice developed proteinuria and glomerulosclerosis, while control mice were resistant. (johnshopkins.edu)
  • Dapagliflozin limited proteinuria, glomerular lesions, and podocyte dysfunction and loss. (jci.org)
  • Experimental studies have shown that the main bioactive components of TSN, astragaloside IV, calycosin, emodin, ferulic acid and quercetin have beneficial effects on diabetic nephropathy by reducing proteinuria, protecting renal function, and inhibiting renal fibrosis [ 13 - 18 ]. (hindawi.com)
  • More importantly, astragaloside IV (the main component of Astragali Radix) and emodin (the main component of Rhei Radix Et Rhizoma) ameliorate podocyte damage in diabetic nephropathy by enhancing podocyte autophagy [ 13 , 16 ]. (hindawi.com)
  • Faulty podocyte structure and filtration also characterize diabetic nephropathy and glomerular diseases (e.g., focal and segmental glomerular sclerosis), which were once considered orphan diseases but have become more prevalent in recent years as sedentary lifestyles and diets high in processed foods have become commonplace. (sciencedaily.com)
  • Overflow proteinuria is most commonly associated with increased production of abnormal low molecular weight proteins (eg, light chains in multiple myeloma, myoglobin in rhabdomyolysis) that exceeds the reabsorption capacity of the proximal tubule, leading to spilling of the protein into the urine. (medscape.com)
  • A yeast two-hybrid screening of kidney cDNA proved to find dendrin in the kidney podocytes, where it connects to cytoskeleton proteins: S-S-SCAM and CIN85. (wikipedia.org)
  • Experimental research found a markedly decreased expression of autophagy-related proteins such as Beclin-1, Atg12-Atg5, and LC3-II in a diabetic mouse model and in a high glucose-induced podocyte injury model [ 4 ]. (hindawi.com)
  • The impact of hantaviral nucleocapsid proteins (N proteins) on motility was examined by transfection of podocytes. (biomedcentral.com)
  • The direct impairment of migration capacity of renal cells by hantaviral N proteins may contribute substantially to proteinuria observed in the clinical picture of hantavirus infection. (biomedcentral.com)
  • Damage to or loss of these cells can result in larger and larger proteins being lost from the blood (proteinuria), causing kidney damage and ultimately, Chronic Kidney Disease (CKD). (ncl.ac.uk)
  • Patients with nephrotic syndrome lose too many necessary proteins into the urine (proteinuria). (petmd.com)
  • Transient proteinuria occurs in persons with normal kidney function, bland urine sediment, and normal blood pressure. (medscape.com)
  • Noteworthy, the podocytes that are encountered in the urine are viable despite the glomerular hostile environment and the urinary acidity. (degruyter.com)
  • Neph1 is essential for the maintenance of podocytes--neuron-like cells with long finger-like projections that wrap around the glomerular capillaries, serving as the final barrier between the blood and the urine. (sciencedaily.com)
  • When podocyte structure fails, the kidney is no longer able to act as an effective filter, and excessive protein escapes the capillaries into the urine. (sciencedaily.com)
  • My current research concerns podocytes, the specialised cells in the kidney glomerulus that form the sieve to filter waste products from the blood into the urine. (ncl.ac.uk)
  • Cathepsin L levels were elevated in the urine of the renal disease group, in keeping with the notion that Cathepsin L proteolysis plays a critical role in the various forms of proteinuria. (wits.ac.za)
  • 3.5 g of proteinuria on a spot urine protein-to-creatinine ratio. (medscape.com)
  • The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for evaluating and managing chronic kidney disease (CKD) includes proteinuria in the staging of CKD. (medscape.com)
  • A tripartite complex of suPAR, APOL1 risk variants and αvβ3 integrin on podocytes mediates chronic kidney disease. (nephcure.org)
  • Proteinuria identifies patients with kidney damage and those at risk for worsening kidney disease and increased cardiovascular morbidity. (medscape.com)
  • Neutral endopeptidase, a podocyte antigen that can digest biologically active peptides, was identified as the target antigen in a subset of patients with antenatal membranous nephropathy. (medscape.com)
  • In contrast, patients with secondary FSGS are more likely to present with slowly increasing proteinuria that may be in the nephrotic-range, but the patients do not develop full-blown nephrotic syndrome (with hypoalbuminemia). (renalandurologynews.com)
  • Patients have normal renal function and proteinuria usually is less than 1 g/day with no hematuria. (medscape.com)
  • Patients who respond (ie, have cessation of proteinuria or a diuresis if edema is present) should continue prednisone for another 2 weeks and change to a maintenance regimen to minimize toxicity (2 to 3 mg/kg on alternate days for 4 to 6 weeks in children and for 8 to 12 weeks in adults, tapering during the next 4 months). (msdmanuals.com)
  • To mimic activation of Gα12 pathways, constitutively active Gα12 (QL) was conditionally expressed in podocytes using Nphs2-Cre and LacZ/floxed QLα12 transgenic mice. (medscape.com)
  • QLα12 LacZ+/Cre+ mice showed no changes in podocyte number, apoptosis, proliferation or Rho/Src activation. (medscape.com)
  • To investigate the role of MYH9 in kidney disease, we selectively deleted Myh9 from mouse podocytes and found that mutant C57BL/6 mice did not develop renal insufficiency or proteinuria compared to control littermates, even when the mice were aged for 9 months. (johnshopkins.edu)
  • To explain the surprisingly normal phenotype, we considered genetic redundancy with the paralog Myh10 in podocytes, but we found that Myh10 was not expressed in podocytes in Myh9-deficient or control mice. (johnshopkins.edu)
  • In summary, Myh9 podocyte deletion in C57BL/6 mice results in susceptibility to experimental doxorubicin hydrochloride glomerulopathy. (johnshopkins.edu)
  • The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. (hindawi.com)
  • Urinary podocyte loss is a silent phenomenon that precedes proteinuria in glomerular diseases [ 3 , 4 ]. (hindawi.com)
  • Therefore, in diseases that can threaten the glomerular normal environment, the presence and the quantification of urinary podocytes can be of remarkable relevance, as it can herald or accompany the appearance of proteinuria, and could offer another view to the interpretation and clinical approach and outcome of proteinuria. (degruyter.com)
  • Accumulation of α-synuclein mediates podocyte injury in Fabry nephropathy. (uib.no)
  • The human podocyte cell line was derived from human normal podocytes conditionally transformed with a temperature-sensitive mutant of the simian virus 40 (SV40) large T antigen. (biomedcentral.com)
  • After amiloride prescription, his proteinuria turned negative and was detected as microalbuminuria, while podocyturia decreased to control rates. (hindawi.com)
  • Herein, in vitro experiments using a high glucose-induced podocyte injury model were performed. (hindawi.com)
  • Results showed that TSN treatment enhanced the weakened nephrin expression and autophagic activity of podocytes and inhibited the mTORC1 pathway (p-mTOR, mTOR, p-p70S6K, p70S6K, ULK1, and 4EBP1) under high glucose conditions. (hindawi.com)
  • In summary, TSN reduces podocyte damage induced by high glucose via inhibiting mTORC1 pathway and downstream targets and restoring podocyte autophagy. (hindawi.com)
  • TSN has also been confirmed to reduce podocyte damage in DN rats and high glucose-cultured podocytes [ 11 , 12 ]. (hindawi.com)
  • We have now determined that in cultured podocytes, high glucose led to increases in activation of EGFR signaling but decreases in autophagy activity as indicated by decreased beclin-1 and inhibition of LC3B autophagosome formation as well as increased rubicon (an autophagy inhibitor) and SQSTM1 (autophagy substrate). (diabetesjournals.org)
  • the more severe the proteinuria, the more significant the glomerular disease. (medscape.com)
  • The laboratory's research interest is focused the molecular biology of glomerular disease, and particularly on injury to podocytes, a key cell type in the glomerulus. (bidmc.org)
  • Alport syndrome is a rare genetic kidney disorder caused by mutations in COL4A3/4/5 genes, characterized by podocyte injury and impaired kidney filter function leading to proteinuria. (ozarksfirst.com)
  • The laboratory studies how transcriptional regulation by WT1 and other transcription factors regulates the podocyte response to injury, thus determining whether injury may be repaired or leads to irreversible kidney diseases such as focal segmental glomerular sclerosis (FSGS). (bidmc.org)
  • This histopathological lesion may be caused by a primary podocyte injury (idiopathic FSGS) but is also associated with other pathologies (secondary FSGS). (nephcure.org)
  • Since primary FSGS is caused by a circulating "permeability factor" that is toxic to the podocyte, evidence of podocyte damage must be visible as equally distributed among all glomerular capillary loops. (renalandurologynews.com)
  • Taken together, these studies suggest that Gα12 activation promotes glomerular injury without podocyte depletion through a novel mechanism regulating collagen (α)IV expression, and supports the notion that glomerular damage may accrue through persistent GPCR activation in podocytes. (medscape.com)
  • Within the brain, dendrin is normally found in the forebrain and hippocampus and in the kidneys, dendrin is normally found in the slit diaphragm and podocytes. (wikipedia.org)
  • In normal mature kidneys, dendrin is found only in the podocytes near the slit diaphragm. (wikipedia.org)
  • Several diseases cause a nephrotic syndrome, as they damage the glomerular podocytes. (nih.gov)
  • Nephrotic syndrome is neither a single gested that IL-1 has a significant role in the disease nor even a heterogeneous group of immunopathogenesis of proteinuria [ 7 ] and related diseases. (who.int)
  • The impaired motility depends on viral replication and transfection of podocytes with N protein of PUUV or HTNV reveals that the expression of N protein alone is sufficient to deteriorate podocyte function. (biomedcentral.com)
  • These findings are generally consistent with previous assessments, providing stronger evidence of protein restoration and the disease modifying effect of ELX-02 and potential for improvement in proteinuria with longer duration of treatment. (ozarksfirst.com)
  • It can be classified on the basis of the amount of protein (nephrotic or non-nephrotic), the type of protein (albuminuria or low molecular weight proteinuria), or the underlying pathological damage (glomerular vs non-glomerular). (medscape.com)
  • The infection of renal cells by hantaviruses may contribute to proteinuria and may represent a determinant in the clinical course of HFRS. (biomedcentral.com)
  • Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. (hindawi.com)
  • Primary podocytes (Lonza) were maintained in RPMI medium (Capricorn) supplemented with 10% fetal calf serum (FCS). (biomedcentral.com)
  • To determine if the levels of Cathepsin L and Dynamin correlates with the degree of proteinuria. (wits.ac.za)
  • Podocyturia is irreversible and any attempt to decrease its amount, particularly in early phases of a glomerulopathy, should be accompanied by reductions in proteinuria and delays in kidney function decline. (hindawi.com)
  • Podocyturia can precede proteinuria and can aggravate it. (degruyter.com)
  • Glomerular proteinuria can also be categorized according to whether pathological damage of the glomerulus is present. (medscape.com)
  • Types that do not result from pathological damage to the glomerulus include transient and orthostatic proteinuria. (medscape.com)
  • Types in which the patient has no pathological damage to the glomerulus include transient and orthostatic proteinuria. (medscape.com)
  • In our earlier investigation, the therapeutic effects of four kinds of TCM on streptozotocin (STZ) induced DN rats were observed and WSJPR has shown significant effect on decreasing proteinuria. (biomedcentral.com)
  • Cilnidipine suppresses podocyte injury and proteinuria in metabolic syndrome rats: possible involvement of N-type calcium channel in podocyte. (lktlabs.com)
  • Serum Dynamin (r = 0.12, p-value = 0.49) had a positive correlation to the degree of proteinuria but vi the correlation was not significant at the 5% significance level. (wits.ac.za)
  • Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been shown to be helpful to reduce kidney function decline, particularly when proteinuria exists [ 2 ]. (hindawi.com)
  • We have recently begun studying how transitions in the repertoire of integrin adhesion receptors for the glomerular basement membrane during podocyte injury affect the transcriptional response. (bidmc.org)
  • Gα12/13 are expressed in podocytes and couple to angiotensin II, thrombin, endothelin and LPA receptors, which are important in renal injury. (medscape.com)